CRISPR/CAS-RELATED METHODS AND COMPOSITIONS FOR TREATING CYSTIC FIBROSIS

- EDITAS MEDICINE, INC.

CRISPR/CAS-related compositions and methods for treatment of Cystic Fibrosis (CF).

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Description
REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No. 15/288,475, filed Oct. 7, 2016, which is a continuation of PCT International Patent Application No. PCT/US2015/023960, filed on Apr. 1, 2015, which claims the benefit of U.S. Provisional Application No. 61/977,488, filed Apr. 9, 2014, the contents of each of which are hereby incorporated by reference in their entirety herein, and to each of which priority is claimed.

SEQUENCE LISTING

The specification further incorporates by reference the Sequence Listing submitted herewith via EFS on Apr. 30, 2021. Pursuant to 37 C.F.R. § 1.52(e)(5), the Sequence Listing text file, identified as 084177_0247SEQ.txt, is 6,269,340 bytes and was created on Apr. 30, 2021. The Sequence Listing, electronically filed herewith, does not extend beyond the scope of the specification and thus does not contain new matter.

FIELD OF THE INVENTION

The invention relates to CRISPR/CAS-related methods and components for editing of a target nucleic acid sequence, and applications thereof in connection with Cystic Fibrosis (CF) or CF-like disease.

BACKGROUND

Cystic fibrosis (CF) is an autosomal recessive, hereditary disease caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene encodes a cAMP-gated channel that is involved in chloride and bicarbonate transport. It regulates sodium transport through inhibition of the epithelial sodium channel, which is encoded by the SCNN1A gene. CFTR is expressed on the apical surface of epithelial cells in the airway, gastrointestinal tract, reproductive tract, sweat glands and submucosal glands.

CF affects one in 3,500 children born in the United States. It is the most common fatal autosomal recessive disease in individuals of European descent (Tobias 2011; Essential Medical Genetics, John Wiley & Sons, ed. p. 312). There are approximately 30,000 subjects in the United States with the disease (From The Cystic Fibrosis Foundation; cff.org, accessed on Mar. 19, 2015).

The most common mutation in the CFTR gene is a deletion of the three nucleotides encoding Phenylalanine (F) at position 508 of the CFTR protein (also sometime referred to herein as “F508del”). This mutation is the causative mutation in approximately two-thirds of CF cases. The remaining cases are caused by at least 1000 different mutations, many of which cause a less severe form of the disease.

Subjects having CF can present at birth or in early infancy with pancreatic insufficiency. Pancreatic dysfunction leads to malabsorption of fat and fat-soluble vitamins, which causes poor growth as well as gallstones and biliary disease. The lung manifestations of the disease can be more severe but may present slightly after pancreatic manifestations, in infancy or early childhood. Aberrant chloride and sodium transport due to decreased CFTR activity causes lowered apical surface fluid levels in the lungs, which leads to “sticky” mucous and lower airway obstruction. Subjects having CF or CF-like disease suffer from frequent infections due to inability to clear mucous. Local inflammatory mediators try to clear the infection but have difficulty. The triad of inflammation, infection and obstruction leads to progressive destruction of the lung parenchyma. Eventually, many subjects having CF or CF-like disease die in their late 30's due to respiratory failure.

Current treatments for CF or CF-like disease delay lung destruction and slow disease progression. Treatments for the pulmonary manifestations of CF or CF-like disease include: antibiotics (oral, inhaled and intravenous), CFTR modulators (including CFTR potentiators), DNase, chest physiotherapy to loosen secretions and anti-inflammatory therapeutics. Treatment of the gastrointestinal manifestations includes supplemental gut soluble vitamins, high calorie diet and oral pancreatic enzymes. Subjects who develop diabetes are treated with insulin injections or an insulin pump. At the end stage, patients may benefit from lung transplant. Lung transplant may be combined with liver and/or pancreatic transplant.

Current treatments do not reverse the damage to the lungs or cure CF or CF-like disease. The average life expectancy for subjects having CF or CF-like disease is 37 years of age (MacKenzie et al., 2014; Annals of Internal Medicine 161(4):233-41). 80% of patients with CF or CF-like disease die from end-stage lung disease.

In spite of current therapies, there is a need for a therapy that prevents or delays the progression of disease in CF or CF-like disease.

SUMMARY OF THE INVENTION

Methods and compositions discussed herein provide for the treatment and prevention of Cystic Fibrosis (CF) and CF-like disease. The approach described herein aims to restore CFTR channel function, restore chloride, bicarbonate and/or sodium balance, and/or decrease mucous viscosity within the lungs, airways, gastrointestinal tract and reproductive tract.

CFTR modulators (both approved and in development) improve the functioning of mutant CFTR. These therapeutics improve CFTR functioning but do not return functionality to wild type levels. The approach described herein is expected to restore CFTR function through complete correction of the gene.

Gene therapy approaches are in development that deliver the CFTR channel gene to the lungs of CF or CF-like disease patients. However, gene therapy may require constant readministration over the course of the lifetime of a subject due to high cell turnover in target epithelial cells. The approach described herein is expected to restore CFTR function and/or ameliorate SCNN1A disinhibition permanently through one, two or several doses.

The CFTR gene encodes a 180-kDA cAMP-gated chloride (Cl—) channel. The channel has six transmembrane spanning domains and is expressed by epithelial cells, lymphocytes and cardiac myocytes. The CFTR regulates the viscosity of mucous through its activity in the epithelial cells of the lungs, gastrointestinal tract and reproductive tract. Mutations in the CFTR result in decreased CFTR activity. Decreased CFTR activity can lead to aberrant ion transport, which gives rise to various disease symptoms in the lungs and other tissues, such as accumulation of sticky mucus, airway obstruction, infection and inflammation. Correction of CFTR mutations will ameliorate or cure lung, gastrointestinal and/or reproductive symptoms of CF or CF-like disease.

The SCNN1A gene encodes the alpha subunit of the epithelial sodium channel (ENaC). The channel, comprised of alpha, beta and gamma subunits, regulates sodium transport into epithelial cells, including the epithelium of the lungs, sweat glands and kidneys. Mutations in the SCNN1A gene, (e.g. Val114ILE) have been shown to cause CF-like disease, characterized by pulmonary disease, including bronchiectasis. Mutations in SCNN1A also cause pseudohypoaldosteronism, a severe disease of the kidney. Pseudohypoaldosteronism is due to defective sodium transport within kidney epithelial cells; it is not caused by defective sodium transport in other tissues. The methods described herein include the targeted knockout of SCNN1A in the lung, gastrointestinal tract and/or reproductive tract. The methods described herein will not target kidney epithelium and will avoid the negative consequences of SCNN1A mutations within the kidney epithelium. One mutation in the SCNN1A gene, a 1477T>G substitution (W493R) has been identified in subjects who also have a mutation in CFTR. This mutation is associated with a severe CF or CF-like disease phenotype, including severe bronchiectasis, chronic bronchitis and/or severe gastrointestinal symptoms. This mutation has been found to be associated with 4-fold overactivity of the ENaC channel (Azad et al., 2009; Human Mutation 30: 1093-1103). Overactivity of the SCNN1A-encoded ENaC channel can contribute to CF and CF-like disease. In all subjects, the CFTR is involved in inhibition of ENaC. CFTR mutations in subjects with CF or CF-like disease leads to ENaC disinhibition, leading to overactivity of the ENaC channel. ENaC overactivity can lead to further reduction in viscosity of mucous in CF or CF-like disease subjects, as more sodium is absorbed at the apical surface of epithelial cells, followed by increased fluid absorption from the mucous layer within the lung (Baker et al., 2012; Medicine & Science in Sports and Exercise 44(12): 2315-2321). Increased fluid absorption from the mucous layer reduces mucous viscosity. Inhibition of ENaC through SCNN1A knockout and/or knockdown in subjects with CF or CF-like disease can ameliorate the symptoms of CF or CF-like disease. Mutations in the CFTR gene (also known as ABC35, ATP-binding cassette sub-family C, member 7, CFTR/MRP, dJ760C5.1, MRP7 and TNR-CFTR) have been shown to cause CF and/or CF-like disease. Mutations in the CFTR gene leading to CF and/or CF-like disease can be described based on their target position in the CFTR protein. In an embodiment, the target position is F508, e.g., F508del (also sometimes referred to herein as “ΔF508”), in the CFTR protein, which corresponds to a deletion of three nucleotides c.1521_1523delCTT in the CFTR gene (e.g., c.1521_1523delCTT (p.Phe508delPhe)). In an embodiment, the target position is G551, e.g., G551D, in the CFTR protein, which corresponds to c.1652G>A in the CFTR gene. In an embodiment, the target position is G542, e.g., G542X, in the CFTR protein, which corresponds to c.1624G>T in the CFTR gene. In an embodiment, the target position is N1303, e.g., N1303K, in the CFTR protein, which corresponds to c.3909C>G in the CFTR gene. In an embodiment, the target position is R117, e.g., R117H, in the CFTR protein, which corresponds to c.350G>A in the CFTR gene. In an embodiment, the target position is W1282, e.g., W1282X, in the CFTR protein, which corresponds to c. c.3846G>A in the CFTR gene. In an embodiment, the target position is R553, e.g., R553X, in the CFTR protein, which corresponds to c.1657C>T in the CFTR gene. In an embodiment, the target position is c.3717+12191, also known as c.3849+10kb, which corresponds to 3717+12191C>T in the CFTR gene. In an embodiment, the target position is c.2657+5, also known as c.2789+5, which corresponds to 2657+5G>A in the CFTR gene. In an embodiment, the target position is c.3140-26, also known as c.3272-26, which corresponds to c.3140-26A>G in the CFTR gene.

Overactivity of the SCNN1A gene has been shown to contribute to bronchiectasis, bronchitis, and gastrointestinal symptoms in subjects with CF and in subjects with CF-like disease. In another aspect, methods and compositions discussed herein may be used to alter the SCNN1A gene (also known as sodium channel, non-voltage-gated 1 alpha subunit; amiloride-sensitive epithelial sodium channel alpha subunit; BESC2; ENaCa; SCNEA; SCNN1; ENaCalpha) to treat or prevent CF or CF-like disease, by targeting the SCNN1A gene, e.g., the non-coding or coding regions, e.g., a promoter region, or a transcribed sequence, e.g., intronic or exonic sequence. In an embodiment, the target position is V114, which corresponds to V114I in the SCNN1A gene. SCNN1A encodes an epithelial sodium channel, ENaC, that is negatively regulated by CFTR. In subjects with CFTR mutations, knocking out or knocking down the SCNN1A gene in certain cells will reduce or reverse the effect of defective CFTR. In subjects with no CFTR mutations but CF-like disease caused by SCNN1A mutations or other mechanisms, knocking out or knocking down the SCNN1A gene in certain cells will improve the viscosity of mucous and ameliorate disease.

Methods and compositions disclosed herein provide a number of approaches for treating or preventing CF and/or CF-like disease. As is discussed in more detail below, methods described herein provide for treating or preventing CF or CF-like disease by correcting a target position in the CFTR gene to provide corrected, or functional, e.g., wild type, CFTR. Other methods described herein allow for treating or preventing CF or CF-like disease by inducing or introducing a mutation that reduces the level of functional SCNN1A gene product.

In one aspect, methods and compositions discussed herein, provide for the correction of the underlying cause of CF or CF-like disease, e.g., the correction of a mutation at a target position in the CFTR gene, e.g., correction of a mutation in the CFTR gene that corresponds to amino acid position 508, e.g., an F508 deletion (F508del), in CFTR protein.

“CF target mutant position”, as used herein, refers to a target position in the CFTR gene, which, if mutated, can result in a mutant protein and give rise to CF or CF-like disease. In an embodiment, the target position comprises one, two, or three nucleotides. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at F508, e.g., F508del. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G551, e.g., G551D. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G542, e.g., G542X, in the CFTR protein, which corresponds to c.1624G>T in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at N1303, e.g., N1303K, in the CFTR protein, which corresponds to c.3909C>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at R117, e.g., R117H, in the CFTR protein, which corresponds to c.350G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at W1282, e.g., W1282X, in the CFTR protein, which corresponds to c. c.3846G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at R553, e.g., R553X, in the CFTR protein, which corresponds to c.1657C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.3717+12191, also known as c.3849+10kb, which corresponds to 3717+12191C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.2657+5, also known as c.2789+5, which corresponds to 2657+5G>A in the CFTR gene. In an embodiment, the CF target mutant position is c.3140-26, also known as c.3272-26, which corresponds to c.3140-26A>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the SCNN1A gene at which a change can give rise to a mutant protein having a mutation at V114, which corresponds to V114I in the SCNN1A gene.

While some of the disclosure herein is presented in the context of the mutation in the CFTR gene that gives rise to an F508 mutant protein (e.g., a F508del mutant protein), a G551 mutant protein (e.g., a G551D mutant protein), a G542 mutant protein (e.g., G542X mutant protein), a N1303 mutant protein (e.g., a N1303K mutant protein), a R117 mutant protein (e.g., an R117H mutant protein), a W1282 mutant protein (e.g., a W1282X mutant protein), an R553 mutant protein (e.g., an R553X mutant protein), a c.2789+5bp intronic mutant (e.g., a c.2789+5bp G>A mutant), or a c.3272-26bp intronic mutant (e.g., a c.3272-26bp A>G mutant), the methods and compositions herein are broadly applicable to any mutation, e.g., a point mutation or a deletion, in the CFTR gene that gives rise to CF or CF-like disease.

While not wishing to be bound by theory, it is believed that, in an embodiment, a mutation at a CF target mutant position is corrected by homology directed repair (HDR), as described herein.

In another aspect, methods and compositions discussed herein may be used to alter the SCNN1A gene (also known as sodium channel, non-voltage-gated 1 alpha subunit) to treat or prevent CF or CF-like disease, by targeting the SCNN1A gene, e.g., the non-coding or coding regions, e.g., a promoter region, or a transcribed sequence, e.g., intronic or exonic sequence. SCNN1A encodes an epithelial sodium channel that is negatively regulated by CFTR. By knocking out the SCNN1A gene in certain cells, the effect of defective CFTR can be reduced or reversed.

In another aspect, the methods and compositions discussed herein may be used to alter the SCNN1A gene to treat or prevent CF or CF-like disease by targeting the coding sequence of the SCNN1A gene. In one embodiment, the gene, e.g., the coding sequence of the SCNN1A gene, is targeted to knockout the gene, e.g., to eliminate expression of the gene, e.g., to knockout one or both alleles of the SCNN1A gene, e.g., by induction of an alteration comprising a deletion or mutation in the SCNN1A gene. In an embodiment, the method provides an alteration that comprises an insertion or deletion.

In an embodiment, coding region, e.g., an early coding region, of the SCNN1A gene, is targeted for alteration and knockout. In one embodiment, an early coding region of the SCNN1A gene is targeted to knockout the SCNN1A gene. In an embodiment, targeting affects both alleles of the SCNN1A gene. In an embodiment, targeting affects one allele of the SCNN1A gene. In an embodiment, a targeted knockout approach reduces or eliminates expression of functional SCNN1A gene product. In an embodiment, the method provides an alteration in the SCNN1A gene that comprises an insertion or deletion.

In another aspect, the methods and compositions discussed herein may be used to alter the SCNN1A gene to treat or prevent CF or CF-like disease by targeting non-coding sequence of the SCNN1A gene, e.g., promoter, an enhancer, an intron, 3′UTR, and/or polyadenylation signal. In an embodiment, the gene, e.g., the non-coding sequence of the SCNN1A gene, is targeted to knockout the gene, e.g., to eliminate expression of the gene, e.g., to knockout one or both alleles of the SCNN1A gene, e.g., by induction of an alteration comprising a deletion or mutation in the SCNN1A gene. In an embodiment, the method provides an alteration that comprises an insertion or deletion.

As described herein, in an embodiment, a targeted knockout approach is mediated by non-homologous end joining (NHEJ) using a CRISPR/Cas system comprising an enzymatically active Cas9 (eaCas9).

“CF target knockout position”, as used herein, refers to a position in the SCNN1A gene, which if altered by NHEJ-mediated alteration, results in alleviation of a symptom of CF or CF-like disease. In an embodiment, the alteration results in reduction or elimination of expression of functional SCNN1A gene product. In an embodiment, the position is in the SCNN1A coding region, e.g., an early coding region.

In an embodiment, the promoter region of the SCNN1A gene is targeted to knock down the expression of the SCNN1A gene. This type of alteration is also sometimes referred to as “knocking down” the SCNN1A gene. While not wishing to be bound by theory, in an embodiment, a targeted knockdown approach is mediated by a CRISPR/Cas system comprising a Cas9 molecule, e.g., an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain or chromatin modifying protein), as described herein. In an embodiment, the SCNN1A gene is targeted to alter (e.g., to block, reduce, or decrease) the transcription of the SCNN1A gene. In another embodiment, the SCNN1A gene is targeted to alter the chromatin structure (e.g., one or more histone and/or DNA modifications) of the SCNN1A gene. In an embodiment, a CF target knockdown position is targeted by genome editing using the CRISPR/Cas9 system. In an embodiment, one or more gRNA molecules comprising a targeting domain are configured to target an enzymatically inactive Cas9 (eiCas9) or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF target knockdown position to reduce, decrease or repress expression of the SCNN1A gene.

“CF target knockdown position”, as used herein, refers to a position in the SCNN1A gene, which if targeted, e.g., by an eiCas9 molecule or an eiCas9 fusion described herein, results in reduction or elimination of expression of functional SCNN1A gene product. In an embodiment, the transcription of the SCNN1A gene is reduced or eliminated. In another embodiment, the chromatin structure of the SCNN1A gene is altered.

“CF target knockin position”, as used herein, refers to a sequence, which if modified by the insertion of CFTR sequence, results in an optimization of CFTR activity, e.g., by resulting in a CFTR sequence that encodes a protein having wild type activity. Exemplary CF target knockin position include: CFTR sequence within intron 2, into which, e.g., can be introduced CFTR sequence that codes for CFTR exons 3-27; and sequence within CFTR intron 10, into which sequence that codes for CFTR exons 11-27 can be introduced. In an embodiment, a CF target knockin position includes CFTR intronic sequence between a second and a third exon (e.g., intron 2), and CFTR sequence encoding the third exon through the final exon (exon 27), is introduced, resulting in a CFTR sequence that is free of one or more cryptic splice sites and that encodes a CFTR protein having wild type activity. In an embodiment, a CF target knockin position, is a position which is upstream of a mutation, or upstream of an intron having a mutation, and introduction of wild-type CFTR sequence results in a CFTR sequence that is free of the mutation. In an embodiment the CF target knockin position is in CFTR intronic sequence: between exon2 and exon 3; or between exon10 and exon 11. In an embodiment, the resulting CFTR sequence comprises subject sequence upstream from the CF target knockin position and newly introduced sequence downstream from the CF target knockin position, which taken together, encode a CFTR protein having wild type activity. In an embodiment, the point of insertion is 3′ to a splice donor site and 5′ from a splice acceptor site. In an embodiment, CFTR sequence encoding exons 3-27 is inserted under control of the promoter, e.g., at the transcription start site. In an embodiment, CFTR sequence introduced can exclude introns, e.g., a sequence encoding exons, but without introns, is inserted, e.g., CFTR CDNA sequence is introduced.

“CF target position”, as used herein, refers to a CF target mutant position, CF target knockout position, CF target knockdown position, and/or CF target knockin position, as described herein.

In one aspect, disclosed herein is a gRNA molecule, e.g., an isolated or non-naturally occurring gRNA molecule, comprising a targeting domain which is complementary with a target domain from the CFTR gene or SCNN1A gene.

In an embodiment, the targeting domain of the gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNN1A gene to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNN1A gene. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of a CF target position. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of a CF target position in the CFTR gene or SCNN1A gene.

In an embodiment, a second gRNA molecule comprising a second targeting domain is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to the CF target position in the CFTR gene or SCNN1A gene, to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of the CF target position in the CFTR gene or SCNN1A gene, either alone or in combination with the break positioned by said first gRNA molecule. In an embodiment, the targeting domains of the first and second gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules, within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position. In an embodiment, the breaks, e.g., double strand or single strand breaks, are positioned on both sides of a nucleotide of a CF target position in the CFTR gene or SCNN1A gene. In an embodiment, the breaks, e.g., double strand or single strand breaks, are positioned on one side, e.g., upstream or downstream, of a nucleotide of a CF target position in the CFTR gene or SCNN1A gene.

In an embodiment, a single strand break is accompanied by an additional single strand break, positioned by a second gRNA molecule, as discussed below. For example, the targeting domains are configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of a CF target position. In an embodiment, the first and second gRNA molecules are configured such, that when guiding a Cas9 molecule, e.g., a Cas9 nickase, a single strand break will be accompanied by an additional single strand break, positioned by a second gRNA, sufficiently close to one another to result in alteration of a CF target position in the CFTR gene or SCNN1A gene. In an embodiment, the first and second gRNA molecules are configured such that a single strand break positioned by said second gRNA is within 10, 20, 30, 40, or 50 nucleotides of the break positioned by said first gRNA molecule, e.g., when the Cas9 molecule is a nickase. In an embodiment, the two gRNA molecules are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, e.g., essentially mimicking a double strand break.

In an embodiment, a double strand break can be accompanied by an additional double strand break, positioned by a second gRNA molecule, as is discussed below. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of a CF target position in the CFTR gene or SCNN1A gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position; and the targeting domain of a second gRNA molecule is configured such that a double strand break is positioned downstream of a CF target position in the CFTR gene or SCNN1A gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position.

In an embodiment, a double strand break can be accompanied by two additional single strand breaks, positioned by a second gRNA molecule and a third gRNA molecule. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of a CF target position in the CFTR gene or SCNN1A gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position; and the targeting domains of a second and third gRNA molecule are configured such that two single strand breaks are positioned downstream of a CF target position in the CFTR gene or SCNN1A gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position. In an embodiment, the targeting domain of the first, second and third gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules.

In an embodiment, a first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule. For example, the targeting domain of a first and second gRNA molecule are configured such that two single strand breaks are positioned upstream of a CF target position in the CFTR gene or SCNN1A gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of a CF target position in the CFTR gene or SCNN1A gene, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 225, 250, or 300 nucleotides of the target position.

It is contemplated herein that, in an embodiment, when multiple gRNAs are used to generate (1) two single stranded breaks in close proximity, (2) two double stranded breaks, e.g., flanking a CF target position, e.g., a mutation (e.g., to remove a piece of DNA, e.g., to introduce a deletion mutation) or to create more than one indel in the gene, e.g., in a coding region, e.g., an early coding region, (3) one double stranded break and two paired nicks flanking a CF target position, e.g., a mutation (e.g., to remove a piece of DNA, e.g., to introduce a deletion mutation) or (4) four single stranded breaks, two on each side of a position, e.g., a mutation, that they are targeting the same CF target position. It is further contemplated herein that multiple gRNAs may be used to target more than one CF target position (e.g., mutation) in the same gene.

In an embodiment, the targeting domain of the first gRNA molecule and the targeting domain of the second gRNA molecules are complementary to opposite strands of the target nucleic acid molecule. In an embodiment, the gRNA molecule and the second gRNA molecule are configured such that the PAMs are oriented outward.

In an embodiment, the targeting domain of a gRNA molecule is configured to avoid unwanted target chromosome elements, such as repeat elements, e.g., Alu repeats, in the target domain. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule, as described herein.

In an embodiment, the targeting domain of a gRNA molecule is configured to position a cleavage event sufficiently far from a preselected nucleotide, e.g., the nucleotide of a coding region, such that the nucleotide is not altered. In an embodiment, the targeting domain of a gRNA molecule is configured to position an intronic cleavage event sufficiently far from an intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule, as described herein.

In an embodiment, a CF target mutant position, e.g., a deletion in the CFTR gene, e.g., at F508, e.g., F508del, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 1A-1E, 10A-10C, 11A-11E or 12A-12C. In some embodiments, the targeting domain is independently selected from those in Tables 1A-1E, 10A-10C, 11A-11E or 12A-12C. For example, in certain embodiments, the targeting domain is independently selected from:

(SEQ ID NO: 387) GAGGGUAAAAUUAAGCACAG; (SEQ ID NO: 388) AGUUUCUUACCUCUUCUAGU; (SEQ ID NO: 389) AAUGGUGCCAGGCAUAAUCC; (SEQ ID NO: 390) GGUAAAAUUAAGCACAG; (SEQ ID NO: 391) AGCAUGCCAACUAGAAG; or (SEQ ID NO: 392) GUAUCUAUAUUCAUCAU.

In an embodiment, when the CF target mutant position is F508, e.g., F508del, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 1A-1E, 10A-10C, 11A-11E or 12A-12C.

In an embodiment, a CF target mutant position, e.g., a mutation in the CFTR gene, e.g., at G551, e.g., G551D, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 2A-2E, 16A-16D, 17A-17E, or 18A-18C. In some embodiments, the targeting domain is independently selected from those in Tables 2A-2E, 16A-16D, 17A-17E, or 18A-18C. For example, in certain embodiments, the targeting domain is independently selected from:

(SEQ ID NO: 453) GAGAAAGACAAUAUAGUUCU; (SEQ ID NO: 454) GGUGGAAUCACACUGAGUGG; (SEQ ID NO: 455) CCCACUAGCCAUAAAACCCC; (SEQ ID NO: 456) GGUGGAAUCACACUGAG; (SEQ ID NO: 457) GGAAUCACACUGAGUGG; (SEQ ID NO: 458) GGGGUUUUAUGGCUAGU; or (SEQ ID NO: 459) ACUAGCCAUAAAACCCC.

In an embodiment, more than one gRNA is used to position breaks, e.g., two single stranded breaks or two double stranded breaks, or a combination of single strand and double strand breaks, e.g., to create one or more indels, in the target nucleic acid sequence. In an embodiment, the targeting domain of each guide RNA is independently selected from one of Tables 2A-2E, 16A-16D, 17A-17E, or 18A-18C.

In an embodiment, a mutation in the CFTR gene, e.g., at N1303, e.g., N1303K, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 19A-19D, 20A-20E, or 21A-21B. In some embodiments, the targeting domain is independently selected from those in Tables 19A-19D, 20A-20E, or 21A-21B. For example, in certain embodiments, the targeting domain is selected from:

(SEQ ID NO: 2223) GGAGUGAUCAAGAAAUA; (SEQ ID NO: 2224) GAGUACCCUAACAUACC; (SEQ ID NO: 2225) GUGUGUGCACAACUUUAAAA; (SEQ ID NO: 2226) GGAAAGUUGCAGAUGAGGUA; (SEQ ID NO: 2227) GAACUUGAUGGUAAGUACAU; or (SEQ ID NO: 2228) GCUAUAUCAGCCAUUUGUGU.

In an embodiment, when the CF target mutant position is N1303, e.g., N1303K, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 19A-19D, 20A-20E, or 21A-21B.

In an embodiment, a mutation in the CFTR gene, e.g., at W1282, e.g., W1282X, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 28A-28D, 29A-29E, or 30A-30B. In some embodiments, the targeting domain is independently selected from those in Tables 28A-28D, 29A-29E, or 30A-30B. For example, in certain embodiments, the targeting domain is selected from:

(SEQ ID NO: 2993) GAAUUAUGUUUAUGGCA; (SEQ ID NO: 2994) GGAGAAAUCCAGAUCGA; (SEQ ID NO: 2995) GGCCUCUUGGGAAGAAC; (SEQ ID NO: 2996) GUCCUUUUGCUCACCUG; (SEQ ID NO: 2997) GAUCGAUGGUGUGUCUU; (SEQ ID NO: 2998) GAAGGAGAAAUCCAGAUCGA; (SEQ ID NO: 2999) GUGGGCCUCUUGGGAAGAAC.

In an embodiment, when the CF target mutant position is W1282, e.g., W1282X, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 28A-28D, 29A-29E, or 30A-30B.

In an embodiment, a mutation in the CFTR gene, e.g., at R553, e.g., R553X, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 25A-25D, 26A-26E, or 27A-27D. In some embodiments, the targeting domain is independently selected from those in Tables 25A-25D, 26A-26E, or 27A-27D. For example, in certain embodiments, the targeting domain is selected from:

(SEQ ID NO: 466) GCUUUAUAUUCUGUUUC; (SEQ ID NO: 456) GGUGGAAUCACACUGAG; (SEQ ID NO: 457) GGAAUCACACUGAGUGG; (SEQ ID NO: 464) GUUCAAAAUUUCAACUG; (SEQ ID NO: 465) GGUGAAUAACUAAUUAU; (SEQ ID NO: 458) GGGGUUUUAUGGCUAGU; (SEQ ID NO: 462) GAGCAAGAAUUUCUUUAGCA; (SEQ ID NO: 460) GACAAUAUAGUUCUUGGAGA; (SEQ ID NO: 461) GAAGGUGGAAUCACACUGAG; (SEQ ID NO: 454) GGUGGAAUCACACUGAGUGG; or (SEQ ID NO: 453) GAGAAAGACAAUAUAGUUCU.

In an embodiment, when the CF target mutant position is R553, e.g., R553X, and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 25A-25D, 26A-26E, or 27A-27D.

In an embodiment, a mutation in the CFTR gene, e.g., at 3717+12191C>T, also known as 3849+10kbC>T is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 34A-34D, 35A-35D, or 36A-36D. In some embodiments, the targeting domain is independently selected from those in Tables 34A-34D, 35A-35D, or 36A-36D. For example, in certain embodiments, the targeting domain is selected from:

(SEQ ID NO: 3344) GAGUAAGACACCCUGAA; (SEQ ID NO: 3345) GAUUUCUGGAGACCACA; (SEQ ID NO: 3346) GGUUUUAGCUAUUACUC; (SEQ ID NO: 3347) GUAGUUGAAUCAUUCAG; (SEQ ID NO: 3348) GAACUCAGUUUUUAGGU; (SEQ ID NO: 3349) GAAAGGAAAUGUUCUAUUCA; (SEQ ID NO: 3350) GUUUUUAGGUUGGGAAAGAC; (SEQ ID NO: 3351) GCACAUAAUAAUUAGUUUCC; (SEQ ID NO: 3352) GAGAACUCAGUUUUUAGGUU; or (SEQ ID NO: 3353) GAAAACACUGACUUAGAUUU.

In an embodiment, when the CF target mutant position is 3717+12191C>T and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 34A-34D, 35A-35D, or 36A-36D.

In an embodiment, a mutation in the CFTR gene, e.g., at 2657+5G>A, also known as 2789+5G>A is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 4A-4D, 5A-5E, or 6A-6C. In some embodiments, the targeting domain is independently selected from those in Tables 4A-4D, 5A-5E, or 6A-6C. For example, in certain embodiments, the targeting domain is selected from:

(SEQ ID NO: 937) GAAGCAGCCACCUGGAA; (SEQ ID NO: 938) GGAAUAUUCACUUUCCA; (SEQ ID NO: 939) GAAUUUAGAUGUGGGCA; (SEQ ID NO: 940) GUGUCUUGUUCCAUUCC; (SEQ ID NO: 941) GUGGGCAUGGGAGGAAU; (SEQ ID NO: 942) GUUGUGCUGUGGCUCCU; (SEQ ID NO: 943) GAUGUGAAUUUAGAUGU; (SEQ ID NO: 944) GACCCAGGAACACAAAGCAA; (SEQ ID NO: 945) GUGUCACCUCACCCAACUAA; (SEQ ID NO: 946) GUGUCUUGUUCCAUUCCAGG; (SEQ ID NO: 947) GAUGUGGGCAUGGGAGGAAU; (SEQ ID NO: 948) GUGAAUUUAGAUGUGGGCAU.

In an embodiment, when the CF target mutant position is 2657+5G>A and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 4A-4D, 5A-5E, or 6A-6C.

In an embodiment, a mutation in the CFTR gene, e.g., at 3140-26A>G, also known as 3272-26A>G, is targeted, e.g., for correction. In an embodiment, the targeting domain of a gRNA molecule comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 7A-7D, 8A-8E, or 9A-9B. In some embodiments, the targeting domain is independently selected from those in Tables 7A-7D, 8A-8E, or 9A-9B. For example, in certain embodiments, the targeting domain is selected from:

(SEQ ID NO: 1282) GUAAGGCUGCCGUCCGA; (SEQ ID NO: 1283) GGAAAUAUUUCACAGGC; (SEQ ID NO: 1284) GUAAAUUCAGAGCUUUG; (SEQ ID NO: 1285) GGACACUUCGUGCCUUCGGA; (SEQ ID NO: 1286) GGAACCAGCGCAGUGUUGAC; (SEQ ID NO: 1287) GUAACAAGAUGAGUGAAAAU.

In an embodiment, when the CF target mutant position is 3140-26A>G and two gRNAs are used to position two breaks, e.g., two single stranded breaks, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 7A-7D, 8A-8E, or 9A-9B.

In another embodiment, a CF target knockout position, e.g., a position in the coding region, e.g., the early coding region, of the SCNN1A gene is targeted, e.g., for knockout. In an embodiment, the targeting domain comprises a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 3A-3D, 43A-43E, 44A-44G, or 45A-45E. In an embodiment, the targeting domain is independently selected from those in Tables 3A-3D, 43A-43E, 44A-44G, or 45A-45E. In another embodiment, the targeting domain is independently selected from:

(SEQ ID NO: 497) GCCCAUACCAGGUCUCAUGG; (SEQ ID NO: 498) CCAUACCAGGUCUCAUGGAG; (SEQ ID NO: 499) GCCCUCCACAGUCCACUCCA; (SEQ ID NO: 500) CCCCUCCAUGAGACCUGGUA; (SEQ ID NO: 501) AUACCAGGUCUCAUGGA; or (SEQ ID NO: 502) CUCCAUGAGACCUGGUA.

In an embodiment, when the CF target knockout position is the SCNN1A coding region, e.g., early coding region, and more than one gRNA is used to position breaks, e.g., two single stranded breaks or two double stranded breaks, or a combination of single strand and double strand breaks, e.g., to create one or more indels, in the target nucleic acid sequence, each guide RNA is independently selected from one of Tables 3A-3D, 43A-43E, 44A-44G, or 45A-45E.

In an embodiment, the targeting domain of the gRNA molecule is configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a SCNN1A transcription start site (TSS) to reduce (e.g., block) transcription, e.g., transcription initiation or elongation, binding of one or more transcription enhancers or activators, and/or RNA polymerase. In an embodiment, the targeting domain is configured to target between 1000 bp upstream and 1000 bp downstream (e.g., between 500 bp upstream and 1000 bp downstream, between 1000 bp upstream and 500 bp downstream, between 500 bp upstream and 500 bp downstream, within 500 bp upstream, or within 500 bp downstream) of the TSS of the SCNN1A gene. One or more gRNAs may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

In an embodiment, when the SCNN1A promoter region is targeted, e.g., for knockdown, the targeting domain can comprise a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any one of Tables 46A-46E, 47A-47G, or 48A-48E. In an embodiment, the targeting domain is independently selected from those in Tables 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the targeting domain is independently selected from those in Table 46A. In an embodiment, the targeting domain is independently selected from those in Table 47A. In an embodiment, the targeting domain is independently selected from those in Table 48A.

In an embodiment, when the CF target knockdown position is the SCNN1A promoter region and more than one gRNA is used to position an eiCas9 molecule or an eiCas9-fusion protein (e.g., an eiCas9-transcription repressor domain fusion protein), in the target nucleic acid sequence, the targeting domain for each guide RNA is independently selected from one of Tables 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the gRNA, e.g., a gRNA comprising a targeting domain, which is complementary with the CFTR gene or SCNN1A gene, is a modular gRNA. In other embodiments, the gRNA is a unimolecular or chimeric gRNA.

In an embodiment, the targeting domain which is complementary with a target domain from the CF target position in the CFTR gene or SCNN1A gene is 16 nucleotides or more in length. In an embodiment, the targeting domain is 16 nucleotides in length. In an embodiment, the targeting domain is 17 nucleotides in length. In another embodiment, the targeting domain is 18 nucleotides in length. In still another embodiment, the targeting domain is 19 nucleotides in length. In still another embodiment, the targeting domain is 20 nucleotides in length. In still another embodiment, the targeting domain is 21 nucleotides in length. In still another embodiment, the targeting domain is 22 nucleotides in length. In still another embodiment, the targeting domain is 23 nucleotides in length. In still another embodiment, the targeting domain is 24 nucleotides in length. In still another embodiment, the targeting domain is 25 nucleotides in length. In still another embodiment, the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

A gRNA as described herein may comprise from 5′ to 3′: a targeting domain (comprising a “core domain”, and optionally a “secondary domain”); a first complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain. In some embodiments, the proximal domain and tail domain are taken together as a single domain.

In an embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In another embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In another embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 35 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In another embodiment, a gRNA comprises a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

A cleavage event, e.g., a double strand or single strand break, is generated by a Cas9 molecule. The Cas9 molecule may be an enzymatically active Cas9 (eaCas9) molecule, e.g., an eaCas9 molecule that forms a double strand break in a target nucleic acid or an eaCas9 molecule forms a single strand break in a target nucleic acid (e.g., a nickase molecule).

In an embodiment, the eaCas9 molecule catalyzes a double strand break.

In some embodiments, the eaCas9 molecule comprises HNH-like domain cleavage activity but has no, or no significant, N-terminal RuvC-like domain cleavage activity. In this case, the eaCas9 molecule is an HNH-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at D10, e.g., D10A. In other embodiments, the eaCas9 molecule comprises N-terminal RuvC-like domain cleavage activity but has no, or no significant, HNH-like domain cleavage activity. In an embodiment, the eaCas9 molecule is an N-terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at H840, e.g., H840A. In an embodiment, the eaCas9 molecule is an N-terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at N863, e.g., an N863A mutation.

In an embodiment, a single strand break is formed in the strand of the target nucleic acid to which the targeting domain of said gRNA is complementary. In another embodiment, a single strand break is formed in the strand of the target nucleic acid other than the strand to which the targeting domain of said gRNA is complementary.

In another aspect, disclosed herein is a nucleic acid, e.g., an isolated or non-naturally occurring nucleic acid, e.g., DNA, that comprises (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain, e.g., with a CF target position, in the CFTR gene or SCNN1A gene as disclosed herein.

In an embodiment, the nucleic acid encodes a gRNA molecule, e.g., a first gRNA molecule, comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNN1A gene to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNN1A gene.

In an embodiment, the nucleic acid encodes a gRNA molecule, e.g., a first gRNA molecule, comprising a targeting domain configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF knockdown target position to reduce, decrease or repress expression of the SCNN1A gene.

In an embodiment, the nucleic acid encodes a gRNA molecule, e.g., the first gRNA molecule, comprising a targeting domain comprising a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence as described herein, e.g., from any one of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In an embodiment, the nucleic acid encodes a gRNA molecule comprising a targeting domain as described herein, e.g., that is selected from those in Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the nucleic acid encodes a modular gRNA, e.g., one or more nucleic acids encode a modular gRNA. In another embodiment, the nucleic acid encodes a chimeric gRNA. The nucleic acid may encode a gRNA, e.g., the first gRNA molecule, comprising a targeting domain comprising 16 nucleotides or more in length. In an embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 16 nucleotides in length. In another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 17 nucleotides in length. In yet another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 18 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 19 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 20 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 21 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 22 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 23 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 24 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 25 nucleotides in length. In still another embodiment, the nucleic acid encodes a gRNA, e.g., the first gRNA molecule, comprising a targeting domain that is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

In an embodiment, a nucleic acid encodes a gRNA comprising from 5′ to 3′: a targeting domain (comprising a “core domain”, and optionally a “secondary domain”); a first complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain. In some embodiments, the proximal domain and tail domain are taken together as a single domain.

In an embodiment, a nucleic acid encodes a gRNA e.g., the first gRNA molecule, comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a gRNA e.g., the first gRNA molecule, comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a gRNA e.g., the first gRNA molecule, comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 35 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a gRNA comprising e.g., the first gRNA molecule, a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid comprises (a) a sequence that encodes a gRNA molecule, e.g., the first gRNA molecule, comprising a targeting domain that is complementary with a target domain in the CFTR gene or SCNN1A gene as disclosed herein, and further comprising (b) a sequence that encodes a Cas9 molecule.

The Cas9 molecule may be a nickase molecule, an enzymatically activating Cas9 (eaCas9) molecule, e.g., an eaCas9 molecule that forms a double strand break in a target nucleic acid and/or an eaCas9 molecule forms a single strand break in a target nucleic acid. In an embodiment, a single strand break is formed in the strand of the target nucleic acid to which the targeting domain of said gRNA is complementary. In another embodiment, a single strand break is formed in the strand of the target nucleic acid other than the strand to which to which the targeting domain of said gRNA is complementary.

In an embodiment, the eaCas9 molecule catalyzes a double strand break.

In an embodiment, the eaCas9 molecule comprises HNH-like domain cleavage activity but has no, or no significant, N-terminal RuvC-like domain cleavage activity. In another embodiment, the said eaCas9 molecule is an HNH-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at D10, e.g., D10A. In another embodiment, the eaCas9 molecule comprises N-terminal RuvC-like domain cleavage activity but has no, or no significant, HNH-like domain cleavage activity. In another embodiment, the eaCas9 molecule is an N-terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at H840, e.g., H840A. In another embodiment, the eaCas9 molecule is an N-terminal RuvC-like domain nickase, e.g., the eaCas9 molecule comprises a mutation at N863, e.g., an N863A mutation.

A nucleic acid disclosed herein may comprise (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR and/or SCNN1A gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule.

In an embodiment, the Cas9 molecule is an enzymatically active Cas9 (eaCas9) molecule. In an embodiment, the Cas9 molecule is an enzymatically inactive Cas9 (eiCas9) molecule or a modified eiCas9 molecule, e.g., the eiCas9 molecule is fused to Krüppel-associated box (KRAB) to generate an eiCas9-KRAB fusion protein molecule.

A nucleic acid disclosed herein may comprise (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR gene or SCNN1A gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule; and further may comprise (c)(i) a sequence that encodes a second gRNA molecule described herein having a targeting domain that is complementary to a second target domain of the CFTR gene or SCNN1A gene, and optionally, (c)(ii) a sequence that encodes a third gRNA molecule described herein having a targeting domain that is complementary to a third target domain of the CFTR gene or SCNN1A gene; and optionally, (c)(iii) a sequence that encodes a fourth gRNA molecule described herein having a targeting domain that is complementary to a fourth target domain of the CFTR gene or SCNN1A gene.

In an embodiment, a nucleic acid encodes a second gRNA molecule comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNN1A gene, to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNN1A gene, either alone or in combination with the break positioned by said first gRNA molecule.

In an embodiment, a nucleic acid encodes a second gRNA molecule comprising a targeting domain configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF knockdown target position to reduce, decrease or repress expression of the SCNN1A gene.

In an embodiment, a nucleic acid encodes a third gRNA molecule comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNN1A gene to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNN1A gene, either alone or in combination with the break positioned by the first and/or second gRNA molecule.

In an embodiment, a nucleic acid encodes a third gRNA molecule comprising a targeting domain configured to target an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain), sufficiently close to a CF knockdown target position to reduce, decrease or repress expression of the SCNN1A gene.

In an embodiment, a nucleic acid encodes a fourth gRNA molecule comprising a targeting domain configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to a CF target position in the CFTR gene or SCNN1A gene to allow alteration, e.g., alteration associated with, respectively, HDR or NHEJ, of a CF target position in the CFTR gene or SCNN1A gene, either alone or in combination with the break positioned by the first gRNA molecule, the second gRNA molecule and/or the third gRNA molecule.

In an embodiment, the nucleic acid encodes a second gRNA molecule. The second gRNA is selected to target the same CF target position as the first gRNA molecule. Optionally, the nucleic acid may encode a third gRNA, and further optionally, the nucleic acid may encode a fourth gRNA molecule. The third gRNA molecule and the fourth gRNA molecule are selected to target the same CF target position as the first and second gRNA molecules.

In an embodiment, the nucleic acid encodes a second gRNA molecule comprising a targeting domain comprising a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from one of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In an embodiment, the nucleic acid encodes a second gRNA molecule comprising a targeting domain selected from those in Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In an embodiment, when a third or fourth gRNA molecule are present, the third and fourth gRNA molecules may independently comprise a targeting domain comprising a sequence that is the same as, or differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from one of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E. In a further embodiment, when a third or fourth gRNA molecule are present, the third and fourth gRNA molecules may independently comprise a targeting domain selected from those in Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the nucleic acid encodes a second gRNA which is a modular gRNA, e.g., wherein one or more nucleic acid molecules encode a modular gRNA. In another embodiment, the nucleic acid encoding a second gRNA is a chimeric gRNA. In another embodiment, when a nucleic acid encodes a third or fourth gRNA, the third and fourth gRNA may be a modular gRNA or a chimeric gRNA. When multiple gRNAs are used, any combination of modular or chimeric gRNAs may be used.

A nucleic acid may encode a second, a third, and/or a fourth gRNA, each independently, comprising a targeting domain comprising 16 nucleotides or more in length. In an embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 16 nucleotides in length. In an embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 17 nucleotides in length. In another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 18 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 19 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 20 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 21 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 22 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 23 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 24 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 25 nucleotides in length. In still another embodiment, the nucleic acid encodes a second gRNA comprising a targeting domain that is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA, each independently, comprising from 5′ to 3′: a targeting domain (comprising a “core domain”, and optionally a “secondary domain”); a first complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain. In some embodiments, the proximal domain and tail domain are taken together as a single domain.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 20 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 30 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 35 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, a nucleic acid encodes a second, a third, and/or a fourth gRNA comprising a linking domain of no more than 25 nucleotides in length; a proximal and tail domain, that taken together, are at least 40 nucleotides in length; and a targeting domain equal to or greater than 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, when the CFTR gene is corrected by HDR, the nucleic acid encodes (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR gene as disclosed herein; (b) a sequence that encodes a Cas9 molecule; optionally, (c)(i) a sequence that encodes a second gRNA molecule described herein having a targeting domain that is complementary to a second target domain of the CFTR gene, and further optionally, (c)(ii) a sequence that encodes a third gRNA molecule described herein having a targeting domain that is complementary to a third target domain of the CFTR gene; and still further optionally, (c)(iii) a sequence that encodes a fourth gRNA molecule described herein having a targeting domain that is complementary to a fourth target domain of the CFTR gene; and further may comprise (d) a template nucleic acid, e.g., a template nucleic acid described herein.

In an embodiment, the template nucleic acid is a single stranded nucleic acid. In another embodiment, the template nucleic acid is a double stranded nucleic acid. In an embodiment, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that will be added to or will template a change in the target nucleic acid. In another embodiment, the template nucleic acid comprises a nucleotide sequence that may be used to modify the target position. In another embodiment, the template nucleic acid comprises a nucleotide sequence, e.g., of one or more nucleotides, that corresponds to wild type sequence of the target nucleic acid, e.g., of the target position.

The template nucleic acid may comprise a replacement sequence, e.g., a replacement sequence from the Table 49. In some embodiments, the template nucleic acid comprises a 5′ homology arm, e.g., a 5′ homology arm from Table 49. In other embodiments, the template nucleic acid comprises a 3′ homology arm, e.g., a 3′ homology arm from Table 49.

In an embodiment, a nucleic acid encodes (a) a sequence that encodes a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR gene or SCNN1A gene as disclosed herein, and (b) a sequence that encodes a Cas9 molecule, e.g., a Cas9 molecule described herein. In an embodiment, (a) and (b) are present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., the same adeno-associated virus (AAV) vector. In an embodiment, the nucleic acid molecule is an AAV vector. Exemplary AAV vectors that may be used in any of the described compositions and methods include an AAV2 vector, a modified AAV2 vector, an AAV3 vector, a modified AAV3 vector, an AAV6 vector, a modified AAV6 vector, an AAV8 vector and an AAV9 vector.

In another embodiment, (a) is present on a first nucleic acid molecule, e.g. a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (b) is present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecules may be AAV vectors.

In another embodiment, the nucleic acid may further comprise (c) a sequence that encodes a second, third and/or fourth gRNA molecule as described herein. In another embodiment, the nucleic acid comprises (a), (b) and (c)(i). Each of (a) and (c)(i) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., the same adeno-associated virus (AAV) vector. In an embodiment, the nucleic acid molecule is an AAV vector.

In another embodiment, (a) and (c)(i) are on different vectors. For example, (a) may be present on a first nucleic acid molecule, e.g. a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (c)(i) may be present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. In an embodiment, the first and second nucleic acid molecules are AAV vectors.

In another embodiment, each of (a), (b), and (c)(i) are present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, one of (a), (b), and (c)(i) is encoded on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, e.g., a first AAV vector; and a second and third of (a), (b), and (c)(i) is encoded on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

In an embodiment, (a) is present on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, a first AAV vector; and (b) and (c)(i) are present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

In another embodiment, (b) is present on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (a) and (c)(i) are present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

In another embodiment, (c)(i) is present on a first nucleic acid molecule, e.g., a first vector, e.g., a first viral vector, e.g., a first AAV vector; and (b) and (a) are present on a second nucleic acid molecule, e.g., a second vector, e.g., a second vector, e.g., a second AAV vector. The first and second nucleic acid molecule may be AAV vectors.

In another embodiment, each of (a), (b) and (c)(i) are present on different nucleic acid molecules, e.g., different vectors, e.g., different viral vectors, e.g., different AAV vector. For example, (a) may be on a first nucleic acid molecule, (b) on a second nucleic acid molecule, and (c)(i) on a third nucleic acid molecule. The first, second and third nucleic acid molecule may be AAV vectors.

In another embodiment, when a third and/or fourth gRNA molecule are present, each of (a), (b), (c)(i), (c)(ii) and (c)(iii) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii) and (c)(iii) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i), (c)(ii) and (c)(iii) may be present on more than one nucleic acid molecule, but fewer than five nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), and (d) may be present on more than one nucleic acid molecule, but fewer than three nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i) and (d) may be present on more than one nucleic acid molecule, but fewer than four nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i), (c)(ii) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i), (c)(ii) and (d) may be present on more than one nucleic acid molecule, but fewer than five nucleic acid molecules, e.g., AAV vectors.

In another embodiment, when (d) a template nucleic acid is present, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on the same nucleic acid molecule, e.g., the same vector, e.g., the same viral vector, e.g., an AAV vector. In an embodiment, the nucleic acid molecule is an AAV vector. In an alternate embodiment, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on the different nucleic acid molecules, e.g., different vectors, e.g., the different viral vectors, e.g., different AAV vectors. In a further embodiment, each of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d) may be present on more than one nucleic acid molecule, but fewer than six nucleic acid molecules, e.g., AAV vectors.

The nucleic acids described herein may comprise a promoter operably linked to the sequence that encodes the gRNA molecule of (a), e.g., a promoter described herein. The nucleic acid may further comprise a second promoter operably linked to the sequence that encodes the second, third and/or fourth gRNA molecule of (c), e.g., a promoter described herein. The promoter and second promoter differ from one another. In some embodiments, the promoter and second promoter are the same.

The nucleic acids described herein may further comprise a promoter operably linked to the sequence that encodes the Cas9 molecule of (b), e.g., a promoter described herein.

In another aspect, disclosed herein is a composition comprising (a) a gRNA molecule comprising a targeting domain that is complementary with a target domain in the CFTR gene or SCNN1A gene, as described herein. The composition of (a) may further comprise (b) a Cas9 molecule, e.g., a Cas9 molecule as described herein. A composition of (a) and (b) may further comprise (c) a second, third and/or fourth gRNA molecule, e.g., a second, third and/or fourth gRNA molecule described herein. A composition of (a), (b) and (c) may further comprise (d) a template nucleic acid, e.g., a template nucleic acid described herein. In an embodiment, the composition is a pharmaceutical composition. The compositions described herein, e.g., pharmaceutical compositions described herein, can be used in the treatment or prevention of CF or CF-like disease in a subject, e.g., in accordance with a method disclosed herein.

In another aspect, disclosed herein is a method of altering a cell, e.g., altering the structure, e.g., altering the sequence, of a target nucleic acid of a cell, comprising contacting said cell with: (a) a gRNA that targets the CFTR gene or SCNN1A gene, e.g., a gRNA as described herein; (b) a Cas9 molecule, e.g., a Cas9 molecule as described herein; and optionally, (c) a second, third and/or fourth gRNA that targets CFTR gene or SCNN1A gene, e.g., a second, third and/or fourth gRNA as described herein; and optionally, (d) a template nucleic acid, e.g., a template nucleic acid as described herein.

In an embodiment, the method comprises contacting said cell with (a) and (b).

In an embodiment, the method comprises contacting said cell with (a), (b), and (c).

In an embodiment, the method comprises contacting said cell with (a), (b), (c) and (d).

The gRNA of (a) and optionally (c) may be selected from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E, or a gRNA that differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the method comprises contacting a cell from a subject suffering from or likely to develop CF or CF-like disease. The cell may be from a subject having a mutation at a CF target position in the CFTR gene or a subject which would benefit from having a mutation at a CF target position in the SCNN1A gene.

In an embodiment, the cell being contacted in the disclosed method is an epithelial cell, e.g., a pulmonary epithelial cell, e.g., a bronchial epithelial cell or an alveolar epithelial cell. The contacting may be performed ex vivo and the contacted cell may be returned to the subject's body after the contacting step. In other embodiments, the contacting step may be performed in vivo.

In an embodiment, the method of altering a cell as described herein comprises acquiring knowledge of the sequence at a CF target position in said cell, prior to the contacting step. Acquiring knowledge of the sequence at a CF target position in the cell may be by sequencing the CFTR gene or SCNN1A gene, or a portion of the CFTR gene or SCNN1A gene.

In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses at least one of (a), (b), and (c). In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses each of (a), (b), and (c). In another embodiment, the contacting step of the method comprises delivering to the cell a Cas9 molecule of (b) and a nucleic acid which encodes a gRNA of (a) and optionally, a second gRNA (c)(i) and further optionally, a third gRNA (c)(ii) and/or fourth gRNA (c)(iii)).

In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses at least one of (a), (b), (c) and (d). In an embodiment, the contacting step of the method comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, that expresses each of (a), (b), and (c). In another embodiment, the contacting step of the method comprises delivering to the cell a Cas9 molecule of (b), a nucleic acid which encodes a gRNA of (a) and a template nucleic acid of (d), and optionally, a second gRNA (c)(i) and further optionally, a third gRNA (c)(ii) and/or fourth gRNA (c)(iii).

In an embodiment, contacting comprises contacting the cell with a nucleic acid, e.g., a vector, e.g., an AAV vector, e.g., an AAV2 vector, a modified AAV2 vector, an AAV3 vector, a modified AAV3 vector, an AAV6 vector, a modified AAV6 vector, an AAV8 vector or an AAV9 vector, as described herein.

In an embodiment, contacting comprises delivering to the cell a Cas9 molecule of (b), as a protein or an mRNA, and a nucleic acid which encodes a gRNA of (a) and optionally a second, third and/or fourth gRNA of (c).

In an embodiment, contacting comprises delivering to the cell a Cas9 molecule of (b), as a protein or an mRNA, said gRNA of (a), as an RNA, and optionally said second, third and/or fourth gRNA of (c), as an RNA.

In an embodiment, contacting comprises delivering to the cell a gRNA of (a) as an RNA, optionally the second, third and/or fourth gRNA of (c) as an RNA, and a nucleic acid that encodes the Cas9 molecule of (b).

In another aspect, disclosed herein is a method of treating or preventing a subject suffering from or likely to develop CF or CF-like disease, e.g., altering the structure, e.g., sequence, of a target nucleic acid of the subject, comprising contacting the subject (or a cell from the subject) with:

    • (a) a gRNA that targets the CFTR gene or SCNN1A gene, e.g., a gRNA disclosed herein;
    • (b) a Cas9 molecule, e.g., a Cas9 molecule disclosed herein; and
    • optionally, (c)(i) a second gRNA that targets the CFTR gene or SCNN1A gene, e.g., a second gRNA disclosed herein, and
    • further optionally, (c)(ii) a third gRNA, and still further optionally, (c)(iii) a fourth gRNA that target the CFTR gene or SCNN1A gene, e.g., a third and fourth gRNA disclosed herein.

The method of treating a subject may further comprise contacting the subject (or a cell from the subject) with (d) a template nucleic acid, e.g., a template nucleic acid disclosed herein. A template nucleic acid is used when the method of treating a subject uses HDR to alter the sequence of the target nucleic acid of the subject.

In some embodiments, contacting comprises contacting with (a) and (b).

In some embodiments, contacting comprises contacting with (a), (b), and (c)(i).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i) and (c)(ii).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i), (c)(ii) and (c)(iii).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i) and (d).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i), (c)(ii) and (d).

In some embodiments, contacting comprises contacting with (a), (b), (c)(i), (c)(ii), (c)(iii) and (d).

The gRNA of (a) or (c) (e.g., (c)(i), (c)(ii), or (c)(iii)) may be selected from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E, or a gRNA that differs by no more than 1, 2, 3, 4, or 5 nucleotides from, a targeting domain sequence from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

In an embodiment, the method comprises acquiring knowledge of the sequence (e.g., a mutation) of a CF target position in said subject.

In an embodiment, the method comprises acquiring knowledge of the sequence (e.g., a mutation) of a CF target position in said subject by sequencing the CFTR gene or SCNN1A gene or a portion of the CFTR gene or SCNN1A gene.

In an embodiment, the method comprises correcting a mutation at a CF target position in the CFTR gene.

In an embodiment, the method comprises correcting a mutation at a CF target position in the CFTR gene by HDR.

In an embodiment, the method comprises introducing a mutation at a CF target position in the SCNN1A gene.

In an embodiment, the method comprises introducing a mutation at a CF target position in the SCNN1A gene by NHEJ.

When the method comprises correcting the mutation at a CF target position by HDR, a Cas9 of (b), at least one guide RNA, e.g., a guide RNA of (a) and a template nucleic acid of (d) are included in the contacting step.

In an embodiment, a cell of the subject is contacted ex vivo with (a), (b), (d) and optionally (c). In an embodiment, said cell is returned to the subject's body.

In an embodiment, a cell of the subject is contacted is in vivo with (a), (b) (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the cell of the subject is contacted in vivo by inhalation delivery, e.g., via nebulizer, of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the cell of the subject is contacted in vivo by intravenous delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the cell of the subject is contacted in vivo by intraparenchymal delivery of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii), e.g., to lung tissue or bronchial tree.

In an embodiment, the contacting step comprises contacting the subject with a nucleic acid, e.g., a vector, e.g., an AAV vector, described herein, e.g., a nucleic acid that encodes at least one of (a), (b), (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the contacting step comprises delivering to said subject said Cas9 molecule of (b), as a protein or mRNA, and a nucleic acid which encodes (a), a nucleic acid of (d) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii).

In an embodiment, the contacting step comprises delivering to the subject the Cas9 molecule of (b), as a protein or mRNA, the gRNA of (a), as an RNA, a nucleic acid of (d) and optionally the second gRNA of (c)(i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA.

In an embodiment, the contacting step comprises delivering to the subject the gRNA of (a), as an RNA, optionally said second gRNA of (c)(i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA, a nucleic acid that encodes the Cas9 molecule of (b), and a nucleic acid of (d).

When the method comprises (1) introducing a mutation at a CF target position by NHEJ or (2) knocking down expression of the SCNN1A gene by targeting the promoter region, a Cas9 of (b) and at least one guide RNA, e.g., a guide RNA of (a) are included in the contacting step.

In an embodiment, a cell of the subject is contacted ex vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii). In an embodiment, said cell is returned to the subject's body.

In an embodiment, a population of cells from a subject is contacted ex vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d) to correct the F508del or G551D mutation in the CFTR gene and a second population of cells from the subject is contacted ex vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii), to introduce a mutation in the SCNN1A gene to knockout the SCNN1A gene. A mixture of the two cell populations may be returned to the subject's body to treat or prevent CF or CF-like disease.

In an embodiment, a cell of the subject is contacted is in vivo with (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d). In an embodiment, the cell of the subject is contacted in vivo by inhalation delivery, e.g., via nebulizer, of (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d). In an embodiment, the cell of the subject is contacted in vivo by intravenous delivery of (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d). In an embodiment, the cell of the subject is contacted in vivo by intraparenchymal delivery of (a), (b) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d), e.g., to lung tissue or bronchial tree.

In an embodiment, contacting comprises contacting the subject with a nucleic acid, e.g., a vector, e.g., an AAV vector, described herein, e.g., a nucleic acid that encodes at least one of (a), (b), and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d).

In an embodiment, contacting comprises delivering to said subject said Cas9 molecule of (b), as a protein or mRNA, and a nucleic acid which encodes (a) and optionally (c)(i), further optionally (c)(ii), and still further optionally (c)(iii) and/or (d).

In an embodiment, contacting comprises delivering to the subject the Cas9 molecule of (b), as a protein or mRNA, the gRNA of (a), as an RNA, and optionally the second gRNA of (c)(i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA, and further optionally the template nucleic acid of (d) as a DNA.

In an embodiment, contacting comprises delivering to the subject the gRNA of (a), as an RNA, optionally said second gRNA of (c)(i), further optionally said third gRNA of (c)(ii), and still further optionally said fourth gRNA of (c)(iii), as an RNA, and a nucleic acid that encodes the Cas9 molecule of (b), and optionally a nucleic acid that encodes the template nucleic acid of (d).

In another aspect, disclosed herein is a reaction mixture comprising a gRNA molecule, a nucleic acid, or a composition described herein, and a cell, e.g., a cell from a subject having, or likely to develop CF or CF-like disease, or a subject having a mutation at a CF target position in the CFTR gene, or a cell from a subject which would benefit from having a mutation at a CF target position in the SCNN1A gene.

In another aspect, disclosed herein is a kit comprising, (a) a gRNA molecule described herein, or nucleic acid that encodes the gRNA, and one or more of the following:

    • (b) a Cas9 molecule, e.g., a Cas9 molecule described herein, or a nucleic acid or mRNA that encodes the Cas9;
    • (c)(i) a second gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(i);
    • (c)(ii) a third gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(ii);
    • (c)(iii) a fourth gRNA molecule, e.g., a second gRNA molecule described herein or a nucleic acid that encodes (c)(iii); and
    • (d) a template nucleic acid, e.g, a template nucleic acid described herein.

In an embodiment, the kit comprises nucleic acid, e.g., an AAV vector, that encodes one or more of (a), (b), (c)(i), (c)(ii), (c)(iii) and (d).

In another aspect, disclosed herein is non-naturally occurring template nucleic acid described herein.

In yet another aspect, disclosed herein is a gRNA molecule, e.g., a gRNA molecule described herein, for use in treating or preventing CF or CF-like disease in a subject, e.g., in accordance with a method of treating or preventing CF or CF-like disease as described herein.

In an embodiment, the gRNA molecule in used in combination with a Cas9 molecule, e.g., a Cas9 molecule described herein. Additionally or alternatively, in an embodiment, the gRNA molecule is used in combination with a second, third and/or fourth gRNA molecule, e.g., a second, third and/or fourth gRNA molecule described herein.

In still another aspect, disclosed herein is use of a gRNA molecule, e.g., a gRNA molecule described herein, in the manufacture of a medicament for treating or preventing CF or CF-like disease in a subject, e.g., in accordance with a method of treating or preventing CF or CF-like disease as described herein.

In an embodiment, the medicament comprises a Cas9 molecule, e.g., a Cas9 molecule described herein. Additionally or alternatively, in an embodiment, the medicament comprises a second, third and/or fourth gRNA molecule, e.g., a second, third and/or fourth gRNA molecule described herein.

The gRNA molecules and methods, as disclosed herein, can be used in combination with a governing gRNA molecule. As used herein, a governing gRNA molecule refers to a gRNA molecule comprising a targeting domain which is complementary to a target domain on a nucleic acid that encodes a component of the CRISPR/Cas system introduced into a cell or subject. For example, the methods described herein can further include contacting a cell or subject with a governing gRNA molecule or a nucleic acid encoding a governing molecule. In an embodiment, the governing gRNA molecule targets a nucleic acid that encodes a Cas9 molecule or a nucleic acid that encodes a target gene gRNA molecule. In an embodiment, the governing gRNA comprises a targeting domain that is complementary to a target domain in a sequence that encodes a Cas9 component, e.g., a Cas9 molecule or target gene gRNA molecule. In an embodiment, the target domain is designed with, or has, minimal homology to other nucleic acid sequences in the cell, e.g., to minimize off-target cleavage. For example, the targeting domain on the governing gRNA can be selected to reduce or minimize off-target effects. In an embodiment, a target domain for a governing gRNA can be disposed in the control or coding region of a Cas9 molecule or disposed between a control region and a transcribed region. In an embodiment, a target domain for a governing gRNA can be disposed in the control or coding region of a target gene gRNA molecule or disposed between a control region and a transcribed region for a target gene gRNA. While not wishing to be bound by theory, in an embodiment, it is believed that altering, e.g., inactivating, a nucleic acid that encodes a Cas9 molecule or a nucleic acid that encodes a target gene gRNA molecule can be effected by cleavage of the targeted nucleic acid sequence or by binding of a Cas9 molecule/governing gRNA molecule complex to the targeted nucleic acid sequence.

The compositions, reaction mixtures and kits, as disclosed herein, can also include a governing gRNA molecule, e.g., a governing gRNA molecule disclosed herein.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

Headings, including numeric and alphabetical headings and subheadings, are for organization and presentation and are not intended to be limiting.

Other features and advantages of the invention will be apparent from the detailed description, drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-1I are representations of several exemplary gRNAs.

FIG. 1A depicts a modular gRNA molecule derived in part (or modeled on a sequence in part) from Streptococcus pyogenes (S. pyogenes) as a duplexed structure (SEQ ID NOS: 42 and 43, respectively, in order of appearance);

FIG. 1B depicts a unimolecular (or chimeric) gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 44);

FIG. 1C depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 45);

FIG. 1D depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 46);

FIG. 1E depicts a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 47);

FIG. 1F depicts a modular gRNA molecule derived in part from Streptococcus thermophilus (S. thermophilus) as a duplexed structure (SEQ ID NOS: 48 and 49, respectively, in order of appearance);

FIG. 1G depicts an alignment of modular gRNA molecules of S. pyogenes and S. thermophilus (SEQ ID NOS: 50-53, respectively, in order of appearance).

FIGS. 1H-1I depicts additional exemplary structures of unimolecular gRNA molecules. FIG. 1H shows an exemplary structure of a unimolecular gRNA molecule derived in part from S. pyogenes as a duplexed structure (SEQ ID NO: 45). FIG. 1I shows an exemplary structure of a unimolecular gRNA molecule derived in part from S. aureus as a duplexed structure (SEQ ID NO: 40).

FIGS. 2A-2G depict an alignment of Cas9 sequences from Chylinski et al. (RNA Biol. 2013; 10(5): 726-737). The N-terminal RuvC-like domain is boxed and indicated with a “Y”. The other two RuvC-like domains are boxed and indicated with a “B”. The HNH-like domain is boxed and indicated by a “G”. Sm: S. mutans (SEQ ID NO: 1); Sp: S. pyogenes (SEQ ID NO: 2); St: S. thermophilus (SEQ ID NO: 3); Li: L. innocua (SEQ ID NO: 4). Motif: this is a motif based on the four sequences: residues conserved in all four sequences are indicated by single letter amino acid abbreviation; “*” indicates any amino acid found in the corresponding position of any of the four sequences; and “−” indicates any amino acid, e.g., any of the 20 naturally occurring amino acids, or absent.

FIGS. 3A-3B show an alignment of the N-terminal RuvC-like domain from the Cas9 molecules disclosed in Chylinski et al (SEQ ID NOS: 54-103, respectively, in order of appearance). The last line of FIG. 3B identifies 4 highly conserved residues.

FIGS. 4A-4B show an alignment of the N-terminal RuvC-like domain from the Cas9 molecules disclosed in Chylinski et al. with sequence outliers removed (SEQ ID NOS: 104-177, respectively, in order of appearance). The last line of FIG. 4B identifies 3 highly conserved residues.

FIGS. 5A-5C show an alignment of the HNH-like domain from the Cas9 molecules disclosed in Chylinski et al (SEQ ID NOS: 178-252, respectively, in order of appearance). The last line of FIG. 5C identifies conserved residues.

FIGS. 6A-6B show an alignment of the HNH-like domain from the Cas9 molecules disclosed in Chylinski et al. with sequence outliers removed (SEQ ID NOS: 253-302, respectively, in order of appearance). The last line of FIG. 6B identifies 3 highly conserved residues.

FIGS. 7A-7B depict an alignment of Cas9 sequences from S. pyogenes and Neisseria meningitidis (N. meningitidis). The N-terminal RuvC-like domain is boxed and indicated with a “Y”. The other two RuvC-like domains are boxed and indicated with a “B”. The HNH-like domain is boxed and indicated with a “G”. Sp: S. pyogenes; Nm: N. meningitidis. Motif: this is a motif based on the two sequences: residues conserved in both sequences are indicated by a single amino acid designation; “*” indicates any amino acid found in the corresponding position of any of the two sequences; “−” indicates any amino acid, e.g., any of the 20 naturally occurring amino acids, and “−” indicates any amino acid, e.g., any of the 20 naturally occurring amino acids, or absent.

FIG. 8 shows a nucleic acid sequence encoding Cas9 of N. meningitidis (SEQ ID NO: 303). Sequence indicated by an “R” is an SV40 NLS; sequence indicated as “G” is an HA tag; and sequence indicated by an “O” is a synthetic NLS sequence; the remaining (unmarked) sequence is the open reading frame (ORF).

FIGS. 9A and 9B are schematic representations of the domain organization of S. pyogenes Cas 9. FIG. 9A shows the organization of the Cas9 domains, including amino acid positions, in reference to the two lobes of Cas9 (recognition (REC) and nuclease (NUC) lobes). FIG. 9B shows the percent homology of each domain across 83 Cas9 orthologs.

DETAILED DESCRIPTION Definitions

“CF target mutant position”, as used herein, refers to a target position in the CFTR gene, which, if mutated, can result in a mutant protein and give rise to CF or CF-like disease. In an embodiment, the target position comprises one, two, or three nucleotides. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at F508, e.g., F508del. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G551, e.g., G551D. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at G542, e.g., G542X, in the CFTR protein, which corresponds to c.1624G>T in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at N1303, e.g., N1303K, in the CFTR protein, which corresponds to c.3909C>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at R117, e.g., R117H, in the CFTR protein, which corresponds to c.350G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at W1282, e.g., W1282X, in the CFTR protein, which corresponds to c. c.3846G>A in the CFTR gene. In an embodiment, the CF target mutant position is a position in the CFTR gene at which a change can give rise to a mutant protein having a mutation at R553, e.g., R553X, in the CFTR protein, which corresponds to c.1657C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.3717+12191, also known as c.3849+10kb, which corresponds to 3717+12191C>T in the CFTR gene. In an embodiment, the CF target mutant position is c.2657+5, also known as c.2789+5, which corresponds to 2657+5G>A in the CFTR gene. In an embodiment, the CF target mutant position is c.3140-26, also known as c.3272-26, which corresponds to c.3140-26A>G in the CFTR gene. In an embodiment, the CF target mutant position is a position in the SCNN1A gene at which a change can give rise to a mutant protein having a mutation at V114, which corresponds to V114I in the SCNN1A gene.

“CF target knockout position”, as used herein, refers to a position in the CFTR and/or SCNN1A gene, which if altered by NHEJ-mediated alteration, results in alleviation of a symptom of CF or CF-like disease. In an embodiment, the alteration restores expression of functional CFTR gene product. In an embodiment, the position is in the CFTR non-coding region, e.g., an intronic region (e.g., the alternation corrects a cryptic splice site). In an embodiment, the alteration results in reduction or elimination of expression of functional SCNN1A gene product. In an embodiment, the position is in the SCNN1A coding region, e.g., an early coding region.

“CF target knockdown position”, as used herein, refers to a position in the SCNN1A gene, which if targeted, e.g., by an eiCas9 molecule or an eiCas9 fusion described herein, results in reduction or elimination of expression of functional SCNN1A gene product. In an embodiment, the transcription of the SCNN1A gene is reduced or eliminated. In another embodiment, the chromatin structure of the SCNN1A gene is altered. In an embodiment, the position is in the SCNN1A early coding region sequence. In an embodiment, a position in early coding region of the SCNN1A gene is targeted by an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein, as described herein.

“CF target knockin position”, as used herein, refers to a sequence, which if modified by the insertion of CFTR sequence, results in an optimization of CFTR activity, e.g., by resulting in a CFTR sequence that encodes a protein having wild type activity. Exemplary CF target knockin position include: CFTR sequence within intron 2, into which, e.g., can be introduced CFTR sequence that codes for CFTR exons 3-27; and sequence within CFTR intron 10, into which sequence that codes for CFTR exons 11-27 can be introduced. In an embodiment, a CF target knockin position includes CFTR intronic sequence between a second and a third exon (e.g., intron 2), and CFTR sequence encoding the third exon through the final exon (exon 27), is introduced, resulting in a CFTR sequence that is free of one or more cryptic splice sites and that encodes a CFTR protein having wild type activity. In an embodiment, a CF target knockin position, is a position which is upstream of a mutation, or upstream of an intron having a mutation, and introduction of wild-type CFTR sequence results in a CFTR sequence that is free of the mutation. In an embodiment the CF target knockin position is in CFTR intronic sequence: between exon2 and exon 3; or between exon10 and exon 11. In an embodiment, the resulting CFTR sequence comprises subject sequence upstream from the CF target knockin position and newly introduced sequence downstream from the CF target knockin position, which taken together, encode a CFTR protein having wild type activity. In an embodiment, the point of insertion is 3′ to a splice donor site and 5′ from a splice acceptor site. In an embodiment, CFTR sequence encoding exons 3-27 is inserted under control of the promoter, e.g., at the transcription start site. In an embodiment, CFTR sequence introduced can exclude introns, e.g., a sequence encoding exons, but without introns, is inserted, e.g., CFTR CDNA sequence is introduced.

“CF target position”, as used herein, refers to a CF target mutant position, CF target knockout position, CF target knockdown position, and/or CF target knockin position, as described herein.

“Domain”, as used herein, is used to describe segments of a protein or nucleic acid. Unless otherwise indicated, a domain is not required to have any specific functional property.

Calculations of homology or sequence identity between two sequences (the terms are used interchangeably herein) are performed as follows. The sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). The optimal alignment is determined as the best score using the GAP program in the GCG software package with a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frame shift gap penalty of 5. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences.

“Governing gRNA molecule”, as used herein, refers to a gRNA molecule that comprises a targeting domain that is complementary to a target domain on a nucleic acid that comprises a sequence that encodes a component of the CRISPR/Cas system that is introduced into a cell or subject. A governing gRNA does not target an endogenous cell or subject sequence. In an embodiment, a governing gRNA molecule comprises a targeting domain that is complementary with a target sequence on: (a) a nucleic acid that encodes a Cas9 molecule; (b) a nucleic acid that encodes a gRNA which comprises a targeting domain that targets the CFTR or SCNN1A gene (a target gene gRNA); or on more than one nucleic acid that encodes a CRISPR/Cas component, e.g., both (a) and (b). In an embodiment, a nucleic acid molecule that encodes a CRISPR/Cas component, e.g., that encodes a Cas9 molecule or a target gene gRNA, comprises more than one target domain that is complementary with a governing gRNA targeting domain. While not wishing to be bound by theory, in an embodiment, it is believed that a governing gRNA molecule complexes with a Cas9 molecule and results in Cas9 mediated inactivation of the targeted nucleic acid, e.g., by cleavage or by binding to the nucleic acid, and results in cessation or reduction of the production of a CRISPR/Cas system component. In an embodiment, the Cas9 molecule forms two complexes: a complex comprising a Cas9 molecule with a target gene gRNA, which complex will alter the CFTR or SCNN1A gene; and a complex comprising a Cas9 molecule with a governing gRNA molecule, which complex will act to prevent further production of a CRISPR/Cas system component, e.g., a Cas9 molecule or a target gene gRNA molecule. In an embodiment, a governing gRNA molecule/Cas9 molecule complex binds to or promotes cleavage of a control region sequence, e.g., a promoter, operably linked to a sequence that encodes a Cas9 molecule, a sequence that encodes a transcribed region, an exon, or an intron, for the Cas9 molecule. In an embodiment, a governing gRNA molecule/Cas9 molecule complex binds to or promotes cleavage of a control region sequence, e.g., a promoter, operably linked to a gRNA molecule, or a sequence that encodes the gRNA molecule. In an embodiment, the governing gRNA, e.g., a Cas9-targeting governing gRNA molecule, or a target gene gRNA-targeting governing gRNA molecule, limits the effect of the Cas9 molecule/target gene gRNA molecule complex-mediated gene targeting. In an embodiment, a governing gRNA places temporal, level of expression, or other limits, on activity of the Cas9 molecule/target gene gRNA molecule complex. In an embodiment, a governing gRNA reduces off-target or other unwanted activity. In an embodiment, a governing gRNA molecule inhibits, e.g., entirely or substantially entirely inhibits, the production of a component of the Cas9 system and thereby limits, or governs, its activity.

“Modulator”, as used herein, refers to an entity, e.g., a drug, that can alter the activity (e.g., enzymatic activity, transcriptional activity, or translational activity), amount, distribution, or structure of a subject molecule or genetic sequence. In an embodiment, modulation comprises cleavage, e.g., breaking of a covalent or non-covalent bond, or the forming of a covalent or non-covalent bond, e.g., the attachment of a moiety, to the subject molecule. In an embodiment, a modulator alters the, three dimensional, secondary, tertiary, or quaternary structure, of a subject molecule. A modulator can increase, decrease, initiate, or eliminate a subject activity.

“Large molecule”, as used herein, refers to a molecule having a molecular weight of at least 2, 3, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 kD. Large molecules include proteins, polypeptides, nucleic acids, biologics, and carbohydrates.

“Polypeptide”, as used herein, refers to a polymer of amino acids having less than 100 amino acid residues. In an embodiment, it has less than 50, 20, or 10 amino acid residues.

“Reference molecule”, e.g., a reference Cas9 molecule or reference gRNA, as used herein, refers to a molecule to which a subject molecule, e.g., a subject Cas9 molecule of subject gRNA molecule, e.g., a modified or candidate Cas9 molecule is compared. For example, a Cas9 molecule can be characterized as having no more than 10% of the nuclease activity of a reference Cas9 molecule. Examples of reference Cas9 molecules include naturally occurring unmodified Cas9 molecules, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, S. aureus or S. thermophilus. In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology with the Cas9 molecule to which it is being compared. In an embodiment, the reference Cas9 molecule is a sequence, e.g., a naturally occurring or known sequence, which is the parental form on which a change, e.g., a mutation has been made.

“Replacement”, or “replaced”, as used herein with reference to a modification of a molecule does not require a process limitation but merely indicates that the replacement entity is present.

“Small molecule”, as used herein, refers to a compound having a molecular weight less than about 2 kD, e.g., less than about 2 kD, less than about 1.5 kD, less than about 1 kD, or less than about 0.75 kD.

“Subject”, as used herein, may mean either a human or non-human animal. The term includes, but is not limited to, mammals (e.g., humans, other primates, pigs, rodents (e.g., mice and rats or hamsters), rabbits, guinea pigs, cows, horses, cats, dogs, sheep, and goats). In an embodiment, the subject is a human. In other embodiments, the subject is poultry.

“Treat”, “treating” and “treatment”, as used herein, mean the treatment of a disease in a mammal, e.g., in a human, including (a) inhibiting the disease, i.e., arresting or preventing its development; (b) relieving the disease, i.e., causing regression of the disease state; and (c) curing the disease.

“X” as used herein in the context of an amino acid sequence, refers to any amino acid (e.g., any of the twenty natural amino acids) unless otherwise specified.

Cystic Fibrosis and CF-Like Disease

Cystic fibrosis (CF) is an autosomal recessive hereditary disease caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene encodes a cAMP-gated channel that is involved in chloride and bicarbonate transport. It regulates sodium transport through inhibition of the epithelial sodium channel, which is encoded by the SCNN1A gene. CFTR is expressed on the apical surface of epithelial cells in the airway, gastrointestinal tract, reproductive tract, sweat glands and submucosal glands.

Subjects having CF or CF-like disease may present at birth or in early infancy with pancreatic insufficiency. Pancreatic dysfunction leads to malabsorption of fat and fat-soluble vitamins, which causes poor growth as well as gallstones and biliary disease. The lung manifestations of the disease can be more severe but may present slightly after pancreatic manifestations, in infancy or early childhood. Aberrant chloride and sodium transport due to decreased CFTR activity causes lowered apical surface fluid levels in the lungs, which leads to “sticky” mucous and lower airway obstruction. Subjects having CF or CF-like disease suffer from frequent infections due to inability to clear mucous. Local inflammatory mediators try to clear the infection but have difficulty. The triad of inflammation, infection and obstruction leads to progressive destruction of the lung parenchyma. Eventually, many subjects having CF or CF-like disease die in their late 30's due to respiratory failure.

Current treatments for CF or CF-like disease can increase the life expectancy of subjects with CF or CF-like disease. These treatments delay lung destruction and slow disease progression. These treatments do not reverse the damage to the lungs or cure CF or CF-like disease. Subjects having CF or CF-like disease eventually suffer from end-stage lung disease.

Treatments for the pulmonary manifestations of CF or CF-like disease include: antibiotics (oral, inhaled and intravenous), CFTR modulators (including CFTR potentiators), DNase, chest physiotherapy to loosen secretions and anti-inflammatory therapeutics. Treatment of the gastrointestinal manifestations includes supplemental gut soluble vitamins, high calorie diet and oral pancreatic enzymes. Subjects who develop diabetes are treated with insulin injections or an insulin pump. At the end stage, patients may benefit from lung transplant. Lung transplant may be combined with liver and/or pancreatic transplant. The average life expectancy for subjects having CF or CF-like disease is nearing 40 years of age.

Methods and compositions discussed herein provide for the treatment and prevention of Cystic Fibrosis (CF) and CF-like disease. The approach described herein aims to restore CFTR channel function, restore chloride, bicarbonate and/or sodium balance, and/or decrease mucous viscosity within the lungs, airways, gastrointestinal tract and reproductive tract.

CFTR modulators (both approved and in development) improve the functioning of mutant CFTR. These therapeutics improve CFTR functioning but do not return functionality to wild type levels. The approach described herein is expected to restore CFTR function through complete correction of the gene.

Gene therapy approaches are in development that deliver the CFTR channel gene to the lungs of CF patients. However, gene therapy may require constant readministration over the course of the lifetime of a subject due to high cell turnover in target epithelial cells. The approach described herein is expected to restore CFTR function and/or ameliorate SCNN1A disinhibition permanently through one, two or several doses.

The CFTR gene encodes a 180-kDA cAMP-gated chloride (Cl—) channel. The channel has six transmembrane spanning domains and is expressed by epithelial cells, lymphocytes and cardiac myocytes. The CFTR regulates the viscosity of mucous through its activity in the epithelial cells of the lungs, gastrointestinal tract and reproductive tract. Mutations in the CFTR result in decreased CFTR activity. Decreased CFTR activity can lead to aberrant ion transport, which gives rise to various disease symptoms in the lungs and other tissues, such as accumulation of sticky mucus, airway obstruction, infection and inflammation. Correction of CFTR mutations will ameliorate or cure lung, gastrointestinal and/or reproductive symptoms of CF.

The SCNN1A gene encodes the alpha subunit of the epithelial sodium channel (ENaC). The channel, comprised of alpha, beta and gamma subunits, regulates sodium transport into epithelial cells, including the epithelium of the lungs, sweat glands and kidneys. Mutations in the SCNN1A gene, (e.g. Val114ILE) have been shown to cause CF-like disease, characterized by pulmonary disease, including bronchiectasis. Mutations in SCNN1A also cause pseudohypoaldosteronism, a severe disease of the kidney. Pseudohypoaldosteronism is due to defective sodium transport within kidney epithelial cells; it is not caused by defective sodium transport in other tissues. The methods described herein include the targeted knockout of SCNN1A in the lung, gastrointestinal tract and/or reproductive tract. The methods described herein will not target kidney epithelium and will avoid the negative consequences of SCNN1A mutations within the kidney epithelium. One mutation in the SCNN1A gene, a 1477T>G substitution (W493R) has been identified in subjects who also have a mutation in CFTR. This mutation is associated with a severe CF phenotype, including severe bronchiectasis, chronic bronchitis and/or severe gastrointestinal symptoms. This mutation has been found to be associated with 4-fold overactivity of the ENaC channel (Azad et al., 2009; Human Mutation 30: 1093-1103). Overactivity of the SCNN1A-encoded ENaC channel can contribute to CF and CF-like disease. In all subjects, the CFTR is involved in inhibition of ENaC. CFTR mutations in subjects with CF or CF-like disease leads to ENaC disinhibition, leading to overactivity of the ENaC channel. ENaC overactivity can lead to further reduction in viscosity of mucous in CF or CF-like disease subjects, as more sodium is absorbed at the apical surface of epithelial cells, followed by increased fluid absorption from the mucous layer within the lung (Baker et al., 2012; Medicine & Science in Sports and Exercise 44(12): 2315-2321). Increased fluid absorption from the mucous layer reduces mucous viscosity. Inhibition of ENaC through SCNN1A knockout and/or knockdown in subjects with CF or CF-like disease can ameliorate the symptoms of CF or CF-like disease.

One common mutation in the CFTR gene is a deletion of the three nucleotides encoding Phenylalanine (F) at position 508 of the CFTR protein F508del (also sometime referred to herein as “F508del” or “delF508”). This mutation is the causative mutation in approximately two-thirds of CF cases. The remaining cases are caused by at least 1000 different mutations, many of which cause a less severe form of the disease.

Overactivity of the SCNN1A gene has been shown to contribute to bronchiectasis, bronchitis, and gastrointestinal symptoms in subjects with CF and in subjects with CF-like disease. In another aspect, methods and compositions discussed herein may be used to alter the SCNN1A gene (also known as sodium channel, non-voltage-gated 1 alpha subunit; amiloride-sensitive epithelial sodium channel alpha subunit; BESC2; ENaCa; SCNEA; SCNN1; ENaCalpha) to treat or prevent CF or CF-like disease, by targeting the SCNN1A gene, e.g., the non-coding or coding regions, e.g., a promoter region, or a transcribed sequence, e.g., intronic or exonic sequence. In an embodiment, the target position is V114, which corresponds to V114I in the SCNN1A gene. SCNN1A encodes an epithelial sodium channel, ENaC, that is negatively regulated by CFTR. In subjects with CFTR mutations, knocking out or knocking down the SCNN1A gene in certain cells will reduce or reverse the effect of defective CFTR. In subjects with no CFTR mutations but CF-like disease caused by SCNN1A mutations or other mechanisms, knocking out or knocking down the SCNN1A gene in certain cells will improve the viscosity of mucous and ameliorate disease.

Methods to Treat or Prevent Cystic Fibrosis and Cystic Fibrosis-Like Disease

Correction of the CFTR mutation (e.g., F508 deletion, e.g., G551D substitution, e.g., G542X nonsense mutation, e.g., N1303K substitution, e.g., R117H substitution, e.g., W1282X nonsense mutation, e.g., R553X nonsense mutation, e.g., 3849+10kbC>T substitution, e.g., 2789+5G>A substitution, e.g., 3273-26A>G substitution) or inactivation or knockdown of the SCNN1A gene, e.g., using the methods disclosed herein, can ameliorate the disease. In an embodiment, the method leads to normalized ion transport, less viscous mucous, and/or reduced mucous plugging and inflammation, e.g., early in the disease course. In an embodiment, the method results in fewer infections, decreased lung tissue destruction, and/or slowing in progression of disease. In an embodiment, the method improves mucous production and/or reduce frequency and/or length of infections, e.g., in later stages of the disease. In an embodiment, the method reduces or prevents further damage by ameliorating the triad of inflammation, infection and obstruction. In an embodiment, the method delays progression of the disease. In an embodiment, the method reduces or prevents further damage by ameliorating the triad of inflammation, infection and obstruction. In an embodiment, the method leads to normalized ion transport, and restoration of fertility. In an embodiment, the method leads to normalized ion transport, and improved gastrointestinal motility, absorption, and/or function.

Disclosed herein are the approaches to treat or prevent CF or CF-like disease, using the compositions and methods described herein.

While not wishing to be bound by theory, it is believed that, in an embodiment described herein, the CFTR channel is corrected and chloride and bicarbonate balance restored, e.g., within the lung, e.g., within the airway, e.g., within the gastrointestinal tract, e.g., within the reproductive tract, e.g., in the hepatobiliary epithelium, e.g. in the pancreas. CFTR modulators (both approved and in development) improve the functioning of mutant CFTR. These therapeutics improve CFTR functioning but do not return functionality to wild type levels.

In an embodiment, the approach described herein restores CFTR function through complete correction of the CFTR gene. In another embodiment, the approach described herein inactivates the SCNN1A gene, e.g., in the pulmonary epithelium, e.g., in the airway epithelium, e.g., in the gastrointestinal epithelium, e.g. in the reproductive epithelium, e.g., in the hepatobiliary epithelium, e.g. in the pancreatic ducts, in order to inhibit the abnormal sodium ion transport associated with reduced CFTR activity and/or in order to inhibit abnormal sodium ion transport associated with overactive ENaC activity. In an embodiment, these two approaches are combined to treat or prevent CF or CF-like disease. In an embodiment, the approaches described herein provide advantages over CFTR modulators.

It is contemplated that the compositions disclosed herein may be administered once or more than once (e.g., 2, 3, 4, 5, or more times) to correct a mutation in the CFTR gene or to inactivate or knock-down the SCNN1A gene. It is further contemplated that when the compositions disclosed herein are administered more than one time that the multiple administrations are intended to increase the number of cells (e.g., the number of cells in the subject) containing the corrected form of the CFTR gene and/or the inactivated/knocked-down form of the SCNN1A gene, thereby increasing the effectiveness of the treatment.

The methods of treatment described herein can be initiated for subjects at all stages of the disease. In an embodiment, the treatment is initiated after disease onset, e.g., as the subject presents with lung infections, wheezing and obstructed airways, and/or pancreatic insufficiency, decreased gastrointestinal function, malabsorption, and/or infertility. While not wishing to be bound by theory, in an embodiment, repair of the CFTR gene or inactivation/knock-down of the SCNN1A gene after disease onset but early in the disease course reduces or prevents progression of the disease. In an embodiment, the method comprises treating a subject with advanced disease. In an embodiment, the method reduces or prevents further progression of symptoms, with or without reversing pathology.

In an embodiment, the treatment is initiated prior to disease onset. In another embodiment, the treatment is initiated at an early stage of the disease, e.g., before the subject has noticed any decline in function or symptoms.

In an embodiment, treatment is initiated in utero.

In an embodiment, treatment is initiated after birth.

In an embodiment, treatment is initiated prior to the age of 1.

In an embodiment, treatment is initiated prior to the age of 2.

In an embodiment, treatment is initiated prior to the age of 5.

In an embodiment, treatment is initiated prior to the age of 10.

In an embodiment, the subject has tested positive for a mutation in the CFTR gene, e.g., a mutation described herein.

In an embodiment, the subject has tested positive for a mutation in the SCNN1A gene, e.g., a mutation described herein.

In an embodiment, the treatment is initiated at appearance of a symptom of CF or CF-like disease, e.g., any of the following symptoms: frequent lung infections, chronic cough, sputum production, or chronic wheeze. In an embodiment, the subject has a positive “sweat test” or elevated sweat Chloride indicating dysfunction of the CFTR channel and/or overactivity of the SCNN1A channel. In an embodiment, the subject has an elevated sweat Chloride, bronchiectasis and is found to have no mutation in the CFTR gene.

In an embodiment, the treatment is initiated if the subject is tested positive for a defect, e.g., a genetic defect, in the CFTR gene.

In an embodiment, the treatment is initiated if the subject is tested positive for a defect, e.g., a genetic defect, in the SCNN1A gene.

In an embodiment, the treatment is initiated if a family member of the subject has been diagnosed with CF or CF-like disease. In an embodiment, the subject has a symptom or sign of CF or CF-like disease. In an embodiment, the subject has a mutation in the CFTR gene, e.g., a mutation described herein.

In an embodiment, the treatment is initiated at the appearance of any of the following findings consistent with CF or CF-like disease, including but not limited to, obstructive lung disease on lung function tests; persistent colonization with B. cepacia, P. aeruginosa and S. aureus and other CF-related pathogens; chronic radiologic abnormalities on chest x-ray; or chronic sinusitis.

In an embodiment, the method comprises initiating treatment at the appearance of any of the following gastrointestinal findings consistent with CF or CF-like disease, including but not limited to: failure to thrive, steatorrhea, hypoproteinemia, vitamin deficiency due to fat-soluble vitamin malabsorption, meconium ileus, rectal prolapse, malabsorption, pancreatic insufficiency, pancreatitis, or chronic hepatobiliary disease. Evidence of chronic hepatobiliary disease can include, e.g., elevated transaminases and/or hyperbilirubinemia.

In an embodiment, a cell is treated ex vivo. In an embodiment, the cell is returned to the subject.

In an embodiment, it is contemplated herein that a population of cells from a subject may be contacted ex vivo to correct a mutation in the CFTR gene, e.g., F508del, e.g., G542X, e.g., G551D, e.g., N1303K, e.g., R117H, e.g., W1282X, e.g., R553X, e.g., 3849+10kbC>T, e.g., 2789+5G>A, e.g., 3273-26A>G, and a second population of cells from the subject is contacted ex vivo to introduce a mutation in the SCNN1A gene to knockout or knockdown SCNN1A. A mixture of the two cell populations may be returned to the subject's body to prevent or treat CF or CF-like disease.

In an embodiment, the cell is harvested from epidermis, pulmonary tree, hepatobiliary tree, gastrointestinal tract, reproductive tract, or other organ. In an embodiment, the cell is reprogrammed to an induced pluripotent stem (iPS) cell. In an embodiment, the iPS cell is differentiated into airway epithelium, pulmonary epithelium, submucosal glands, submucosal ducts, biliary epithelium, gastrointestinal epithelium, pancreatic duct cells, reproductive epithelium, epidydimal cells, and/or cells of the hepatobiliary tree, e.g., clara cells, e.g., ciliated cells, e.g., goblet cells, e.g., basal cells, e.g., acinus cells, e.g., bronchioalveolar stem cell e.g., lung epithelial cells, e.g., nasal epithelial cells, e.g., tracheal epithelial cells, e.g., bronchial epithelial cells, e.g., enteroendocrine cells, e.g., Brunner's gland cells, e.g., epididymal epithelium. In an embodiment, the CFTR gene in the cell is corrected with the method described herein. In an embodiment, the SCNN1A gene in the cell is corrected with the method described herein. In an embodiment, the CFTR gene and the SCNN1A gene in the cell is corrected with the method described herein. In an embodiment, the cell is re-introduced into an appropriate location in the subject, e.g., airway, pulmonary tree, bile duct system, gastrointestinal tract, pancreas, hepatobiliary tree, and/or reproductive tract.

In an embodiment, an autologous stem cell can be treated ex vivo, differentiated into airway epithelium, pulmonary epithelium, submucosal glands, submucosal ducts, biliary epithelium, gastrointestinal epithelium, pancreatic duct cells, reproductive epithelium, epidydimal cells, and/or cells of the hepatobiliary tree, e.g., clara cells, e.g., ciliated cells, e.g., goblet cells, e.g., basal cells, e.g., acinus cells, e.g., bronchioalveolar stem cell e.g., lung epithelial cells, e.g., nasal epithelial cells, e.g., tracheal epithelial cells, e.g., bronchial epithelial cells, e.g., enteroendocrine cells, e.g., Brunner's gland cells, e.g., epididymal epithelium, and transplanted into the subject.

In an embodiment, a heterologous stem cell can be treated ex vivo, differentiated into airway epithelium, pulmonary epithelium, submucosal glands, submucosal ducts, biliary epithelium, gastrointestinal epithelium, pancreatic duct cells, reproductive epithelium, epidydimal cells, and/or cells of the hepatobiliary tree, e.g., clara cells, e.g., ciliated cells, e.g., goblet cells, e.g., basal cells, e.g., acinus cells, e.g., bronchioalveolar stem cell e.g., lung epithelial cells, e.g., nasal epithelial cells, e.g., tracheal epithelial cells, e.g., bronchial epithelial cells, e.g., enteroendocrine cells, e.g., Brunner's gland cells, e.g., epididymal epithelium, and transplanted into the subject.

In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, by inhalation, e.g., via nebulizer. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid by intravenous administration. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid by intraparenchymal injection into lung tissue. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, by intraparenchymal, intralveolar, intrabronchial, intratracheal injection into the trachea, bronchial tree and/or alveoli. In an embodiment, the method described herein comprises delivery of gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, by intravenous, intraparenchymal or other directed injection or administration to any of the following locations: the portal circulation, liver parenchyma, pancreas, pancreatic duct, bile duct, jejunum, ileum, duodenum, stomach, upper intestine, lower intestine, gastrointestinal tract, epididymis, or reproductive tract.

In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, by AAV, e.g., via nebulizer, or via nasal spray or inhaled, with or without accelerants to aid in absorption. In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, by Sendai virus, adenovirus, lentivirus or other modified or unmodified viral delivery particle.

In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, via nebulizer or jet nebulizer, nasal spray, or inhalation. In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid, is formulated in an aerosolized cationic liposome, lipid nanoparticle, lipoplex, non-lipid polymer complex or dry powder, e.g., for delivery via nebulizer, with or without accelerants to aid in absorption.

In an embodiment, a gRNA or other components described herein, e.g., a Cas9 molecule and a template nucleic acid are delivered, e.g., to a subject, via liposome GL67A. GL67A is described, e.g., www.cfgenetherapy.org.uk/clinical/product.html; Eastman et al., Hum Gene Ther. 1997 Apr. 10; 8(6):765-73.

Disclosed herein are methods for altering the CF target position in the CFTR and/or SCNN1A genes.

Methods and compositions disclosed herein provide a number of approaches for treating or preventing CF and CF-like disease. In an embodiment, methods described herein provide for treating or preventing CF and CF-like disease by correcting a target position in the CFTR gene to provide corrected, or functional, e.g., wild type, CFTR. In an embodiment, methods described herein allow for treating or preventing CF and CF-like disease by inducing or introducing a mutation that reduces the level of functional SCNN1A gene product. In subjects with CF or CF-like disease, these methods can be used alone, e.g. CFTR correction, e.g., SCNN1A knockout or knockdown, or in combination, e.g., CFTR correction with SCNN1A knockout or knockdown.

Several approaches are detailed in the following, including target positions and mutations amenable to approach. In the description below, approaches 1, 2 and 3 (e.g., 3A and 3B) correspond to methods to alter CFTR. In the description below, approach 4 and 6 correspond to methods to alter SCNN1A. One or more of the approaches can be used alone or in combination. For example, approaches 1, 2, and 3 can be used alone or approach 1 can be combined with approach 4, or approach 2 can be combined with approach 4 or approach 3 (e.g., 3A or 3B) can be combined with approach 4.

Methods to Alter CFTR

In one aspect, methods and compositions discussed herein, provide for the correction of the underlying cause of CF or CF-like disease, e.g., the correction of a mutation at a target position in the CFTR gene.

As disclosed herein, the CFTR gene can be altered by gene editing, e.g., using CRISPR-Cas9 mediated methods as described herein. Methods and compositions discussed herein, provide for altering a CF target position in the CFTR gene. A CF target position can be altered by gene editing, e.g., using CRISPR-Cas9 mediated methods to alter the CFTR gene.

In an embodiment, while some of the disclosure herein is presented in the context of the mutation in the CFTR gene that gives rise to an F508 mutant protein (e.g., F508del mutant protein) or a G551 mutant protein (e.g., G551D mutant protein), or a G542 mutant protein (e.g., G542X mutant protein), or a mutant protein (e.g., mutant protein), or a N1303 mutant protein (e.g., N1303K mutant protein), or a R117 mutant protein (e.g., R117H mutant protein), or a W1282 mutant protein (e.g., W1282X mutant protein), or a R553 mutant protein (e.g., R553X mutant protein), or a c.3717+12191 mutant protein (e.g., c.3717+12191C>T mutant protein), or a c.2657+5 mutant protein (e.g., c.2657+5G>A mutant protein), or a c.3140-26 mutant protein (e.g., c.3140-26A>G mutant protein), the methods and compositions herein are broadly applicable to any mutation, e.g., a point mutation or a deletion, in the CFTR gene that gives rise to CF or CF-like disease.

The alteration of the CFTR gene can be mediated by any mechanism. Exemplary mechanisms that can be associated with the alteration of the CFTR gene include, but are not limited to, non-homologous end joining (e.g., classical or alternative), microhomology-mediated end joining (MMEJ), homology-directed repair (e.g., endogenous donor template mediated), SDSA (synthesis dependent strand annealing) or single strand annealing or single strand invasion, all with or without the addition of an endogenous-promoter driven cDNA encoding the CFTR gene.

Approach 1:

In an embodiment, one approach to treat or prevent CF or CF-like disease is to repair (i.e., correct) one or more mutations in the CFTR gene, e.g., by HDR. While not wishing to be bound by theory, it is believed that correction of the mutation(s) (e.g., mediated by HDR) restore the mutant CFTR gene to its wild type state. In an embodiment, single stranded oligonucleotides (ssODNs) are used as a donor template. In another embodiment, double stranded DNA donor is used as a donor template. Donor templates contain DNA sequence which, upon incorporation, result in the expression of a functional version of the CFTR protein. In an embodiment, one CFTR allele is repaired in the subject. In another embodiment, both CFTR alleles are repaired in the subject. In one aspect, methods and compositions discussed herein, provide for the correction of the underlying genetic cause of CF or CF-like disease, e.g., the correction of a mutation at a target position in the CFTR gene, e.g., correction of a mutation (e.g., delF508, G551DG542X, N1303K, R117H, W1282X, or R553X) in the CFTR gene.

Mutations in the CFTR gene amenable to the approach described herein include, but are not limited to any of the following mutations, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, the homology-directed repair of genomic sequence including the mutation at the CF target position (e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X) gives rise to alteration of the CFTR gene. This approach leads to the cessation of production of mutant CFTR channel and results in the production of wild-type CFTR channel. This approach will prevent the development or progression of lung, gastrointestinal and/or reproductive disease in subjects with CFTR mutations.

In an embodiment, the method provides for the correction of a mutation at a target position in the CFTR gene, e.g., correction of a mutation, e.g., an F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X substitution in the CFTR gene. As described herein, in an embodiment, the method comprises the introduction of one or more breaks (e.g., single strand breaks or double strand breaks) sufficiently close to (e.g., either 5′ or 3′ to) the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, the targeting domain of the gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5′ or 3′ to) the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X to allow correction, e.g., an alteration in the CFTR gene, e.g., an alternation associated with HDR. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, a second, third and/or fourth gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5′ or 3′ to) the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X to allow correction, e.g., an alteration associated with HDR in the CFTR gene. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, a single strand break is accompanied by an additional single strand break, positioned by a second, third and/or fourth gRNA molecule, as discussed below. For example, The targeting domains bind configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X. In an embodiment, the first and second gRNA molecules are configured such, that when guiding a Cas9 nickase, a single strand break will be accompanied by an additional single strand break, positioned by a second gRNA, sufficiently close to one another to result in an alteration of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X. In an embodiment, the first and second gRNA molecules are configured such that a single strand break positioned by said second gRNA is within 10, 20, 30, 40, or 50 nucleotides of the break positioned by said first gRNA molecule, e.g., when the Cas9 is a nickase. In an embodiment, the two gRNA molecules are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, e.g., essentially mimicking a double strand break.

In an embodiment, a double strand break can be accompanied by an additional double strand break, positioned by a second, third and/or fourth gRNA molecule, as is discussed below. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position; and the targeting domain of a second gRNA molecule is configured such that a double strand break is positioned downstream the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position.

In an embodiment, a double strand break can be accompanied by two additional single strand breaks, positioned by a second gRNA molecule and a third gRNA molecule. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position; and the targeting domains of a second and third gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position. In an embodiment, the targeting domain of the first, second and third gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules.

In an embodiment, a first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule. For example, the targeting domain of a first and second gRNA molecule are configured such that two single strand breaks are positioned upstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450 or 500 nucleotides of the target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, or R553X.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream of (e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Approach 2:

HDR-mediated knockin of cDNA to alter the CFTR gene. In an embodiment, a CF target knockin position is altered. Altering the CF target knockin position refers to homology-directed knockin of genomic sequence, including the delivery of cDNA template of contiguous exons (X+1) through exon 27 of CFTR gene, wherein exon X is any exon between exon 1 and exon 27. Targeted knockin of CFTR cDNA leads to the cessation of production of mutant or truncated CFTR protein and results in the production of functional CFTR protein. In an embodiment, a donor template is provided to mediate HDR-mediated knockin. In an embodiment, said donor template comprise homology arms, splice acceptor, contiguous coding sequence of exons (X+1) through exon 27 of CFTR gene and polyadenylation signal. While not wishing to be bound by theory, it is believed that correction of the mutation(s) (e.g., mediated by HDR) restore the mutant CFTR gene to its wild type state. In another embodiment, double stranded DNA donor is used as a donor template. Donor templates contain DNA sequence which, upon incorporation, would result in the expression of a functional version of the CFTR protein. In an embodiment, one CFTR allele is repaired in the subject. In another embodiment, both CFTR alleles are repaired in the subject. In one aspect, methods and compositions discussed herein, provide for the correction of the underlying genetic cause of CF or CF-like disease, e.g., the correction of a mutation at a CF target position in the CFTR gene, e.g., correction of a mutation. This approach leads to the cessation of production of mutant or truncated CFTR protein and results in the production of functional CFTR protein. This approach prevents the development or progression of lung, gastrointestinal and/or reproductive disease in a subject due to the cessation of production of mutant CFTR protein and restoration of functional CFTR protein production. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exon (X+1) through exon 27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is after exon X.

In an embodiment, homology-directed repair of the CFTR gene in any subjects with CF mutations in exons 3 through 27 and introns 2 through 26 by targeting intronic region between exons 2 and 3 and with delivery of a homology-directed repair template including homology arms, splice acceptor, coding sequence of contiguous exons 3-27 of CFTR gene and polyadenylation signal.

In an embodiment, the CF target position is the intronic region between exons 2 and 3. Altering the CF target position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of exons 3-27 of CFTR gene. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exons 3-27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is on or after the second intron, including but not limited to the following mutations: e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, R553X, c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G.

In an embodiment, the CF target position is the intronic region between exons 10 and 11. Altering the CF target position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of exons 11-27 of CFTR gene. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exons 11-27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is on or after the second intron, including but not limited to the following mutations: e.g., F508del.

In an embodiment, the method provides for the correction of a mutation at a target position in the CFTR gene, e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, R553X, c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G. As described herein, in one embodiment, the method comprises the introduction of one or more breaks (e.g., single strand breaks or double strand breaks) sufficiently close to (e.g., either 5′ or 3′ to) the target position in the CFTR gene, e.g., intron 2 or intron 10.

In an embodiment, the targeting domain of the gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5′ or 3′ to) the target position e.g., intron 2 or intron 10 allow correction, e.g., an alteration in the CFTR gene, e.g., an alternation associated with HDR. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10.

In an embodiment, a second, third and/or fourth gRNA molecule is configured to provide a cleavage event, e.g., a double strand break or a single strand break, sufficiently close to (e.g., either 5′ or 3′ to) the target position e.g., intron 2 or intron 10 to allow correction, e.g., an alteration associated with HDR in the CFTR gene. In an embodiment, the targeting domain is configured such that a cleavage event, e.g., a double strand or single strand break, is positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10. The break, e.g., a double strand or single strand break, can be positioned upstream or downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10.

In an embodiment, a single strand break is accompanied by an additional single strand break, positioned by a second, third and/or fourth gRNA molecule, as discussed below. For example, The targeting domains bind configured such that a cleavage event, e.g., the two single strand breaks, are positioned within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10. In an embodiment, the first and second gRNA molecules are configured such, that when guiding a Cas9 nickase, a single strand break will be accompanied by an additional single strand break, positioned by a second gRNA, sufficiently close to one another to result in an alteration of the target position in the CFTR gene, e.g., intron 2 or intron 10. In an embodiment, the first and second gRNA molecules are configured such that a single strand break positioned by said second gRNA is within 10, 20, 30, 40, or 50 nucleotides of the break positioned by said first gRNA molecule, e.g., when the Cas9 is a nickase. In an embodiment, the two gRNA molecules are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, e.g., essentially mimicking a double strand break.

In an embodiment, a double strand break can be accompanied by an additional double strand break, positioned by a second, third and/or fourth gRNA molecule, as is discussed below. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position; and the targeting domain of a second gRNA molecule is configured such that a double strand break is positioned downstream the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position.

In an embodiment, a double strand break can be accompanied by two additional single strand breaks, positioned by a second gRNA molecule and a third gRNA molecule. For example, the targeting domain of a first gRNA molecule is configured such that a double strand break is positioned upstream of the target position in the CFTR gene, e.g., intron 2 or intron 10 e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position; and the targeting domains of a second and third gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position. In an embodiment, the targeting domain of the first, second and third gRNA molecules are configured such that a cleavage event, e.g., a double strand or single strand break, is positioned, independently for each of the gRNA molecules.

In an embodiment, a first and second single strand breaks can be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule. For example, the targeting domain of a first and second gRNA molecule are configured such that two single strand breaks are positioned upstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10; and the targeting domains of a third and fourth gRNA molecule are configured such that two single strand breaks are positioned downstream of the target position in the CFTR gene, e.g., intron 2 or intron 10, e.g., within 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, or 200 nucleotides of the target position in the CFTR gene, e.g., intron 2 or intron 10.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream of (e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Approach 3A:

In an embodiment, Cas9-mediated removal and/or disruption of an intronic segment of DNA, within a CFTR intron, to restore post-transcriptional processing accuracy, e.g., without the use of homology-directed repair. CFTR mutations (e.g., c.3717+12191C>T, e.g., 2657+5G>A, e.g., c.3140-26A>G) can cause abbarent post-transcriptional processing, such as missplicing by the creation of novel splice sites which can lead to the early truncation of non-functional CFTR protein resulting in aberrant CFTR channel formation. In one aspect, methods and compositions discussed herein, provide for altering the CF target position in the CFTR gene. The CF target position (e.g. c.3717+12191, also known as c.3849+10kb, e.g., c.2657+5, also known as c.2789+5, e.g., c.3140-26A, also known as c.3272-26) can be altered, e.g., by non-homologous end-joining mediated removal and/or disruption of a splice site mutation. In the case of a subject with a 3717+12191C>T mutation, the CF target position is 500 bp upstream and/or downstream of c.3717+12191 within intron 22. In the case of a subject with a c.2657+5G>A mutation, the CF target position is 200 bp upstream within exon 16, and intron 16 and intron 15 and/or downstream of c.2657+5 within intron 16. In the case of a subject with a c.3140-26A>G mutation, the CF target position is 200 bp upstream and/or downstream of c.3140-26 within intron 19 and exon 20. The removal, disruption and/or repair of a splice site mutation will restore accurate splicing and cease production of aberrant truncation of CFTR protein. This approach will lead to the cessation of production of truncated non-functional CFTR channel and will lead to the production of wild-type CFTR channel. This approach will prevent the development or progression of lung, gastrointestinal and/or reproductive disease in subjects with CFTR mutations.

In an embodiment, methods and compositions discussed herein, provide for altering the CF target position in the CFTR gene. The alteration can be achieved by (1) break-induced introduction of an indel (also referred to herein as NHEJ-mediated introduction of an indel) in close proximity to or including a CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G), or (2) break-induced deletion (also referred to herein as NHEJ-mediated deletion) of genomic sequence including the mutation at a CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). Both approaches give rise to the loss or destruction of the abbarent post-transcriptional processing.

In an embodiment, the method comprises introducing a break-induced indel in close proximity to or including the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). As described herein, in one embodiment, the method comprises the introduction of a double strand break sufficiently close to (e.g., either 5′ or 3′ to) the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. A single gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, is configured to position a double strand break sufficiently close to the CF target position in the CFTR gene. The double strand break may be positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ-mediated repair of the double strand break allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

In another embodiment, the method comprises the introduction of a pair of single strand breaks sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two single strand breaks sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ mediated repair of the pair of single strand breaks allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position. In an embodiment, the pair of single strand breaks may be accompanied by an additional double strand break, positioned by a third gRNA molecule, as is discussed below. In another embodiment, the pair of single strand breaks may be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule, as is discussed below.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., a pair of double strand breaks targeted by two gRNAs) sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., a pair of double strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ mediated repair of two sets of breaks (e.g., a pair of double strand breaks) allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., one double strand break and a pair of single strand breaks targeted by three gRNAs) sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., one double strand break and a pair of single strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ mediated repair of two sets of breaks (e.g., one double strand break and a pair of single strand breaks) allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., two pairs of single strand breaks targeted by four gRNAs) sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G). such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., two pairs of single strand breaks s) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, 200, 300, 400 or 500 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that NHEJ mediated repair of two sets of breaks (e.g., two pairs of single strand breaks) allows for the NHEJ-mediated introduction of an indel in close proximity to or including the CF target position.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 500 bp, e.g., within 200 bp upstream) or downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 500 bp, e.g., within 200 bp upstream) or downstream of (e.g., within 500 bp, e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) or downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 500 bp, e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 500 bp, e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 500 bp, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 500 bp upstream) or downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 500 bp upstream) or downstream of (e.g., within 500 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 500 bp upstream) or downstream (e.g., within 500 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 500 bp upstream) and a second single strand break is positioned downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 500 bp upstream) and a second double strand break is positioned downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 500 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 500 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 500 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Approach 3B:

In an embodiment, Cas9-mediated removal and/or disruption of an intronic segment of DNA, within a CFTR intron, to restore post-transcriptional processing accuracy, e.g., with the use of homology-directed repair. CFTR mutations e.g., c.2657+5 (also known as c.2789+5), or c.3140-26A (also known as c.3272-26) can cause abbarent post-transcriptional processing, such as missplicing by the creation of novel splice sites which can lead to production of non-functional CFTR protein resulting in aberrant CFTR channel formation. In one aspect, methods and compositions discussed herein, provide for altering the CF target position in the CFTR gene. The CF target position (e.g., c.2657+5, e.g., c.3140-26A) can be altered by non-homologous end-joining mediated removal of a splice site mutation. In the case of a subject with a c.2657+5G>A mutation, the CF target position is 200 bp upstream and/or downstream of c.2657+5 within within exon 16, and intron 16 and intron 15. In the case of a subject with a c.3140-26A>G mutation, the CF target position is 200 bp upstream and/or downstream of c.3140-26 within exon 20 and intron 19. In an embodiment, in a subject with a target mutation in close proximity to an exon (including, but not limited to the mutations, e.g., 2789+5G>A, e.g., 3272-26A>G), approach may include Cas-9 mediated removal and/or disruption of an intronic segment at or near the target site with homology-directed repair with delivery of Cas9 nuclease (or nickase, or dead-Cas9), CRISPR-gRNAs, and homology-directed repair donor templates. In an embodiment, the donor template will be comprised of a single-strand oligonucleotide donor of 50 NT to 200 NT (or more as the technology becomes available). In an embodiment, the donor template will be comprised of a double-strand DNA donor with homology arms of length 700 bps to 1200 bps. The repair of a splice site mutation will restore accurate splicing and cease aberrant truncation of CFTR transcript. This approach will lead to the cessation of production of truncated CFTR channel and will lead to the production of wild-type CFTR channel. This approach will prevent the development or progression of lung, gastrointestinal and/or reproductive disease in subjects with CFTR mutations.

In an embodiment, the method comprises the introduction of a double strand break sufficiently close to (e.g., either 5′ or 3′ to) the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. A single gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, is configured to position a double strand break sufficiently close to the CF target position in the CFTR gene (e.g., 2657+5G>A, or c.3140-26A>G). The double strand break may be positioned within 200 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In another embodiment, the method comprises the introduction of a pair of single strand breaks sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two single strand breaks sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein. In an embodiment, the pair of single strand breaks may be accompanied by an additional double strand break, positioned by a third gRNA molecule, as is discussed below. In another embodiment, the pair of single strand breaks may be accompanied by two additional single strand breaks positioned by a third gRNA molecule and a fourth gRNA molecule, as is discussed below.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., a pair of double strand breaks targeted by two gRNAs) sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., a pair of double strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., one double strand break and a pair of single strand breaks targeted by three gRNAs) sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., one double strand break and a pair of single strand breaks) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In another embodiment, the method comprises the introduction of two sets of breaks (e.g., two pairs of single strand breaks targeted by four gRNAs) sufficiently close to (either 5′ or 3′ to, respectively) the mutation at the CF target position (e.g., c2657+5G>A, or c.3140-26A>G), such that the break-induced indel could be reasonably expected to span the mutation. Two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two sets of breaks (e.g., two pairs of single strand breaks s) sufficiently close to the CF target position in the CFTR gene. In an embodiment, the pair of single strand breaks is positioned within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) upstream of the CF target position, or within 500 nucleotides (e.g., within 1, 2, 3, 4, 5, 10, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 100, or 200 nucleotides) downstream of the CF target position. While not wishing to be bound by theory, in an embodiment, it is believed that HDR mediated repair of the break(s) restores the functional CFTR protein.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 200 bp upstream) or downstream of (e.g., within 200 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned upstream (e.g., within 200 bp upstream) or downstream (e.g., within 200 bp downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 200 bp upstream) and a second single strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 200 bp upstream) and a second double strand break is positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank an CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 200 bp upstream or downstream) of the CF target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (within 200 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the CFTR gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank an CF target position in the CFTR gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 200 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 200 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

When two or more gRNAs are used to position two or more cleavage events, e.g., double strand or single strand breaks, in a target nucleic acid, it is contemplated that the two or more cleavage events may be made by the same or different Cas9 proteins. For example, when two gRNAs are used to position two double strand breaks, a single Cas9 nuclease may be used to create both double strand breaks. When two or more gRNAs are used to position two or more single stranded breaks (single strand breaks), a single Cas9 nickase may be used to create the two or more single strand breaks. When two or more gRNAs are used to position at least one double strand break and at least one single strand break, two Cas9 proteins may be used, e.g., one Cas9 nuclease and one Cas9 nickase. It is contemplated that when two or more Cas9 proteins are used that the two or more Cas9 proteins may be delivered sequentially to control specificity of a double strand versus a single strand break at the desired position in the target nucleic acid.

In some embodiments, the targeting domain of the first gRNA molecule and the targeting domain of the second gRNA molecule hybridize to the target domain through complementary base pairing to opposite strands of the target nucleic acid molecule. In some embodiments, the gRNA molecule and the second gRNA molecule are configured such that the PAMs are oriented outward.

In an embodiment, the targeting domain of a gRNA molecule is configured to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat, or the endogenous CFTR splice sites, in the target domain. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule.

In an embodiment, the targeting domain of a gRNA molecule is configured to position a cleavage event sufficiently far from a preselected nucleotide, e.g., the nucleotide of a coding region, such that the nucleotide is not altered. In an embodiment, the targeting domain of a gRNA molecule is configured to position an intronic cleavage event sufficiently far from an intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events. The gRNA molecule may be a first, second, third and/or fourth gRNA molecule, as described herein.

In an embodiment, the targeting domain of said gRNA molecule is configured to position a cleavage event sufficiently far from a preselected nucleotide, e.g., the nucleotide of a coding region, such that the nucleotide is not be altered. In an embodiment, the targeting domain of said gRNA molecule is configured to position an intronic cleavage event sufficiently far from an intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events.

Methods to Alter SCNN1A

As disclosed herein, the SCNN1A gene can be altered by gene editing, e.g., using CRISPR-Cas9 mediated methods as described herein. A CF or CF-like target position can be altered by gene editing, e.g., using CRISPR-Cas9 mediated methods to alter the SCNN1A gene. The alteration of the SCNN1A gene can be mediated by any mechanism. In an embodiment, CRISPR-Cas9 mediated methods to knockdown or knockout the SCNN1A gene may be applied to any subject with any CF mutation, including but not limited to, e.g., F508del, e.g., G551D, e.g., G542X, e.g., N1303K, e.g., R117H, e.g., W1282X, e.g., R553X, e.g., c.3717+12191, e.g., c.2657+5, e.g., c.3140-26A and/or any subject with any CF-like mutation, including but not limited to a SCNN1A mutation, e.g., V114I. Exemplary mechanisms that can be associated with the alteration of the SCNNA1 gene include, but are not limited to, non-homologous end joining (e.g., classical or alternative), microhomology-mediated end joining (MMEJ), SDSA (synthesis dependent strand annealing) or single strand annealing or single strand invasion, all with or without the alteration of the CFTR gene, including but not limited to the addition of an endogenous-promoter driven cDNA encoding the CFTR gene, or homology-directed repair mediated correction of mutations within the CFTR gene or CRISPR-cas9 mediated repair of splice mutations within the CFTR gene.

As disclosed herein, the SCNN1A gene can be targeted (e.g., altered) by gene editing, e.g., using CRISPR-Cas9 mediated methods as described herein.

Methods and compositions discussed herein, provide for targeting (e.g., altering) a CF target position in the SCNN1A gene. A CF target position can be targeted (e.g., altered) by gene editing, e.g., using CRISPR-Cas9 mediated methods to target (e.g. alter) the SCNN1A gene.

Disclosed herein are methods for targeting (e.g., altering) a SCNN1A target position in the SCNN1A gene. Targeting (e.g., altering) the CF target position is achieved, e.g., by:

    • (1) knocking out the SCNN1A gene by insertion or deletion (e.g., NHEJ-mediated insertion or deletion) of one or more nucleotides in close proximity to or within the early coding region of the SCNN1A gene, or
    • (2) knocking down the SCNN1A gene mediated by enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein by targeting non-coding region, e.g., a promoter region, of the gene.

All approaches give rise to targeting (e.g., alteration) of the SCNN1A gene.

In an embodiment, methods described herein introduce one or more breaks near the early coding region in at least one allele of the SCNN1A gene. In another embodiment, methods described herein introduce two or more breaks to flank at least a portion of the SCNN1A gene. The two or more breaks remove (e.g., delete) a genomic sequence including at least a portion of the SCNN1A gene. In another embodiment, methods described herein comprise knocking down the SCNN1A gene mediated by enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9-fusion protein by targeting the promoter region of SCNN1A target knockdown position. All methods described herein result in targeting (e.g., alteration) of the SCNN1A gene.

The targeting (e.g., alteration) of the SCNN1A gene can be mediated by any mechanism. Exemplary mechanisms that can be associated with the alteration of the SCNN1A gene include, but are not limited to, non-homologous end joining (e.g., classical or alternative), microhomology-mediated end joining (MMEJ), homology-directed repair (e.g., endogenous donor template mediated), SDSA (synthesis dependent strand annealing), single strand annealing or single strand invasion.

Approach 4: Knocking Out SCNN1A by Introducing an Indel or a Deletion in the SCNN1A Gene

In an embodiment, the method comprises introducing an insertion or deletion of one more nucleotides in close proximity to the SCNN1A target knockout position (e.g., the early coding region) of the SCNN1A gene. As described herein, in one embodiment, the method comprises the introduction of one or more breaks (e.g., single strand breaks or double strand breaks) sufficiently close to (e.g., either 5′ or 3′ to) the early coding region of the CF target knockout position, such that the break-induced indel could be reasonably expected to span the CF target knockout position (e.g., the early coding region in the SCNN1A gene). While not wishing to be bound by theory, it is believed that NHEJ-mediated repair of the break(s) allows for the NHEJ-mediated introduction of an indel in close proximity to within the early coding region of the CF target knockout position.

In an embodiment, the method comprises introducing a deletion of a genomic sequence comprising at least a portion of the SCNN1A gene. As described herein, in an embodiment, the method comprises the introduction of two double stand breaks—one 5′ and the other 3′ to (i.e., flanking) the CF target position. In an embodiment, two gRNAs, e.g., unimolecular (or chimeric) or modular gRNA molecules, are configured to position the two double strand breaks on opposite sides of the CF target knockout position in the SCNN1A gene.

In an embodiment, a single strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nickase) is used to create a single strand break at or in close proximity to the CF target position, e.g., the gRNA is configured such that the single strand break is positioned either upstream (e.g., within 500 bp upstream, e.g., within 200 bp upstream) or downstream (e.g., within 500 bp downstream, e.g., within 200 bp downstream) of the CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, a double strand break is introduced (e.g., positioned by one gRNA molecule) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, a single gRNA molecule (e.g., with a Cas9 nuclease other than a Cas9 nickase) is used to create a double strand break at or in close proximity to the CF target position, e.g., the gRNA molecule is configured such that the double strand break is positioned either upstream (e.g., within 500 bp upstream, upstream) or downstream of (e.g., within 500 bp downstream) of a CF target position. In an embodiment, the break is positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two single strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the CF target position, e.g., the gRNAs molecules are configured such that both of the single strand breaks are positioned e.g., within 500 bp upstream, upstream) or downstream (e.g., within 500 bp downstream downstream) of the CF target position. In another embodiment, two gRNA molecules (e.g., with two Cas9 nickcases) are used to create two single strand breaks at or in close proximity to the SCNN1A target position, e.g., the gRNAs molecules are configured such that one single strand break is positioned upstream (e.g., within 500 bp upstream) and a second single strand break is positioned downstream (e.g., within 500 bp downstream) of the SCNN1A target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two double strand breaks are introduced (e.g., positioned by two gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, two gRNA molecules (e.g., with one or two Cas9 nucleases that are not Cas9 nickases) are used to create two double strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that one double strand break is positioned upstream (e.g., within 500 bp upstream) and a second double strand break is positioned downstream (e.g., within 500 bp downstream) of the SCNN1A target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, one double strand break and two single strand breaks are introduced (e.g., positioned by three gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, three gRNA molecules (e.g., with a Cas9 nuclease other than a Cas9 nickase and one or two Cas9 nickases) to create one double strand break and two single strand breaks to flank a CF target position, e.g., the gRNA molecules are configured such that the double strand break is positioned upstream or downstream of (e.g., within 500 bp upstream or downstream) of the SCNN1A target position, and the two single strand breaks are positioned at the opposite site, e.g., downstream or upstream (e.g., within 500 bp downstream or upstream), of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, four single strand breaks are introduced (e.g., positioned by four gRNA molecules) at or in close proximity to a CF target position in the SCNN1A gene. In an embodiment, four gRNA molecule (e.g., with one or more Cas9 nickases are used to create four single strand breaks to flank a CF target position in the SCNN1A gene, e.g., the gRNA molecules are configured such that a first and second single strand breaks are positioned upstream (e.g., within 500 bp upstream) of the CF target position, and a third and a fourth single stranded breaks are positioned downstream (e.g., within 500 bp downstream) of the CF target position. In an embodiment, the breaks are positioned to avoid unwanted target chromosome elements, such as repeat elements, e.g., an Alu repeat.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two ore more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Approach 5: Knocking Down SCNN1A Mediated by an Enzymatically Inactive Cas9 (eiCas9) Molecule

A targeted knockdown approach reduces or eliminates expression of functional SCNN1A gene product. As described herein, in an embodiment, a targeted knockdown is mediated by targeting an enzymatically inactive Cas9 (eiCas9) molecule or an eiCas9 fused to a transcription repressor domain or chromatin modifying protein to alter transcription, e.g., to block, reduce, or decrease transcription, of the SCNN1A gene.

Methods and compositions discussed herein may be used to alter the expression of the SCNN1A gene to treat or prevent CF or CF-like disease by targeting a promoter region of the SCNN1A gene. In an embodiment, the promoter region is targeted to knock down expression of the SCNN1A gene. A targeted knockdown approach reduces or eliminates expression of functional SCNN1A gene product. As described herein, in an embodiment, a targeted knockdown is mediated by targeting an enzymatically inactive Cas9 (eiCas9) or an eiCas9 fused to a transcription repressor domain or chromatin modifying protein to alter transcription, e.g., to block, reduce, or decrease transcription, of the SCNN1A gene. In an embodiment, one or more eiCas9 molecules may be used to block binding of one or more endogenous transcription factors.

In another embodiment, an eiCas9 molecule can be fused to a chromatin modifying protein. Altering chromatin status can result in decreased expression of the target gene. One or more eiCas9 molecules fused to one or more chromatin modifying proteins may be used to alter chromatin status.

An eiCas9 mediated knock down of one of two SCNN1A allele/s by targeting the transcription start site of SCNN1A gene in exon I of all transcripts (including 500 bp upstream and downstream of transcription start site on all transcripts). This approach is performed in any subject with CF or CF-like disease, with or without a CFTR mutation and a WT or mutant SCNN1A. The CF or CF-like target position is at or near the transcription start site of the SCNN1A gene. Or, altering the CF or CF-like target position refers to delivering a dCas9 that sterically hinders transcription of either or both SCNN1A allele/s. This approach gives rise to the loss or destruction of transcription of the SCNN1A gene. This approach will lead to the reduction or cessation of production of ENaC. This approach will prevent the disinhibition of the ENaC channel in subjects with CF or CF-like disease. The viscosity of lung, gastrointestinal and reproductive tract mucous in subjects with CF or CF-like disease will not be further increased. This will lead to a reduction in viscosity of mucous within the lung, gastrointestinal and reproductive tract mucous in subjects with CF or CF-like disease. This approach will prevent the progression of CF and CF-like disease.

I. gRNA Molecules

A gRNA molecule, as that term is used herein, refers to a nucleic acid that promotes the specific targeting or homing of a gRNA molecule/Cas9 molecule complex to a target nucleic acid. gRNA molecules can be unimolecular (having a single RNA molecule), sometimes referred to herein as “chimeric” gRNAs, or modular (comprising more than one, and typically two, separate RNA molecules). A gRNA molecule comprises a number of domains. The gRNA molecule domains are described in more detail below.

Several exemplary gRNA structures, with domains indicated thereon, are provided in FIGS. 1A-1G. While not wishing to be bound by theory, in an embodiment, with regard to the three dimensional form, or intra- or inter-strand interactions of an active form of a gRNA, regions of high complementarity are sometimes shown as duplexes in FIGS. 1A-1G and other depictions provided herein.

In an embodiment, a unimolecular, or chimeric, gRNA comprises, preferably from 5′ to 3′:

    • a targeting domain (which is complementary to a target nucleic acid in the CFTR gene or SCNN1A gene, e.g., a targeting domain as described herein, e.g., a targeting domain from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, and 48A-48E;
    • a first complementarity domain;
    • a linking domain;
    • a second complementarity domain (which is complementary to the first complementarity domain);
    • a proximal domain; and
    • optionally, a tail domain.

In an embodiment, a modular gRNA comprises:

    • a first strand comprising, preferably from 5′ to 3′;
      • a targeting domain (which is complementary to a target nucleic acid in the CFTR gene or SCNN1A gene, e.g., a targeting domain as described herein, e.g., a targeting domain from any of Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E); and
      • a first complementarity domain; and
    • a second strand, comprising, preferably from 5′ to 3′:
      • optionally, a 5′ extension domain;
      • a second complementarity domain;
      • a proximal domain; and
      • optionally, a tail domain.

The domains are discussed briefly below.

The Targeting Domain

FIGS. 1A-1G provide examples of the placement of targeting domains.

The targeting domain comprises a nucleotide sequence that is complementary, e.g., at least 80, 85, 90, or 95% complementary, e.g., fully complementary, to the target sequence on the target nucleic acid. The targeting domain is part of an RNA molecule and will therefore comprise the base uracil (U), while any DNA encoding the gRNA molecule will comprise the base thymine (T). While not wishing to be bound by theory, in an embodiment, it is believed that the complementarity of the targeting domain with the target sequence contributes to specificity of the interaction of the gRNA molecule/Cas9 molecule complex with a target nucleic acid. It is understood that in a targeting domain and target sequence pair, the uracil bases in the targeting domain will pair with the adenine bases in the target sequence. In an embodiment, the target domain itself comprises in the 5′ to 3′ direction, an optional secondary domain, and a core domain. In an embodiment, the core domain is fully complementary with the target sequence. In an embodiment, the targeting domain is 5 to 50 nucleotides in length. The strand of the target nucleic acid with which the targeting domain is complementary is referred to herein as the complementary strand. Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

In an embodiment, the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain is 18 nucleotides in length.

In an embodiment, the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain is 22 nucleotides in length.

In an embodiment, the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

Targeting domains are discussed in more detail below.

The First Complementarity Domain

FIGS. 1A-1G provide examples of first complementarity domains.

The first complementarity domain is complementary with the second complementarity domain, and in an embodiment, has sufficient complementarity to the second complementarity domain to form a duplexed region under at least some physiological conditions. In an embodiment, the first complementarity domain is 5 to 30 nucleotides in length. In an embodiment, the first complementarity domain is 5 to 25 nucleotides in length. In an embodiment, the first complementary domain is 7 to 25 nucleotides in length. In an embodiment, the first complementary domain is 7 to 22 nucleotides in length. In an embodiment, the first complementary domain is 7 to 18 nucleotides in length. In an embodiment, the first complementary domain is 7 to 15 nucleotides in length. In an embodiment, the first complementary domain is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length.

In an embodiment, the first complementarity domain comprises 3 subdomains, which, in the 5′ to 3′ direction are: a 5′ subdomain, a central subdomain, and a 3′ subdomain. In an embodiment, the 5′ subdomain is 4 to 9, e.g., 4, 5, 6, 7, 8 or 9 nucleotides in length. In an embodiment, the central subdomain is 1, 2, or 3, e.g., 1, nucleotide in length. In an embodiment, the 3′ subdomain is 3 to 25, e.g., 4 to 22, 4 to 18, or 4 to 10, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length.

The first complementarity domain can share homology with, or be derived from, a naturally occurring first complementarity domain. In an embodiment, it has at least 50% homology with a first complementarity domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, first complementarity domain.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

First complementarity domains are discussed in more detail below.

The Linking Domain

FIGS. 1A-1G provide examples of linking domains.

A linking domain serves to link the first complementarity domain with the second complementarity domain of a unimolecular gRNA. The linking domain can link the first and second complementarity domains covalently or non-covalently. In an embodiment, the linkage is covalent. In an embodiment, the linking domain covalently couples the first and second complementarity domains, see, e.g., FIGS. 1B-1E. In an embodiment, the linking domain is, or comprises, a covalent bond interposed between the first complementarity domain and the second complementarity domain. Typically the linking domain comprises one or more, e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides.

In modular gRNA molecules the two molecules are associated by virtue of the hybridization of the complementarity domains see e.g., FIG. 1A.

A wide variety of linking domains are suitable for use in unimolecular gRNA molecules. Linking domains can consist of a covalent bond, or be as short as one or a few nucleotides, e.g., 1, 2, 3, 4, or 5 nucleotides in length. In an embodiment, a linking domain is 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25 or more nucleotides in length. In an embodiment, a linking domain is 2 to 50, 2 to 40, 2 to 30, 2 to 20, 2 to 10, or 2 to 5 nucleotides in length. In an embodiment, a linking domain shares homology with, or is derived from, a naturally occurring sequence, e.g., the sequence of a tracrRNA that is 5′ to the second complementarity domain. In an embodiment, the linking domain has at least 50% homology with a linking domain disclosed herein.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

Linking domains are discussed in more detail below.

The 5′ Extension Domain

In an embodiment, a modular gRNA can comprise additional sequence, 5′ to the second complementarity domain, referred to herein as the 5′ extension domain, see, e.g., FIG. 1A. In an embodiment, the 5′ extension domain is, 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, 2 to 4 nucleotides in length. In an embodiment, the 5′ extension domain is 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more nucleotides in length.

The Second Complementarity Domain

FIGS. 1A-1G provide examples of second complementarity domains.

The second complementarity domain is complementary with the first complementarity domain, and in an embodiment, has sufficient complementarity to the second complementarity domain to form a duplexed region under at least some physiological conditions. In an embodiment, e.g., as shown in FIGS. 1A-1B, the second complementarity domain can include sequence that lacks complementarity with the first complementarity domain, e.g., sequence that loops out from the duplexed region.

In an embodiment, the second complementarity domain is 5 to 27 nucleotides in length. In an embodiment, it is longer than the first complementarity region. In an embodiment the second complementary domain is 7 to 27 nucleotides in length. In an embodiment, the second complementary domain is 7 to 25 nucleotides in length. In an embodiment, the second complementary domain is 7 to 20 nucleotides in length. In an embodiment, the second complementary domain is 7 to 17 nucleotides in length. In an embodiment, the complementary domain is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleotides in length.

In an embodiment, the second complementarity domain comprises 3 subdomains, which, in the 5′ to 3′ direction are: a 5′ subdomain, a central subdomain, and a 3′ subdomain. In an embodiment, the 5′ subdomain is 3 to 25, e.g., 4 to 22, 4 to 18, or 4 to 10, or 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides in length. In an embodiment, the central subdomain is 1, 2, 3, 4 or 5, e.g., 3, nucleotides in length. In an embodiment, the 3′ subdomain is 4 to 9, e.g., 4, 5, 6, 7, 8 or 9 nucleotides in length.

In an embodiment, the 5′ subdomain and the 3′ subdomain of the first complementarity domain, are respectively, complementary, e.g., fully complementary, with the 3′ subdomain and the 5′ subdomain of the second complementarity domain.

The second complementarity domain can share homology with or be derived from a naturally occurring second complementarity domain. In an embodiment, it has at least 50% homology with a second complementarity domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, first complementarity domain.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

A Proximal Domain

FIGS. 1A-1G provide examples of proximal domains.

In an embodiment, the proximal domain is 5 to 20 nucleotides in length. In an embodiment, the proximal domain can share homology with or be derived from a naturally occurring proximal domain. In an embodiment, it has at least 50% homology with a proximal domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, proximal domain.

Some or all of the nucleotides of the domain can have a modification, e.g., a modification found in Section VIII herein.

A Tail Domain

FIGS. 1A-1G provide examples of tail domains.

As can be seen by inspection of the tail domains in FIGS. 1A-1E, a broad spectrum of tail domains are suitable for use in gRNA molecules. In an embodiment, the tail domain is 0 (absent), 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides in length. In embodiment, the tail domain nucleotides are from or share homology with sequence from the 5′ end of a naturally occurring tail domain, see e.g., FIG. 1D or FIG. 1E. In an embodiment, the tail domain includes sequences that are complementary to each other and which, under at least some physiological conditions, form a duplexed region.

In an embodiment, the tail domain is absent or is 1 to 50 nucleotides in length. In an embodiment, the tail domain can share homology with or be derived from a naturally occurring proximal tail domain. In an embodiment, it has at least 50% homology with a tail domain disclosed herein, e.g., an S. pyogenes, S. aureus or S. thermophilus, tail domain.

In an embodiment, the tail domain includes nucleotides at the 3′ end that are related to the method of in vitro or in vivo transcription. When a T7 promoter is used for in vitro transcription of the gRNA, these nucleotides may be any nucleotides present before the 3′ end of the DNA template. When a U6 promoter is used for in vivo transcription, these nucleotides may be the sequence UUUUUU. When alternate pol-III promoters are used, these nucleotides may be various numbers or uracil bases or may include alternate bases.

The domains of gRNA molecules are described in more detail below.

The Targeting Domain

The “targeting domain” of the gRNA is complementary to the “target domain” on the target nucleic acid. The strand of the target nucleic acid comprising the nucleotide sequence complementary to the core domain of the gRNA is referred to herein as the “complementary strand” of the target nucleic acid. Guidance on the selection of targeting domains can be found, e.g., in Fu Y et al., Nat Biotechnol 2014 (doi: 10.1038/nbt.2808) and Sternberg S H et al., Nature 2014 (doi: 10.1038/nature13011).

In an embodiment, the targeting domain is 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain is 18 nucleotides in length.

In an embodiment, the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain is 22 nucleotides in length.

In an embodiment, the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises 16 nucleotides.

In an embodiment, the targeting domain comprises 17 nucleotides.

In an embodiment, the targeting domain comprises 18 nucleotides.

In an embodiment, the targeting domain comprises 19 nucleotides.

In an embodiment, the targeting domain comprises 20 nucleotides.

In an embodiment, the targeting domain comprises 21 nucleotides.

In an embodiment, the targeting domain comprises 22 nucleotides.

In an embodiment, the targeting domain comprises 23 nucleotides.

In an embodiment, the targeting domain comprises 24 nucleotides.

In an embodiment, the targeting domain comprises 25 nucleotides.

In an embodiment, the targeting domain comprises 26 nucleotides.

In an embodiment, the targeting domain is 10+/−5, 20+/−5, 30+/−5, 40+/−5, 50+/−5, 60+/−5, 70+/−5, 80+/−5, 90+/−5, or 100+/−5 nucleotides, in length.

In an embodiment, the targeting domain is 20+/−5 nucleotides in length.

In an embodiment, the targeting domain is 20+/−10, 30+/−10, 40+/−10, 50+/−10, 60+/−10, 70+/−10, 80+/−10, 90+/−10, or 100+/−10 nucleotides, in length.

In an embodiment, the targeting domain is 30+/−10 nucleotides in length.

In an embodiment, the targeting domain is 10 to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 10 to 20 or 10 to 15 nucleotides in length. In another embodiment, the targeting domain is 20 to 100, 20 to 90, 20 to 80, 20 to 70, 20 to 60, 20 to 50, 20 to 40, 20 to 30, or 20 to 25 nucleotides in length.

Typically the targeting domain has full complementarity with the target sequence. In an embodiment the targeting domain has or includes 1, 2, 3, 4, 5, 6, 7 or 8 nucleotides that are not complementary with the corresponding nucleotide of the targeting domain.

In an embodiment, the target domain includes 1, 2, 3, 4 or 5 nucleotides that are complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 5′ end. In an embodiment, the target domain includes 1, 2, 3, 4 or 5 nucleotides that are complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 3′ end.

In an embodiment, the target domain includes 1, 2, 3, or 4 nucleotides that are not complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 5′ end. In an embodiment, the target domain includes 1, 2, 3, or 4 nucleotides that are not complementary with the corresponding nucleotide of the targeting domain within 5 nucleotides of its 3′ end.

In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

In an embodiment, the targeting domain comprises two consecutive nucleotides that are not complementary to the target domain (“non-complementary nucleotides”), e.g., two consecutive noncomplementary nucleotides that are within 5 nucleotides of the 5′ end of the targeting domain, within 5 nucleotides of the 3′ end of the targeting domain, or more than 5 nucleotides away from one or both ends of the targeting domain.

In an embodiment, no two consecutive nucleotides within 5 nucleotides of the 5′ end of the targeting domain, within 5 nucleotides of the 3′ end of the targeting domain, or within a region that is more than 5 nucleotides away from one or both ends of the targeting domain, are not complementary to the targeting domain.

In an embodiment, there are no noncomplementary nucleotides within 5 nucleotides of the 5′ end of the targeting domain, within 5 nucleotides of the 3′ end of the targeting domain, or within a region that is more than 5 nucleotides away from one or both ends of the targeting domain.

In an embodiment, the targeting domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the targeting domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the targeting domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment, a nucleotide of the targeting domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII.

In an embodiment, the targeting domain includes 1, 2, 3, 4, 5, 6, 7 or 8 or more modifications. In an embodiment, the targeting domain includes 1, 2, 3, or 4 modifications within 5 nucleotides of its 5′ end. In an embodiment, the targeting domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3′ end.

In an embodiment, the targeting domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5′ end of the targeting domain, within 5 nucleotides of the 3′ end of the targeting domain, or more than 5 nucleotides away from one or both ends of the targeting domain.

In an embodiment, no two consecutive nucleotides are modified within 5 nucleotides of the 5′ end of the targeting domain, within 5 nucleotides of the 3′ end of the targeting domain, or within a region that is more than 5 nucleotides away from one or both ends of the targeting domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5′ end of the targeting domain, within 5 nucleotides of the 3′ end of the targeting domain, or within a region that is more than 5 nucleotides away from one or both ends of the targeting domain.

Modifications in the targeting domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate targeting domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in a system in Section IV. The candidate targeting domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, all of the modified nucleotides are complementary to and capable of hybridizing to corresponding nucleotides present in the target domain. In another embodiment, 1, 2, 3, 4, 5, 6, 7 or 8 or more modified nucleotides are not complementary to or capable of hybridizing to corresponding nucleotides present in the target domain.

In an embodiment, the targeting domain comprises, preferably in the 5′→3′ direction: a secondary domain and a core domain. These domains are discussed in more detail below.

The Core Domain and Secondary Domain of the Targeting Domain

The “core domain” of the targeting domain is complementary to the “core domain target” on the target nucleic acid. In an embodiment, the core domain comprises about 8 to about 13 nucleotides from the 3′ end of the targeting domain (e.g., the most 3′ 8 to 13 nucleotides of the targeting domain).

In an embodiment, the core domain and targeting domain, are independently, 6+/−2, 7+/−2, 8+/−2, 9+/−2, 10+/−2, 11+/−2, 12+/−2, 13+/−2, 14+/−2, 15+/−2, or 16+−2, nucleotides in length.

In an embodiment, the core domain and targeting domain, are independently, 10+/−2 nucleotides in length.

In an embodiment, the core domain and targeting domain, are independently, 10+/−4 nucleotides in length.

In an embodiment, the core domain and targeting domain are independently 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 nucleotides in length.

In an embodiment, the core domain and targeting domain are independently 3 to 20, 4 to 20, 5 to 20, 6 to 20, 7 to 20, 8 to 20, 9 to 20 10 to 20 or 15 to 20 nucleotides in length.

In an embodiment, the core domain and targeting domain are independently 3 to 15, e.g., 6 to 15, 7 to 14, 7 to 13, 6 to 12, 7 to 12, 7 to 11, 7 to 10, 8 to 14, 8 to 13, 8 to 12, 8 to 11, 8 to 10 or 8 to 9 nucleotides in length.

The core domain is complementary with the core domain target. Typically the core domain has exact complementarity with the core domain target. In some embodiments, the core domain can have 1, 2, 3, 4 or 5 nucleotides that are not complementary with the corresponding nucleotide of the core domain. In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

The “secondary domain” of the targeting domain of the gRNA is complementary to the “secondary domain target” of the target nucleic acid.

In an embodiment, the secondary domain is positioned 5′ to the core domain.

In an embodiment, the secondary domain is absent or optional.

In an embodiment, if the targeting domain is 26 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 12 to 17 nucleotides in length.

In an embodiment, if the targeting domain is 25 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 12 to 17 nucleotides in length.

In an embodiment, if the targeting domain is 24 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 11 to 16 nucleotides in length.

In an embodiment, if the targeting domain is 23 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 10 to 15 nucleotides in length.

In an embodiment, if the targeting domain is 22 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 9 to 14 nucleotides in length.

In an embodiment, if the targeting domain is 21 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 8 to 13 nucleotides in length.

In an embodiment, if the targeting domain is 20 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 7 to 12 nucleotides in length.

In an embodiment, if the targeting domain is 19 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 6 to 11 nucleotides in length.

In an embodiment, if the targeting domain is 18 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 5 to 10 nucleotides in length.

In an embodiment, if the targeting domain is 17 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 4 to 9 nucleotides in length.

In an embodiment, if the targeting domain is 16 nucleotides in length and the core domain (counted from the 3′ end of the targeting domain) is 8 to 13 nucleotides in length, the secondary domain is 3 to 8 nucleotides in length.

In an embodiment, the secondary domain is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 nucleotides in length.

The secondary domain is complementary with the secondary domain target. Typically the secondary domain has exact complementarity with the secondary domain target. In an embodiment, the secondary domain can have 1, 2, 3, 4 or 5 nucleotides that are not complementary with the corresponding nucleotide of the secondary domain. In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

In an embodiment, the core domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the core domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the core domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the core domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII. Typically, a core domain will contain no more than 1, 2, or 3 modifications.

Modifications in the core domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate core domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate core domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the secondary domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the secondary domain comprises one or more modifications, e.g., modifications that render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the secondary domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the secondary domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII. Typically, a secondary domain will contain no more than 1, 2, or 3 modifications.

Modifications in the secondary domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate secondary domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate secondary domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, (1) the degree of complementarity between the core domain and its target, and (2) the degree of complementarity between the secondary domain and its target, may differ. In an embodiment, (1) may be greater than (2). In an embodiment, (1) may be less than (2). In an embodiment, (1) and (2) are the same, e.g., each may be completely complementary with its target.

In an embodiment, (1) the number of modifications (e.g., modifications from Section VIII) of the nucleotides of the core domain and (2) the number of modifications (e.g., modifications from Section VIII) of the nucleotides of the secondary domain may differ. In an embodiment, (1) may be less than (2). In an embodiment, (1) may be greater than (2). In an embodiment, (1) and (2) may be the same, e.g., each may be free of modifications.

The First and Second Complementarity Domains

The first complementarity domain is complementary with the second complementarity domain.

Typically the first domain does not have exact complementarity with the second complementarity domain target. In some embodiments, the first complementarity domain can have 1, 2, 3, 4 or 5 nucleotides that are not complementary with the corresponding nucleotide of the second complementarity domain. In an embodiment, 1, 2, 3, 4, 5 or 6, e.g., 3 nucleotides, will not pair in the duplex, and, e.g., form a non-duplexed or looped-out region. In an embodiment, an unpaired, or loop-out, region, e.g., a loop-out of 3 nucleotides, is present on the second complementarity domain. In an embodiment, the unpaired region begins 1, 2, 3, 4, 5, or 6, e.g., 4, nucleotides from the 5′ end of the second complementarity domain.

In an embodiment, the degree of complementarity, together with other properties of the gRNA, is sufficient to allow targeting of a Cas9 molecule to the target nucleic acid.

In an embodiment, the first and second complementarity domains are:

    • independently, 6+/−2, 7+/−2, 8+/−2, 9+/−2, 10+/−2, 11+/−2, 12+/−2, 13+/−2, 14+/−2, 15+/−2, 16+/−2, 17+/−2, 18+/−2, 19+/−2, or 20+/−2, 21+/−2, 22+/−2, 23+/−2, or 24+/−2 nucleotides in length;
    • independently, 6, 7, 8, 9, 10, 11, 12, 13, 14, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26, nucleotides in length; or
    • independently, 5 to 24, 5 to 23, 5 to 22, 5 to 21, 5 to 20, 7 to 18, 9 to 16, or 10 to 14 nucleotides in length.

In an embodiment, the second complementarity domain is longer than the first complementarity domain, e.g., 2, 3, 4, 5, or 6, e.g., 6, nucleotides longer.

In an embodiment, the first and second complementary domains, independently, do not comprise modifications, e.g., modifications of the type provided in Section VIII.

In an embodiment, the first and second complementary domains, independently, comprise one or more modifications, e.g., modifications that the render the domain less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII.

In an embodiment, the first and second complementary domains, independently, include 1, 2, 3, 4, 5, 6, 7 or 8 or more modifications. In an embodiment, the first and second complementary domains, independently, include 1, 2, 3, or 4 modifications within 5 nucleotides of its 5′ end. In an embodiment, the first and second complementary domains, independently, include as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3′ end.

In an embodiment, the first and second complementary domains, independently, include modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5′ end of the domain, within 5 nucleotides of the 3′ end of the domain, or more than 5 nucleotides away from one or both ends of the domain. In an embodiment, the first and second complementary domains, independently, include no two consecutive nucleotides that are modified, within 5 nucleotides of the 5′ end of the domain, within 5 nucleotides of the 3′ end of the domain, or within a region that is more than 5 nucleotides away from one or both ends of the domain. In an embodiment, the first and second complementary domains, independently, include no nucleotide that is modified within 5 nucleotides of the 5′ end of the domain, within 5 nucleotides of the 3′ end of the domain, or within a region that is more than 5 nucleotides away from one or both ends of the domain.

Modifications in a complementarity domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate complementarity domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described in Section IV. The candidate complementarity domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the first complementarity domain has at least 60, 70, 80, 85%, 90% or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference first complementarity domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, first complementarity domain, or a first complementarity domain described herein, e.g., from FIGS. 1A-1G.

In an embodiment, the second complementarity domain has at least 60, 70, 80, 85%, 90%, or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference second complementarity domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, second complementarity domain, or a second complementarity domain described herein, e.g., from FIGS. 1A-1G.

The duplexed region formed by first and second complementarity domains is typically 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 or 22 base pairs in length (excluding any looped out or unpaired nucleotides).

In some embodiments, the first and second complementarity domains, when duplexed, comprise 11 paired nucleotides, for example, in the gRNA sequence (one paired strand underlined, one bolded):

(SEQ ID NO: 5) NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAGAAAUAGCAAGUUAAA AUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC.

In some embodiments, the first and second complementarity domains, when duplexed, comprise 15 paired nucleotides, for example in the gRNA sequence (one paired strand underlined, one bolded):

(SEQ ID NO: 27) NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGAAAAGCAUAG CAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACC GAGUCGGUGC.

In some embodiments the first and second complementarity domains, when duplexed, comprise 16 paired nucleotides, for example in the gRNA sequence (one paired strand underlined, one bolded):

(SEQ ID NO: 28) NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGGAAACAGCAU AGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCA CCGAGUCGGUGC.

In some embodiments the first and second complementarity domains, when duplexed, comprise 21 paired nucleotides, for example in the gRNA sequence (one paired strand underlined, one bolded):

(SEQ ID NO: 29) NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAUGCUGUUUUGGAAA CAAAACAGCAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUU GAAAAAGUGGCACCGAGUCGGUGC.

In some embodiments, nucleotides are exchanged to remove poly-U tracts, for example in the gRNA sequences (exchanged nucleotides underlined):

(SEQ ID NO: 30) NNNNNNNNNNNNNNNNNNNNGUAUUAGAGCUAGAAAUAGCAAGUUAAUA UAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC; (SEQ ID NO: 31)  NNNNNNNNNNNNNNNNNNNNGUUUAAGAGCUAGAAAUAGCAAGUUUAAA UAAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC;  or (SEQ ID NO: 32) NNNNNNNNNNNNNNNNNNNNGUAUUAGAGCUAUGCUGUAUUGGAAACAA UACAGCAUAGCAAGUUAAUAUAAGGCUAGUCCGUUAUCAACUUGAAAAA GUGGCACCGAGUCGGUGC.

The 5′ Extension Domain

In an embodiment, a modular gRNA can comprise additional sequence, 5′ to the second complementarity domain. In an embodiment, the 5′ extension domain is 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, or 2 to 4 nucleotides in length. In an embodiment, the 5′ extension domain is 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more nucleotides in length.

In an embodiment, the 5′ extension domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the 5′ extension domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the 5′ extension domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment, a nucleotide of the 5′ extension domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII.

In an embodiment, the 5′ extension domain can comprise as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications. In an embodiment, the 5′ extension domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 5′ end, e.g., in a modular gRNA molecule. In an embodiment, the 5′ extension domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3′ end, e.g., in a modular gRNA molecule.

In an embodiment, the 5′ extension domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5′ end of the 5′ extension domain, within 5 nucleotides of the 3′ end of the 5′ extension domain, or more than 5 nucleotides away from one or both ends of the 5′ extension domain. In an embodiment, no two consecutive nucleotides are modified within 5 nucleotides of the 5′ end of the 5′ extension domain, within 5 nucleotides of the 3′ end of the 5′ extension domain, or within a region that is more than 5 nucleotides away from one or both ends of the 5′ extension domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5′ end of the 5′ extension domain, within 5 nucleotides of the 3′ end of the 5′ extension domain, or within a region that is more than 5 nucleotides away from one or both ends of the 5′ extension domain.

Modifications in the 5′ extension domain can be selected so as to not interfere with gRNA molecule efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate 5′ extension domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate 5′ extension domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the 5′ extension domain has at least 60, 70, 80, 85, 90 or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference 5′ extension domain, e.g., a naturally occurring, e.g., an S. pyogenes, or S. aureus S. thermophilus, 5′ extension domain, or a 5′ extension domain described herein, e.g., from FIGS. 1A-1G.

The Linking Domain

In a unimolecular gRNA molecule the linking domain is disposed between the first and second complementarity domains. In a modular gRNA molecule, the two molecules are associated with one another by the complementarity domains.

In an embodiment, the linking domain is 10+/−5, 20+/−5, 30+/−5, 40+/−5, 50+/−5, 60+/−5, 70+/−5, 80+/−5, 90+/−5, or 100+/−5 nucleotides, in length.

In an embodiment, the linking domain is 20+/−10, 30+/−10, 40+/−10, 50+/−10, 60+/−10, 70+/−10, 80+/−10, 90+/−10, or 100+/−10 nucleotides, in length.

In an embodiment, the linking domain is 10 to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 10 to 20 or 10 to 15 nucleotides in length. In other embodiments, the linking domain is 20 to 100, 20 to 90, 20 to 80, 20 to 70, 20 to 60, 20 to 50, 20 to 40, 20 to 30, or 20 to 25 nucleotides in length.

In an embodiment, the linking domain is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 17, 18, 19, or 20 nucleotides in length.

In an embodiment, the linking domain is a covalent bond.

In an embodiment, the linking domain comprises a duplexed region, typically adjacent to or within 1, 2, or 3 nucleotides of the 3′ end of the first complementarity domain and/or the 5-end of the second complementarity domain. In an embodiment, the duplexed region can be 20+/−10 base pairs in length. In an embodiment, the duplexed region can be 10+/−5, 15+/−5, 20+/−5, or 30+/−5 base pairs in length. In an embodiment, the duplexed region can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 base pairs in length.

Typically the sequences forming the duplexed region have exact complementarity with one another, though in some embodiments as many as 1, 2, 3, 4, 5, 6, 7 or 8 nucleotides are not complementary with the corresponding nucleotides.

In an embodiment, the linking domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the linking domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the linking domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the linking domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII. In some embodiments, the linking domain can comprise as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications.

Modifications in a linking domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate linking domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated a system described in Section IV. A candidate linking domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the linking domain has at least 60, 70, 80, 85, 90 or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference linking domain, e.g., a linking domain described herein, e.g., from FIGS. 1A-1G.

The Proximal Domain

In an embodiment, the proximal domain is 6+/−2, 7+/−2, 8+/−2, 9+/−2, 10+/−2, 11+/−2, 12+/−2, 13+/−2, 14+/−2, 14+/−2, 16+/−2, 17+/−2, 18+/−2, 19+/−2, or 20+/−2 nucleotides in length.

In an embodiment, the proximal domain is 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the proximal domain is 5 to 20, 7, to 18, 9 to 16, or 10 to 14 nucleotides in length.

In an embodiment, the proximal domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the proximal domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the proximal domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the proximal domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII.

In an embodiment, the proximal domain can comprise as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications. In an embodiment, the proximal domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 5′ end, e.g., in a modular gRNA molecule. In an embodiment, the target domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3′ end, e.g., in a modular gRNA molecule.

In an embodiment, the proximal domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5′ end of the proximal domain, within 5 nucleotides of the 3′ end of the proximal domain, or more than 5 nucleotides away from one or both ends of the proximal domain. In an embodiment, no two consecutive nucleotides are modified within 5 nucleotides of the 5′ end of the proximal domain, within 5 nucleotides of the 3′ end of the proximal domain, or within a region that is more than 5 nucleotides away from one or both ends of the proximal domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5′ end of the proximal domain, within 5 nucleotides of the 3′ end of the proximal domain, or within a region that is more than 5 nucleotides away from one or both ends of the proximal domain.

Modifications in the proximal domain can be selected so as to not interfere with gRNA molecule efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate proximal domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described at Section IV. The candidate proximal domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the proximal domain has at least 60, 70, 80, 85 90 or 95% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference proximal domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, proximal domain, or a proximal domain described herein, e.g., from FIGS. 1A-1G.

The Tail Domain

In an embodiment, the tail domain is 10+/−5, 20+/−5, 30+/−5, 40+/−5, 50+/−5, 60+/−5, 70+/−5, 80+/−5, 90+/−5, or 100+/−5 nucleotides, in length.

In an embodiment, the tail domain is 20+/−5 nucleotides in length.

In an embodiment, the tail domain is 20+/−10, 30+/−10, 40+/−10, 50+/−10, 60+/−10, 70+/−10, 80+/−10, 90+/−10, or 100+/−10 nucleotides, in length.

In an embodiment, the tail domain is 25+/−10 nucleotides in length.

In an embodiment, the tail domain is 10 to 100, 10 to 90, 10 to 80, 10 to 70, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 10 to 20 or 10 to 15 nucleotides in length.

In other embodiments, the tail domain is 20 to 100, 20 to 90, 20 to 80, 20 to 70, 20 to 60, 20 to 50, 20 to 40, 20 to 30, or 20 to 25 nucleotides in length.

In an embodiment, the tail domain is 1 to 20, 1 to 15, 1 to 10, or 1 to 5 nucleotides in length.

In an embodiment, the tail domain nucleotides do not comprise modifications, e.g., modifications of the type provided in Section VIII. However, in an embodiment, the tail domain comprises one or more modifications, e.g., modifications that it render it less susceptible to degradation or more bio-compatible, e.g., less immunogenic. By way of example, the backbone of the tail domain can be modified with a phosphorothioate, or other modification(s) from Section VIII. In an embodiment a nucleotide of the tail domain can comprise a 2′ modification, e.g., a 2-acetylation, e.g., a 2′ methylation, or other modification(s) from Section VIII.

In some embodiments, the tail domain can have as many as 1, 2, 3, 4, 5, 6, 7 or 8 modifications. In an embodiment, the target domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 5′ end. In an embodiment, the target domain comprises as many as 1, 2, 3, or 4 modifications within 5 nucleotides of its 3′ end.

In an embodiment, the tail domain comprises a tail duplex domain, which can form a tail duplexed region. In an embodiment, the tail duplexed region can be 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 base pairs in length. In an embodiment, a further single stranded domain, exists 3′ to the tail duplexed domain. In an embodiment, this domain is 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides in length. In an embodiment it is 4 to 6 nucleotides in length.

In an embodiment, the tail domain has at least 60, 70, 80, or 90% homology with, or differs by no more than 1, 2, 3, 4, 5, or 6 nucleotides from, a reference tail domain, e.g., a naturally occurring, e.g., an S. pyogenes, S. aureus or S. thermophilus, tail domain, or a tail domain described herein, e.g., from FIGS. 1A-1G.

In an embodiment, the proximal and tail domain, taken together, comprise the following sequences:

(SEQ ID NO: 33) AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCU,  or (SEQ ID NO: 34) AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGGU GC, or (SEQ ID NO: 35)  AAGGCUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCG  GAUC, or (SEQ ID NO: 36)  AAGGCUAGUCCGUUAUCAACUUGAAAAAGUG,  or (SEQ ID NO: 37) AAGGCUAGUCCGUUAUCA,  or (SEQ ID NO: 38) AAGGCUAGUCCG.

In an embodiment, the tail domain comprises the 3′ sequence UUUUUU, e.g., if a U6 promoter is used for transcription.

In an embodiment, the tail domain comprises the 3′ sequence UUUU, e.g., if an H1 promoter is used for transcription.

In an embodiment, tail domain comprises variable numbers of 3′ Us depending, e.g., on the termination signal of the pol-III promoter used.

In an embodiment, the tail domain comprises variable 3′ sequence derived from the DNA template if a T7 promoter is used.

In an embodiment, the tail domain comprises variable 3′ sequence derived from the DNA template, e.g., if in vitro transcription is used to generate the RNA molecule.

In an embodiment, the tail domain comprises variable 3′ sequence derived from the DNA template, e., if a pol-II promoter is used to drive transcription.

Modifications in the tail domain can be selected so as to not interfere with targeting efficacy, which can be evaluated by testing a candidate modification in the system described in Section IV. gRNAs having a candidate tail domain having a selected length, sequence, degree of complementarity, or degree of modification, can be evaluated in the system described in Section IV. The candidate tail domain can be placed, either alone, or with one or more other candidate changes in a gRNA molecule/Cas9 molecule system known to be functional with a selected target and evaluated.

In an embodiment, the tail domain comprises modifications at two consecutive nucleotides, e.g., two consecutive nucleotides that are within 5 nucleotides of the 5′ end of the tail domain, within 5 nucleotides of the 3′ end of the tail domain, or more than 5 nucleotides away from one or both ends of the tail domain. In an embodiment, no two consecutive nucleotides are modified within 5 nucleotides of the 5′ end of the tail domain, within 5 nucleotides of the 3′ end of the tail domain, or within a region that is more than 5 nucleotides away from one or both ends of the tail domain. In an embodiment, no nucleotide is modified within 5 nucleotides of the 5′ end of the tail domain, within 5 nucleotides of the 3′ end of the tail domain, or within a region that is more than 5 nucleotides away from one or both ends of the tail domain.

In an embodiment a gRNA has the following structure:

    • 5′ [targeting domain]-[first complementarity domain]-[linking domain]-[second complementarity domain]-[proximal domain]-[tail domain]-3′
    • wherein, the targeting domain comprises a core domain and optionally a secondary domain, and is 10 to 50 nucleotides in length;
    • the first complementarity domain is 5 to 25 nucleotides in length and, In an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference first complementarity domain disclosed herein;
    • the linking domain is 1 to 5 nucleotides in length;
    • the second complementarity domain is 5 to 27 nucleotides in length and, in an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference second complementarity domain disclosed herein;
    • the proximal domain is 5 to 20 nucleotides in length and, in an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference proximal domain disclosed herein; and
    • the tail domain is absent or a nucleotide sequence is 1 to 50 nucleotides in length and, in an embodiment has at least 50, 60, 70, 80, 85, 90 or 95% homology with a reference tail domain disclosed herein.

Exemplary Chimeric gRNAs

In an embodiment, a unimolecular, or chimeric, gRNA comprises, preferably from 5′ to 3′:

    • a targeting domain (which is complementary to a target nucleic acid);
    • a first complementarity domain, e.g., comprising 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleotides;
    • a linking domain;
    • a second complementarity domain (which is complementary to the first complementarity domain);
    • a proximal domain; and
    • a tail domain,
    • wherein,
    • (a) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides;
    • (b) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain; or
    • (c) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the sequence from (a), (b), or (c), has at least 60, 75, 80, 85, 90, 95, or 99% homology with the corresponding sequence of a naturally occurring gRNA, or with a gRNA described herein.

In an embodiment, the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides (e.g., 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the unimolecular, or chimeric, gRNA molecule (comprising a targeting domain, a first complementary domain, a linking domain, a second complementary domain, a proximal domain and, optionally, a tail domain) comprises the following sequence in which the targeting domain is depicted as 20 Ns but could be any sequence and range in length from 16 to 26 nucleotides and in which the gRNA sequence is followed by 6 Us, which serve as a termination signal for the U6 promoter, but which could be either absent or fewer in number: NNNNNNNNNNNNNNNNNNNNGUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGG CUAGUCCGUUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGCUUUUUU (SEQ ID NO: 45). In an embodiment, the unimolecular, or chimeric, gRNA molecule is a S. pyogenes gRNA molecule.

In some embodiments, the unimolecular, or chimeric, gRNA molecule (comprising a targeting domain, a first complementary domain, a linking domain, a second complementary domain, a proximal domain and, optionally, a tail domain) comprises the following sequence in which the targeting domain is depicted as 20 Ns but could be any sequence and range in length from 16 to 26 nucleotides and in which the gRNA sequence is followed by 6 Us, which serve as a termination signal for the U6 promoter, but which could be either absent or fewer in number: NNNNNNNNNNNNNNNNNNNNGUUUUAGUACUCUGGAAACAGAAUCUACUAAAAC AAGGCAAAAUGCCGUGUUUAUCUCGUCAACUUGUUGGCGAGAUUUUUU (SEQ ID NO: 40). In an embodiment, the unimolecular, or chimeric, gRNA molecule is a S. aureus gRNA molecule.

Exemplary Modular gRNAs

In an embodiment, a modular gRNA comprises:

    • a first strand comprising, preferably from 5′ to 3′;
      • a targeting domain, e.g., comprising 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 nucleotides;
      • a first complementarity domain; and
      • a second strand, comprising, preferably from 5′ to 3′:
      • optionally a 5′ extension domain;
      • a second complementarity domain;
      • a proximal domain; and
      • a tail domain,
    • wherein:
    • (a) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides;
    • (b) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain; or
    • (c) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the sequence from (a), (b), or (c), has at least 60, 75, 80, 85, 90, 95, or 99% homology with the corresponding sequence of a naturally occurring gRNA, or with a gRNA described herein.

In an embodiment, the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides (e.g., 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 16 nucleotides (e.g., 16 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 16 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 17 nucleotides (e.g., 17 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 17 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 18 nucleotides (e.g., 18 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 18 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 19 nucleotides (e.g., 19 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 19 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 20 nucleotides (e.g., 20 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 20 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 21 nucleotides (e.g., 21 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 21 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 22 nucleotides (e.g., 22 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 22 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 23 nucleotides (e.g., 23 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 23 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 24 nucleotides (e.g., 24 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 24 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 25 nucleotides (e.g., 25 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 25 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain.

In an embodiment, the targeting domain comprises, has, or consists of, 26 nucleotides (e.g., 26 consecutive nucleotides) having complementarity with the target domain, e.g., the targeting domain is 26 nucleotides in length; and there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain.

II. Methods for Designing gRNAs

Methods for designing gRNAs are described herein, including methods for selecting, designing and validating target domains. Exemplary targeting domains are also provided herein. Targeting Domains discussed herein can be incorporated into the gRNAs described herein.

Methods for selection and validation of target sequences as well as off-target analyses are described, e.g., in Mali et al., 2013 SCIENCE 339(6121): 823-826; Hsu et al. NAT BIOTECHNOL, 31(9): 827-32; Fu et al., 2014 NAT BIOTECHNOL, doi: 10.1038/nbt.2808. PubMed PMID: 24463574; Heigwer et al., 2014 NAT METHODS 11(2):122-3. doi: 10.1038/nmeth.2812. PubMed PMID: 24481216; Bae et al., 2014 BIOINFORMATICS PubMed PMID: 24463181; Xiao A et al., 2014 BIOINFORMATICS PubMed PMID: 24389662.

For example, a software tool can be used to optimize the choice of gRNA within a user's target sequence, e.g., to minimize total off-target activity across the genome. Off target activity may be other than cleavage. For each possible gRNA choice using S. pyogenes Cas9, the tool can identify all off-target sequences (preceding either NAG or NGG PAMs) across the genome that contain up to certain number (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) of mismatched base-pairs. The cleavage efficiency at each off-target sequence can be predicted, e.g., using an experimentally-derived weighting scheme. Each possible gRNA is then ranked according to its total predicted off-target cleavage; the top-ranked gRNAs represent those that are likely to have the greatest on-target and the least off-target cleavage. Other functions, e.g., automated reagent design for CRISPR construction, primer design for the on-target Surveyor assay, and primer design for high-throughput detection and quantification of off-target cleavage via next-gen sequencing, can also be included in the tool. Candidate gRNA molecules can be evaluated by art-known methods or as described in Section IV herein.

The Targeting Domains discussed herein can be incorporated into the gRNAs described herein.

Strategies to Identify gRNAs for S. pyogenes, S. aureus, and N. meningitidis to Knock Out the SCNN1A Gene

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

In the first strategy, guide RNAs (gRNAs) for use with the S. pyogenes Cas9 (Tables 3A-3C) were identified using the publically available web-based ZiFiT server (Fu et al., Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014 Jan. 26. doi: 10.1038/nbt.2808. PubMed PMID: 24463574, for the original references see Sander et al., 2007, NAR 35:W599-605; Sander et al., 2010, NAR 38: W462-8). In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available Repeat-Masker program. RepeatMmasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence. Following identification, gRNAs for use with a S. pyogenes Cas9 were ranked into 3 or 4 tiers, as described below.

The gRNAs in tier 1 were selected based on their distance to the target site and their orthogonality in the genome (based on the ZiFiT identification of close matches in the human genome containing an NGG PAM). As an example, for all targets, both 17-mer and 20-mer gRNAs were designed. gRNAs were also selected both for single-gRNA nuclease cutting and for the dual gRNA nickase strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for which strategy is based on several considerations:

    • 1. For the dual nickase strategy, gRNA pairs should be oriented on the DNA such that PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5′ overhangs.
    • 2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, it will also often result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus just causing indel mutations at the site of one gRNA.

While it can be desirable to have gRNAs start with a 5′ G, this requirement was relaxed for some gRNAs in tier 1 in order to identify guides in the correct orientation, within a reasonable distance to the mutation and with a high level of orthogonality. In order to find a pair for the dual-nickase strategy it was necessary to either extend the distance from the mutation or remove the requirement for the 5′G. For selection of tier 2 gRNAs, the distance restriction was relaxed in some cases such that a longer sequence was scanned, but the 5′G was required for all gRNAs. Whether or not the distance requirement was relaxed depended on how many sites were found within the original search window. Tier 3 uses the same distance restriction as tier 2, but removes the requirement for a 5′G. Note that tiers are non-inclusive (each gRNA is listed only once).

As discussed above, gRNAs were identified for single-gRNA nuclease cleavage as well as for a dual-gRNA paired “nickase” strategy, as indicated.

gRNAs for use with the S. aureus (Tables 3D) Cas9s were identified manually by scanning genomic DNA sequence for the presence of PAM sequences. These gRNAs were not separated into tiers, but are provided in single lists for each species.

In a second strategy, Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases, Bioinformatics. 2014 Feb. 17. Bae S, Park J, Kim J S. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off-target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are computationally determined, an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5′ G (based on identification of close matches in the human genome containing a relevant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A “high level of orthogonality” or “good orthogonality” may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22-mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 43A-43E, 44A-44G or 45A-45E, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 43A-43E, 44A-44G or 45A-45E. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired “nickase” strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired “nickase” strategy is based on two considerations:

    • 1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5′ overhangs.
    • 2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.
      The targeting domains discussed herein can be incorporated into the gRNAs described herein.

gRNAs were identified and ranked into 5 tiers for S. pyogenes (Tables 43A-43E), and N. meningitidis (Tables 45A-45E); and 7 tiers for S. aureus (Tables 44A-44G). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality and (3) the presence of 5′G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon) and (2) the presence of 5′G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon). The targeting domain for tier 5 gRNA molecules were selected based on distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon). For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality, (3) the presence of 5′G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon) and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) distance to a target site (e.g., start codon), e.g., within 500 bp (e.g., downstream) of the target site (e.g., start codon) and (2) PAM is NNGRRV. The targeting domain for tier 5 gRNA molecules were selected based on (1) distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon), (2) the presence of 5′G and (3) PAM is NNGRRT. The targeting domain for tier 6 gRNA molecules were selected based on (1) distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon) and (2) PAM is NNGRRT. The targeting domain for tier 7 gRNA molecules were selected based on (1) distance to the target site (e.g., start codon), e.g., within reminder of the coding sequence, e.g., downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon) and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

Strategies to Identify gRNAs for S. pyogenes, S. aureus, and N. meningitidis to Knock Down the SCNN1A Gene

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases, Bioinformatics. 2014 Feb. 17. Bae S, Park J, Kim J S. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off-target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are computationally determined, an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5′ G (based on identification of close matches in the human genome containing a relevant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A “high level of orthogonality” or “good orthogonality” may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22-mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 46A-46E, 47A-47G or 48A-48E, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 46A-46E, 47A-47G or 48A-48E.

The targeting domains discussed herein can be incorporated into the gRNAs described herein.

gRNAs were identified and ranked into 5 tiers for S. pyogenes (Tables 46A-46E), and N. meningitidis (Tables 48A-48E); and 7 tiers for S. aureus (Tables 47A-47G). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), (2) a high level of orthogonality and (3) the presence of 5′G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) the presence of 5′G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS). The targeting domain for tier 5 gRNA molecules were selected based on distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS. For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), (2) a high level of orthogonality, (3) the presence of 5′G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and (2) PAM is NNGRRV. The targeting domain for tier 5 gRNA molecules were selected based on (1) distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS, (2) the presence of 5′G and (3) PAM is NNGRRT. The targeting domain for tier 6 gRNA molecules were selected based on (1) distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS and (2) PAM is NNGRRT. The targeting domain for tier 7 gRNA molecules were selected based on (1) distance to the target site, e.g., within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

Strategies to Identify gRNAs for S. pyogenes, S. aureus, and N. For Correcting a Mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) in the CFTR Gene

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

In the first strategy, guide RNAs (gRNAs) for use with the S. pyogenes Cas9 (Tables 1A-1C or 2A-2C) were identified using the publically available web-based ZiFiT server (Fu et al., Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol. 2014 Jan. 26. doi: 10.1038/nbt.2808. PubMed PMID: 24463574, for the original references see Sander et al., 2007, NAR 35:W599-605; Sander et al., 2010, NAR 38: W462-8). In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available Repeat-Masker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence. Following identification, gRNAs for use with a S. pyogenes Cas9 were ranked into 3 or 4 tiers, as described below.

The gRNAs in tier 1 were selected based on their distance to the target site and their orthogonality in the genome (based on the ZiFiT identification of close matches in the human genome containing an NGG PAM). As an example, for all targets, both 17-mer and 20-mer gRNAs were designed. gRNAs were also selected both for single-gRNA nuclease cutting and for the dual gRNA nickase strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for which strategy is based on several considerations:

    • 3. For the dual nickase strategy, gRNA pairs should be oriented on the DNA such that PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5′ overhangs.
    • 4. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, it will also often result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus just causing indel mutations at the site of one gRNA.

While it can be desirable to have gRNAs start with a 5′ G, this requirement was relaxed for some gRNAs in tier 1 in order to identify guides in the correct orientation, within a reasonable distance to the mutation and with a high level of orthogonality. In order to find a pair for the dual-nickase strategy it was necessary to either extend the distance from the mutation or remove the requirement for the 5′G. For selection of tier 2 gRNAs, the distance restriction was relaxed in some cases such that a longer sequence was scanned, but the 5′G was required for all gRNAs. Whether or not the distance requirement was relaxed depended on how many sites were found within the original search window. Tier 3 uses the same distance restriction as tier 2, but removes the requirement for a 5′G. Note that tiers are non-inclusive (each gRNA is listed only once).

As discussed above, gRNAs were identified for single-gRNA nuclease cleavage as well as for a dual-gRNA paired “nickase” strategy, as indicated.

gRNAs for use with the N. meningitidis (Tables 1E or 2E) and S. aureus (Tables 1D or 2D) Cas9s were identified manually by scanning genomic DNA sequence for the presence of PAM sequences. These gRNAs were not separated into tiers, but are provided in single lists for each species.

In a second strategy, Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases, Bioinformatics. 2014 Feb. 17. Bae S, Park J, Kim J S. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off-target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are computationally determined, an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5′ G (based on identification of close matches in the human genome containing a relevant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A “high level of orthogonality” or “good orthogonality” may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22-mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, or 30A-30B. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired “nickase” strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired “nickase” strategy is based on two considerations:

    • 1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5′ overhangs.
    • 2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.
      The targeting domains discussed herein can be incorporated into the gRNAs described herein.

In an embodiment, gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 4A-4D, 7A-7D, 10A-10C, 13A-13D, 16A-16D, 19A-19D, 12A-12D, 22A-22D, 25A-25D or 28A-28D), and N. meningitidis (Tables 6A-6C, 9A-9B, 12A-12C, 15A-15C, 18A-18C, 21A-21B, 24A-24D, 27A-27D, or 30A-30B); and 5 tiers for S. aureus (Tables 5A-5E, 8A-8E, 11A-11E, 14A-14E, 17A-17E, 20A-20E, 23A-23E, 26A-26E, or 29A-29E). For S. pyogenes, and N. meningitidis, the targeting domain or tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G), (2) a high level of orthogonality and (3) the presence of 5′G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) the presence of 5′G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G). For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G), (2) a high level of orthogonality, (3) the presence of 5′G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G), (2) the presence of a 5′G and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) PAM is NNGRRT. The targeting domain for tier 5 gRNA molecules were selected based on (1) (1) distance to a target site, e.g., within 200 bp from a mutation (e.g., delF508, G551D, G542X, N1303K, R117H, W1282X, R553X, 2789+5G->A, or 3272-26A->G) and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

Strategies to Identify gRNAs for S. pyogenes, S. aureus, and N. meningitidis for Targeting an Intronic Mutation (e.g., 3849+10kbC->T or 3272-26A->G) Regions of the CFTR Gene (e.g., Mediated by NHEJ)

As an example, three strategies were utilized to identify gRNAs for use with S. pyogenes, S. aureus and N. meningitidis Cas9 enzymes.

Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases, Bioinformatics. 2014 Feb. 17. Bae S, Park J, Kim J S. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off-target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are computationally determined, an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5′ G (based on identification of close matches in the human genome containing a relavant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A “high level of orthogonality” or “good orthogonality” may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22-mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired “nickase” strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired “nickase” strategy is based on two considerations:

    • 1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5′ overhangs.
    • 2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.
      The targeting domains discussed herein can be incorporated into the gRNAs described herein.

In an embodiment, gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 31A-31D or 34A-34D), and N. meningitidis (Tables 33A-33B or 36A-36D); and 4 tiers for S. aureus (Tables 32A-32D or 35A-35D). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G), (2) a high level of orthogonality and (3) the presence of 5′G. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G) and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G) and (2) the presence of 5′G. The targeting domain for tier 4 gRNA molecules were selected based on distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G). For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G), (2) a high level of orthogonality, (3) the presence of 5′G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G), (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G) and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) (1) distance to a target site, e.g., within 500 bp, e.g., within 200 bp from a mutation (e.g., 3849+10kbC->T or 3272-26A->G) and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

Strategies to Identify gRNAs for S. pyogenes, S. aureus, and N. for Targeting an Intronic Region (e.g., Intron 2 or Intron 10) of the CFTR Gene (e.g., Mediated by cDNA)

Guide RNAs (gRNAs) for use with S. pyogenes, S. aureus and N. meningitidis Cas9s were identified using a DNA sequence searching algorithm. Guide RNA design was carried out using a custom guide RNA design software based on the public tool cas-offinder (reference:Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases, Bioinformatics. 2014 Feb. 17. Bae S, Park J, Kim J S. PMID:24463181). Said custom guide RNA design software scores guides after calculating their genomewide off-target propensity. Typically matches ranging from perfect matches to 7 mismatches are considered for guides ranging in length from 17 to 24. Once the off-target sites are computationally determined, an aggregate score is calculated for each guide and summarized in a tabular output using a web-interface. In addition to identifying potential gRNA sites adjacent to PAM sequences, the software also identifies all PAM adjacent sequences that differ by 1, 2, 3 or more nucleotides from the selected gRNA sites. Genomic DNA sequence for each gene was obtained from the UCSC Genome browser and sequences were screened for repeat elements using the publically available RepeatMasker program. RepeatMasker searches input DNA sequences for repeated elements and regions of low complexity. The output is a detailed annotation of the repeats present in a given query sequence.

Following identification, gRNAs were ranked into tiers based on their distance to the target site, their orthogonality and presence of a 5′ G (based on identification of close matches in the human genome containing a relavant PAM (e.g., in the case of S. pyogenes, a NGG PAM, in the case of S. aureus, a NNGRRT or NNGRRV PAM, and in the case of N. meningitidis, a NNNNGATT or NNNNGCTT PAM). Orthogonality refers to the number of sequences in the human genome that contain a minimum number of mismatches to the target sequence. A “high level of orthogonality” or “good orthogonality” may, for example, refer to 20-mer gRNAs that have no identical sequences in the human genome besides the intended target, nor any sequences that contain one or two mismatches in the target sequence. Targeting domains with good orthogonality are selected to minimize off-target DNA cleavage.

As an example, for S. pyogenes and N. meningitidis targets, 17-mer, or 20-mer gRNAs were designed. As another example, for S. aureus targets, 18-mer, 19-mer, 20-mer, 21-mer, 22-mer, 23-mer and 24-mer gRNAs were designed. Targeting domains, disclosed herein, may comprise the 17-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 18 or more nucleotides may comprise the 17-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 18-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 19 or more nucleotides may comprise the 18-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 19-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 20 or more nucleotides may comprise the 19-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 20-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 21 or more nucleotides may comprise the 20-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 21-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 22 or more nucleotides may comprise the 21-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 22-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 23 or more nucleotides may comprise the 22-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 23-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 24 or more nucleotides may comprise the 23-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. Targeting domains, disclosed herein, may comprises the 24-mer described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D, e.g., the targeting domains of 25 or more nucleotides may comprise the 24-mer gRNAs described in Tables 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, or 42A-42D. gRNAs were identified for both single-gRNA nuclease cleavage and for a dual-gRNA paired “nickase” strategy. Criteria for selecting gRNAs and the determination for which gRNAs can be used for the dual-gRNA paired “nickase” strategy is based on two considerations:

    • 1. gRNA pairs should be oriented on the DNA such that PAMs are facing out and cutting with the D10A Cas9 nickase will result in 5′ overhangs.
    • 2. An assumption that cleaving with dual nickase pairs will result in deletion of the entire intervening sequence at a reasonable frequency. However, cleaving with dual nickase pairs can also result in indel mutations at the site of only one of the gRNAs. Candidate pair members can be tested for how efficiently they remove the entire sequence versus causing indel mutations at the site of one gRNA.
      The targeting domains discussed herein can be incorporated into the gRNAs described herein.

In an embodiment, gRNAs were identified and ranked into 4 tiers for S. pyogenes (Tables 37A-37D or 40A-40D), and N. meningitidis (Tables 39A-39D or 42A-42D); and 4 tiers for S. aureus (Tables 38A-38E or 41A-41E). For S. pyogenes, and N. meningitidis, the targeting domain for tier 1 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) a high level of orthogonality and (3) the presence of 5′G. The targeting domain for tier 2 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10 and (2) a high level of orthogonality. The targeting domain for tier 3 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10 and (2) the presence of 5′G. The targeting domain for tier 4 gRNA molecules were selected based on target position, e.g., intron 2 or intron 10. For S. aureus, the targeting domain for tier 1 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) a high level of orthogonality, (3) the presence of 5′G and (4) PAM is NNGRRT. The targeting domain for tier 2 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) a high level of orthogonality, and (3) PAM is NNGRRT. The targeting domain for tier 3 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10, (2) the presence of a 5′G and (2) PAM is NNGRRT. The targeting domain for tier 4 gRNA molecules were selected based on (1) target position, e.g., intron 2 or intron 10 and (2) PAM is NNGRRT. The targeting domain for tier 5 gRNA molecules were selected based on (1) (1) target position, e.g., intron 2 or intron 10 and (2) PAM is NNGRRV. Note that tiers are non-inclusive (each gRNA is listed only once for the strategy). In certain instances, no gRNA was identified based on the criteria of the particular tier.

In an embodiment, two or more (e.g., three or four) gRNA molecules are used with one Cas9 molecule. In another embodiment, when two or more (e.g., three or four) gRNAs are used with two or more Cas9 molecules, at least one Cas9 molecule is from a different species than the other Cas9 molecule(s). For example, when two gRNA molecules are used with two Cas9 molecules, one Cas9 molecule can be from one species and the other Cas9 molecule can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

Any of the targeting domains in the tables described herein can be used with a Cas9 nickase molecule to generate a single strand break.

Any of the targeting domains in the tables described herein can be used with a Cas9 nuclease molecule to generate a double strand break.

When two gRNAs designed for use to target two Cas9 molecules, one Cas9 can be one species, the second Cas9 can be from a different species. Both Cas9 species are used to generate a single or double-strand break, as desired.

It is contemplated herein that any upstream gRNA described herein may be paired with any downstream gRNA described herein. When an upstream gRNA designed for use with one species of Cas9 is paired with a downstream gRNA designed for use from a different species of Cas9, both Cas9 species are used to generate a single or double-strand break, as desired.

Exemplary Targeting Domains

Table 1A provides exemplary targeting domains for the F508del target position in the CFTR gene selected according to the first tier parameters. The targeting domains are selected based on close proximity to mutation and orthogonality in the human genome. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp. In an embodiment, two 17-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., CFTR-18 and CFTR-16 are used.

TABLE A Target DNA  Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-1 GAGGGUAAAAUUAAGCACAG 20 387 CFTR-6 + AGUUUCUUACCUCUUCUAGU 20 388 CFTR-10 + AAUGGUGCCAGGCAUAAUCC 20 389 CFTR-12 GGUAAAAUUAAGCACAG 17 390 CFTR-16 AGCAUGCCAACUAGAAG 17 391 CFTR-18 + GUAUCUAUAUUCAUCAU 17 392

Table 1B provides exemplary targeting domains for the F508del target position in the CFTR gene selected according to the second tier parameters. The targeting domains are selected based on the presence of a 5′ G and reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 1B Tar- get DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-19 + GAUGAUAUUUUCUUUAA 17 393 CFTR-21 + GGUGCCAGGCAUAAUCC 17 394 CFTR-24 - GAUAAUGACCUAAUAAUGAU 20 395 CFTR-29 - GGGAGAACUGGAGCCUUCAG 20 396 CFTR-30 - GGAGAACUGGAGCCUUCAGA 20 397 CFTR-37 + GUAGACUAACCGAUUGAAUA 20 398 CFTR-44 + GUCAUUAUCAAAUCACGCUC 20 399 CFTR-50 - GGUGAUUAUGGGAGAAC 17 400 CFTR-52 - GAACUGGAGCCUUCAGA 17 401 CFTR-57 - GGGUAAGCUACUGUGAA 17 402 CFTR-59 + GACUAACCGAUUGAAUA 17 403 CFTR-60 + GAGCCAAAUAUAUAAUU 17 404

Table 1C provides exemplary targeting domains for the F508del target position in the CFTR gene selected according to the third tier parameters. The targeting domains are selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 1C Target gRNA  DNA  Site Seq Name Strand Targeting Domain Length ID CFTR-2 - CAUUCUGUUCUCAGUUUUCC 20 405 CFTR-3 - CAGUUUUCCUGGAUUAUGCC 20 406 CFTR-4 - AUUAAAGAAAAUAUCAUCUU 20 407 CFTR-5 - CAAAGCAUGCCAACUAGAAG 20 408 CFTR-6 + AGUUUCUUACCUCUUCUAGU 20 388 CFTR-7 + UCUGUAUCUAUAUUCAUCAU 20 409 CFTR-8 + AAAGAUGAUAUUUUCUUUAA 20 410 CFTR-9 + AUAUUUUCUUUAAUGGUGCC 20 411 CFTR-10 + AAUGGUGCCAGGCAUAAUCC 20 389 CFTR-11 + UGCUUAAUUUUACCCUCUGA 20 412 CFTR-13 - UCUGUUCUCAGUUUUCC 17 413 CFTR-14 - UUUUCCUGGAUUAUGCC 17 414 CFTR-15 - AAAGAAAAUAUCAUCUU 17 415 CFTR-16 - AGCAUGCCAACUAGAAG 17 391 CFTR-17 + UUCUUACCUCUUCUAGU 17 416 CFTR-20 + UUUUCUUUAAUGGUGCC 17 417 CFTR-22 + UUAAUUUUACCCUCUGA 17 418 CFTR-23 - UGAUAAUGACCUAAUAAUGA 20 419 CFTR-25 - UUUCCAGACUUCACUUCUAA 20 420 CFTR-26 - UUCACUUCUAAUGGUGAUUA 20 421 CFTR-27 - UCACUUCUAAUGGUGAUUAU 20 422 CFTR-28 - AAUGGUGAUUAUGGGAGAAC 20 423 CFTR-31 - CACUACCCAAAUUAUAUAUU 20 424 CFTR-32 - UAUUUGGCUCCAUAUUCAAU 20 425 CFTR-33 - AUAUAUUUAUGUUUCCUCUA 20 426 CFTR-34 - UAUAUUUAUGUUUCCUCUAU 20 427 CFTR-35 - UAUGGGUAAGCUACUGUGAA 20 428 CFTR-36 + UCACAGUAGCUUACCCAUAG 20 429 CFTR-38 + AUGGAGCCAAAUAUAUAAUU 20 430 CFTR-39 + UGGAGCCAAAUAUAUAAUUU 20 431 CFTR-40 + AUAUAAUUUGGGUAGUGUGA 20 432 CFTR-41 + UAUAAUUUGGGUAGUGUGAA 20 433 CFTR-42 + UCACCAUUAGAAGUGAAGUC 20 434 CFTR-43 + AAAUAAAACCCAUCAUUAUU 20 435 CFTR-45 - UAAUGACCUAAUAAUGA 17 436 CFTR-46 - AAUGACCUAAUAAUGAU 17 437 CFTR-47 - CCAGACUUCACUUCUAA 17 438 CFTR-48 - ACUUCUAAUGGUGAUUA 17 439 CFTR-49 - CUUCUAAUGGUGAUUAU 17 440 CFTR-51 - AGAACUGGAGCCUUCAG 17 441 CFTR-53 - UACCCAAAUUAUAUAUU 17 442 CFTR-54 - UUGGCUCCAUAUUCAAU 17 443 CFTR-55 - UAUUUAUGUUUCCUCUA 17 444 CFTR-56 - AUUUAUGUUUCCUCUAU 17 445 CFTR-58 + CAGUAGCUUACCCAUAG 17 446 CFTR-61 + AGCCAAAUAUAUAAUUU 17 447 CFTR-62 + UAAUUUGGGUAGUGUGA 17 448 CFTR-63 + AAUUUGGGUAGUGUGAA 17 449 CFTR-64 + CCAUUAGAAGUGAAGUC 17 450 CFTR-65 + UAAAACCCAUCAUUAUU 17 451 CFTR-66 + AUUAUCAAAUCACGCUC 17 452

Table 1D provides exemplary targeting domains for the F508del target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. aureus Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. aureus Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 1D Target DNA  Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-111 - UAAUUGGAGGCAAGUGAAUC 20 655 CFTR-112 - UUGAUAAUGACCUAAUAAUG 20 656 CFTR-113 - CUUCACUUCUAAUGGUGAUU 20 657 CFTR-26 - UUCACUUCUAAUGGUGAUUA 20 421 CFTR-27 - UCACUUCUAAUGGUGAUUAU 20 422 CFTR-116 - ACUUCUAAUGGUGAUUAUGG 20 658 CFTR-117 - UAAUGGUGAUUAUGGGAGAA 20 659 CFTR-28 - AAUGGUGAUUAUGGGAGAAC 20 423 CFTR-119 - UAUGGGAGAACUGGAGCCUU 20 660 CFTR-120 - UGGGAGAACUGGAGCCUUCA 20 661 CFTR-121 - AGAGGGUAAAAUUAAGCACA 20 662 CFTR-1 - GAGGGUAAAAUUAAGCACAG 20 387 CFTR-123 - GGUAAAAUUAAGCACAGUGG 20 663 CFTR-124 - UCAUUCUGUUCUCAGUUUUC 20 664 CFTR-125 - GAUUAUGCCUGGCACCAUUA 20 665 CFTR-126 - CAUCUUUGGUGUUUCCUAUG 20 666 CFTR-127 - UCCUAUGAUGAAUAUAGAUA 20 667 CFTR-128 - CGUCAUCAAAGCAUGCCAAC 20 668 CFTR-129 - CAUCAAAGCAUGCCAACUAG 20 669 CFTR-130 - GCAUGCCAACUAGAAGAGGU 20 670 CFTR-131 - UAGAAGAGGUAAGAAACUAU 20 671 CFTR-132 - AAAACUUUUUGAUUAUGCAU 20 672 CFTR-133 - CAUAUAUUUAUGUUUCCUCU 20 673 CFTR-134 - UCCUCUAUGGGUAAGCUACU 20 674 CFTR-135 - CUAUGGGUAAGCUACUGUGA 20 675 CFTR-136 + GGUCAUUAUCAAAUCACGCU 20 676 CFTR-42 + UCACCAUUAGAAGUGAAGUC 20 434 CFTR-138 + AUCACCAUUAGAAGUGAAGU 20 677 CFTR-139 + UCCCAUAAUCACCAUUAGAA 20 678 CFTR-140 + AGUUCUCCCAUAAUCACCAU 20 679 CFTR-141 + ACUGUGCUUAAUUUUACCCU 20 680 CFTR-142 + CCAGGAAAACUGAGAACAGA 20 681 CFTR-143 + UAAUCCAGGAAAACUGAGAA 20 682 CFTR-144 + AGGCAUAAUCCAGGAAAACU 20 683 CFTR-145 + CCAGGCAUAAUCCAGGAAAA 20 684 CFTR-10 + AAUGGUGCCAGGCAUAAUCC 20 389 CFTR-147 + UAAUGGUGCCAGGCAUAAUC 20 685 CFTR-7 + UCUGUAUCUAUAUUCAUCAU 20 409 CFTR-149 + UUCUGUAUCUAUAUUCAUCA 20 686 CFTR-150 + UAUAUAAUUUGGGUAGUGUG 20 687 CFTR-151 + AAAUAUAUAAUUUGGGUAGU 20 688 CFTR-152 + UAUGGAGCCAAAUAUAUAAU 20 689 CFTR-37 + GUAGACUAACCGAUUGAAUA 20 398 CFTR-154 + UGUAGACUAACCGAUUGAAU 20 690 CFTR-155 + AAUAUAUGUAGACUAACCGA 20 691 CFTR-36 + UCACAGUAGCUUACCCAUAG 20 429 CFTR-157 + UUCACAGUAGCUUACCCAUA 20 692 CFTR-158 + CAUUCACAGUAGCUUACCCA 20 693 CFTR-159 - UUGGAGGCAAGUGAAUC 17 694 CFTR-160 - AUAAUGACCUAAUAAUG 17 695 CFTR-161 - CACUUCUAAUGGUGAUU 17 696 CFTR-48 - ACUUCUAAUGGUGAUUA 17 439 CFTR-49 - CUUCUAAUGGUGAUUAU 17 440 CFTR-164 - UCUAAUGGUGAUUAUGG 17 697 CFTR-165 - UGGUGAUUAUGGGAGAA 17 698 CFTR-50 - GGUGAUUAUGGGAGAAC 17 400 CFTR-167 - GGGAGAACUGGAGCCUU 17 699 CFTR-168 - GAGAACUGGAGCCUUCA 17 700 CFTR-169 - GGGUAAAAUUAAGCACA 17 701 CFTR-12 - GGUAAAAUUAAGCACAG 17 390 CFTR-171 - AAAAUUAAGCACAGUGG 17 702 CFTR-172 - UUCUGUUCUCAGUUUUC 17 703 CFTR-173 - UAUGCCUGGCACCAUUA 17 704 CFTR-174 - CUUUGGUGUUUCCUAUG 17 705 CFTR-175 - UAUGAUGAAUAUAGAUA 17 706 CFTR-176 - CAUCAAAGCAUGCCAAC 17 707 CFTR-177 - CAAAGCAUGCCAACUAG 17 708 CFTR-178 - UGCCAACUAGAAGAGGU 17 709 CFTR-179 - AAGAGGUAAGAAACUAU 17 710 CFTR-180 - ACUUUUUGAUUAUGCAU 17 711 CFTR-181 - AUAUUUAUGUUUCCUCU 17 712 CFTR-182 - UCUAUGGGUAAGCUACU 17 713 CFTR-183 - UGGGUAAGCUACUGUGA 17 714 CFTR-184 + CAUUAUCAAAUCACGCU 17 715 CFTR-64 + CCAUUAGAAGUGAAGUC 17 450 CFTR-186 + ACCAUUAGAAGUGAAGU 17 716 CFTR-187 + CAUAAUCACCAUUAGAA 17 717 CFTR-188 + UCUCCCAUAAUCACCAU 17 718 CFTR-189 + GUGCUUAAUUUUACCCU 17 719 CFTR-190 + GGAAAACUGAGAACAGA 17 720 CFTR-191 + UCCAGGAAAACUGAGAA 17 721 CFTR-192 + CAUAAUCCAGGAAAACU 17 722 CFTR-193 + GGCAUAAUCCAGGAAAA 17 723 CFTR-21 + GGUGCCAGGCAUAAUCC 17 394 CFTR-195 + UGGUGCCAGGCAUAAUC 17 724 CFTR-18 + GUAUCUAUAUUCAUCAU 17 392 CFTR-197 + UGUAUCUAUAUUCAUCA 17 725 CFTR-198 + AUAAUUUGGGUAGUGUG 17 726 CFTR-199 + UAUAUAAUUUGGGUAGU 17 727 CFTR-200 + GGAGCCAAAUAUAUAAU 17 728 CFTR-59 + GACUAACCGAUUGAAUA 17 403 CFTR-202 + AGACUAACCGAUUGAAU 17 729 CFTR-203 + AUAUGUAGACUAACCGA 17 730 CFTR-58 + CAGUAGCUUACCCAUAG 17 446 CFTR-205 + ACAGUAGCUUACCCAUA 17 731 CFTR-206 + UCACAGUAGCUUACCCA 17 732

Table 1E provides exemplary targeting domains for the F508del target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using N. meningitidis Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE lE Target DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-207 - UGGAGGCAAGUGAAUCCUGA 20 917 CFTR-25 - UUUCCAGACUUCACUUCUAA 20 420 CFTR-209 - UUCAUUCUGUUCUCAGUUUU 20 918 CFTR-210 - UAAGAAACUAUGUGAAAACU 20 919 CFTR-211 + AGGUCAUUAUCAAAUCACGC 20 920 CFTR-212 + AACAUAAAUAUAUGUAGACU 20 921 CFTR-213 - AGGCAAGUGAAUCCUGA 17 922 CFTR-47 - CCAGACUUCACUUCUAA 17 438 CFTR-215 - AUUCUGUUCUCAGUUUU 17 923 CFTR-216 - GAAACUAUGUGAAAACU 17 924 CFTR-217 + UCAUUAUCAAAUCACGC 17 925 CFTR-218 + AUAAAUAUAUGUAGACU 17 926

Table 2A provides exemplary targeting domains for the G55D target position in the CFTR gene selected according to the first tier parameters. The targeting domains are selected based close proximity to mutation and orthogonality in the human genome. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 2A Target DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-71 - GAGAAAGACAAUAUAGUUCU 20 453 CFTR-75 - GGUGGAAUCACACUGAGUGG 20 454 CFTR-86 + CCCACUAGCCAUAAAACCCC 20 455 CFTR-96 - GGUGGAAUCACACUGAG 17 456 CFTR-97 - GGAAUCACACUGAGUGG 17 457 CFTR-106 - GGGGUUUUAUGGCUAGU 17 458 CFTR-108 +  ACUAGCCAUAAAACCCC 17  459

Table 2B provides exemplary targeting domains for the G551D target position in the CFTR gene selected according to the second tier parameters. The targeting domains are selected based on the presence of a 5′ G and reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 2B Target DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-72 - GACAAUAUAGUUCUUGGAGA 20 460 CFTR-74 - GAAGGUGGAAUCACACUGAG 20 461 CFTR-76 - GAGCAAGAAUUUCUUUAGCA 20 462 CFTR-82 - GAAAAAAUCCUGGGGUUUUA 20 463 CFTR-89 - GUUCAAAAUUUCAACUG 17 464 CFTR-99 - GGUGAAUAACUAAUUAU 17 465 CFTR-100 - GCUUUAUAUUCUGUUUC 17 466 CFTR-102 - GGAAUUGAAAAAAUCCU 17 467 CFTR-103 - GAAUUGAAAAAAUCCUG 17 468 CFTR-109 + GUCUUUCUCUGCAAACU 17 469

Table 2C provides exemplary targeting domains for the G551D target position in the CFTR gene selected according to the third tier parameters. The targeting domains are selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 2C Target DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-67 - AAUGUUCAAAAUUUCAACUG 20 470 CFTR-68 - UGAUAUAUGAUUACAUUAGA 20 471 CFTR-69 - ACUCUCUAAUUUUCUAUUUU 20 472 CFTR-70 - AAUUUUCUAUUUUUGGUAAU 20 473 CFTR-73 - AAUAUAGUUCUUGGAGAAGG 20 474 CFTR-77 - CAAGGUGAAUAACUAAUUAU 20 475 CFTR-78 - AUUGCUUUAUAUUCUGUUUC 20 476 CFTR-79 - UUCUGGAAUUGAAAAAAUCC 20 477 CFTR-80 - UCUGGAAUUGAAAAAAUCCU 20 478 CFTR-81 - CUGGAAUUGAAAAAAUCCUG 20 479 CFTR-83 - UCCUGGGGUUUUAUGGCUAG 20 480 CFTR-84 - CCUGGGGUUUUAUGGCUAGU 20 481 CFTR-85 - CAUUUAAGAACUAUAAAUAA 20 482 CFTR-87 + AUUGUCUUUCUCUGCAAACU 20 483 CFTR-88 + AUGCUCAAUCUGAAUUUGAA 20 484 CFTR-90 - UAUAUGAUUACAUUAGA 17 485 CFTR-91 - CUCUAAUUUUCUAUUUU 17 486 CFTR-92 - UUUCUAUUUUUGGUAAU 17 487 CFTR-93 - AAAGACAAUAUAGUUCU 17 488 CFTR-94 - AAUAUAGUUCUUGGAGA 17 489 CFTR-95 - AUAGUUCUUGGAGAAGG 17 490 CFTR-98 - CAAGAAUUUCUUUAGCA 17 491 CFTR-101 - UGGAAUUGAAAAAAUCC 17 492 CFTR-104 - AAAAUCCUGGGGUUUUA 17 493 CFTR-105 - UGGGGUUUUAUGGCUAG 17 494 CFTR-107 - UUAAGAACUAUAAAUAA 17 495 CFTR-110 + CUCAAUCUGAAUUUGAA 17 496

Table 2D provides exemplary targeting domains for the G551D target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. aureus Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. aureus Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 2D Target DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-219 - AGUGUGAUAUAUGAUUACAU 20 733 CFTR-220 - GUGAUAUAUGAUUACAUUAG 20 734 CFTR-68 - UGAUAUAUGAUUACAUUAGA 20 471 CFTR-222 - AUGUGCCUUUCAAAUUCAGA 20 735 CFTR-223 - UAAUUUUCUAUUUUUGGUAA 20 736 CFTR-224 - AUAGGACAUCUCCAAGUUUG 20 737 CFTR-225 - AGGACAUCUCCAAGUUUGCA 20 738 CFTR-226 - AGAGAAAGACAAUAUAGUUC 20 739 CFTR-71 - GAGAAAGACAAUAUAGUUCU 20 453 CFTR-228 - GAAAGACAAUAUAGUUCUUG 20 740 CFTR-229 - CAAUAUAGUUCUUGGAGAAG 20 741 CFTR-73 - AAUAUAGUUCUUGGAGAAGG 20 474 CFTR-231 - UUGGAGAAGGUGGAAUCACA 20 742 CFTR-232 - AGAAGGUGGAAUCACACUGA 20 743 CFTR-74 - GAAGGUGGAAUCACACUGAG 20 461 CFTR-234 - AUCACACUGAGUGGAGGUCA 20 744 CFTR-235 - CUGAGUGGAGGUCAACGAGC 20 745 CFTR-236 - GCAAGAAUUUCUUUAGCAAG 20 746 CFTR-237 - UAUUGCUUUAUAUUCUGUUU 20 747 CFTR-78 - AUUGCUUUAUAUUCUGUUUC 20 476 CFTR-239 - UUUAUAUUCUGUUUCUGGAA 20 748 CFTR-240 - UUUCUGGAAUUGAAAAAAUC 20 749 CFTR-79 - UUCUGGAAUUGAAAAAAUCC 20 477 CFTR-242 - AUCCUGGGGUUUUAUGGCUA 20 750 CFTR-243 - GGUUUUAUGGCUAGUGGGUU 20 751 CFTR-244 - GUGGGUUAAGAAUCACAUUU 20 752 CFTR-245 + CUUUAACCACAGUUGAAAUU 20 753 CFTR-246 + CACUAUUGCUUUAACCACAG 20 754 CFTR-247 + UUAGUAUGCUCAAUCUGAAU 20 755 CFTR-248 + UCACUUUUAGUAUGCUCAAU 20 756 CFTR-249 + UUACCAAAAAUAGAAAAUUA 20 757 CFTR-250 + UAUUACCAAAAAUAGAAAAU 20 758 CFTR-251 + AGAUGUCCUAUUACCAAAAA 20 759 CFTR-87 + AUUGUCUUUCUCUGCAAACU 20 483 CFTR-253 + UAUUGUCUUUCUCUGCAAAC 20 760 CFTR-254 + AGUGUGAUUCCACCUUCUCC 20 761 CFTR-255 + AUUAGUUAUUCACCUUGCUA 20 762 CFTR-256 + AAUGUCUGUAAUUUUUUUAC 20 763 CFTR-257 + AAACAGAAUAUAAAGCAAUA 20 764 CFTR-258 + AGAAACAGAAUAUAAAGCAA 20 765 CFTR-259 + GAUUUUUUCAAUUCCAGAAA 20 766 CFTR-260 + CCCCAGGAUUUUUUCAAUUC 20 767 CFTR-261 - GUGAUAUAUGAUUACAU 17 768 CFTR-262 - AUAUAUGAUUACAUUAG 17 769 CFTR-90 - UAUAUGAUUACAUUAGA 17 485 CFTR-264 - UGCCUUUCAAAUUCAGA 17 770 CFTR-265 - UUUUCUAUUUUUGGUAA 17 771 CFTR-266 - GGACAUCUCCAAGUUUG 17 772 CFTR-267 - ACAUCUCCAAGUUUGCA 17 773 CFTR-268 - GAAAGACAAUAUAGUUC 17 774 CFTR-93 - AAAGACAAUAUAGUUCU 17 488 CFTR-270 - AGACAAUAUAGUUCUUG 17 775 CFTR-271 - UAUAGUUCUUGGAGAAG 17 776 CFTR-95 - AUAGUUCUUGGAGAAGG 17 490 CFTR-273 - GAGAAGGUGGAAUCACA 17 777 CFTR-274 - AGGUGGAAUCACACUGA 17 778 CFTR-96 - GGUGGAAUCACACUGAG 17 456 CFTR-276 - ACACUGAGUGGAGGUCA 17 779 CFTR-277 - AGUGGAGGUCAACGAGC 17 780 CFTR-278 - AGAAUUUCUUUAGCAAG 17 781 CFTR-279 - UGCUUUAUAUUCUGUUU 17 782 CFTR-100 - GCUUUAUAUUCUGUUUC 17 466 CFTR-281 - AUAUUCUGUUUCUGGAA 17 783 CFTR-282 - CUGGAAUUGAAAAAAUC 17 784 CFTR-101 - UGGAAUUGAAAAAAUCC 17 492 CFTR-284 - CUGGGGUUUUAUGGCUA 17 785 CFTR-285 - UUUAUGGCUAGUGGGUU 17 786 CFTR-286 - GGUUAAGAAUCACAUUU 17 787 CFTR-287 + UAACCACAGUUGAAAUU 17 788 CFTR-288 + UAUUGCUUUAACCACAG 17 789 CFTR-289 + GUAUGCUCAAUCUGAAU 17 790 CFTR-290 + CUUUUAGUAUGCUCAAU 17 791 CFTR-291 + CCAAAAAUAGAAAAUUA 17 792 CFTR-292 + UACCAAAAAUAGAAAAU 17 793 CFTR-293 + UGUCCUAUUACCAAAAA 17 794 CFTR-109 + GUCUUUCUCUGCAAACU 17 469 CFTR-295 + UGUCUUUCUCUGCAAAC 17 795 CFTR-296 + GUGAUUCCACCUUCUCC 17 796 CFTR-297 + AGUUAUUCACCUUGCUA 17 797 CFTR-298 + GUCUGUAAUUUUUUUAC 17 798 CFTR-299 + CAGAAUAUAAAGCAAUA 17 799 CFTR-300 + AACAGAAUAUAAAGCAA 17 800 CFTR-301 + UUUUUCAAUUCCAGAAA 17 801 CFTR-302 + CAGGAUUUUUUCAAUUC 17 802

Table 2E provides exemplary targeting domains for the G551D target position in the CFTR gene selected based on reasonable proximity to mutation. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using N. meningitidis Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 2E Target DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-303 - GGUUAAAGCAAUAGUGUGAU 20 927 CFTR-304 - AGGAAGAUGUGCCUUUCAAA 20 928 CFTR-305 + UGCUCGUUGACCUCCACUCA 20 929 CFTR-306 + AACCCACUAGCCAUAAAACC 20 930 CFTR-307 + CCAUUAUUUAUAGUUCUUAA 20 931 CFTR-308 - UAAAGCAAUAGUGUGAU 17 932 CFTR-309 - AAGAUGUGCCUUUCAAA 17 933 CFTR-310 + UCGUUGACCUCCACUCA 17 934 CFTR-311 + CCACUAGCCAUAAAACC 17 935 CFTR-312 + UUAUUUAUAGUUCUUAA 17 936

Table 3A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains are selected based close proximity to start codon and orthogonality in the human genome. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp. In an embodiment, two 20-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., SCNN5A-78 and SCNN1A-9 are used.

TABLE 3A Target DNA  Site Seq  gRNA Name Strand Targeting Domain Length ID SCNN1A-2 - GCCCAUACCAGGUCUCAUGG 20 497 SCNN1A-4 - CCAUACCAGGUCUCAUGGAG 20 498 SCNN1A-9 - GCCCUCCACAGUCCACUCCA 20 499 SCNN1A-78 + CCCCUCCAUGAGACCUGGUA 20 500 SCNN1A-82 - AUACCAGGUCUCAUGGA 17 501 SCNN1A-157 + CUCCAUGAGACCUGGUA 17 502

Table 3B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains are selected based on the presence of a 5′ G and reasonable proximity to start codon. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp. In an embodiment, two 20-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., SCNN2A-78 and SCNN1A-9 are used.

TABLE 3B Target DNA  Site Seq  gRNA Name Strand Targeting Domain Length ID SCNN1A-1 - GCAGCCCAUACCAGGUCUCA 20 503 SCNN1A-7 - GGGGAACAAGCUGGAGGAGC 20 504 SCNN1A-10 - GUCCACUCCAGGGCUCAUGA 20 505 SCNN1A-14 - GGGGAACAAGCGUGAGGAGC 20 506 SCNN1A-15 - GGGAACAAGCGUGAGGAGCA 20 507 SCNN1A-16 - GGAACAAGCGUGAGGAGCAG 20 508 SCNN1A-19 - GGGGCUGGGCCCCGAACCUG 20 509 SCNN1A-21 - GGCGCCCCAGCAGCCCACGG 20 510 SCNN1A-22 - GCCCCAGCAGCCCACGGCGG 20 511 SCNN1A-24 - GCAGCCCACGGCGGAGGAGG 20 512 SCNN1A-31 - GUGCUGUGGCUCUGCACCUU 20 513 SCNN1A-32 - GCACCUUUGGCAUGAUGUAC 20 514 SCNN1A-33 - GGCAUGAUGUACUGGCAAUU 20 515 SCNN1A-36 + GUAGGGAUUGAGGGUGCAGA 20 516 SCNN1A-37 + GAGGGUGCAGAUGGUCACUG 20 517 SCNN1A-39 + GGGUGCAGAUGGUCACUGCG 20 518 SCNN1A-42 + GAGGUUGAUGUUGAGGCUGA 20 519 SCNN1A-44 + GGUUGAUGUUGAGGCUGACG 20 520 SCNN1A-47 + GAGCCACAGCACUGCCCAGA 20 521 SCNN1A-51 + GGUUGUGCUGGGAGCACACC 20 522 SCNN1A-56 + GCGGAUGGCGCCGUGGAUGG 20 523 SCNN1A-58 + GAACUCGAAGAGCUCUCGGU 20 524 SCNN1A-62 + GGAGCGGUGGAACUCGAUCA 20 525 SCNN1A-68 + GUGGGCUGCUGGGGCGCCGC 20 526 SCNN1A-71 + GCUGGGGCGCCGCAGGUUCG 20 527 SCNN1A-76 + GCCCUGGAGUGGACUGUGGA 20 528 SCNN1A-80 - GCCCAUACCAGGUCUCA 17 529 SCNN1A-85 - GGAGGGGAACAAGCUGG 17 530 SCNN1A-86 - GAACAAGCUGGAGGAGC 17 531 SCNN1A-92 - GAAGGGGAACAAGCGUG 17 532 SCNN1A-93 - GAACAAGCGUGAGGAGC 17 533 SCNN1A-96 - GCGUGAGGAGCAGGGGC 17 534 SCNN1A-98 - GCUGGGCCCCGAACCUG 17 535 SCNN1A-99 - GGCGCCCCAGCAGCCCA 17 536 SCNN1A-100 - GCCCCAGCAGCCCACGG 17 537 SCNN1A-102 - GCAGCCCACGGCGGAGG 17 538 SCNN1A-103 - GCCCACGGCGGAGGAGG 17 539 SCNN1A-106 - GCACAACCGCAUGAAGA 17 540 SCNN1A-107 - GCAUGAAGACGGCCUUC 17 541 SCNN1A-115 + GGGAUUGAGGGUGCAGA 17 542 SCNN1A-116 + GGUGCAGAUGGUCACUG 17 543 SCNN1A-117 + GUGCAGAUGGUCACUGC 17 544 SCNN1A-121 + GUUGAUGUUGAGGCUGA 17 545 SCNN1A-131 + GCUGGGAGCACACCAGG 17 546 SCNN1A-132 + GGAGCACACCAGGCGGA 17 547 SCNN1A-134 + GCGGAUGGCGCCGUGGA 17 548 SCNN1A-135 + GAUGGCGCCGUGGAUGG 17 549 SCNN1A-139 + GCUCUCGGUAGGAGCGG 17 550 SCNN1A-141 + GCGGUGGAACUCGAUCA 17 551 SCNN1A-142 + GGCCUCCUCCUCCGCCG 17 552 SCNN1A-143 + GCCUCCUCCUCCGCCGU 17 553 SCNN1A-147 + GGCUGCUGGGGCGCCGC 17 554 SCNN1A-150 + GGGGCGCCGCAGGUUCG 17 555

Table 3C provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the third tier parameters. The targeting domains are selected based on reasonable proximity to start codon. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. pyogenes Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. pyogenes Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp. In an embodiment, two 20-mer RNAs are used to target two Cas9 nucleases or two Cas9 nickases, e.g., SCNN1A-78 and SCNN1A-9 are used.

TABLE 3C Target DNA  Site Seq  gRNA Name Strand Targeting Domain Length ID SCNN1A-3 - CCCAUACCAGGUCUCAUGGA 20 556 SCNN1A-5 - UCUCAUGGAGGGGAACAAGC 20 557 SCNN1A-6 - CAUGGAGGGGAACAAGCUGG 20 558 SCNN1A-8 - AGCCCUCCACAGUCCACUCC 20 559 SCNN1A-11 - UCCACUCCAGGGCUCAUGAA 20 560 SCNN1A-12 - CCACUCCAGGGCUCAUGAAG 20 561 SCNN1A-13 - CAUGAAGGGGAACAAGCGUG 20 562 SCNN1A-17 - CAAGCGUGAGGAGCAGGGGC 20 563 SCNN1A-18 - AAGCGUGAGGAGCAGGGGCU 20 564 SCNN1A-20 - UGCGGCGCCCCAGCAGCCCA 20 565 SCNN1A-23 - CCAGCAGCCCACGGCGGAGG 20 566 SCNN1A-25 - UGCAACAACACCACCAUCCA 20 567 SCNN1A-26 - CAUCCACGGCGCCAUCCGCC 20 568 SCNN1A-27 - CCAGCACAACCGCAUGAAGA 20 569 SCNN1A-28 - ACCGCAUGAAGACGGCCUUC 20 570 SCNN1A-29 - CCGCAUGAAGACGGCCUUCU 20 571 SCNN1A-30 - CGGCCUUCUGGGCAGUGCUG 20 572 SCNN1A-34 - UGGCAAUUCGGCCUGCUUUU 20 573 SCNN1A-35 - CCUCAACAUCAACCUCAACU 20 574 SCNN1A-38 + AGGGUGCAGAUGGUCACUGC 20 575 SCNN1A-40 + AGACGAGCUUGUCCGAGUUG 20 576 SCNN1A-41 + CCGAGUUGAGGUUGAUGUUG 20 577 SCNN1A-43 + AGGUUGAUGUUGAGGCUGAC 20 578 SCNN1A-45 + UGAAGUACUCUCCGAAAAGC 20 579 SCNN1A-46 + UUGCCAGUACAUCAUGCCAA 20 580 SCNN1A-48 + CCCAGAAGGCCGUCUUCAUG 20 581 SCNN1A-49 + CCGUCUUCAUGCGGUUGUGC 20 582 SCNN1A-50 + CGUCUUCAUGCGGUUGUGCU 20 583 SCNN1A-52 + UGUGCUGGGAGCACACCAGG 20 584 SCNN1A-53 + CUGGGAGCACACCAGGCGGA 20 585 SCNN1A-54 + ACACCAGGCGGAUGGCGCCG 20 586 SCNN1A-55 + CAGGCGGAUGGCGCCGUGGA 20 587 SCNN1A-57 + AGAAGAACUCGAAGAGCUCU 20 588 SCNN1A-59 + CGAAGAGCUCUCGGUAGGAG 20 589 SCNN1A-60 + AGAGCUCUCGGUAGGAGCGG 20 590 SCNN1A-61 + AGGAGCGGUGGAACUCGAUC 20 591 SCNN1A-63 + CAGGGCCUCCUCCUCCGCCG 20 592 SCNN1A-64 + AGGGCCUCCUCCUCCGCCGU 20 593 SCNN1A-65 + CCUCCUCCGCCGUGGGCUGC 20 594 SCNN1A-66 + CUCCUCCGCCGUGGGCUGCU 20 595 SCNN1A-67 + UCCUCCGCCGUGGGCUGCUG 20 596 SCNN1A-69 + CUGCUGGGGCGCCGCAGGUU 20 597 SCNN1A-70 + UGCUGGGGCGCCGCAGGUUC 20 598 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20 599 SCNN1A-73 + CCCCUUCAUGAGCCCUGGAG 20 600 SCNN1A-74 + AUGAGCCCUGGAGUGGACUG 20 601 SCNN1A-75 + AGCCCUGGAGUGGACUGUGG 20 602 SCNN1A-77 + UUGUUCCCCUCCAUGAGACC 20 603 SCNN1A-79 + CCCUCCAUGAGACCUGGUAU 20 604 SCNN1A-81 - CAUACCAGGUCUCAUGG 17 605 SCNN1A-83 - UACCAGGUCUCAUGGAG 17 606 SCNN1A-84 - CAUGGAGGGGAACAAGC 17 607 SCNN1A-87 - CCUCCACAGUCCACUCC 17 608 SCNN1A-88 - CUCCACAGUCCACUCCA 17 609 SCNN1A-89 - CACUCCAGGGCUCAUGA 17 610 SCNN1A-90 - ACUCCAGGGCUCAUGAA 17 611 SCNN1A-91 - CUCCAGGGCUCAUGAAG 17 612 SCNN1A-94 - AACAAGCGUGAGGAGCA 17 613 SCNN1A-95 - ACAAGCGUGAGGAGCAG 17 614 SCNN1A-97 - CGUGAGGAGCAGGGGCU 17 615 SCNN1A-101 - CCAGCAGCCCACGGCGG 17 616 SCNN1A-104 - AACAACACCACCAUCCA 17 617 SCNN1A-105 - CCACGGCGCCAUCCGCC 17 618 SCNN1A-108 - CAUGAAGACGGCCUUCU 17 619 SCNN1A-109 - CCUUCUGGGCAGUGCUG 17 620 SCNN1A-110 - CUGUGGCUCUGCACCUU 17 621 SCNN1A-111 - CCUUUGGCAUGAUGUAC 17 622 SCNN1A-112 - AUGAUGUACUGGCAAUU 17 623 SCNN1A-113 - CAAUUCGGCCUGCUUUU 17 624 SCNN1A-114 - CAACAUCAACCUCAACU 17 625 SCNN1A-118 + UGCAGAUGGUCACUGCG 17 626 SCNN1A-119 + CGAGCUUGUCCGAGUUG 17 627 SCNN1A-120 + AGUUGAGGUUGAUGUUG 17 628 SCNN1A-122 + UUGAUGUUGAGGCUGAC 17 629 SCNN1A-123 + UGAUGUUGAGGCUGACG 17 630 SCNN1A-124 + AGUACUCUCCGAAAAGC 17 631 SCNN1A-125 + CCAGUACAUCAUGCCAA 17 632 SCNN1A-126 + CCACAGCACUGCCCAGA 17 633 SCNN1A-127 + AGAAGGCCGUCUUCAUG 17 634 SCNN1A-128 + UCUUCAUGCGGUUGUGC 17 635 SCNN1A-129 + CUUCAUGCGGUUGUGCU 17 636 SCNN1A-130 + UGUGCUGGGAGCACACC 17 637 SCNN1A-133 + CCAGGCGGAUGGCGCCG 17 638 SCNN1A-136 + AGAACUCGAAGAGCUCU 17 639 SCNN1A-137 + CUCGAAGAGCUCUCGGU 17 640 SCNN1A-138 + AGAGCUCUCGGUAGGAG 17 641 SCNN1A-140 + AGCGGUGGAACUCGAUC 17 642 SCNN1A-144 + CCUCCGCCGUGGGCUGC 17 643 SCNN1A-145 + CUCCGCCGUGGGCUGCU 17 644 SCNN1A-146 + UCCGCCGUGGGCUGCUG 17 645 SCNN1A-148 + CUGGGGCGCCGCAGGUU 17 646 SCNN1A-149 + UGGGGCGCCGCAGGUUC 17 647 SCNN1A-151 + UUCCCCUUCAUGAGCCC 17 648 SCNN1A-152 + CUUCAUGAGCCCUGGAG 17 649 SCNN1A-153 + AGCCCUGGAGUGGACUG 17 650 SCNN1A-154 + CCUGGAGUGGACUGUGG 17 651 SCNN1A-155 + CUGGAGUGGACUGUGGA 17 652 SCNN1A-156 + UUCCCCUCCAUGAGACC 17 653 SCNN1A-158 + UCCAUGAGACCUGGUAU 17 654

Table 3D provides exemplary targeting domains for knocking out the SCNN1A gene selected based on reasonable proximity to the start codon. It is contemplated herein that the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that gives double stranded cleavage. Any of the targeting domains in the table can be used with a S. aureus Cas9 single-stranded break nucleases (nickases). In an embodiment, dual targeting is used to create two nicks on opposite DNA strands by using S. aureus Cas9 nickases with two targeting domains that are complementary to opposite DNA strands, e.g., a gRNA comprising any minus strand targeting domain may be paired any gRNA comprising a plus strand targeting domain provided that the two gRNAs are oriented on the DNA such that PAMs face outward and the distance between the 5′ ends of the gRNAs is 0-50 bp.

TABLE 3D Target DNA  Site Seq  gRNA Name Strand Targeting Domain Length ID SCNN1A-159 - UGCAGCCCAUACCAGGUCUC 20 803 SCNN1A-1 - GCAGCCCAUACCAGGUCUCA 20 503 SCNN1A-161 - AGCCCAUACCAGGUCUCAUG 20 804 SCNN1A-2 - GCCCAUACCAGGUCUCAUGG 20 497 SCNN1A-3 - CCCAUACCAGGUCUCAUGGA 20 556 SCNN1A-4 - CCAUACCAGGUCUCAUGGAG 20 498 SCNN1A-165 - GUCUCAUGGAGGGGAACAAG 20 805 SCNN1A-5 - UCUCAUGGAGGGGAACAAGC 20 557 SCNN1A-167 - UCAUGGAGGGGAACAAGCUG 20 806 SCNN1A-6 - CAUGGAGGGGAACAAGCUGG 20 558 SCNN1A-169 - AGGGGAACAAGCUGGAGGAG 20 807 SCNN1A-170 - UAGCCCUCCACAGUCCACUC 20 808 SCNN1A-171 - CACAGUCCACUCCAGGGCUC 20 809 SCNN1A-172 - AGUCCACUCCAGGGCUCAUG 20 810 SCNN1A-10 - GUCCACUCCAGGGCUCAUGA 20 505 SCNN1A-11 - UCCACUCCAGGGCUCAUGAA 20 560 SCNN1A-12 - CCACUCCAGGGCUCAUGAAG 20 561 SCNN1A-176 - GCUCAUGAAGGGGAACAAGC 20 811 SCNN1A-177 - UCAUGAAGGGGAACAAGCGU 20 812 SCNN1A-13 - CAUGAAGGGGAACAAGCGUG 20 562 SCNN1A-179 - AGGGGAACAAGCGUGAGGAG 20 813 SCNN1A-14 - GGGGAACAAGCGUGAGGAGC 20 506 SCNN1A-181 - ACAAGCGUGAGGAGCAGGGG 20 814 SCNN1A-182 - UGAGGAGCAGGGGCUGGGCC 20 815 SCNN1A-183 - CGGCGCCCCAGCAGCCCACG 20 816 SCNN1A-21 - GGCGCCCCAGCAGCCCACGG 20 510 SCNN1A-185 - CGCCCCAGCAGCCCACGGCG 20 817 SCNN1A-22 - GCCCCAGCAGCCCACGGCGG 20 511 SCNN1A-187 - CCCAGCAGCCCACGGCGGAG 20 818 SCNN1A-23 - CCAGCAGCCCACGGCGGAGG 20 566 SCNN1A-189 - GGCGGAGGAGGAGGCCCUGA 20 819 SCNN1A-190 - AUCGAGUUCCACCGCUCCUA 20 820 SCNN1A-191 - CGAGUUCCACCGCUCCUACC 20 821 SCNN1A-192 - CCGCUCCUACCGAGAGCUCU 20 822 SCNN1A-193 - UGUGCUCCCAGCACAACCGC 20 823 SCNN1A-194 - AACCGCAUGAAGACGGCCUU 20 824 SCNN1A-195 - CUGGCAAUUCGGCCUGCUUU 20 825 SCNN1A-34 - UGGCAAUUCGGCCUGCUUUU 20 573 SCNN1A-197 - GCAAUUCGGCCUGCUUUUCG 20 826 SCNN1A-198 - GCCUCAACAUCAACCUCAAC 20 827 SCNN1A-199 + UCCCCUCCAUGAGACCUGGU 20 828 SCNN1A-200 + CCUCCAGCUUGUUCCCCUCC 20 829 SCNN1A-201 + UGGAGUGGACUGUGGAGGGC 20 830 SCNN1A-202 + GAGCCCUGGAGUGGACUGUG 20 831 SCNN1A-74 + AUGAGCCCUGGAGUGGACUG 20 601 SCNN1A-204 + CAUGAGCCCUGGAGUGGACU 20 832 SCNN1A-205 + UCCCCUUCAUGAGCCCUGGA 20 833 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20 599 SCNN1A-207 + CUUGUUCCCCUUCAUGAGCC 20 834 SCNN1A-208 + CCUCACGCUUGUUCCCCUUC 20 835 SCNN1A-69 + CUGCUGGGGCGCCGCAGGUU 20 597 SCNN1A-210 + GCUGCUGGGGCGCCGCAGGU 20 836 SCNN1A-65 + CCUCCUCCGCCGUGGGCUGC 20 594 SCNN1A-212 + UCCUCCUCCGCCGUGGGCUG 20 837 SCNN1A-213 + UCAGGGCCUCCUCCUCCGCC 20 838 SCNN1A-214 + UAGGAGCGGUGGAACUCGAU 20 839 SCNN1A-60 + AGAGCUCUCGGUAGGAGCGG 20 590 SCNN1A-216 + AAGAGCUCUCGGUAGGAGCG 20 840 SCNN1A-58 + GAACUCGAAGAGCUCUCGGU 20 524 SCNN1A-218 + AGAACUCGAAGAGCUCUCGG 20 841 SCNN1A-219 + UGUUGUUGCAGAAGAACUCG 20 842 SCNN1A-220 + UGGUGUUGUUGCAGAAGAAC 20 843 SCNN1A-221 + GGAUGGUGGUGUUGUUGCAG 20 844 SCNN1A-222 + CGUGGAUGGUGGUGUUGUUG 20 845 SCNN1A-223 + CACACCAGGCGGAUGGCGCC 20 846 SCNN1A-224 + UUGUGCUGGGAGCACACCAG 20 847 SCNN1A-50 + CGUCUUCAUGCGGUUGUGCU 20 583 SCNN1A-49 + CCGUCUUCAUGCGGUUGUGC 20 582 SCNN1A-227 + GCCGUCUUCAUGCGGUUGUG 20 848 SCNN1A-228 + UGCAGAGCCACAGCACUGCC 20 849 SCNN1A-229 + AGUACAUCAUGCCAAAGGUG 20 850 SCNN1A-230 + AGUACUCUCCGAAAAGCAGG 20 851 SCNN1A-231 + CGGGGUAGCUGAAGUACUCU 20 852 SCNN1A-232 + UGUUGAGGCUGACGGGGUAG 20 853 SCNN1A-42 + GAGGUUGAUGUUGAGGCUGA 20 519 SCNN1A-234 + UGAGGUUGAUGUUGAGGCUG 20 854 SCNN1A-235 + UGUCCGAGUUGAGGUUGAUG 20 855 SCNN1A-236 + GGAAGACGAGCUUGUCCGAG 20 856 SCNN1A-237 + UGCGGGGAAGACGAGCUUGU 20 857 SCNN1A-238 + AGAUGGUCACUGCGGGGAAG 20 858 SCNN1A-39 + GGGUGCAGAUGGUCACUGCG 20 518 SCNN1A-38 + AGGGUGCAGAUGGUCACUGC 20 575 SCNN1A-37 + GAGGGUGCAGAUGGUCACUG 20 517 SCNN1A-242 + UGAGGGUGCAGAUGGUCACU 20 859 SCNN1A-243 - AGCCCAUACCAGGUCUC 17 860 SCNN1A-80 - GCCCAUACCAGGUCUCA 17 529 SCNN1A-245 - CCAUACCAGGUCUCAUG 17 861 SCNN1A-81 - CAUACCAGGUCUCAUGG 17 605 SCNN1A-82 - AUACCAGGUCUCAUGGA 17 501 SCNN1A-83 - UACCAGGUCUCAUGGAG 17 606 SCNN1A-249 - UCAUGGAGGGGAACAAG 17 862 SCNN1A-84 - CAUGGAGGGGAACAAGC 17 607 SCNN1A-251 - UGGAGGGGAACAAGCUG 17 863 SCNN1A-85 - GGAGGGGAACAAGCUGG 17 530 SCNN1A-253 - GGAACAAGCUGGAGGAG 17 864 SCNN1A-254 - CCCUCCACAGUCCACUC 17 865 SCNN1A-255 - AGUCCACUCCAGGGCUC 17 866 SCNN1A-256 - CCACUCCAGGGCUCAUG 17 867 SCNN1A-89 - CACUCCAGGGCUCAUGA 17 610 SCNN1A-90 - ACUCCAGGGCUCAUGAA 17 611 SCNN1A-91 - CUCCAGGGCUCAUGAAG 17 612 SCNN1A-260 - CAUGAAGGGGAACAAGC 17 868 SCNN1A-261 - UGAAGGGGAACAAGCGU 17 869 SCNN1A-92 - GAAGGGGAACAAGCGUG 17 532 SCNN1A-263 - GGAACAAGCGUGAGGAG 17 870 SCNN1A-93 - GAACAAGCGUGAGGAGC 17 533 SCNN1A-265 - AGCGUGAGGAGCAGGGG 17 871 SCNN1A-266 - GGAGCAGGGGCUGGGCC 17 872 SCNN1A-267 - CGCCCCAGCAGCCCACG 17 873 SCNN1A-100 - GCCCCAGCAGCCCACGG 17 537 SCNN1A-269 - CCCAGCAGCCCACGGCG 17 874 SCNN1A-101 - CCAGCAGCCCACGGCGG 17 616 SCNN1A-271 - AGCAGCCCACGGCGGAG 17 875 SCNN1A-102 - GCAGCCCACGGCGGAGG 17 538 SCNN1A-273 - GGAGGAGGAGGCCCUGA 17 876 SCNN1A-274 - GAGUUCCACCGCUCCUA 17 877 SCNN1A-275 - GUUCCACCGCUCCUACC 17 878 SCNN1A-276 - CUCCUACCGAGAGCUCU 17 879 SCNN1A-277 - GCUCCCAGCACAACCGC 17 880 SCNN1A-278 - CGCAUGAAGACGGCCUU 17 881 SCNN1A-279 - GCAAUUCGGCCUGCUUU 17 882 SCNN1A-113 - CAAUUCGGCCUGCUUUU 17 624 SCNN1A-281 - AUUCGGCCUGCUUUUCG 17 883 SCNN1A-282 - UCAACAUCAACCUCAAC 17 884 SCNN1A-283 + CCUCCAUGAGACCUGGU 17 885 SCNN1A-284 + CCAGCUUGUUCCCCUCC 17 886 SCNN1A-285 + AGUGGACUGUGGAGGGC 17 887 SCNN1A-286 + CCCUGGAGUGGACUGUG 17 888 SCNN1A-153 + AGCCCUGGAGUGGACUG 17 650 SCNN1A-288 + GAGCCCUGGAGUGGACU 17 889 SCNN1A-289 + CCUUCAUGAGCCCUGGA 17 890 SCNN1A-151 + UUCCCCUUCAUGAGCCC 17 648 SCNN1A-291 + GUUCCCCUUCAUGAGCC 17 891 SCNN1A-292 + CACGCUUGUUCCCCUUC 17 892 SCNN1A-148 + CUGGGGCGCCGCAGGUU 17 646 SCNN1A-294 + GCUGGGGCGCCGCAGGU 17 893 SCNN1A-144 + CCUCCGCCGUGGGCUGC 17 643 SCNN1A-296 + UCCUCCGCCGUGGGCUG 17 894 SCNN1A-297 + GGGCCUCCUCCUCCGCC 17 895 SCNN1A-298 + GAGCGGUGGAACUCGAU 17 896 SCNN1A-139 + GCUCUCGGUAGGAGCGG 17 550 SCNN1A-300 + AGCUCUCGGUAGGAGCG 17 897 SCNN1A-137 + CUCGAAGAGCUCUCGGU 17 640 SCNN1A-302 + ACUCGAAGAGCUCUCGG 17 898 SCNN1A-303 + UGUUGCAGAAGAACUCG 17 899 SCNN1A-304 + UGUUGUUGCAGAAGAAC 17 900 SCNN1A-305 + UGGUGGUGUUGUUGCAG 17 901 SCNN1A-306 + GGAUGGUGGUGUUGUUG 17 902 SCNN1A-307 + ACCAGGCGGAUGGCGCC 17 903 SCNN1A-308 + UGCUGGGAGCACACCAG 17 904 SCNN1A-129 + CUUCAUGCGGUUGUGCU 17 636 SCNN1A-128 + UCUUCAUGCGGUUGUGC 17 635 SCNN1A-311 + GUCUUCAUGCGGUUGUG 17 905 SCNN1A-312 + AGAGCCACAGCACUGCC 17 906 SCNN1A-313 + ACAUCAUGCCAAAGGUG 17 907 SCNN1A-314 + ACUCUCCGAAAAGCAGG 17 908 SCNN1A-315 + GGUAGCUGAAGUACUCU 17 909 SCNN1A-316 + UGAGGCUGACGGGGUAG 17 910 SCNN1A-121 + GUUGAUGUUGAGGCUGA 17 545 SCNN1A-318 + GGUUGAUGUUGAGGCUG 17 911 SCNN1A-319 + CCGAGUUGAGGUUGAUG 17 912 SCNN1A-320 + AGACGAGCUUGUCCGAG 17 913 SCNN1A-321 + GGGGAAGACGAGCUUGU 17 914 SCNN1A-322 + UGGUCACUGCGGGGAAG 17 915 SCNN1A-118 + UGCAGAUGGUCACUGCG 17 626 SCNN1A-117 + GUGCAGAUGGUCACUGC 17 544 SCNN1A-116 + GGUGCAGAUGGUCACUG 17 543 SCNN1A-326 + GGGUGCAGAUGGUCACU 17 916

Table 4A provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 4A 1st Tier Target  DNA  Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-2789-1 + GAAGCAGCCACCUGGAA 17 937 CFTR-2789-2 + GGAAUAUUCACUUUCCA 17 938 CFTR-2789-3 - GAAUUUAGAUGUGGGCA 17 939 CFTR-2789-4 - GUGUCUUGUUCCAUUCC 17 940 CFTR-2789-5 - GUGGGCAUGGGAGGAAU 17 941 CFTR-2789-6 - GUUGUGCUGUGGCUCCU 17 942 CFTR-2789-7 - GAUGUGAAUUUAGAUGU 17 943 CFTR-2789-8 - GACCCAGGAACACAAAGCAA 20 944 CFTR-2789-9 + GUGUCACCUCACCCAACUAA 20 945 CFTR-2789-10 - GUGUCUUGUUCCAUUCCAGG 20 946 CFTR-2789-11 - GAUGUGGGCAUGGGAGGAAU 20 947 CFTR-2789-12 - GUGAAUUUAGAUGUGGGCAU 20 948

Table 4B provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 4B  2nd Tier Target  DNA  Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-2789-13 - UUGGUACACACAUCAAA 17 949 CFTR-2789-14 + UCACCUCACCCAACUAA 17 950 CFTR-2789-15 + AUCUACACAAUAGGACA 17 951 CFTR-2789-16 + UGUGUGUACCAAUAUCA 17 952 CFTR-2789-17 - AUGGUAGUGGAAAGAUA 17 953 CFTR-2789-18 - AUUUCUCCCAAGCAUUA 17 954 CFTR-2789-19 + CCAAAGAAGCAGCCACC 17 955 CFTR-2789-20 + CCUUUGCUUUGUGUUCC 17 956 CFTR-2789-21 - CCCAAGCAUUAUGGUAG 17 957 CFTR-2789-22 - UUAGAUGUGGGCAUGGG 17 958 CFTR-2789-23 - CUUCUUUGGUUGUGCUG 17 959 CFTR-2789-24 - UGACCAUUAGUUGGGUG 17 960 CFTR-2789-25 - AAUUUAGAUGUGGGCAU 17 961 CFTR-2789-26 - UGUGUGUACCUUGAUAU 17 962 CFTR-2789-27 + UCCACUACCAUAAUGCU 17 963 CFTR-2789-28 - AAAUGAUGACCAUUAGU 17 964 CFTR-2789-29 + CCACUACCAUAAUGCUU 17 965 CFTR-2789-30 - CCAGGUGGCUGCUUCUU 17 966 CFTR-2789-31 - AUAUUGGUACACACAUCAAA 20 967 CFTR-2789-32 + AAAGAAGCAGCCACCUGGAA 20 968 CFTR-2789-33 + ACAAUCUACACAAUAGGACA 20 969 CFTR-2789-34 - UGUGAAUUUAGAUGUGGGCA 20 970 CFTR-2789-35 + UGAUGUGUGUACCAAUAUCA 20 971 CFTR-2789-36 - AUUAUGGUAGUGGAAAGAUA 20 972 CFTR-2789-37 - UUCAUUUCUCCCAAGCAUUA 20 973 CFTR-2789-38 + CAACCAAAGAAGCAGCCACC 20 974 CFTR-2789-39 - ACUGUGUCUUGUUCCAUUCC 20 975 CFTR-2789-40 + CUUCCUUUGCUUUGUGUUCC 20 976 CFTR-2789-41 + UACAAUACAUACAAACAUAG 20 977 CFTR-2789-42 - UCUCCCAAGCAUUAUGGUAG 20 978 CFTR-2789-43 - AAUUUAGAUGUGGGCAUGGG 20 979 CFTR-2789-44 - CUGCUUCUUUGGUUGUGCUG 20 980 CFTR-2789-45 - UGAUGACCAUUAGUUGGGUG 20 981 CFTR-2789-46 - AAUUGUGUGUACCUUGAUAU 20 982 CFTR-2789-47 - UUGGUUGUGCUGUGGCUCCU 20 983 CFTR-2789-48 + CUUUCCACUACCAUAAUGCU 20 984 CFTR-2789-49 - UUUAAAUGAUGACCAUUAGU 20 985 CFTR-2789-50 - UGUGAUGUGAAUUUAGAUGU 20 986 CFTR-2789-51 + UUUCCACUACCAUAAUGCUU 20 987 CFTR-2789-52 - AUUCCAGGUGGCUGCUUCUU 20 988 CFTR-2789-53 - UUAAAUGAUGACCAUUAGUU 20 989

Table 4C provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 4C  3rd Tier Target  DNA  Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-2789-54 + GGAGGAGCUAGGACUAC 17 990 CFTR-2789-55 + GGAGAAAUGAAACAAAG 17 991 CFTR-2789-56 - GUGUGAUGUGAAUUUAGAUG 20 992

Table 4D provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 4D  4th Tier Target  DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-2789-57 - CCAGGAACACAAAGCAA 17  993 CFTR-2789-58 - AGUCCUAGCUCCUCCAC 17   994 CFTR-2789-59 + AAUACAUACAAACAUAG 17   995 CFTR-2789-60 - UCUUGUUCCAUUCCAGG 17  996 CFTR-2789-61 - UGAUGUGAAUUUAGAUG 17   997 CFTR-2789-62 + AACACAAUCUACACAAU 17  998 CFTR-2789-63 + CUUUGCUUUGUGUUCCU 17  999 CFTR-2789-64 - AAUGAUGACCAUUAGUU 17 1000 CFTR-2789-65 + CAUGGAAUAUUCACUUUCCA 20 1001 CFTR-2789-66 - UGUAGUCCUAGCUCCUCCAC 20 1002 CFTR-2789-67 + UGUGGAGGAGCUAGGACUAC 20 1003 CFTR-2789-68 + UUGGGAGAAAUGAAACAAAG 20 1004 CFTR-2789-69 + UAAAACACAAUCUACACAAU 20 1005 CFTR-2789-70 + UUCCUUUGCUUUGUGUUCCU 20 1006

Table 5A provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 5A  1st Tier DNA  Target Site gRNA Name  Strand Targeting Domain Length Seq ID CFTR-2789-71 + GAUUACAAUACAUACAAACAUA 22 1007 CFTR-2789-72 + GGAUUACAAUACAUACAAACAUA 23 1008 CFTR-2789-73 - GCUGUGGCUCCUUGGAAA 18 1009 CFTR-2789-74 - GUGCUGUGGCUCCUUGGAAA 20 1010 CFTR-2789-75 - GUUGUGCUGUGGCUCCUUGGAAA 23 1011 CFTR-2789-76 - GGUUGUGCUGUGGCUCCUUGGAAA 24 1012 CFTR-2789-77 - GUUUAAAUGAUGACCAUUAG 20 1013 CFTR-2789-78 - GUACACACAUCAAAUGGUGUGAU 23 1014 CFTR-2789-79 - GGUACACACAUCAAAUGGUGUGAU 24 1015

Table 5B provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 5B 2nd Tier Target DNA  Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-2789-80 + UGGGAGAAAUGAAACAAA 18 1016 CFTR-2789-81 + UUGGGAGAAAUGAAACAAA 19 1017 CFTR-2789-82 + CUUGGGAGAAAUGAAACAAA 20 1018 CFTR-2789-83 + ACAAUACAUACAAACAUA 18 1019 CFTR-2789-84 + UACAAUACAUACAAACAUA 19 1020 CFTR-2789-85 + UUACAAUACAUACAAACAUA 20 1021 CFTR-2789-86 + AUUACAAUACAUACAAACAUA 21 1022 CFTR-2789-87 + UGGAUUACAAUACAUACAAACAUA 24 1023 CFTR-2789-88 + ACCAAAGAAGCAGCCACC 18 1024 CFTR-2789-89 + AACCAAAGAAGCAGCCACC 19 1025 CFTR-2789-38 + CAACCAAAGAAGCAGCCACC 20  974 CFTR-2789-90 + UUCCUUUGCUUUGUGUUC 18 1026 CFTR-2789-91 + CUUCCUUUGCUUUGUGUUC 19 1027 CFTR-2789-92 + UCUUCCUUUGCUUUGUGUUC 20 1028 CFTR-2789-93 - UGCUGUGGCUCCUUGGAAA 19 1029 CFTR-2789-94 - UGUGCUGUGGCUCCUUGGAAA 21 1030 CFTR-2789-95 - UUGUGCUGUGGCUCCUUGGAAA 22 1031 CFTR-2789-96 - UUAAAUGAUGACCAUUAG 18 1032 CFTR-2789-97 - UUUAAAUGAUGACCAUUAG 19 1033 CFTR-2789-98 - UGUUUAAAUGAUGACCAUUAG 21 1034 CFTR-2789-99 - UUGUUUAAAUGAUGACCAUUAG 22 1035 CFTR-2789-100 - UUUGUUUAAAUGAUGACCAUUAG 23 1036 CFTR-2789-101 - UUUUGUUUAAAUGAUGACCAUUAG 24 1037 CFTR-2789-102 - UUUAGAUGUGGGCAUGGG 18 1038 CFTR-2789-103 - AUUUAGAUGUGGGCAUGGG 19 1039 CFTR-2789-43 - AAUUUAGAUGUGGGCAUGGG 20  979 CFTR-2789-104 - CACAUCAAAUGGUGUGAU 18 1040 CFTR-2789-105 - ACACAUCAAAUGGUGUGAU 19 1041 CFTR-2789-106 - CACACAUCAAAUGGUGUGAU 20 1042 CFTR-2789-107 - ACACACAUCAAAUGGUGUGAU 21 1043 CFTR-2789-108 - UACACACAUCAAAUGGUGUGAU 22 1044

Table 5C provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), starts with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 5C  3rd Tier DNA  Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-2789-109 + GCUUGGGAGAAAUGAAACAAA 21 1045 CFTR-2789-110 + GUGGAGGAGCUAGGACUAC 19 1046 CFTR-2789-111 + GCACAACCAAAGAAGCAGCCACC 23 1047  CFTR-2789-112 - GAAUUUAGAUGUGGGCAUGGG 21 1048 CFTR-2789-113 - GUGAAUUUAGAUGUGGGCAUGGG 23 1049

Table 5D provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 5D  4th Tier Target  DNA  Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-2789-114 + UGCUUGGGAGAAAUGAAACAAA 22 1050 CFTR-2789-115 + AUGCUUGGGAGAAAUGAAACAAA 23 1051 CFTR-2789-116 + AAUGCUUGGGAGAAAUGAAACAAA 24 1052 CFTR-2789-117 + AAUCUACACAAUAGGACA 18 1053 CFTR-2789-118 + CAAUCUACACAAUAGGACA 19 1054 CFTR-2789-33 + ACAAUCUACACAAUAGGACA 20  969 CFTR-2789-119 + CACAAUCUACACAAUAGGACA 21 1055 CFTR-2789-120 + ACACAAUCUACACAAUAGGACA 22 1056 CFTR-2789-121 + AACACAAUCUACACAAUAGGACA 23 1057 CFTR-2789-122 + AAACACAAUCUACACAAUAGGACA 24 1058 CFTR-2789-123 + UGGAGGAGCUAGGACUAC 18 1059 CFTR-2789-67 + UGUGGAGGAGCUAGGACUAC 20 1003 CFTR-2789-124 + ACAACCAAAGAAGCAGCCACC 21 1060 CFTR-2789-125 + CACAACCAAAGAAGCAGCCACC 22 1061 CFTR-2789-126 + AGCACAACCAAAGAAGCAGCCACC 24 1062 CFTR-2789-127 + AUCUUCCUUUGCUUUGUGUUC 21 1063 CFTR-2789-128 + CAUCUUCCUUUGCUUUGUGUUC 22 1064 CFTR-2789-129 + UCAUCUUCCUUUGCUUUGUGUUC 23 1065 CFTR-2789-130 + UUCAUCUUCCUUUGCUUUGUGUUC 24 1066 CFTR-2789-131 - UGAAUUUAGAUGUGGGCAUGGG 22 1067 CFTR-2789-132 - UGUGAAUUUAGAUGUGGGCAUGGG 24 1068

Table 5E provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 5E  5th Tier DNA  Target Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-2789-133 + AAAACACAAUCUACACAA 18 1069  CFTR-2789-134 + UAAAACACAAUCUACACAA 19 1070  CFTR-2789-135 + AUAAAACACAAUCUACACAA 20 1071 CFTR-2789-136 + AAUAAAACACAAUCUACACAA 21 1072 CFTR-2789-137 + AAAUAAAACACAAUCUACACAA 22 1073 CFTR-2789-138 + GAAAUAAAACACAAUCUACACAA 23 1074 CFTR-2789-139 + AGAAAUAAAACACAAUCUACACAA 24 1075 CFTR-2789-140 + AUUACAAUAUUUAAUCAA 18 1076 CFTR-2789-141 + GAUUACAAUAUUUAAUCAA 19 1077 CFTR-2789-142 + GGAUUACAAUAUUUAAUCAA 20 1078 CFTR-2789-143 + UGGAUUACAAUAUUUAAUCAA 21 1079 CFTR-2789-144 + GUGGAUUACAAUAUUUAAUCAA 22 1080 CFTR-2789-145 + AGUGGAUUACAAUAUUUAAUCAA 23 1081 CFTR-2789-146 + UAGUGGAUUACAAUAUUUAAUCAA 24 1082 CFTR-2789-147 + CCAUAAUGCUUGGGAGAA 18 1083 CFTR-2789-148 + ACCAUAAUGCUUGGGAGAA 19 1084 CFTR-2789-149 + UACCAUAAUGCUUGGGAGAA 20 1085 CFTR-2789-150 + CUACCAUAAUGCUUGGGAGAA 21 1086 CFTR-2789-151 + ACUACCAUAAUGCUUGGGAGAA 22 1087 CFTR-2789-152 + CACUACCAUAAUGCUUGGGAGAA 23 1088 CFTR-2789-153 + CCACUACCAUAAUGCUUGGGAGAA 24 1089 CFTR-2789-154 + AGAAGCAGCCACCUGGAA 18 1090 CFTR-2789-155 + AAGAAGCAGCCACCUGGAA 19 1091 CFTR-2789-32 + AAAGAAGCAGCCACCUGGAA 20  968 CFTR-2789-156 + CAAAGAAGCAGCCACCUGGAA 21 1092 CFTR-2789-157 + CCAAAGAAGCAGCCACCUGGAA 22 1093  CFTR-2789-158 + ACCAAAGAAGCAGCCACCUGGAA 23 1094 CFTR-2789-159 + AACCAAAGAAGCAGCCACCUGGAA 24 1095 CFTR-2789-160 + GGAGCCACAGCACAACCA 18 1096 CFTR-2789-161 + AGGAGCCACAGCACAACCA 19 1097 CFTR-2789-162 + AAGGAGCCACAGCACAACCA 20 1098 CFTR-2789-163 + CAAGGAGCCACAGCACAACCA 21 1099 CFTR-2789-164 + CCAAGGAGCCACAGCACAACCA 22 1100 CFTR-2789-165 + UCCAAGGAGCCACAGCACAACCA 23 1101 CFTR-2789-166 + UUCCAAGGAGCCACAGCACAACCA 24 1102 CFTR-2789-167 + UGGAAUAUUCACUUUCCA 18 1103 CFTR-2789-168 + AUGGAAUAUUCACUUUCCA 19 1104 CFTR-2789-65 + CAUGGAAUAUUCACUUUCCA 20 1001 CFTR-2789-169 + ACAUGGAAUAUUCACUUUCCA 21 1105 CFTR-2789-170 + GACAUGGAAUAUUCACUUUCCA 22 1106 CFTR-2789-171 + GGACAUGGAAUAUUCACUUUCCA 23 1107 CFTR-2789-172 + AGGACAUGGAAUAUUCACUUUCCA 24 1108 CFTR-2789-173 + AAGAAGCAGCCACCUGGA 18 1109 CFTR-2789-174 + AAAGAAGCAGCCACCUGGA 19 1110 CFTR-2789-175 + CAAAGAAGCAGCCACCUGGA 20 1111 CFTR-2789-176 + CCAAAGAAGCAGCCACCUGGA 21 1112 CFTR-2789-177 + ACCAAAGAAGCAGCCACCUGGA 22 1113 CFTR-2789-178 + AACCAAAGAAGCAGCCACCUGGA 23 1114 CFTR-2789-179 + CAACCAAAGAAGCAGCCACCUGGA 24 1115 CFTR-2789-180 + GUGGAGGAGCUAGGACUA 18 1116 CFTR-2789-181 + UGUGGAGGAGCUAGGACUA 19 1117 CFTR-2789-182 + CUGUGGAGGAGCUAGGACUA 20 1118 CFTR-2789-183 + AACCAAAGAAGCAGCCAC 18 1119 CFTR-2789-184 + CAACCAAAGAAGCAGCCAC 19 1120 CFTR-2789-185 + ACAACCAAAGAAGCAGCCAC 20 1121 CFTR-2789-186 + CACAACCAAAGAAGCAGCCAC 21 1122 CFTR-2789-187 + GCACAACCAAAGAAGCAGCCAC 22 1123 CFTR-2789-188 + AGCACAACCAAAGAAGCAGCCAC 23 1124 CFTR-2789-189 + CAGCACAACCAAAGAAGCAGCCAC 24 1125 CFTR-2789-190 + CAAUCUACACAAUAGGAC 18 1126 CFTR-2789-191 + ACAAUCUACACAAUAGGAC 19 1127 CFTR-2789-192 + CACAAUCUACACAAUAGGAC 20 1128 CFTR-2789-193 + ACACAAUCUACACAAUAGGAC 21 1129 CFTR-2789-194 + AACACAAUCUACACAAUAGGAC 22 1130  CFTR-2789-195 + AAACACAAUCUACACAAUAGGAC 23 1131 CFTR-2789-196 + AAAACACAAUCUACACAAUAGGAC 24 1132 CFTR-2789-197 + AUGGAAUAUUCACUUUCC 18 1133 CFTR-2789-198 + CAUGGAAUAUUCACUUUCC 19 1134 CFTR-2789-199 + ACAUGGAAUAUUCACUUUCC 20 1135 CFTR-2789-200 + GACAUGGAAUAUUCACUUUCC 21 1136 CFTR-2789-201 + GGACAUGGAAUAUUCACUUUCC 22 1137 CFTR-2789-202 + AGGACAUGGAAUAUUCACUUUCC 23 1138 CFTR-2789-203 + UAGGACAUGGAAUAUUCACUUUCC 24 1139 CFTR-2789-204 + UUUCCACUACCAUAAUGC 18 1140  CFTR-2789-205 + CUUUCCACUACCAUAAUGC 19 1141 CFTR-2789-206 + UCUUUCCACUACCAUAAUGC 20 1142 CFTR-2789-207 + AUCUUUCCACUACCAUAAUGC 21 1143 CFTR-2789-208 + UAUCUUUCCACUACCAUAAUGC 22 1144  CFTR-2789-209 + UUAUCUUUCCACUACCAUAAUGC 23 1145 CFTR-2789-210 + CUUAUCUUUCCACUACCAUAAUGC 24 1146 CFTR-2789-211 + CACUACCAUAAUGCUUGG 18 1147 CFTR-2789-212 + CCACUACCAUAAUGCUUGG 19 1148 CFTR-2789-213 + UCCACUACCAUAAUGCUUGG 20 1149 CFTR-2789-214 + UUCCACUACCAUAAUGCUUGG 21 1150 CFTR-2789-215 + UUUCCACUACCAUAAUGCUUGG 22 1151 CFTR-2789-216 + CUUUCCACUACCAUAAUGCUUGG 23 1152 CFTR-2789-217 + UCUUUCCACUACCAUAAUGCUUGG 24 1153 CFTR-2789-218 + UUCCACUACCAUAAUGCU 18 1154 CFTR-2789-219 + UUUCCACUACCAUAAUGCU 19 1155 CFTR-2789-48 + CUUUCCACUACCAUAAUGCU 20  984 CFTR-2789-220 + UCUUUCCACUACCAUAAUGCU 21 1156 CFTR-2789-221 + AUCUUUCCACUACCAUAAUGCU 22 1157  CFTR-2789-222 + UAUCUUUCCACUACCAUAAUGCU 23 1158 CFTR-2789-223 + UUAUCUUUCCACUACCAUAAUGCU 24 1159 CFTR-2789-224 + UCCACUACCAUAAUGCUU 18 1160 CFTR-2789-225 + UUCCACUACCAUAAUGCUU 19 1161 CFTR-2789-51 + UUUCCACUACCAUAAUGCUU 20  987 CFTR-2789-226 + CUUUCCACUACCAUAAUGCUU 21 1162 CFTR-2789-227 + UCUUUCCACUACCAUAAUGCUU 22 1163 CFTR-2789-228 + AUCUUUCCACUACCAUAAUGCUU 23 1164 CFTR-2789-229 + UAUCUUUCCACUACCAUAAUGCUU 24 1165 CFTR-2789-230 - CCCAGGAACACAAAGCAA 18 1166 CFTR-2789-231 - ACCCAGGAACACAAAGCAA 19 1167 CFTR-2789-8 - GACCCAGGAACACAAAGCAA 20  944 CFTR-2789-232 - GGACCCAGGAACACAAAGCAA 21 1168 CFTR-2789-233 - UGGACCCAGGAACACAAAGCAA 22 1169  CFTR-2789-234 - CUGGACCCAGGAACACAAAGCAA 23 1170 CFTR-2789-235 - GCUGGACCCAGGAACACAAAGCAA 24 1171 CFTR-2789-236 - ACCCAGGAACACAAAGCA 18 1172 CFTR-2789-237 - GACCCAGGAACACAAAGCA 19 1173 CFTR-2789-238 - GGACCCAGGAACACAAAGCA 20 1174 CFTR-2789-239 - UGGACCCAGGAACACAAAGCA 21 1175 CFTR-2789-240 - CUGGACCCAGGAACACAAAGCA 22 1176 CFTR-2789-241 - GCUGGACCCAGGAACACAAAGCA 23 1177 CFTR-2789-242 - UGCUGGACCCAGGAACACAAAGCA 24 1178 CFTR-2789-243 - UGAAUUUAGAUGUGGGCA 18 1179 CFTR-2789-244 - GUGAAUUUAGAUGUGGGCA 19 1180 CFTR-2789-34 - UGUGAAUUUAGAUGUGGGCA 20  970 CFTR-2789-245 - AUGUGAAUUUAGAUGUGGGCA 21 1181 CFTR-2789-246 - GAUGUGAAUUUAGAUGUGGGCA 22 1182 CFTR-2789-247 - UGAUGUGAAUUUAGAUGUGGGCA  23 1183 CFTR-2789-248 - GUGAUGUGAAUUUAGAUGUGGGCA 24 1184 CFTR-2789-249 - CUCCCAAGCAUUAUGGUA 18 1185 CFTR-2789-250 - UCUCCCAAGCAUUAUGGUA 19 1186 CFTR-2789-251 - UUCUCCCAAGCAUUAUGGUA 20 1187 CFTR-2789-252 - UUUCUCCCAAGCAUUAUGGUA 21 1188 CFTR-2789-253 - AUUUCUCCCAAGCAUUAUGGUA 22 1189 CFTR-2789-254 - CAUUUCUCCCAAGCAUUAUGGUA 23 1190 CFTR-2789-255 - UCAUUUCUCCCAAGCAUUAUGGUA 24 1191 CFTR-2789-256 - UGGUUGUGCUGUGGCUCC 18 1192 CFTR-2789-257 - UUGGUUGUGCUGUGGCUCC 19 1193 CFTR-2789-258 - UUUGGUUGUGCUGUGGCUCC 20 1194 CFTR-2789-259 - CUUUGGUUGUGCUGUGGCUCC 21 1195 CFTR-2789-260 - UCUUUGGUUGUGCUGUGGCUCC 22 1196 CFTR-2789-261 - UUCUUUGGUUGUGCUGUGGCUCC 23 1197 CFTR-2789-262 - CUUCUUUGGUUGUGCUGUGGCUCC 24 1198 CFTR-2789-263 - GUGAAUUUAGAUGUGGGC 18 1199 CFTR-2789-264 - UGUGAAUUUAGAUGUGGGC 19 1200 CFTR-2789-265 - AUGUGAAUUUAGAUGUGGGC 20 1201 CFTR-2789-266 - GAUGUGAAUUUAGAUGUGGGC 21 1202 CFTR-2789-267 - UGAUGUGAAUUUAGAUGUGGGC 22 1203 CFTR-2789-268 - GUGAUGUGAAUUUAGAUGUGGGC 23 1204 CFTR-2789-269 - UGUGAUGUGAAUUUAGAUGUGGGC 24 1205 CFTR-2789-270 - AACACAAAGCAAAGGAAG 18 1206 CFTR-2789-271 - GAACACAAAGCAAAGGAAG 19 1207 CFTR-2789-272 - GGAACACAAAGCAAAGGAAG 20 1208 CFTR-2789-273 - AGGAACACAAAGCAAAGGAAG 21 1209 CFTR-2789-274 - CAGGAACACAAAGCAAAGGAAG 22 1210 CFTR-2789-275 - CCAGGAACACAAAGCAAAGGAAG 23 1211 CFTR-2789-276 - CCCAGGAACACAAAGCAAAGGAAG 24 1212 CFTR-2789-277 - UGGGCAUGGGAGGAAUAG 18 1213 CFTR-2789-278 - GUGGGCAUGGGAGGAAUAG 19 1214 CFTR-2789-279 - UGUGGGCAUGGGAGGAAUAG 20 1215 CFTR-2789-280 - AUGUGGGCAUGGGAGGAAUAG 21 1216 CFTR-2789-281 - GAUGUGGGCAUGGGAGGAAUAG 22 1217 CFTR-2789-282 - AGAUGUGGGCAUGGGAGGAAUAG 23 1218 CFTR-2789-283 - UAGAUGUGGGCAUGGGAGGAAUAG 24 1219 CFTR-2789-284 - UCCCAAGCAUUAUGGUAG 18 1220 CFTR-2789-285 - CUCCCAAGCAUUAUGGUAG 19 1221 CFTR-2789-42 - UCUCCCAAGCAUUAUGGUAG 20  978 CFTR-2789-286 - UUCUCCCAAGCAUUAUGGUAG 21 1222 CFTR-2789-287 - UUUCUCCCAAGCAUUAUGGUAG 22 1223 CFTR-2789-288 - AUUUCUCCCAAGCAUUAUGGUAG 23 1224 CFTR-2789-289 - CAUUUCUCCCAAGCAUUAUGGUAG 24 1225 CFTR-2789-290 - AUUUAGAUGUGGGCAUGG 18 1226 CFTR-2789-291 - AAUUUAGAUGUGGGCAUGG 19 1227 CFTR-2789-292 - GAAUUUAGAUGUGGGCAUGG 20 1228 CFTR-2789-293 - UGAAUUUAGAUGUGGGCAUGG 21 1229 CFTR-2789-294 - GUGAAUUUAGAUGUGGGCAUGG 22 1230 CFTR-2789-295 - UGUGAAUUUAGAUGUGGGCAUGG 23 1231 CFTR-2789-296 - AUGUGAAUUUAGAUGUGGGCAGGU 24 1232 CFTR-2789-297 - AUGAUGACCAUUAGUUGG 18 1233 CFTR-2789-298 - AAUGAUGACCAUUAGUUGG 19 1234 CFTR-2789-299 - AAAUGAUGACCAUUAGUUGG 20 1235 CFTR-2789-300 - UAAAUGAUGACCAUUAGUUGG 21 1236 CFTR-2789-301 - UUAAAUGAUGACCAUUAGUUGG 22 1237 CFTR-2789-302 - UUUAAAUGAUGACCAUUAGUUGG 23 1238 CFTR-2789-303 - GUUUAAAUGAUGACCAUUAGUUGG 24 1239 CFTR-2789-304 - GAAUUUAGAUGUGGGCAU 18 1240 CFTR-2789-305 - UGAAUUUAGAUGUGGGCAU 19 1241 CFTR-2789-12 - GUGAAUUUAGAUGUGGGCAU 20  948 CFTR-2789-306 - UGUGAAUUUAGAUGUGGGCAU 21 1242 CFTR-2789-307 - AUGUGAAUUUAGAUGUGGGCAU 22 1243 CFTR-2789-308 - GAUGUGAAUUUAGAUGUGGGCAU 23 1244 CFTR-2789-309 - UGAUGUGAAUUUAGAUGUGGGCAU 24 1245 CFTR-2789-310 - UGUGAUGUGAAUUUAGAU 18 1246 CFTR-2789-311 - GUGUGAUGUGAAUUUAGAU 19 1247 CFTR-2789-312 - GGUGUGAUGUGAAUUUAGAU 20 1248 CFTR-2789-313 - UGGUGUGAUGUGAAUUUAGAU 21 1249 CFTR-2789-314 - AUGGUGUGAUGUGAAUUUAGAU 22 1250 CFTR-2789-315 - AAUGGUGUGAUGUGAAUUUAGAU 23 1251 CFTR-2789-316 - AAAUGGUGUGAUGUGAAUUUAGAU 24 1252 CFTR-2789-317 - GGUUGUGCUGUGGCUCCU 18 1253 CFTR-2789-318 - UGGUUGUGCUGUGGCUCCU 19 1254 CFTR-2789-47 - UUGGUUGUGCUGUGGCUCCU 20  983 CFTR-2789-319 - UUUGGUUGUGCUGUGGCUCCU 21 1255 CFTR-2789-320 - CUUUGGUUGUGCUGUGGCUCCU 22 1256 CFTR-2789-321 - UCUUUGGUUGUGCUGUGGCUCCU 23 1257 CFTR-2789-322 - UUCUUUGGUUGUGCUGUGGCUCCU 24 1258 CFTR-2789-323 - AGGAAUAGGUGAAGAUGU 18 1259 CFTR-2789-324 - GAGGAAUAGGUGAAGAUGU 19 1260 CFTR-2789-325 - GGAGGAAUAGGUGAAGAUGU 20 1261 CFTR-2789-326 - GGGAGGAAUAGGUGAAGAUGU 21 1262 CFTR-2789-327 - UGGGAGGAAUAGGUGAAGAUGU 22 1263 CFTR-2789-328 - AUGGGAGGAAUAGGUGAAGAUGU 23 1264 CFTR-2789-329 - CAUGGGAGGAAUAGGUGAAGAUGU 24 1265

Table 6A provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 6A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-2789- + GGAAUGGAACAAGACAC 17 1266 330 CFTR-2789- + GCUUGGGAGAAAUGAAACAA 20 1267 331 CFTR-2789- + GUACACACAAUUUCAUCUUC 20 1268 332

Table 6B provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 6B 2nd Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-2789-333 + UGGGAGAAAUGAAACAA 17 1269 CFTR-2789-334 + UUAUCUUUCCACUACCA 17 1270 CFTR-2789-335 + CACACAAUUUCAUCUUC 17 1271 CFTR-2789-336 AGAUUGUGUUUUAUUUC 17 1272 CFTR-2789-337 UAUUCCAUGUCCUAUUG 17 1273 CFTR-2789-338 CUUGUUCCAUUCCAGGU 17 1274 CFTR-2789-339 + ACCUUAUCUUUCCACUACCA 20 1275 CFTR-2789-340 + CCUGGAAUGGAACAAGACAC 20 1276 CFTR-2789-341 UGUAGAUUGUGUUUUAUUUC 20 1277 CFTR-2789-342 + AUUACAAUACAUACAAACAU 20 1278

Table 6C provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 6C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-2789- GAAUAUUCCAUGUCCUAUUG 20 1279 343

Table 6D provides exemplary targeting domains for correcting a mutation (e.g., 2789+5G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 2789+5G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 6D 4th Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-2789- + ACAAUACAUACAAACAU 17 1280 344 CFTR-2789- UGUCUUGUUCCAUUCCAGGU 20 1281 345

Table 7A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 7A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272-1 + GUAAGGCUGCCGUCCGA 17 1282 CFTR-3272-2 GGAAAUAUUUCACAGGC 17 1283 CFTR-3272-3 + GUAAAUUCAGAGCUUUG 17 1284 CFTR-3272-4 GGACACUUCGUGCCUUCGGA 20 1285 CFTR-3272-5 + GGAACCAGCGCAGUGUUGAC 20 1286 CFTR-3272-6 + GUAACAAGAUGAGUGAAAAU 20 1287

Table 7B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 7B 2nd Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-3272-7 CUUGUUACAAGCUUAAA 17 1288 CFTR-3272-8 CAUAUCUAUUCAAAGAA 17 1289 CFTR-3272-9 + UACUUGGCUACCAGAGA 17 1290 CFTR-3272-10 CACUUCGUGCCUUCGGA 17 1291 CFTR-3272-11 CAAGCUUAAAAGGACUA 17 1292 CFTR-3272-12 AUUUACAUACUGCCAAC 17 1293 CFTR-3272-13 + AAAGCUUUUUUUCACAC 17 1294 CFTR-3272-14 CUAUGGAAAUAUUUCAC 17 1295 CFTR-3272-15 + ACCAGCGCAGUGUUGAC 17 1296 CFTR-3272-16 ACCUGUCAACACUGCGC 17 1297 CFTR-3272-17 CUAAUUUAGUCUUUUUC 17 1298 CFTR-3272-18 + CAUAUCACAAAUGUCAU 17 1299 CFTR-3272-19 + ACUUGGCUACCAGAGAU 17 1300 CFTR-3272-20 + UACCCUCUUUUUUUACU 17 1301 CFTR-3272-21 + CAGGUACAAGAACCAGU 17 1302 CFTR-3272-22 UGGACACUUCGUGCCUU 17 1303 CFTR-3272-23 CAUCUUGUUACAAGCUUAAA 20 1304 CFTR-3272-24 AAUCAUAUCUAUUCAAAGAA 20 1305 CFTR-3272-25 + UUUUACUUGGCUACCAGAGA 20 1306 CFTR-3272-26 + AAAGUAAGGCUGCCGUCCGA 20 1307 CFTR-3272-27 UUACAAGCUUAAAAGGACUA 20 1308 CFTR-3272-28 + UGGAACAGAGUUUCAAAGUA 20 1309 CFTR-3272-29 UGAAUUUACAUACUGCCAAC 20 1310 CFTR-3272-30 + UAAAAAGCUUUUUUUCACAC 20 1311 CFTR-3272-31 UUUCUAUGGAAAUAUUUCAC 20 1312 CFTR-3272-32 UGUACCUGUCAACACUGCGC 20 1313 CFTR-3272-33 UAUGGAAAUAUUUCACAGGC 20 1314 CFTR-3272-34 UGGUAGCCAAGUAAAAAAAG 20 1315 CFTR-3272-35 + UAUGUAAAUUCAGAGCUUUG 20 1316 CFTR-3272-36 + AAUCAUAUCACAAAUGUCAU 20 1317 CFTR-3272-37 + UUUACUUGGCUACCAGAGAU 20 1318 CFTR-3272-38 + AGUUACCCUCUUUUUUUACU 20 1319 CFTR-3272-39 + UGACAGGUACAAGAACCAGU 20 1320 CFTR-3272-40 CUAUGGACACUUCGUGCCUU 20 1321

Table 7C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 7C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272- GGUAGCCAAGUAAAAAAAGA 20 1322 41 CFTR-3272- GUUAUUUGCAGUGUUUUCUA 20 1323 42

Table 7D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 7D 4th Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-3272-43 AGCCAAGUAAAAAAAGA 17 1324 CFTR-3272-44 AUUUGCAGUGUUUUCUA 17 1325 CFTR-3272-45 + AACAGAGUUUCAAAGUA 17 1326 CFTR-3272-46 UAGCCAAGUAAAAAAAG 17 1327 CFTR-3272-47 + ACAAGAUGAGUGAAAAU 17 1328 CFTR-3272-48 AUUCUAAUUUAGUCUUUUUC 20 1329

Table 8A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 8A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272-49 + GUCCUUUUAAGCUUGUAA 22 1330 CAAG CFTR-3272-50 + GUACCUGAAAAAGACUAA 20 1331 AU CFTR-3272-51 GUCAACACUGCGCUGGUUC 24 1332 CAAAU

Table 8B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 8B 2nd Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-3272-52 + UUUUAAGCUUGUAACAAG 18 1333 CFTR-3272-53 + CUUUUAAGCUUGUAACAAG 19 1334 CFTR-3272-54 + CCUUUUAAGCUUGUAACAAG 20 1335 CFTR-3272-55 + UCCUUUUAAGCUUGUAACAAG 21 1336 CFTR-3272-56 + AGUCCUUUUAAGCUUGUAACAAG 23 1337 CFTR-3272-57 + UAGUCCUUUUAAGCUUGUAACAAG 24 1338 CFTR-3272-58 + ACCUGAAAAAGACUAAAU 18 1339 CFTR-3272-59 + UACCUGAAAAAGACUAAAU 19 1340 CFTR-3272-60 + UGUACCUGAAAAAGACUAAAU 21 1341 CFTR-3272-61 + UUGUACCUGAAAAAGACUAAAU 22 1342 CFTR-3272-62 + CUUGUACCUGAAAAAGACUAAAU 23 1343 CFTR-3272-63 + UCUUGUACCUGAAAAAGACUAAAU 24 1344 CFTR-3272-64 + UCACACUGGUGCCAUUCU 18 1345 CFTR-3272-65 + UUCACACUGGUGCCAUUCU 19 1346 CFTR-3272-66 + UUUCACACUGGUGCCAUUCU 20 1347 CFTR-3272-67 + UUUUCACACUGGUGCCAUUCU 21 1348 CFTR-3272-68 + UUUUUCACACUGGUGCCAUUCU 22 1349 CFTR-3272-69 + UUUUUUCACACUGGUGCCAUUCU 23 1350 CFTR-3272-70 + UUUUUUUCACACUGGUGCCAUUCU 24 1351 CFTR-3272-71 ACAAAUCAUAUCUAUUCA 18 1352 CFTR-3272-72 AACAAAUCAUAUCUAUUCA 19 1353 CFTR-3272-73 UAACAAAUCAUAUCUAUUCA 20 1354 CFTR-3272-74 AUAACAAAUCAUAUCUAUUCA 21 1355 CFTR-3272-75 AAUAACAAAUCAUAUCUAUUCA 22 1356 CFTR-3272-76 AAAUAACAAAUCAUAUCUAUUCA 23 1357 CFTR-3272-77 AAAAUAACAAAUCAUAUCUAUUCA 24 1358 CFTR-3272-78 UGGAAAUAUUUCACAGGC 18 1359 CFTR-3272-79 AUGGAAAUAUUUCACAGGC 19 1360 CFTR-3272-33 UAUGGAAAUAUUUCACAGGC 20 1314 CFTR-3272-80 ACUGCGCUGGUUCCAAAU 18 1361 CFTR-3272-81 CACUGCGCUGGUUCCAAAU 19 1362 CFTR-3272-82 ACACUGCGCUGGUUCCAAAU 20 1363 CFTR-3272-83 AACACUGCGCUGGUUCCAAAU 21 1364 CFTR-3272-84 CAACACUGCGCUGGUUCCAAAU 22 1365 CFTR-3272-85 UCAACACUGCGCUGGUUCCAAAU 23 1366 CFTR-3272-86 ACUCUGUUCCACAAAGCU 18 1367 CFTR-3272-87 AACUCUGUUCCACAAAGCU 19 1368 CFTR-3272-88 AAACUCUGUUCCACAAAGCU 20 1369

Table 8C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 8C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272-89 + GUAAAUUCAGAGCUUUGUG 22 1370 GAA CFTR-3272-90 + GAUAUGAUUUGUUAUUUUA 22 1371 UUA CFTR-3272-91 GGUAGCCAAGUAAAAAAA 18 1372 CFTR-3272-92 GAAACUCUGUUCCACAAAG 21 1373 CU

Table 8D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 8D 4th Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-3272- + AUUCAGAGCUUUGUGGAA 18 1374 93 CFTR-3272- + AAUUCAGAGCUUUGUGGAA 19 1375 94 CFTR-3272- + AAAUUCAGAGCUUUGUGGAA 20 1376 95 CFTR-3272- + UAAAUUCAGAGCUUUGUGGAA 21 1377 96 CFTR-3272- + UGUAAAUUCAGAGCUUUGUGGAA 23 1378 97 CFTR-3272- + AUGUAAAUUCAGAGCUUUGUGGAA 24 1379 98 CFTR-3272- + UGAUUUGUUAUUUUAUUA 18 1380 99 CFTR-3272- + AUGAUUUGUUAUUUUAUUA 19 1381 100 CFTR-3272- + UAUGAUUUGUUAUUUUAUUA 20 1382 101 CFTR-3272- + AUAUGAUUUGUUAUUUUAUUA 21 1383 102 CFTR-3272- + AGAUAUGAUUUGUUAUUUUAUUA 23 1384 103 CFTR-3272- + UAGAUAUGAUUUGUUAUUUUAUUA 24 1385 104 CFTR-3272- UGGUAGCCAAGUAAAAAAA 19 1386 105 CFTR-3272- CUGGUAGCCAAGUAAAAAAA 20 1387 106 CFTR-3272- UCUGGUAGCCAAGUAAAAAAA 21 1388 107 CFTR-3272- CUCUGGUAGCCAAGUAAAAAAA 22 1389 108 CFTR-3272- UCUCUGGUAGCCAAGUAAAAAAA 23 1390 109 CFTR-3272- AUCUCUGGUAGCCAAGUAAAAAAA 24 1391 110 CFTR-3272- CUAUGGAAAUAUUUCACAGGC 21 1392 111 CFTR-3272- UCUAUGGAAAUAUUUCACAGGC 22 1393 112 CFTR-3272- UUCUAUGGAAAUAUUUCACAGGC 23 1394 113 CFTR-3272- UUUCUAUGGAAAUAUUUCACAGGC 24 1395 114 CFTR-3272- UGAAACUCUGUUCCACAAAGCU 22 1396 115 CFTR-3272- UUGAAACUCUGUUCCACAAAGCU 23 1397 116 CFTR-3272- UUUGAAACUCUGUUCCACAAAGCU 24 1398 117

Table 8E provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 8E 5th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3272-118 + UAACAAGAUGAGUGAAAA 18 1399 CFTR-3272-119 + GUAACAAGAUGAGUGAAAA 19 1400 CFTR-3272-120 + UGUAACAAGAUGAGUGAAAA 20 1401 CFTR-3272-121 + UUGUAACAAGAUGAGUGAAAA 21 1402 CFTR-3272-122 + CUUGUAACAAGAUGAGUGAAAA 22 1403 CFTR-3272-123 + GCUUGUAACAAGAUGAGUGAAAA 23 1404 CFTR-3272-124 + AGCUUGUAACAAGAUGAGUGAAAA 24 1405 CFTR-3272-125 + GCCUGUGAAAUAUUUCCA 18 1406 CFTR-3272-126 + UGCCUGUGAAAUAUUUCCA 19 1407 CFTR-3272-127 + CUGCCUGUGAAAUAUUUCCA 20 1408 CFTR-3272-128 + CCUGCCUGUGAAAUAUUUCCA 21 1409 CFTR-3272-129 + UCCUGCCUGUGAAAUAUUUCCA 22 1410 CFTR-3272-130 + CUCCUGCCUGUGAAAUAUUUCCA 23 1411 CFTR-3272-131 + ACUCCUGCCUGUGAAAUAUUUCCA 24 1412 CFTR-3272-132 + UUACUUGGCUACCAGAGA 18 1413 CFTR-3272-133 + UUUACUUGGCUACCAGAGA 19 1414 CFTR-3272-25 + UUUUACUUGGCUACCAGAGA 20 1306 CFTR-3272-134 + UUUUUACUUGGCUACCAGAGA 21 1415 CFTR-3272-135 + UUUUUUACUUGGCUACCAGAGA 22 1416 CFTR-3272-136 + UUUUUUUACUUGGCUACCAGAGA 23 1417 CFTR-3272-137 + CUUUUUUUACUUGGCUACCAGAGA 24 1418 CFTR-3272-138 + AAGCUUGUAACAAGAUGA 18 1419 CFTR-3272-139 + UAAGCUUGUAACAAGAUGA 19 1420 CFTR-3272-140 + UUAAGCUUGUAACAAGAUGA 20 1421 CFTR-3272-141 + UUUAAGCUUGUAACAAGAUGA 21 1422 CFTR-3272-142 + UUUUAAGCUUGUAACAAGAUGA 22 1423 CFTR-3272-143 + CUUUUAAGCUUGUAACAAGAUGA 23 1424 CFTR-3272-144 + CCUUUUAAGCUUGUAACAAGAUGA 24 1425 CFTR-3272-145 + CUUUUUUUACUUGGCUAC 18 1426 CFTR-3272-146 + UCUUUUUUUACUUGGCUAC 19 1427 CFTR-3272-147 + CUCUUUUUUUACUUGGCUAC 20 1428 CFTR-3272-148 + CCUCUUUUUUUACUUGGCUAC 21 1429 CFTR-3272-149 + CCCUCUUUUUUUACUUGGCUAC 22 1430 CFTR-3272-150 + ACCCUCUUUUUUUACUUGGCUAC 23 1431 CFTR-3272-151 + UACCCUCUUUUUUUACUUGGCUAC 24 1432 CFTR-3272-152 + CGCAGUGUUGACAGGUAC 18 1433 CFTR-3272-153 + GCGCAGUGUUGACAGGUAC 19 1434 CFTR-3272-154 + AGCGCAGUGUUGACAGGUAC 20 1435 CFTR-3272-155 + CAGCGCAGUGUUGACAGGUAC 21 1436 CFTR-3272-156 + CCAGCGCAGUGUUGACAGGUAC 22 1437 CFTR-3272-157 + ACCAGCGCAGUGUUGACAGGUAC 23 1438 CFTR-3272-158 + AACCAGCGCAGUGUUGACAGGUAC 24 1439 CFTR-3272-159 + UUUCAUAAUAUCUUGUAC 18 1440 CFTR-3272-160 + AUUUCAUAAUAUCUUGUAC 19 1441 CFTR-3272-161 + AAUUUCAUAAUAUCUUGUAC 20 1442 CFTR-3272-162 + UAAUUUCAUAAUAUCUUGUAC 21 1443 CFTR-3272-163 + GUAAUUUCAUAAUAUCUUGUAC 22 1444 CFTR-3272-164 + UGUAAUUUCAUAAUAUCUUGUAC 23 1445 CFTR-3272-165 + AUGUAAUUUCAUAAUAUCUUGUAC 24 1446 CFTR-3272-166 + AGGCUGCCGUCCGAAGGC 18 1447 CFTR-3272-167 + AAGGCUGCCGUCCGAAGGC 19 1448 CFTR-3272-168 + UAAGGCUGCCGUCCGAAGGC 20 1449 CFTR-3272-169 + GUAAGGCUGCCGUCCGAAGGC 21 1450 CFTR-3272-170 + AGUAAGGCUGCCGUCCGAAGGC 22 1451 CFTR-3272-171 + AAGUAAGGCUGCCGUCCGAAGGC 23 1452 CFTR-3272-172 + AAAGUAAGGCUGCCGUCCGAAGGC 24 1453 CFTR-3272-173 + UUUACUUGGCUACCAGAG 18 1454 CFTR-3272-174 + UUUUACUUGGCUACCAGAG 19 1455 CFTR-3272-175 + UUUUUACUUGGCUACCAGAG 20 1456 CFTR-3272-176 + UUUUUUACUUGGCUACCAGAG 21 1457 CFTR-3272-177 + UUUUUUUACUUGGCUACCAGAG 22 1458 CFTR-3272-178 + CUUUUUUUACUUGGCUACCAGAG 23 1459 CFTR-3272-179 + UCUUUUUUUACUUGGCUACCAGAG 24 1460 CFTR-3272-180 + UGUAAAUUCAGAGCUUUG 18 1461 CFTR-3272-181 + AUGUAAAUUCAGAGCUUUG 19 1462 CFTR-3272-35 + UAUGUAAAUUCAGAGCUUUG 20 1316 CFTR-3272-182 + GUAUGUAAAUUCAGAGCUUUG 21 1463 CFTR-3272-183 + AGUAUGUAAAUUCAGAGCUUUG 22 1464 CFTR-3272-184 + CAGUAUGUAAAUUCAGAGCUUUG 23 1465 CFTR-3272-185 + GCAGUAUGUAAAUUCAGAGCUUUG 24 1466 CFTR-3272-186 + UACUUGGCUACCAGAGAU 18 1467 CFTR-3272-187 + UUACUUGGCUACCAGAGAU 19 1468 CFTR-3272-37 + UUUACUUGGCUACCAGAGAU 20 1318 CFTR-3272-188 + UUUUACUUGGCUACCAGAGAU 21 1469 CFTR-3272-189 + UUUUUACUUGGCUACCAGAGAU 22 1470 CFTR-3272-190 + UUUUUUACUUGGCUACCAGAGAU 23 1471 CFTR-3272-191 + UUUUUUUACUUGGCUACCAGAGAU 24 1472 CFTR-3272-192 + AAAAUUGGACUCCUGCCU 18 1473 CFTR-3272-193 + GAAAAUUGGACUCCUGCCU 19 1474 CFTR-3272-194 + UGAAAAUUGGACUCCUGCCU 20 1475 CFTR-3272-195 + GUGAAAAUUGGACUCCUGCCU 21 1476 CFTR-3272-196 + AGUGAAAAUUGGACUCCUGCCU 22 1477 CFTR-3272-197 + GAGUGAAAAUUGGACUCCUGCCU 23 1478 CFTR-3272-198 + UGAGUGAAAAUUGGACUCCUGCCU 24 1479 CFTR-3272-199 + UCAAAGUAAGGCUGCCGU 18 1480 CFTR-3272-200 + UUCAAAGUAAGGCUGCCGU 19 1481 CFTR-3272-201 + UUUCAAAGUAAGGCUGCCGU 20 1482 CFTR-3272-202 + GUUUCAAAGUAAGGCUGCCGU 21 1483 CFTR-3272-203 + AGUUUCAAAGUAAGGCUGCCGU 22 1484 CFTR-3272-204 + GAGUUUCAAAGUAAGGCUGCCGU 23 1485 CFTR-3272-205 + AGAGUUUCAAAGUAAGGCUGCCGU 24 1486 CFTR-3272-206 + GUUGGCAGUAUGUAAAUU 18 1487 CFTR-3272-207 + AGUUGGCAGUAUGUAAAUU 19 1488 CFTR-3272-208 + CAGUUGGCAGUAUGUAAAUU 20 1489 CFTR-3272-209 + CCAGUUGGCAGUAUGUAAAUU 21 1490 CFTR-3272-210 + ACCAGUUGGCAGUAUGUAAAUU 22 1491 CFTR-3272-211 + AACCAGUUGGCAGUAUGUAAAUU 23 1492 CFTR-3272-212 + GAACCAGUUGGCAGUAUGUAAAUU 24 1493 CFTR-3272-213 + AUGUAAAUUCAGAGCUUU 18 1494 CFTR-3272-214 + UAUGUAAAUUCAGAGCUUU 19 1495 CFTR-3272-215 + GUAUGUAAAUUCAGAGCUUU 20 1496 CFTR-3272-216 + AGUAUGUAAAUUCAGAGCUUU 21 1497 CFTR-3272-217 + CAGUAUGUAAAUUCAGAGCUUU 22 1498 CFTR-3272-218 + GCAGUAUGUAAAUUCAGAGCUUU 23 1499 CFTR-3272-219 + GGCAGUAUGUAAAUUCAGAGCUUU 24 1500 CFTR-3272-220 CUGGUAGCCAAGUAAAAA 18 1501 CFTR-3272-221 UCUGGUAGCCAAGUAAAAA 19 1502 CFTR-3272-222 CUCUGGUAGCCAAGUAAAAA 20 1503 CFTR-3272-223 UCUCUGGUAGCCAAGUAAAAA 21 1504 CFTR-3272-224 AUCUCUGGUAGCCAAGUAAAAA 22 1505 CFTR-3272-225 CAUCUCUGGUAGCCAAGUAAAAA 23 1506 CFTR-3272-226 CCAUCUCUGGUAGCCAAGUAAAAA 24 1507 CFTR-3272-227 ACACUGCGCUGGUUCCAA 18 1508 CFTR-3272-228 AACACUGCGCUGGUUCCAA 19 1509 CFTR-3272-229 CAACACUGCGCUGGUUCCAA 20 1510 CFTR-3272-230 UCAACACUGCGCUGGUUCCAA 21 1511 CFTR-3272-231 GUCAACACUGCGCUGGUUCCAA 22 1512 CFTR-3272-232 UGUCAACACUGCGCUGGUUCCAA 23 1513 CFTR-3272-233 CUGUCAACACUGCGCUGGUUCCAA 24 1514 CFTR-3272-234 GCUGGUUCCAAAUGAGAA 18 1515 CFTR-3272-235 CGCUGGUUCCAAAUGAGAA 19 1516 CFTR-3272-236 GCGCUGGUUCCAAAUGAGAA 20 1517 CFTR-3272-237 UGCGCUGGUUCCAAAUGAGAA 21 1518 CFTR-3272-238 CUGCGCUGGUUCCAAAUGAGAA 22 1519 CFTR-3272-239 ACUGCGCUGGUUCCAAAUGAGAA 23 1520 CFTR-3272-240 CACUGCGCUGGUUCCAAAUGAGAA 24 1521 CFTR-3272-241 AUCUUGUUACAAGCUUAA 18 1522 CFTR-3272-242 CAUCUUGUUACAAGCUUAA 19 1523 CFTR-3272-243 UCAUCUUGUUACAAGCUUAA 20 1524 CFTR-3272-244 CUCAUCUUGUUACAAGCUUAA 21 1525 CFTR-3272-245 ACUCAUCUUGUUACAAGCUUAA 22 1526 CFTR-3272-246 CACUCAUCUUGUUACAAGCUUAA 23 1527 CFTR-3272-247 UCACUCAUCUUGUUACAAGCUUAA 24 1528 CFTR-3272-248 UAUUUGCAGUGUUUUCUA 18 1529 CFTR-3272-249 UUAUUUGCAGUGUUUUCUA 19 1530 CFTR-3272-42 GUUAUUUGCAGUGUUUUCUA 20 1323 CFTR-3272-250 UGUUAUUUGCAGUGUUUUCUA 21 1531 CFTR-3272-251 AUGUUAUUUGCAGUGUUUUCUA 22 1532 CFTR-3272-252 UAUGUUAUUUGCAGUGUUUUCUA 23 1533 CFTR-3272-253 UUAUGUUAUUUGCAGUGUUUUCUA 24 1534 CFTR-3272-254 AUGGAAAUAUUUCACAGG 18 1535 CFTR-3272-255 UAUGGAAAUAUUUCACAGG 19 1536 CFTR-3272-256 CUAUGGAAAUAUUUCACAGG 20 1537 CFTR-3272-257 UCUAUGGAAAUAUUUCACAGG 21 1538 CFTR-3272-258 UUCUAUGGAAAUAUUUCACAGG 22 1539 CFTR-3272-259 UUUCUAUGGAAAUAUUUCACAGG 23 1540 CFTR-3272-260 UUUUCUAUGGAAAUAUUUCACAGG 24 1541 CFTR-3272-261 UACAAGCUUAAAAGGACU 18 1542 CFTR-3272-262 UUACAAGCUUAAAAGGACU 19 1543 CFTR-3272-263 GUUACAAGCUUAAAAGGACU 20 1544 CFTR-3272-264 UGUUACAAGCUUAAAAGGACU 21 1545 CFTR-3272-265 UUGUUACAAGCUUAAAAGGACU 22 1546 CFTR-3272-266 CUUGUUACAAGCUUAAAAGGACU 23 1547 CFTR-3272-267 UCUUGUUACAAGCUUAAAAGGACU 24 1548 CFTR-3272-268 UCGGACGGCAGCCUUACU 18 1549 CFTR-3272-269 UUCGGACGGCAGCCUUACU 19 1550 CFTR-3272-270 CUUCGGACGGCAGCCUUACU 20 1551 CFTR-3272-271 CCUUCGGACGGCAGCCUUACU 21 1552 CFTR-3272-272 GCCUUCGGACGGCAGCCUUACU 22 1553 CFTR-3272-273 UGCCUUCGGACGGCAGCCUUACU 23 1554 CFTR-3272-274 GUGCCUUCGGACGGCAGCCUUACU 24 1555 CFTR-3272-275 UAUGGACACUUCGUGCCU 18 1556 CFTR-3272-276 CUAUGGACACUUCGUGCCU 19 1557 CFTR-3272-277 ACUAUGGACACUUCGUGCCU 20 1558 CFTR-3272-278 GACUAUGGACACUUCGUGCCU 21 1559 CFTR-3272-279 GGACUAUGGACACUUCGUGCCU 22 1560 CFTR-3272-280 AGGACUAUGGACACUUCGUGCCU 23 1561 CFTR-3272-281 AAGGACUAUGGACACUUCGUGCCU 24 1562 CFTR-3272-282 UUAUUUGCAGUGUUUUCU 18 1563 CFTR-3272-283 GUUAUUUGCAGUGUUUUCU 19 1564 CFTR-3272-284 UGUUAUUUGCAGUGUUUUCU 20 1565 CFTR-3272-285 AUGUUAUUUGCAGUGUUUUCU 21 1566 CFTR-3272-286 UAUGUUAUUUGCAGUGUUUUCU 22 1567 CFTR-3272-287 UUAUGUUAUUUGCAGUGUUUUCU 23 1568 CFTR-3272-288 UUUAUGUUAUUUGCAGUGUUUUCU 24 1569 CFTR-3272-289 UCAAAGAAUGGCACCAGU 18 1570 CFTR-3272-290 UUCAAAGAAUGGCACCAGU 19 1571 CFTR-3272-291 AUUCAAAGAAUGGCACCAGU 20 1572 CFTR-3272-292 UAUUCAAAGAAUGGCACCAGU 21 1573 CFTR-3272-293 CUAUUCAAAGAAUGGCACCAGU 22 1574 CFTR-3272-294 UCUAUUCAAAGAAUGGCACCAGU 23 1575 CFTR-3272-295 AUCUAUUCAAAGAAUGGCACCAGU 24 1576 CFTR-3272-296 UUUCAGGUACAAGAUAUU 18 1577 CFTR-3272-297 UUUUCAGGUACAAGAUAUU 19 1578 CFTR-3272-298 UUUUUCAGGUACAAGAUAUU 20 1579 CFTR-3272-299 CUUUUUCAGGUACAAGAUAUU 21 1580 CFTR-3272-300 UCUUUUUCAGGUACAAGAUAUU 22 1581 CFTR-3272-301 GUCUUUUUCAGGUACAAGAUAUU 23 1582 CFTR-3272-302 AGUCUUUUUCAGGUACAAGAUAUU 24 1583

Table 9A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 9A 2nd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272- AUGGCACCAGUGUGAAA 17 1584 303 CFTR-3272- + UGCCAUUCUUUGAAUAG 17 1585 304 CFTR-3272- + UUGGCAGUAUGUAAAUU 17 1586 305 CFTR-3272- + AAGUGUCCAUAGUCCUU 17 1587 306 CFTR-3272- AGAAUGGCACCAGUGUGAAA 20 1588 307 CFTR-3272- + UGGUGCCAUUCUUUGAAUAG 20 1589 308 CFTR-3272- + ACGAAGUGUCCAUAGUCCUU 20 1590 309

Table 9B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26A->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26A->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 9B 4th Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272- + ACAAAUGUCAUUGGUUA 17 1591 310 CFTR-3272- AACCAAUGACAUUUGUG 17 1592 311 CFTR-3272- UUUUCACUCAUCUUGUU 17 1593 312 CFTR-3272- + AUCACAAAUGUCAUUGGUUA 20 1594 313 CFTR-3272- UUUAACCAAUGACAUUUGUG 20 1595 314 CFTR-3272- + CAGUUGGCAGUAUGUAAAUU 20 1489 208 CFTR-3272- CAAUUUUCACUCAUCUUGUU 20 1596 315

Table 10A provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 10A 1st Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-DeltaF508-1 GGGUAAGCUACUGUGAA 17 402 CFTR-DeltaF508-2 GAACUGGAGCCUUCAGA 17 401 CFTR-DeltaF508-3 + GACUAACCGAUUGAAUA 17 403 CFTR-DeltaF508-4 GGUGAUUAUGGGAGAAC 17 400 CFTR-DeltaF508-5 + GGUGCCAGGCAUAAUCC 17 394 CFTR-DeltaF508-6 GGUAAAAUUAAGCACAG 17 390 CFTR-DeltaF508-7 + GUAUCUAUAUUCAUCAU 17 392 CFTR-DeltaF508-8 + GAGCCAAAUAUAUAAUU 17 404 CFTR-DeltaF508-9 GGAGAACUGGAGCCUUCAGA 20 397 CFTR-DeltaF508-10 + GUAGACUAACCGAUUGAAUA 20 398 CFTR-DeltaF508-11 + GUCAUUAUCAAAUCACGCUC 20 399 CFTR-DeltaF508-12 GAGGGUAAAAUUAAGCACAG 20 387 CFTR-DeltaF508-13 GGGAGAACUGGAGCCUUCAG 20 396 CFTR-DeltaF508-14 GAUAAUGACCUAAUAAUGAU 20 395

Table 10B provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 10B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-15 + AAUUUGGGUAGUGUGAA 17 449 CFTR-DeltaF508-16 CCAGACUUCACUUCUAA 17 438 CFTR-DeltaF508-17 UAAUGACCUAAUAAUGA 17 436 CFTR-DeltaF508-18 + UUAAUUUUACCCUCUGA 17 418 CFTR-DeltaF508-19 + UAAUUUGGGUAGUGUGA 17 448 CFTR-DeltaF508-20 UUUUCCUGGAUUAUGCC 17 414 CFTR-DeltaF508-21 + UUUUCUUUAAUGGUGCC 17 417 CFTR-DeltaF508-22 UCUGUUCUCAGUUUUCC 17 413 CFTR-DeltaF508-23 + AUUAUCAAAUCACGCUC 17 452 CFTR-DeltaF508-24 + CCAUUAGAAGUGAAGUC 17 450 CFTR-DeltaF508-25 AGCAUGCCAACUAGAAG 17 391 CFTR-DeltaF508-26 AGAACUGGAGCCUUCAG 17 441 CFTR-DeltaF508-27 + CAGUAGCUUACCCAUAG 17 446 CFTR-DeltaF508-28 UUGGCUCCAUAUUCAAU 17 443 CFTR-DeltaF508-29 CUUCUAAUGGUGAUUAU 17 440 CFTR-DeltaF508-30 + UUCUUACCUCUUCUAGU 17 416 CFTR-DeltaF508-31 UACCCAAAUUAUAUAUU 17 442 CFTR-DeltaF508-32 UAUGGGUAAGCUACUGUGAA 20 428 CFTR-DeltaF508-33 + UAUAAUUUGGGUAGUGUGAA 20 433 CFTR-DeltaF508-34 UUUCCAGACUUCACUUCUAA 20 420 CFTR-DeltaF508-35 + ACCAAUGAUAUUUUCUUUAA 20 1597 CFTR-DeltaF508-36 UGAUAAUGACCUAAUAAUGA 20 419 CFTR-DeltaF508-37 + UGCUUAAUUUUACCCUCUGA 20 412 CFTR-DeltaF508-38 + AUAUAAUUUGGGUAGUGUGA 20 432 CFTR-DeltaF508-39 UUCACUUCUAAUGGUGAUUA 20 421 CFTR-DeltaF508-40 AAUGGUGAUUAUGGGAGAAC 20 423 CFTR-DeltaF508-41 CAGUUUUCCUGGAUUAUGCC 20 406 CFTR-DeltaF508-42 + AUAUUUUCUUUAAUGGUGCC 20 411 CFTR-DeltaF508-43 + AAUGGUGCCAGGCAUAAUCC 20 389 CFTR-DeltaF508-44 CAUUCUGUUCUCAGUUUUCC 20 405 CFTR-DeltaF508-45 + UCACCAUUAGAAGUGAAGUC 20 434 CFTR-DeltaF508-46 CAAAGCAUGCCAACUAGAAG 20 408 CFTR-DeltaF508-47 + UCACAGUAGCUUACCCAUAG 20 429 CFTR-DeltaF508-48 UAUUUGGCUCCAUAUUCAAU 20 425 CFTR-DeltaF508-49 + UCUGUAUCUAUAUUCAUCAU 20 409 CFTR-DeltaF508-50 ACCAUUAAAGAAAAUAUCAU 20 1598 CFTR-DeltaF508-51 UCACUUCUAAUGGUGAUUAU 20 422 CFTR-DeltaF508-52 + AGUUUCUUACCUCUUCUAGU 20 388 CFTR-DeltaF508-53 + AUGGAGCCAAAUAUAUAAUU 20 430 CFTR-DeltaF508-54 CACUACCCAAAUUAUAUAUU 20 424

Table 10C provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 10C 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-55 + AAUGAUAUUUUCUUUAA 17 1599 CFTR-DeltaF508-56 UAUUUAUGUUUCCUCUA 17 444 CFTR-DeltaF508-57 ACUUCUAAUGGUGAUUA 17 439 CFTR-DeltaF508-58 AUUAAAGAAAAUAUCAU 17 1600 CFTR-DeltaF508-59 AAUGACCUAAUAAUGAU 17 437 CFTR-DeltaF508-60 AUUUAUGUUUCCUCUAU 17 445 CFTR-DeltaF508-61 + UAAAACCCAUCAUUAUU 17 451 CFTR-DeltaF508-62 + AGCCAAAUAUAUAAUUU 17 447 CFTR-DeltaF508-63 AUAUAUUUAUGUUUCCUCUA 20 426 CFTR-DeltaF508-64 UAUAUUUAUGUUUCCUCUAU 20 427 CFTR-DeltaF508-65 + AAAUAAAACCCAUCAUUAUU 20 435 CFTR-DeltaF508-66 + UGGAGCCAAAUAUAUAAUUU 20 431

Table 11A provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 11A 1st Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-67 + GAAUAUGGAGCCAAAUAUAUAAU 23 1601 CFTR-DeltaF508-68 + GUCAUUAUCAAAUCACGCU 19 1602 CFTR-DeltaF508-69 + GGUCAUUAUCAAAUCACGCU 20 676 CFTR-DeltaF508-70 GGAGAACUGGAGCCUUCA 18 1603 CFTR-DeltaF508-71 GGGAGAACUGGAGCCUUCA 19 1604 CFTR-DeltaF508-72 GUAAAAUUAAGCACAGUGG 19 1605 CFTR-DeltaF508-73 GGUAAAAUUAAGCACAGUGG 20 663 CFTR-DeltaF508-74 GGGUAAAAUUAAGCACAGUGG 21 1606 CFTR-DeltaF508-75 GAGGGUAAAAUUAAGCACAGUGG 23 1607 CFTR-DeltaF508-76 GAUAAUGACCUAAUAAUG 18 1608 CFTR-DeltaF508-77 GAUUUGAUAAUGACCUAAUAAUG 23 1609 CFTR-DeltaF508-78 GUUUCCUCUAUGGGUAAGCUACU 23 1610

Table 11B provides exemplary targeting domains for correcting a mutation (e.g., deltaF8) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 11B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-79 + AUCCAGGAAAACUGAGAA 18 1611 CFTR-DeltaF508-80 + AAUCCAGGAAAACUGAGAA 19 1612 CFTR-DeltaF508-81 + UAAUCCAGGAAAACUGAGAA 20 682 CFTR-DeltaF508-82 + UAUAUGUAGACUAACCGA 18 1613 CFTR-DeltaF508-83 + AUAUAUGUAGACUAACCGA 19 1614 CFTR-DeltaF508-84 + AAUAUAUGUAGACUAACCGA 20 691 CFTR-DeltaF508-85 + AAAUAUAUGUAGACUAACCGA 21 1615 CFTR-DeltaF508-86 + UAAAUAUAUGUAGACUAACCGA 22 1616 CFTR-DeltaF508-87 + AUAAAUAUAUGUAGACUAACCGA 23 1617 CFTR-DeltaF508-88 + CAUAAAUAUAUGUAGACUAACCGA 24 1618 CFTR-DeltaF508-89 + UAUAAUUUGGGUAGUGUG 18 1619 CFTR-DeltaF508-90 + AUAUAAUUUGGGUAGUGUG 19 1620 CFTR-DeltaF508-91 + UAUAUAAUUUGGGUAGUGUG 20 687 CFTR-DeltaF508-92 + AUAUAUAAUUUGGGUAGUGUG 21 1621 CFTR-DeltaF508-93 + AAUAUAUAAUUUGGGUAGUGUG 22 1622 CFTR-DeltaF508-94 + AAAUAUAUAAUUUGGGUAGUGUG 23 1623 CFTR-DeltaF508-95 + CAAAUAUAUAAUUUGGGUAGUGUG 24 1624 CFTR-DeltaF508-96 + UGGAGCCAAAUAUAUAAU 18 1625 CFTR-DeltaF508-97 + AUGGAGCCAAAUAUAUAAU 19 1626 CFTR-DeltaF508-98 + UAUGGAGCCAAAUAUAUAAU 20 689 CFTR-DeltaF508-99 + AUAUGGAGCCAAAUAUAUAAU 21 1627 CFTR-DeltaF508-100 + AAUAUGGAGCCAAAUAUAUAAU 22 1628 CFTR-DeltaF508-101 + UGAAUAUGGAGCCAAAUAUAUAAU 24 1629 CFTR-DeltaF508-102 + UCAUUAUCAAAUCACGCU 18 1630 CFTR-DeltaF508-103 + AGGUCAUUAUCAAAUCACGCU 21 1631 CFTR-DeltaF508-104 + UAGGUCAUUAUCAAAUCACGCU 22 1632 CFTR-DeltaF508-105 + UUAGGUCAUUAUCAAAUCACGCU 23 1633 CFTR-DeltaF508-106 + AUUAGGUCAUUAUCAAAUCACGCU 24 1634 CFTR-DeltaF508-107 UGGGAGAACUGGAGCCUUCA 20 661 CFTR-DeltaF508-108 AUGGGUAAGCUACUGUGA 18 1635 CFTR-DeltaF508-109 UAUGGGUAAGCUACUGUGA 19 1636 CFTR-DeltaF508-110 CUAUGGGUAAGCUACUGUGA 20 675 CFTR-DeltaF508-111 UCUAUGGGUAAGCUACUGUGA 21 1637 CFTR-DeltaF508-112 CUCUAUGGGUAAGCUACUGUGA 22 1638 CFTR-DeltaF508-113 CCUCUAUGGGUAAGCUACUGUGA 23 1639 CFTR-DeltaF508-114 UCCUCUAUGGGUAAGCUACUGUGA 24 1640 CFTR-DeltaF508-115 AUUCUGUUCUCAGUUUUC 18 1641 CFTR-DeltaF508-116 CAUUCUGUUCUCAGUUUUC 19 1642 CFTR-DeltaF508-117 UCAUUCUGUUCUCAGUUUUC 20 664 CFTR-DeltaF508-118 UUCAUUCUGUUCUCAGUUUUC 21 1643 CFTR-DeltaF508-119 UUUCAUUCUGUUCUCAGUUUUC 22 1644 CFTR-DeltaF508-120 AUUUCAUUCUGUUCUCAGUUUUC 23 1645 CFTR-DeltaF508-121 AAUUUCAUUCUGUUCUCAGUUUUC 24 1646 CFTR-DeltaF508-122 UAAAAUUAAGCACAGUGG 18 1647 CFTR-DeltaF508-123 AGGGUAAAAUUAAGCACAGUGG 22 1648 CFTR-DeltaF508-124 AGAGGGUAAAAUUAAGCACAGUGG 24 1649 CFTR-DeltaF508-125 UGAUAAUGACCUAAUAAUG 19 1650 CFTR-DeltaF508-126 UUGAUAAUGACCUAAUAAUG 20 656 CFTR-DeltaF508-127 UUUGAUAAUGACCUAAUAAUG 21 1651 CFTR-DeltaF508-128 AUUUGAUAAUGACCUAAUAAUG 22 1652 CFTR-DeltaF508-129 UGAUUUGAUAAUGACCUAAUAAUG 24 1653 CFTR-DeltaF508-130 UCAUUGGUGUUUCCUAUG 18 1654 CFTR-DeltaF508-131 AUCAUUGGUGUUUCCUAUG 19 1655 CFTR-DeltaF508-132 UAUCAUUGGUGUUUCCUAUG 20 1656 CFTR-DeltaF508-133 AUAUCAUUGGUGUUUCCUAUG 21 1657 CFTR-DeltaF508-134 AAUAUCAUUGGUGUUUCCUAUG 22 1658 CFTR-DeltaF508-135 AAAUAUCAUUGGUGUUUCCUAUG 23 1659 CFTR-DeltaF508-136 AAAAUAUCAUUGGUGUUUCCUAUG 24 1660 CFTR-DeltaF508-137 CUCUAUGGGUAAGCUACU 18 1661 CFTR-DeltaF508-138 CCUCUAUGGGUAAGCUACU 19 1662 CFTR-DeltaF508-139 UCCUCUAUGGGUAAGCUACU 20 674 CFTR-DeltaF508-140 UUCCUCUAUGGGUAAGCUACU 21 1663 CFTR-DeltaF508-141 UUUCCUCUAUGGGUAAGCUACU 22 1664 CFTR-DeltaF508-142 UGUUUCCUCUAUGGGUAAGCUACU 24 1665 CFTR-DeltaF508-143 UAUAUUUAUGUUUCCUCU 18 1666 CFTR-DeltaF508-144 AUAUAUUUAUGUUUCCUCU 19 1667 CFTR-DeltaF508-145 CAUAUAUUUAUGUUUCCUCU 20 673 CFTR-DeltaF508-146 ACAUAUAUUUAUGUUUCCUCU 21 1668 CFTR-DeltaF508-147 UACAUAUAUUUAUGUUUCCUCU 22 1669 CFTR-DeltaF508-148 CUACAUAUAUUUAUGUUUCCUCU 23 1670 CFTR-DeltaF508-149 UCUACAUAUAUUUAUGUUUCCUCU 24 1671

Table 11C provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 11C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR- + GCAUAAUCCAGGAAAACU 23 1672 DeltaF508- GAGAA 150 CFTR- + GGCAUAAUCCAGGAAAACU 24 1673 DeltaF508- GAGAA 151

Table 11D provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 11D 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-152 + AUAAUCCAGGAAAACUGAGAA 21 1674 CFTR-DeltaF508-153 + CAUAAUCCAGGAAAACUGAGAA 22 1675 CFTR-DeltaF508-154 AUGGGAGAACUGGAGCCUUCA 21 1676 CFTR-DeltaF508-155 UAUGGGAGAACUGGAGCCUUCA 22 1677 CFTR-DeltaF508-156 UUAUGGGAGAACUGGAGCCUUCA 23 1678 CFTR-DeltaF508-157 AUUAUGGGAGAACUGGAGCCUUCA 24 1679

Table 11E provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 11E 5th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-158 + AGGCAUAAUCCAGGAAAA 18 1680 CFTR-DeltaF508-159 + CAGGCAUAAUCCAGGAAAA 19 1681 CFTR-DeltaF508-160 + CCAGGCAUAAUCCAGGAAAA 20 684 CFTR-DeltaF508-161 + GCCAGGCAUAAUCCAGGAAAA 21 1682 CFTR-DeltaF508-162 + UGCCAGGCAUAAUCCAGGAAAA 22 1683 CFTR-DeltaF508-163 + GUGCCAGGCAUAAUCCAGGAAAA 23 1684 CFTR-DeltaF508-164 + GGUGCCAGGCAUAAUCCAGGAAAA 24 1685 CFTR-DeltaF508-165 + CCAUAAUCACCAUUAGAA 18 1686 CFTR-DeltaF508-166 + CCCAUAAUCACCAUUAGAA 19 1687 CFTR-DeltaF508-167 + UCCCAUAAUCACCAUUAGAA 20 678 CFTR-DeltaF508-168 + CUCCCAUAAUCACCAUUAGAA 21 1688 CFTR-DeltaF508-169 + UCUCCCAUAAUCACCAUUAGAA 22 1689 CFTR-DeltaF508-170 + UUCUCCCAUAAUCACCAUUAGAA 23 1690 CFTR-DeltaF508-171 + GUUCUCCCAUAAUCACCAUUAGAA 24 1691 CFTR-DeltaF508-172 + UUCACAGUAGCUUACCCA 18 1692 CFTR-DeltaF508-173 + AUUCACAGUAGCUUACCCA 19 1693 CFTR-DeltaF508-174 + CAUUCACAGUAGCUUACCCA 20 693 CFTR-DeltaF508-175 + CCAUUCACAGUAGCUUACCCA 21 1694 CFTR-DeltaF508-176 + UCCAUUCACAGUAGCUUACCCA 22 1695 CFTR-DeltaF508-177 + AUCCAUUCACAGUAGCUUACCCA 23 1696 CFTR-DeltaF508-178 + GAUCCAUUCACAGUAGCUUACCCA 24 1697 CFTR-DeltaF508-179 + CUGUAUCUAUAUUCAUCA 18 1698 CFTR-DeltaF508-180 + UCUGUAUCUAUAUUCAUCA 19 1699 CFTR-DeltaF508-181 + UUCUGUAUCUAUAUUCAUCA 20 686 CFTR-DeltaF508-182 + CUUCUGUAUCUAUAUUCAUCA 21 1700 CFTR-DeltaF508-183 + GCUUCUGUAUCUAUAUUCAUCA 22 1701 CFTR-DeltaF508-184 + CGCUUCUGUAUCUAUAUUCAUCA 23 1702 CFTR-DeltaF508-185 + ACGCUUCUGUAUCUAUAUUCAUCA 24 1703 CFTR-DeltaF508-186 + AGGAAAACUGAGAACAGA 18 1704 CFTR-DeltaF508-187 + CAGGAAAACUGAGAACAGA 19 1705 CFTR-DeltaF508-188 + CCAGGAAAACUGAGAACAGA 20 681 CFTR-DeltaF508-189 + UCCAGGAAAACUGAGAACAGA 21 1706 CFTR-DeltaF508-190 + AUCCAGGAAAACUGAGAACAGA 22 1707 CFTR-DeltaF508-191 + AAUCCAGGAAAACUGAGAACAGA 23 1708 CFTR-DeltaF508-192 + UAAUCCAGGAAAACUGAGAACAGA 24 1709 CFTR-DeltaF508-193 + AGACUAACCGAUUGAAUA 18 1710 CFTR-DeltaF508-194 + UAGACUAACCGAUUGAAUA 19 1711 CFTR-DeltaF508-10 + GUAGACUAACCGAUUGAAUA 20 398 CFTR-DeltaF508-195 + UGUAGACUAACCGAUUGAAUA 21 1712 CFTR-DeltaF508-196 + AUGUAGACUAACCGAUUGAAUA 22 1713 CFTR-DeltaF508-197 + UAUGUAGACUAACCGAUUGAAUA 23 1714 CFTR-DeltaF508-198 + AUAUGUAGACUAACCGAUUGAAUA 24 1715 CFTR-DeltaF508-199 + CACAGUAGCUUACCCAUA 18 1716 CFTR-DeltaF508-200 + UCACAGUAGCUUACCCAUA 19 1717 CFTR-DeltaF508-201 + UUCACAGUAGCUUACCCAUA 20 692 CFTR-DeltaF508-202 + AUUCACAGUAGCUUACCCAUA 21 1718 CFTR-DeltaF508-203 + CAUUCACAGUAGCUUACCCAUA 22 1719 CFTR-DeltaF508-204 + CCAUUCACAGUAGCUUACCCAUA 23 1720 CFTR-DeltaF508-205 + UCCAUUCACAGUAGCUUACCCAUA 24 1721 CFTR-DeltaF508-206 + UGGUGCCAGGCAUAAUCC 18 1722 CFTR-DeltaF508-207 + AUGGUGCCAGGCAUAAUCC 19 1723 CFTR-DeltaF508-43 + AAUGGUGCCAGGCAUAAUCC 20 389 CFTR-DeltaF508-208 + UAAUGGUGCCAGGCAUAAUCC 21 1724 CFTR-DeltaF508-209 + UUAAUGGUGCCAGGCAUAAUCC 22 1725 CFTR-DeltaF508-210 + UUUAAUGGUGCCAGGCAUAAUCC 23 1726 CFTR-DeltaF508-211 + CUUUAAUGGUGCCAGGCAUAAUCC 24 1727 CFTR-DeltaF508-212 + AUGGUGCCAGGCAUAAUC 18 1728 CFTR-DeltaF508-213 + AAUGGUGCCAGGCAUAAUC 19 1729 CFTR-DeltaF508-214 + UAAUGGUGCCAGGCAUAAUC 20 685 CFTR-DeltaF508-215 + UUAAUGGUGCCAGGCAUAAUC 21 1730 CFTR-DeltaF508-216 + UUUAAUGGUGCCAGGCAUAAUC 22 1731 CFTR-DeltaF508-217 + CUUUAAUGGUGCCAGGCAUAAUC 23 1732 CFTR-DeltaF508-218 + UCUUUAAUGGUGCCAGGCAUAAUC 24 1733 CFTR-DeltaF508-219 + ACCAUUAGAAGUGAAGUC 18 1734 CFTR-DeltaF508-220 + CACCAUUAGAAGUGAAGUC 19 1735 CFTR-DeltaF508-45 + UCACCAUUAGAAGUGAAGUC 20 434 CFTR-DeltaF508-221 + AUCACCAUUAGAAGUGAAGUC 21 1736 CFTR-DeltaF508-222 + AAUCACCAUUAGAAGUGAAGUC 22 1737 CFTR-DeltaF508-223 + UAAUCACCAUUAGAAGUGAAGUC 23 1738 CFTR-DeltaF508-224 + AUAAUCACCAUUAGAAGUGAAGUC 24 1739 CFTR-DeltaF508-225 + ACAGUAGCUUACCCAUAG 18 1740 CFTR-DeltaF508-226 + CACAGUAGCUUACCCAUAG 19 1741 CFTR-DeltaF508-47 + UCACAGUAGCUUACCCAUAG 20 429 CFTR-DeltaF508-227 + UUCACAGUAGCUUACCCAUAG 21 1742 CFTR-DeltaF508-228 + AUUCACAGUAGCUUACCCAUAG 22 1743 CFTR-DeltaF508-229 + CAUUCACAGUAGCUUACCCAUAG 23 1744 CFTR-DeltaF508-230 + CCAUUCACAGUAGCUUACCCAUAG 24 1745 CFTR-DeltaF508-231 + UAGACUAACCGAUUGAAU 18 1746 CFTR-DeltaF508-232 + GUAGACUAACCGAUUGAAU 19 1747 CFTR-DeltaF508-233 + UGUAGACUAACCGAUUGAAU 20 690 CFTR-DeltaF508-234 + AUGUAGACUAACCGAUUGAAU 21 1748 CFTR-DeltaF508-235 + UAUGUAGACUAACCGAUUGAAU 22 1749 CFTR-DeltaF508-236 + AUAUGUAGACUAACCGAUUGAAU 23 1750 CFTR-DeltaF508-237 + UAUAUGUAGACUAACCGAUUGAAU 24 1751 CFTR-DeltaF508-238 + UUCUCCCAUAAUCACCAU 18 1752 CFTR-DeltaF508-239 + GUUCUCCCAUAAUCACCAU 19 1753 CFTR-DeltaF508-240 + AGUUCUCCCAUAAUCACCAU 20 679 CFTR-DeltaF508-241 + CAGUUCUCCCAUAAUCACCAU 21 1754 CFTR-DeltaF508-242 + CCAGUUCUCCCAUAAUCACCAU 22 1755 CFTR-DeltaF508-243 + UCCAGUUCUCCCAUAAUCACCAU 23 1756 CFTR-DeltaF508-244 + CUCCAGUUCUCCCAUAAUCACCAU 24 1757 CFTR-DeltaF508-245 + UGUAUCUAUAUUCAUCAU 18 1758 CFTR-DeltaF508-246 + CUGUAUCUAUAUUCAUCAU 19 1759 CFTR-DeltaF508-49 + UCUGUAUCUAUAUUCAUCAU 20 409 CFTR-DeltaF508-247 + UUCUGUAUCUAUAUUCAUCAU 21 1760 CFTR-DeltaF508-248 + CUUCUGUAUCUAUAUUCAUCAU 22 1761 CFTR-DeltaF508-249 + GCUUCUGUAUCUAUAUUCAUCAU 23 1762 CFTR-DeltaF508-250 + CGCUUCUGUAUCUAUAUUCAUCAU 24 1763 CFTR-DeltaF508-251 + GCAUAAUCCAGGAAAACU 18 1764 CFTR-DeltaF508-252 + GGCAUAAUCCAGGAAAACU 19 1765 CFTR-DeltaF508-253 + AGGCAUAAUCCAGGAAAACU 20 683 CFTR-DeltaF508-254 + CAGGCAUAAUCCAGGAAAACU 21 1766 CFTR-DeltaF508-255 + CCAGGCAUAAUCCAGGAAAACU 22 1767 CFTR-DeltaF508-256 + GCCAGGCAUAAUCCAGGAAAACU 23 1768 CFTR-DeltaF508-257 + UGCCAGGCAUAAUCCAGGAAAACU 24 1769 CFTR-DeltaF508-258 + UGUGCUUAAUUUUACCCU 18 1770 CFTR-DeltaF508-259 + CUGUGCUUAAUUUUACCCU 19 1771 CFTR-DeltaF508-260 + ACUGUGCUUAAUUUUACCCU 20 680 CFTR-DeltaF508-261 + CACUGUGCUUAAUUUUACCCU 21 1772 CFTR-DeltaF508-262 + CCACUGUGCUUAAUUUUACCCU 22 1773 CFTR-DeltaF508-263 + UCCACUGUGCUUAAUUUUACCCU 23 1774 CFTR-DeltaF508-264 + UUCCACUGUGCUUAAUUUUACCCU 24 1775 CFTR-DeltaF508-265 + CACCAUUAGAAGUGAAGU 18 1776 CFTR-DeltaF508-266 + UCACCAUUAGAAGUGAAGU 19 1777 CFTR-DeltaF508-267 + AUCACCAUUAGAAGUGAAGU 20 677 CFTR-DeltaF508-268 + AAUCACCAUUAGAAGUGAAGU 21 1778 CFTR-DeltaF508-269 + UAAUCACCAUUAGAAGUGAAGU 22 1779 CFTR-DeltaF508-270 + AUAAUCACCAUUAGAAGUGAAGU 23 1780 CFTR-DeltaF508-271 + CAUAAUCACCAUUAGAAGUGAAGU 24 1781 CFTR-DeltaF508-272 + AUAUAUAAUUUGGGUAGU 18 1782 CFTR-DeltaF508-273 + AAUAUAUAAUUUGGGUAGU 19 1783 CFTR-DeltaF508-274 + AAAUAUAUAAUUUGGGUAGU 20 688 CFTR-DeltaF508-275 + CAAAUAUAUAAUUUGGGUAGU 21 1784 CFTR-DeltaF508-276 + CCAAAUAUAUAAUUUGGGUAGU 22 1785 CFTR-DeltaF508-277 + GCCAAAUAUAUAAUUUGGGUAGU 23 1786 CFTR-DeltaF508-278 + AGCCAAAUAUAUAAUUUGGGUAGU 24 1787 CFTR-DeltaF508-279 AUGGUGAUUAUGGGAGAA 18 1788 CFTR-DeltaF508-280 AAUGGUGAUUAUGGGAGAA 19 1789 CFTR-DeltaF508-281 UAAUGGUGAUUAUGGGAGAA 20 659 CFTR-DeltaF508-282 CUAAUGGUGAUUAUGGGAGAA 21 1790 CFTR-DeltaF508-283 UCUAAUGGUGAUUAUGGGAGAA 22 1791 CFTR-DeltaF508-284 UUCUAAUGGUGAUUAUGGGAGAA 23 1792 CFTR-DeltaF508-285 CUUCUAAUGGUGAUUAUGGGAGAA 24 1793 CFTR-DeltaF508-286 AGGGUAAAAUUAAGCACA 18 1794 CFTR-DeltaF508-287 GAGGGUAAAAUUAAGCACA 19 1795 CFTR-DeltaF508-288 AGAGGGUAAAAUUAAGCACA 20 662 CFTR-DeltaF508-289 CAGAGGGUAAAAUUAAGCACA 21 1796 CFTR-DeltaF508-290 UCAGAGGGUAAAAUUAAGCACA 22 1797 CFTR-DeltaF508-291 UUCAGAGGGUAAAAUUAAGCACA 23 1798 CFTR-DeltaF508-292 CUUCAGAGGGUAAAAUUAAGCACA 24 1799 CFTR-DeltaF508-293 CUAUGAUGAAUAUAGAUA 18 1800 CFTR-DeltaF508-294 CCUAUGAUGAAUAUAGAUA 19 1801 CFTR-DeltaF508-295 UCCUAUGAUGAAUAUAGAUA 20 667 CFTR-DeltaF508-296 UUCCUAUGAUGAAUAUAGAUA 21 1802 CFTR-DeltaF508-297 UUUCCUAUGAUGAAUAUAGAUA 22 1803 CFTR-DeltaF508-298 GUUUCCUAUGAUGAAUAUAGAUA 23 1804 CFTR-DeltaF508-299 UGUUUCCUAUGAUGAAUAUAGAUA 24 1805 CFTR-DeltaF508-300 UUAUGCCUGGCACCAUUA 18 1806 CFTR-DeltaF508-301 AUUAUGCCUGGCACCAUUA 19 1807 CFTR-DeltaF508-302 GAUUAUGCCUGGCACCAUUA 20 665 CFTR-DeltaF508-303 GGAUUAUGCCUGGCACCAUUA 21 1808 CFTR-DeltaF508-304 UGGAUUAUGCCUGGCACCAUUA 22 1809 CFTR-DeltaF508-305 CUGGAUUAUGCCUGGCACCAUUA 23 1810 CFTR-DeltaF508-306 CCUGGAUUAUGCCUGGCACCAUUA 24 1811 CFTR-DeltaF508-307 CACUUCUAAUGGUGAUUA 18 1812 CFTR-DeltaF508-308 UCACUUCUAAUGGUGAUUA 19 1813 CFTR-DeltaF508-39 UUCACUUCUAAUGGUGAUUA 20 421 CFTR-DeltaF508-309 CUUCACUUCUAAUGGUGAUUA 21 1814 CFTR-DeltaF508-310 ACUUCACUUCUAAUGGUGAUUA 22 1815 CFTR-DeltaF508-311 GACUUCACUUCUAAUGGUGAUUA 23 1816 CFTR-DeltaF508-312 AGACUUCACUUCUAAUGGUGAUUA 24 1817 CFTR-DeltaF508-313 UCAUCAAAGCAUGCCAAC 18 1818 CFTR-DeltaF508-314 GUCAUCAAAGCAUGCCAAC 19 1819 CFTR-DeltaF508-315 CGUCAUCAAAGCAUGCCAAC 20 668 CFTR-DeltaF508-316 GCGUCAUCAAAGCAUGCCAAC 21 1820 CFTR-DeltaF508-317 AGCGUCAUCAAAGCAUGCCAAC 22 1821 CFTR-DeltaF508-318 AAGCGUCAUCAAAGCAUGCCAAC 23 1822 CFTR-DeltaF508-319 GAAGCGUCAUCAAAGCAUGCCAAC 24 1823 CFTR-DeltaF508-320 UGGUGAUUAUGGGAGAAC 18 1824 CFTR-DeltaF508-321 AUGGUGAUUAUGGGAGAAC 19 1825 CFTR-DeltaF508-40 AAUGGUGAUUAUGGGAGAAC 20 423 CFTR-DeltaF508-322 UAAUGGUGAUUAUGGGAGAAC 21 1826 CFTR-DeltaF508-323 CUAAUGGUGAUUAUGGGAGAAC 22 1827 CFTR-DeltaF508-324 UCUAAUGGUGAUUAUGGGAGAAC 23 1828 CFTR-DeltaF508-325 UUCUAAUGGUGAUUAUGGGAGAAC 24 1829 CFTR-DeltaF508-326 AUUGGAGGCAAGUGAAUC 18 1830 CFTR-DeltaF508-327 AAUUGGAGGCAAGUGAAUC 19 1831 CFTR-DeltaF508-328 UAAUUGGAGGCAAGUGAAUC 20 655 CFTR-DeltaF508-329 GGGUAAAAUUAAGCACAG 18 1832 CFTR-DeltaF508-330 AGGGUAAAAUUAAGCACAG 19 1833 CFTR-DeltaF508-12 GAGGGUAAAAUUAAGCACAG 20 387 CFTR-DeltaF508-331 AGAGGGUAAAAUUAAGCACAG 21 1834 CFTR-DeltaF508-332 CAGAGGGUAAAAUUAAGCACAG 22 1835 CFTR-DeltaF508-333 UCAGAGGGUAAAAUUAAGCACAG 23 1836 CFTR-DeltaF508-334 UUCAGAGGGUAAAAUUAAGCACAG 24 1837 CFTR-DeltaF508-335 UCAAAGCAUGCCAACUAG 18 1838 CFTR-DeltaF508-336 AUCAAAGCAUGCCAACUAG 19 1839 CFTR-DeltaF508-337 CAUCAAAGCAUGCCAACUAG 20 669 CFTR-DeltaF508-338 UCAUCAAAGCAUGCCAACUAG 21 1840 CFTR-DeltaF508-339 GUCAUCAAAGCAUGCCAACUAG 22 1841 CFTR-DeltaF508-340 CGUCAUCAAAGCAUGCCAACUAG 23 1842 CFTR-DeltaF508-341 GCGUCAUCAAAGCAUGCCAACUAG 24 1843 CFTR-DeltaF508-342 UUCUAAUGGUGAUUAUGG 18 1844 CFTR-DeltaF508-343 CUUCUAAUGGUGAUUAUGG 19 1845 CFTR-DeltaF508-344 ACUUCUAAUGGUGAUUAUGG 20 658 CFTR-DeltaF508-345 CACUUCUAAUGGUGAUUAUGG 21 1846 CFTR-DeltaF508-346 UCACUUCUAAUGGUGAUUAUGG 22 1847 CFTR-DeltaF508-347 UUCACUUCUAAUGGUGAUUAUGG 23 1848 CFTR-DeltaF508-348 CUUCACUUCUAAUGGUGAUUAUGG 24 1849 CFTR-DeltaF508-349 AACUUUUUGAUUAUGCAU 18 1850 CFTR-DeltaF508-350 AAACUUUUUGAUUAUGCAU 19 1851 CFTR-DeltaF508-351 AAAACUUUUUGAUUAUGCAU 20 672 CFTR-DeltaF508-352 GAAAACUUUUUGAUUAUGCAU 21 1852 CFTR-DeltaF508-353 UGAAAACUUUUUGAUUAUGCAU 22 1853 CFTR-DeltaF508-354 GUGAAAACUUUUUGAUUAUGCAU 23 1854 CFTR-DeltaF508-355 UGUGAAAACUUUUUGAUUAUGCAU 24 1855 CFTR-DeltaF508-356 GAAGAGGUAAGAAACUAU 18 1856 CFTR-DeltaF508-357 AGAAGAGGUAAGAAACUAU 19 1857 CFTR-DeltaF508-358 UAGAAGAGGUAAGAAACUAU 20 671 CFTR-DeltaF508-359 CUAGAAGAGGUAAGAAACUAU 21 1858 CFTR-DeltaF508-360 ACUAGAAGAGGUAAGAAACUAU 22 1859 CFTR-DeltaF508-361 AACUAGAAGAGGUAAGAAACUAU 23 1860 CFTR-DeltaF508-362 CAACUAGAAGAGGUAAGAAACUAU 24 1861 CFTR-DeltaF508-363 ACUUCUAAUGGUGAUUAU 18 1862 CFTR-DeltaF508-364 CACUUCUAAUGGUGAUUAU 19 1863 CFTR-DeltaF508-51 UCACUUCUAAUGGUGAUUAU 20 422 CFTR-DeltaF508-365 UUCACUUCUAAUGGUGAUUAU 21 1864 CFTR-DeltaF508-366 CUUCACUUCUAAUGGUGAUUAU 22 1865 CFTR-DeltaF508-367 ACUUCACUUCUAAUGGUGAUUAU 23 1866 CFTR-DeltaF508-368 GACUUCACUUCUAAUGGUGAUUAU 24 1867 CFTR-DeltaF508-369 AUGCCAACUAGAAGAGGU 18 1868 CFTR-DeltaF508-370 CAUGCCAACUAGAAGAGGU 19 1869 CFTR-DeltaF508-371 GCAUGCCAACUAGAAGAGGU 20 670 CFTR-DeltaF508-372 AGCAUGCCAACUAGAAGAGGU 21 1870 CFTR-DeltaF508-373 AAGCAUGCCAACUAGAAGAGGU 22 1871 CFTR-DeltaF508-374 AAAGCAUGCCAACUAGAAGAGGU 23 1872 CFTR-DeltaF508-375 CAAAGCAUGCCAACUAGAAGAGGU 24 1873 CFTR-DeltaF508-376 UCACUUCUAAUGGUGAUU 18 1874 CFTR-DeltaF508-377 UUCACUUCUAAUGGUGAUU 19 1875 CFTR-DeltaF508-378 CUUCACUUCUAAUGGUGAUU 20 657 CFTR-DeltaF508-379 ACUUCACUUCUAAUGGUGAUU 21 1876 CFTR-DeltaF508-380 GACUUCACUUCUAAUGGUGAUU 22 1877 CFTR-DeltaF508-381 AGACUUCACUUCUAAUGGUGAUU 23 1878 CFTR-DeltaF508-382 CAGACUUCACUUCUAAUGGUGAUU 24 1879 CFTR-DeltaF508-383 UGGGAGAACUGGAGCCUU 18 1880 CFTR-DeltaF508-384 AUGGGAGAACUGGAGCCUU 19 1881 CFTR-DeltaF508-385 UAUGGGAGAACUGGAGCCUU 20 660 CFTR-DeltaF508-386 UUAUGGGAGAACUGGAGCCUU 21 1882 CFTR-DeltaF508-387 AUUAUGGGAGAACUGGAGCCUU 22 1883 CFTR-DeltaF508-388 GAUUAUGGGAGAACUGGAGCCUU 23 1884 CFTR-DeltaF508-389 UGAUUAUGGGAGAACUGGAGCCUU 24 1885

Table 12A provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 12A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-DeltaF508- GAAACUAUGUGAAAACU 17 924 390

Table 12B provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 12B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-16 CCAGACUUCACUUCUAA 17 438 CFTR-DeltaF508-391 + AGAAUGAAAUUCUUCCA 17 1886 CFTR-DeltaF508-392 AGGCAAGUGAAUCCUGA 17 922 CFTR-DeltaF508-393 + UCAUUAUCAAAUCACGC 17 925 CFTR-DeltaF508-394 + CUUACCUCUUCUAGUUG 17 1887 CFTR-DeltaF508-34 UUUCCAGACUUCACUUCUAA 20 420 CFTR-DeltaF508-395 UGGAGGCAAGUGAAUCCUGA 20 917 CFTR-DeltaF508-396 + UUCUAGUUGGCAUGCUUUGA 20 1888 CFTR-DeltaF508-397 + AGGUCAUUAUCAAAUCACGC 20 920 CFTR-DeltaF508-398 UAAGAAACUAUGUGAAAACU 20 919

Table 12C provides exemplary targeting domains for correcting a mutation (e.g., deltaF508) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., deltaF508). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 12C 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-DeltaF508-399 + UAGUUGGCAUGCUUUGA 17 1889 CFTR-DeltaF508-400 + AUAAAUAUAUGUAGACU 17 926 CFTR-DeltaF508-401 AUUCUGUUCUCAGUUUU 17 923 CFTR-DeltaF508-402 + AACAGAAUGAAAUUCUUCCA 20 1890 CFTR-DeltaF508-403 + UUUCUUACCUCUUCUAGUUG 20 1891 CFTR-DeltaF508-404 + AACAUAAAUAUAUGUAGACU 20 921 CFTR-DeltaF508-405 UUCAUUCUGUUCUCAGUUUU 20 918

Table 13A provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 13A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-1 GCUUUAUAUUCUGUUUC 17 466 CFTR-G542X-2 GGUGGAAUCACACUGAG 17 456 CFTR-G542X-3 GGAAUCACACUGAGUGG 17 457 CFTR-G542X-4 GUUCAAAAUUUCAACUG 17 464 CFTR-G542X-5 GGUGAAUAACUAAUUAU 17 465 CFTR-G542X-6 GGGGUUUUAUGGCUAGU 17 458 CFTR-G542X-7 GAGCAAGAAUUUCUUUAGCA 20 462 CFTR-G542X-8 GAAGGUGGAAUCACACUGAG 20 461 CFTR-G542X-9 GGUGGAAUCACACUGAGUGG 20 454

Table 13B provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 13B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G542X-10 + CUCAAUCUGAAUUUGAA 17 496 CFTR-G542X-11 CAAGAAUUUCUUUAGCA 17 491 CFTR-G542X-12 UAUAUGAUUACAUUAGA 17 485 CFTR-G542X-13 AAAAUCCUGGGGUUUUA 17 493 CFTR-G542X-14 + ACUAGCCAUAAAACCCC 17 459 CFTR-G542X-15 UGGGGUUUUAUGGCUAG 17 494 CFTR-G542X-16 AUAGUUCUUUGAGAAGG 17 1892 CFTR-G542X-17 + AUGCUCAAUCUGAAUUUGAA 20 484 CFTR-G542X-18 UGAUAUAUGAUUACAUUAGA 20 471 CFTR-G542X-19 + CCCACUAGCCAUAAAACCCC 20 455 CFTR-G542X-20 UUCUGGAAUUGAAAAAAUCC 20 477 CFTR-G542X-21 CUGGAAUUGAAAAAAUCCUG 20 479 CFTR-G542X-22 CAAGGUGAAUAACUAAUUAU 20 475 CFTR-G542X-23 CCUGGGGUUUUAUGGCUAGU 20 481

Table 13C provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 13C 3rd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G542X-24 GAAUUGAAAAAAUCCUG 17 468 CFTR-G542X-25 + GUCUUUCUCUGCAAACU 17 469 CFTR-G542X-26 GGAAUUGAAAAAAUCCU 17 467 CFTR-G542X-27 GACAAUAUAGUUCUUUGAGA 20 1893 CFTR-G542X-28 GAAAAAAUCCUGGGGUUUUA 20 463

Table 13D provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 13D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G542X-29 AAUUGCAUUUGAAAUAA 17 1894 CFTR-G542X-30 AAUAUAGUUCUUUGAGA 17 1895 CFTR-G542X-31 UGGAAUUGAAAAAAUCC 17  492 CFTR-G542X-32 UUUCUAUUUUUGGUAAU 17  487 CFTR-G542X-33 CUCUAAUUUUCUAUUUU 17  486 CFTR-G542X-34 AUAAAUUGCAUUUGAAAUAA 20 1896 CFTR-G542X-35 AUUGCUUUAUAUUCUGUUUC 20  476 CFTR-G542X-36 UCCUGGGGUUUUAUGGCUAG 20  480 CFTR-G542X-37 AAUAUAGUUCUUUGAGAAGG 20 1897 CFTR-G542X-38 AAUGUUCAAAAUUUCAACUG 20  470 CFTR-G542X-39 AAUUUUCUAUUUUUGGUAAU 20  473 CFTR-G542X-40 + AUUGUCUUUCUCUGCAAACU 20  483 CFTR-G542X-41 UCUGGAAUUGAAAAAAUCCU 20  478 CFTR-G542X-42 ACUCUCUAAUUUUCUAUUUU 20  472

Table 14A provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 14A 1st Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-43 + GAUUUUUUCAAUUCCAGAAA 20  766 CFTR-G542X-44 + GGAUUUUUUCAAUUCCAGAAA 21 1898 CFTR-G542X-45 + GUCACUUUUAGUAUGCUCAAU 21 1899 CFTR-G542X-46 + GAGUCACUUUUAGUAUGCUCAAU 23 1900 CFTR-G542X-47 GAGUGGAGGUCAACGAGC 18 1901 CFTR-G542X-48 GCAAGAAUUUCUUUAGCAAG 20  746 CFTR-G542X-49 GAGCAAGAAUUUCUUUAGCAAG 22 1902 CFTR-G542X-50 GUUUUAUGGCUAGUGGGUU 19 1903 CFTR-G542X-51 GGUUUUAUGGCUAGUGGGUU 20  751 CFTR-G542X-52 GGGUUUUAUGGCUAGUGGGUU 21 1904 CFTR-G542X-53 GGGGUUUUAUGGCUAGUGGGUU 22 1905

Table 14B provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 14B 2nd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-54 + UUUUUUCAAUUCCAGAAA 18 1906 CFTR-G542X-55 + AUUUUUUCAAUUCCAGAAA 19 1907 CFTR-G542X-56 + AGGAUUUUUUCAAUUCCAGAAA 22 1908 CFTR-G542X-57 + CAGGAUUUUUUCAAUUCCAGAAA 23 1909 CFTR-G542X-58 + CCAGGAUUUUUUCAAUUCCAGAAA 24 1910 CFTR-G542X-59 + UGUCUGUAAUUUUUUUAC 18 1911 CFTR-G542X-60 + AUGUCUGUAAUUUUUUUAC 19 1912 CFTR-G542X-61 + AAUGUCUGUAAUUUUUUUAC 20  763 CFTR-G542X-62 + CCACUAGCCAUAAAACCC 18 1913 CFTR-G542X-63 + CCCACUAGCCAUAAAACCC 19 1914 CFTR-G542X-64 + ACCCACUAGCCAUAAAACCC 20 1915 CFTR-G542X-65 + AACCCACUAGCCAUAAAACCC 21 1916 CFTR-G542X-66 + UAACCCACUAGCCAUAAAACCC 22 1917 CFTR-G542X-67 + UUAACCCACUAGCCAUAAAACCC 23 1918 CFTR-G542X-68 + CUUAACCCACUAGCCAUAAAACCC 24 1919 CFTR-G542X-69 + ACUUUUAGUAUGCUCAAU 18 1920 CFTR-G542X-70 + CACUUUUAGUAUGCUCAAU 19 1921 CFTR-G542X-71 + UCACUUUUAGUAUGCUCAAU 20  756 CFTR-G542X-72 + AGUCACUUUUAGUAUGCUCAAU 22 1922 CFTR-G542X-73 + AGAGUCACUUUUAGUAUGCUCAAU 24 1923 CFTR-G542X-74 CCUGGGGUUUUAUGGCUA 18 1924 CFTR-G542X-75 UCCUGGGGUUUUAUGGCUA 19 1925 CFTR-G542X-76 AUCCUGGGGUUUUAUGGCUA 20  750 CFTR-G542X-77 AAUCCUGGGGUUUUAUGGCUA 21 1926 CFTR-G542X-78 AAAUCCUGGGGUUUUAUGGCUA 22 1927 CFTR-G542X-79 AAAAUCCUGGGGUUUUAUGGCUA 23 1928 CFTR-G542X-80 AAAAAUCCUGGGGUUUUAUGGCUA 24 1929 CFTR-G542X-81 UGAGUGGAGGUCAACGAGC 19 1930 CFTR-G542X-82 CUGAGUGGAGGUCAACGAGC 20  745 CFTR-G542X-83 UGCUUUAUAUUCUGUUUC 18 1931 CFTR-G542X-84 UUGCUUUAUAUUCUGUUUC 19 1932 CFTR-G542X-35 AUUGCUUUAUAUUCUGUUUC 20  476 CFTR-G542X-85 UAUUGCUUUAUAUUCUGUUUC 21 1933 CFTR-G542X-86 CUAUUGCUUUAUAUUCUGUUUC 22 1934 CFTR-G542X-87 UCUAUUGCUUUAUAUUCUGUUUC 23 1935 CFTR-G542X-88 CUCUAUUGCUUUAUAUUCUGUUUC 24 1936 CFTR-G542X-89 AAGAAUUUCUUUAGCAAG 18 1937 CFTR-G542X-90 CAAGAAUUUCUUUAGCAAG 19 1938 CFTR-G542X-91 AGCAAGAAUUUCUUUAGCAAG 21 1939 CFTR-G542X-92 CGAGCAAGAAUUUCUUUAGCAAG 23 1940 CFTR-G542X-93 ACGAGCAAGAAUUUCUUUAGCAAG 24 1941 CFTR-G542X-94 UUUUAUGGCUAGUGGGUU 18 1942 CFTR-G542X-95 UGGGGUUUUAUGGCUAGUGGGUU 23 1943 CFTR-G542X-96 CUGGGGUUUUAUGGCUAGUGGGUU 24 1944

Table 14C provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 14C 3rd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-97 + GAAAUGUCUGUAAUUUUUUUAC 22 1945 CFTR-G542X-98 + GAGAAAUGUCUGUAAUUUUUUUAC 24 1946 CFTR-G542X-99 GUUCUUUGAGAAGGUGGAAUCACA 24 1947 CFTR-G542X-100 GUUUCUGGAAUUGAAAAAAUCC 22 1948 CFTR-G542X-101 GACAAUAUAGUUCUUUGAGAAGG 23 1949

Table 14D provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 14D 4th Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-102 + ACCAAAAAUAGAAAAUUA 18 1950 CFTR-G542X-103 + UACCAAAAAUAGAAAAUUA 19 1951 CFTR-G542X-104 + UUACCAAAAAUAGAAAAUUA 20  757 CFTR-G542X-105 + AUUACCAAAAAUAGAAAAUUA 21 1952 CFTR-G542X-106 + UAUUACCAAAAAUAGAAAAUUA 22 1953 CFTR-G542X-107 + CUAUUACCAAAAAUAGAAAAUUA 23 1954 CFTR-G542X-108 + CCUAUUACCAAAAAUAGAAAAUUA 24 1955 CFTR-G542X-109 + AAAUGUCUGUAAUUUUUUUAC 21 1956 CFTR-G542X-110 + AGAAAUGUCUGUAAUUUUUUUAC 23 1957 CFTR-G542X-111 UGAGAAGGUGGAAUCACA 18 1958 CFTR-G542X-112 UUGAGAAGGUGGAAUCACA 19 1959 CFTR-G542X-113 UUUGAGAAGGUGGAAUCACA 20 1960 CFTR-G542X-114 CUUUGAGAAGGUGGAAUCACA 21 1961 CFTR-G542X-115 UCUUUGAGAAGGUGGAAUCACA 22 1962 CFTR-G542X-116 UUCUUUGAGAAGGUGGAAUCACA 23 1963 CFTR-G542X-117 CUGGAAUUGAAAAAAUCC 18 1964 CFTR-G542X-118 UCUGGAAUUGAAAAAAUCC 19 1965 CFTR-G542X-20 UUCUGGAAUUGAAAAAAUCC 20  477 CFTR-G542X-119 UUUCUGGAAUUGAAAAAAUCC 21 1966 CFTR-G542X-120 UGUUUCUGGAAUUGAAAAAAUCC 23 1967 CFTR-G542X-121 CUGUUUCUGGAAUUGAAAAAAUCC 24 1968 CFTR-G542X-122 ACUGAGUGGAGGUCAACGAGC 21 1969 CFTR-G542X-123 CACUGAGUGGAGGUCAACGAGC 22 1970 CFTR-G542X-124 ACACUGAGUGGAGGUCAACGAGC 23 1971 CFTR-G542X-125 CACACUGAGUGGAGGUCAACGAGC 24 1972 CFTR-G542X-126 UAUAGUUCUUUGAGAAGG 18 1973 CFTR-G542X-127 AUAUAGUUCUUUGAGAAGG 19 1974 CFTR-G542X-37 AAUAUAGUUCUUUGAGAAGG 20 1897 CFTR-G542X-128 CAAUAUAGUUCUUUGAGAAGG 21 1975 CFTR-G542X-129 ACAAUAUAGUUCUUUGAGAAGG 22 1976 CFTR-G542X-130 AGACAAUAUAGUUCUUUGAGAAGG 24 1977

Table 14E provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 14E 5th Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-131 + AUGUCCUAUUACCAAAAA 18 1978 CFTR-G542X-132 + GAUGUCCUAUUACCAAAAA 19 1979 CFTR-G542X-133 + AGAUGUCCUAUUACCAAAAA 20 759 CFTR-G542X-134 + GAGAUGUCCUAUUACCAAAAA 21 1980 CFTR-G542X-135 + GGAGAUGUCCUAUUACCAAAAA 22 1981 CFTR-G542X-136 + UGGAGAUGUCCUAUUACCAAAAA 23 1982 CFTR-G542X-137 + UUGGAGAUGUCCUAUUACCAAAAA 24 1983 CFTR-G542X-138 + AAACAGAAUAUAAAGCAA 18 1984 CFTR-G542X-139 + GAAACAGAAUAUAAAGCAA 19 1985 CFTR-G542X-140 + AGAAACAGAAUAUAAAGCAA 20  765 CFTR-G542X-141 + CAGAAACAGAAUAUAAAGCAA 21 1986 CFTR-G542X-142 + CCAGAAACAGAAUAUAAAGCAA 22 1987 CFTR-G542X-143 + UCCAGAAACAGAAUAUAAAGCAA 23 1988 CFTR-G542X-144 + UUCCAGAAACAGAAUAUAAAGCAA 24 1989 CFTR-G542X-145 + UGUGAUUCCACCUUCUCA 18 1990 CFTR-G542X-146 + GUGUGAUUCCACCUUCUCA 19 1991 CFTR-G542X-147 + AGUGUGAUUCCACCUUCUCA 20 1992 CFTR-G542X-148 + CAGUGUGAUUCCACCUUCUCA 21 1993 CFTR-G542X-149 + UCAGUGUGAUUCCACCUUCUCA 22 1994 CFTR-G542X-150 + CUCAGUGUGAUUCCACCUUCUCA 23 1995 CFTR-G542X-151 + ACUCAGUGUGAUUCCACCUUCUCA 24 1996 CFTR-G542X-152 + ACAGAAUAUAAAGCAAUA 18 1997 CFTR-G542X-153 + AACAGAAUAUAAAGCAAUA 19 1998 CFTR-G542X-154 + AAACAGAAUAUAAAGCAAUA 20  764 CFTR-G542X-155 + GAAACAGAAUAUAAAGCAAUA 21 1999 CFTR-G542X-156 + AGAAACAGAAUAUAAAGCAAUA 22 2000 CFTR-G542X-157 + CAGAAACAGAAUAUAAAGCAAUA 23 2001 CFTR-G542X-158 + CCAGAAACAGAAUAUAAAGCAAUA 24 2002 CFTR-G542X-159 + UAGUUAUUCACCUUGCUA 18 2003 CFTR-G542X-160 + UUAGUUAUUCACCUUGCUA 19 2004 CFTR-G542X-161 + AUUAGUUAUUCACCUUGCUA 20  762 CFTR-G542X-162 + AAUUAGUUAUUCACCUUGCUA 21 2005 CFTR-G542X-163 + UAAUUAGUUAUUCACCUUGCUA 22 2006 CFTR-G542X-164 + AUAAUUAGUUAUUCACCUUGCUA 23 2007 CFTR-G542X-165 + AAUAAUUAGUUAUUCACCUUGCUA 24 2008 CFTR-G542X-166 + UUGUCUUUCUCUGCAAAC 18 2009 CFTR-G542X-167 + AUUGUCUUUCUCUGCAAAC 19 2010 CFTR-G542X-168 + UAUUGUCUUUCUCUGCAAAC 20  760 CFTR-G542X-169 + AUAUUGUCUUUCUCUGCAAAC 21 2011 CFTR-G542X-170 + UAUAUUGUCUUUCUCUGCAAAC 22 2012 CFTR-G542X-171 + CUAUAUUGUCUUUCUCUGCAAAC 23 2013 CFTR-G542X-172 + ACUAUAUUGUCUUUCUCUGCAAAC 24 2014 CFTR-G542X-173 + CCAGGAUUUUUUCAAUUC 18 2015 CFTR-G542X-174 + CCCAGGAUUUUUUCAAUUC 19 2016 CFTR-G542X-175 + CCCCAGGAUUUUUUCAAUUC 20  767 CFTR-G542X-176 + ACCCCAGGAUUUUUUCAAUUC 21 2017 CFTR-G542X-177 + AACCCCAGGAUUUUUUCAAUUC 22 2018 CFTR-G542X-178 + AAACCCCAGGAUUUUUUCAAUUC 23 2019 CFTR-G542X-179 + AAAACCCCAGGAUUUUUUCAAUUC 24 2020 CFTR-G542X-180 + CUAUUGCUUUAACCACAG 18 2021 CFTR-G542X-181 + ACUAUUGCUUUAACCACAG 19 2022 CFTR-G542X-182 + CACUAUUGCUUUAACCACAG 20  754 CFTR-G542X-183 + ACACUAUUGCUUUAACCACAG 21 2023 CFTR-G542X-184 + CACACUAUUGCUUUAACCACAG 22 2024 CFTR-G542X-185 + UCACACUAUUGCUUUAACCACAG 23 2025 CFTR-G542X-186 + AUCACACUAUUGCUUUAACCACAG 24 2026 CFTR-G542X-187 + UUACCAAAAAUAGAAAAU 18 2027 CFTR-G542X-188 + AUUACCAAAAAUAGAAAAU 19 2028 CFTR-G542X-189 + UAUUACCAAAAAUAGAAAAU 20  758 CFTR-G542X-190 + CUAUUACCAAAAAUAGAAAAU 21 2029 CFTR-G542X-191 + CCUAUUACCAAAAAUAGAAAAU 22 2030 CFTR-G542X-192 + UCCUAUUACCAAAAAUAGAAAAU 23 2031 CFTR-G542X-193 + GUCCUAUUACCAAAAAUAGAAAAU 24 2032 CFTR-G542X-194 + AGUAUGCUCAAUCUGAAU 18 2033 CFTR-G542X-195 + UAGUAUGCUCAAUCUGAAU 19 2034 CFTR-G542X-196 + UUAGUAUGCUCAAUCUGAAU 20  755 CFTR-G542X-197 + UUUAGUAUGCUCAAUCUGAAU 21 2035 CFTR-G542X-198 + UUUUAGUAUGCUCAAUCUGAAU 22 2036 CFTR-G542X-199 + CUUUUAGUAUGCUCAAUCUGAAU 23 2037 CFTR-G542X-200 + ACUUUUAGUAUGCUCAAUCUGAAU 24 2038 CFTR-G542X-201 + UGUCUUUCUCUGCAAACU 18 2039 CFTR-G542X-202 + UUGUCUUUCUCUGCAAACU 19 2040 CFTR-G542X-40 + AUUGUCUUUCUCUGCAAACU 20  483 CFTR-G542X-203 + UAUUGUCUUUCUCUGCAAACU 21 2041 CFTR-G542X-204 + AUAUUGUCUUUCUCUGCAAACU 22 2042 CFTR-G542X-205 + UAUAUUGUCUUUCUCUGCAAACU 23 2043 CFTR-G542X-206 + CUAUAUUGUCUUUCUCUGCAAACU 24 2044 CFTR-G542X-207 + UUAACCACAGUUGAAAUU 18 2045 CFTR-G542X-208 + UUUAACCACAGUUGAAAUU 19 2046 CFTR-G542X-209 + CUUUAACCACAGUUGAAAUU 20  753 CFTR-G542X-210 + GCUUUAACCACAGUUGAAAUU 21 2047 CFTR-G542X-211 + UGCUUUAACCACAGUUGAAAUU 22 2048 CFTR-G542X-212 + UUGCUUUAACCACAGUUGAAAUU 23 2049 CFTR-G542X-213 + AUUGCUUUAACCACAGUUGAAAUU 24 2050 CFTR-G542X-214 UAUAUUCUGUUUCUGGAA 18 2051 CFTR-G542X-215 UUAUAUUCUGUUUCUGGAA 19 2052 CFTR-G542X-216 UUUAUAUUCUGUUUCUGGAA 20  748 CFTR-G542X-217 CUUUAUAUUCUGUUUCUGGAA 21 2053 CFTR-G542X-218 GCUUUAUAUUCUGUUUCUGGAA 22 2054 CFTR-G542X-219 UGCUUUAUAUUCUGUUUCUGGAA 23 2055 CFTR-G542X-220 UUGCUUUAUAUUCUGUUUCUGGAA 24 2056 CFTR-G542X-221 AAAUUGCAUUUGAAAUAA 18 2057 CFTR-G542X-222 UAAAUUGCAUUUGAAAUAA 19 2058 CFTR-G542X-34 AUAAAUUGCAUUUGAAAUAA 20 1896 CFTR-G542X-223 AUUUUCUAUUUUUGGUAA 18 2059 CFTR-G542X-224 AAUUUUCUAUUUUUGGUAA 19 2060 CFTR-G542X-225 UAAUUUUCUAUUUUUGGUAA 20  736 CFTR-G542X-226 CUAAUUUUCUAUUUUUGGUAA 21 2061 CFTR-G542X-227 UCUAAUUUUCUAUUUUUGGUAA 22 2062 CFTR-G542X-228 CUCUAAUUUUCUAUUUUUGGUAA 23 2063 CFTR-G542X-229 UCUCUAAUUUUCUAUUUUUGGUAA 24 2064 CFTR-G542X-230 GACAUCUCCAAGUUUGCA 18 2065 CFTR-G542X-231 GGACAUCUCCAAGUUUGCA 19 2066 CFTR-G542X-232 AGGACAUCUCCAAGUUUGCA 20  738 CFTR-G542X-233 UAGGACAUCUCCAAGUUUGCA 21 2067 CFTR-G542X-234 AUAGGACAUCUCCAAGUUUGCA 22 2068 CFTR-G542X-235 AAUAGGACAUCUCCAAGUUUGCA 23 2069 CFTR-G542X-236 UAAUAGGACAUCUCCAAGUUUGCA 24 2070 CFTR-G542X-237 CACACUGAGUGGAGGUCA 18 2071 CFTR-G542X-238 UCACACUGAGUGGAGGUCA 19 2072 CFTR-G542X-239 AUCACACUGAGUGGAGGUCA 20  744 CFTR-G542X-240 AAUCACACUGAGUGGAGGUCA 21 2073 CFTR-G542X-241 GAAUCACACUGAGUGGAGGUCA 22 2074 CFTR-G542X-242 GGAAUCACACUGAGUGGAGGUCA 23 2075 CFTR-G542X-243 UGGAAUCACACUGAGUGGAGGUCA 24 2076 CFTR-G542X-244 GUGCCUUUCAAAUUCAGA 18 2077 CFTR-G542X-245 UGUGCCUUUCAAAUUCAGA 19 2078 CFTR-G542X-246 AUGUGCCUUUCAAAUUCAGA 20  735 CFTR-G542X-247 GAUGUGCCUUUCAAAUUCAGA 21 2079 CFTR-G542X-248 AGAUGUGCCUUUCAAAUUCAGA 22 2080 CFTR-G542X-249 AAGAUGUGCCUUUCAAAUUCAGA 23 2081 CFTR-G542X-250 GAAGAUGUGCCUUUCAAAUUCAGA 24 2082 CFTR-G542X-251 AUAUAUGAUUACAUUAGA 18 2083 CFTR-G542X-252 GAUAUAUGAUUACAUUAGA 19 2084 CFTR-G542X-18 UGAUAUAUGAUUACAUUAGA 20  471 CFTR-G542X-253 GUGAUAUAUGAUUACAUUAGA 21 2085 CFTR-G542X-254 UGUGAUAUAUGAUUACAUUAGA 22 2086 CFTR-G542X-255 GUGUGAUAUAUGAUUACAUUAGA 23 2087 CFTR-G542X-256 AGUGUGAUAUAUGAUUACAUUAGA 24 2088 CFTR-G542X-257 AAGGUGGAAUCACACUGA 18 2089 CFTR-G542X-258 GAAGGUGGAAUCACACUGA 19 2090 CFTR-G542X-259 AGAAGGUGGAAUCACACUGA 20  743 CFTR-G542X-260 GAGAAGGUGGAAUCACACUGA 21 2091 CFTR-G542X-261 UGAGAAGGUGGAAUCACACUGA 22 2092 CFTR-G542X-262 UUGAGAAGGUGGAAUCACACUGA 23 2093 CFTR-G542X-263 UUUGAGAAGGUGGAAUCACACUGA 24 2094 CFTR-G542X-264 UAAAUUGCAUUUGAAAUA 18 2095 CFTR-G542X-265 AUAAAUUGCAUUUGAAAUA 19 2096 CFTR-G542X-266 AAUAAAUUGCAUUUGAAAUA 20 2097 CFTR-G542X-267 UCUGGAAUUGAAAAAAUC 18 2098 CFTR-G542X-268 UUCUGGAAUUGAAAAAAUC 19 2099 CFTR-G542X-269 UUUCUGGAAUUGAAAAAAUC 20  749 CFTR-G542X-270 GUUUCUGGAAUUGAAAAAAUC 21 2100 CFTR-G542X-271 UGUUUCUGGAAUUGAAAAAAUC 22 2101 CFTR-G542X-272 CUGUUUCUGGAAUUGAAAAAAUC 23 2102 CFTR-G542X-273 UCUGUUUCUGGAAUUGAAAAAAUC 24 2103 CFTR-G542X-274 AUAUAGUUCUUUGAGAAG 18 2104 CFTR-G542X-275 AAUAUAGUUCUUUGAGAAG 19 2105 CFTR-G542X-276 CAAUAUAGUUCUUUGAGAAG 20 2106 CFTR-G542X-277 ACAAUAUAGUUCUUUGAGAAG 21 2107 CFTR-G542X-278 GACAAUAUAGUUCUUUGAGAAG 22 2108 CFTR-G542X-279 AGACAAUAUAGUUCUUUGAGAAG 23 2109 CFTR-G542X-280 AAGACAAUAUAGUUCUUUGAGAAG 24 2110 CFTR-G542X-281 AGGUGGAAUCACACUGAG 18 2111 CFTR-G542X-282 AAGGUGGAAUCACACUGAG 19 2112 CFTR-G542X-8 GAAGGUGGAAUCACACUGAG 20  461 CFTR-G542X-283 AGAAGGUGGAAUCACACUGAG 21 2113 CFTR-G542X-284 GAGAAGGUGGAAUCACACUGAG 22 2114 CFTR-G542X-285 UGAGAAGGUGGAAUCACACUGAG 23 2115 CFTR-G542X-286 UUGAGAAGGUGGAAUCACACUGAG 24 2116 CFTR-G542X-287 GAUAUAUGAUUACAUUAG 18 2117 CFTR-G542X-288 UGAUAUAUGAUUACAUUAG 19 2118 CFTR-G542X-289 GUGAUAUAUGAUUACAUUAG 20  734 CFTR-G542X-290 UGUGAUAUAUGAUUACAUUAG 21 2119 CFTR-G542X-291 GUGUGAUAUAUGAUUACAUUAG 22 2120 CFTR-G542X-292 AGUGUGAUAUAUGAUUACAUUAG 23 2121 CFTR-G542X-293 UAGUGUGAUAUAUGAUUACAUUAG 24 2122 CFTR-G542X-294 AGGACAUCUCCAAGUUUG 18 2123 CFTR-G542X-295 UAGGACAUCUCCAAGUUUG 19 2124 CFTR-G542X-296 AUAGGACAUCUCCAAGUUUG 20  737 CFTR-G542X-297 AAUAGGACAUCUCCAAGUUUG 21 2125 CFTR-G542X-298 UAAUAGGACAUCUCCAAGUUUG 22 2126 CFTR-G542X-299 GUAAUAGGACAUCUCCAAGUUUG 23 2127 CFTR-G542X-300 GGUAAUAGGACAUCUCCAAGUUUG 24 2128 CFTR-G542X-301 UGUGAUAUAUGAUUACAU 18 2129 CFTR-G542X-302 GUGUGAUAUAUGAUUACAU 19 2130 CFTR-G542X-303 AGUGUGAUAUAUGAUUACAU 20  733 CFTR-G542X-304 UAGUGUGAUAUAUGAUUACAU 21 2131 CFTR-G542X-305 AUAGUGUGAUAUAUGAUUACAU 22 2132 CFTR-G542X-306 AAUAGUGUGAUAUAUGAUUACAU 23 2133 CFTR-G542X-307 CAAUAGUGUGAUAUAUGAUUACAU 24 2134 CFTR-G542X-308 GAAAGACAAUAUAGUUCU 18 2135 CFTR-G542X-309 AGAAAGACAAUAUAGUUCU 19 2136 CFTR-G542X-310 GAGAAAGACAAUAUAGUUCU 20  453 CFTR-G542X-311 AGAGAAAGACAAUAUAGUUCU 21 2137 CFTR-G542X-312 CAGAGAAAGACAAUAUAGUUCU 22 2138 CFTR-G542X-313 GCAGAGAAAGACAAUAUAGUUCU 23 2139 CFTR-G542X-314 UGCAGAGAAAGACAAUAUAGUUCU 24 2140 CFTR-G542X-315 AAGACAAUAUAGUUCUUU 18 2141 CFTR-G542X-316 AAAGACAAUAUAGUUCUUU 19 2142 CFTR-G542X-317 GAAAGACAAUAUAGUUCUUU 20 2143 CFTR-G542X-318 AGAAAGACAAUAUAGUUCUUU 21 2144 CFTR-G542X-319 GAGAAAGACAAUAUAGUUCUUU 22 2145 CFTR-G542X-320 AGAGAAAGACAAUAUAGUUCUUU 23 2146 CFTR-G542X-321 CAGAGAAAGACAAUAUAGUUCUUU 24 2147 CFTR-G542X-322 UUGCUUUAUAUUCUGUUU 18 2148 CFTR-G542X-323 AUUGCUUUAUAUUCUGUUU 19 2149 CFTR-G542X-324 UAUUGCUUUAUAUUCUGUUU 20  747 CFTR-G542X-325 CUAUUGCUUUAUAUUCUGUUU 21 2150 CFTR-G542X-326 UCUAUUGCUUUAUAUUCUGUUU 22 2151 CFTR-G542X-327 CUCUAUUGCUUUAUAUUCUGUUU 23 2152 CFTR-G542X-328 UCUCUAUUGCUUUAUAUUCUGUUU 24 2153

Table 15A provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 15A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G542X-329 + GUAAUCAUAUAUCACAC 17 2154 CFTR-G542X-330 GGUUAAAGCAAUAGUGUGAU 20  927

Table 15B provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 15B 2nd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-331 + UCGUUGACCUCCACUCA 17  934 CFTR-G542X-332 + CCACUAGCCAUAAAACC 17  935 CFTR-G542X-333 + UGAAUGACAUUUACAGC 17 2155 CFTR-G542X-334 UAAAGCAAUAGUGUGAU 17  932 CFTR-G542X-335 AGGAAGAUGUGCCUUUCAAA 20  928 CFTR-G542X-336 + UGCUCGUUGACCUCCACUCA 20  929 CFTR-G542X-337 + AAUGUAAUCAUAUAUCACAC 20 2156 CFTR-G542X-338 + AACCCACUAGCCAUAAAACC 20  930 CFTR-G542X-339 + ACAUGAAUGACAUUUACAGC 20 2157

Table 15C provides exemplary targeting domains for correcting a mutation (e.g., G542X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G542X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 15C 4th Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G542X-340 AAGAUGUGCCUUUCAAA 17  933 CFTR-G542X-341 AAUUACAGACAUUUCUC 17 2158 CFTR-G542X-342 AAAAAUUACAGACAUUUCUC 20 2159

Table 16A provides exemplary targeting domains for correcting a mutation (e.g., G55D) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 16A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G551D-1 GCUUUAUAUUCUGUUUC 17 466 CFTR-G551D-2 GGUGGAAUCACACUGAG 17 456 CFTR-G551D-3 GUUCAAAAUUUCAACUG 17 464 CFTR-G551D-4 GGUGAAUAACUAAUUAU 17 465 CFTR-G551D-5 GGGGUUUUAUGGCUAGU 17 458 CFTR-G551D-6 GAGCAAGAAUUUCUUUAGCA 20 462 CFTR-G551D-7 GACAAUAUAGUUCUUGGAGA 20 460 CFTR-G551D-8 GAAGGUGGAAUCACACUGAG 20 461 CFTR-G551D-9 GAGAAAGACAAUAUAGUUCU 20 453

Table 16B provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G55D) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 16B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G551D-10 + CUCAAUCUGAAUUUGAA 17 496 CFTR-G551D-11 CAAGAAUUUCUUUAGCA 17 491 CFTR-G551D-12 AAUAUAGUUCUUGGAGA 17 489 CFTR-G551D-13 UAUAUGAUUACAUUAGA 17 485 CFTR-G551D-14 AAAAUCCUGGGGUUUUA 17 493 CFTR-G551D-15 + ACUAGCCAUAAAACCCC 17 459 CFTR-G551D-16 UGGGGUUUUAUGGCUAG 17 494 CFTR-G551D-17 AUAGUUCUUGGAGAAGG 17 490 CFTR-G551D-18 AAAGACAAUAUAGUUCU 17 488 CFTR-G551D-19 + AUGCUCAAUCUGAAUUUGAA 20 484 CFTR-G551D-20 UGAUAUAUGAUUACAUUAGA 20 471 CFTR-G551D-21 + CCCACUAGCCAUAAAACCCC 20 455 CFTR-G551D-22 UUCUGGAAUUGAAAAAAUCC 20 477 CFTR-G551D-23 AAUAUAGUUCUUGGAGAAGG 20 474 CFTR-G551D-24 CUGGAAUUGAAAAAAUCCUG 20 479 CFTR-G551D-25 CAAGGUGAAUAACUAAUUAU 20 475 CFTR-G551D-26 CCUGGGGUUUUAUGGCUAGU 20 481

Table 16C provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 16C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G551D-27 GAAUUGAAAAAAUCCUG 17 468 CFTR-G551D-28 + GUCUUUCUCUGCAAACU 17 469 CFTR-G551D-29 GGAAUUGAAAAAAUCCU 17 467 CFTR-G551D-30 GAAAAAAUCCUGGGGUUUUA 20 463

Table 16D provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 16D 4th Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G551D-31 UUAAGAACUAUAAAUAA 17 495 CFTR-G551D-32 UGGAAUUGAAAAAAUCC 17 492 CFTR-G551D-33 UUUCUAUUUUUGGUAAU 17 487 CFTR-G551D-34 CUCUAAUUUUCUAUUUU 17 486 CFTR-G551D-35 CAUUUAAGAACUAUAAAUAA 20 482 CFTR-G551D-36 AUUGCUUUAUAUUCUGUUUC 20 476 CFTR-G551D-37 UCCUGGGGUUUUAUGGCUAG 20 480 CFTR-G551D-38 AAUGUUCAAAAUUUCAACUG 20 470 CFTR-G551D-39 AAUUUUCUAUUUUUGGUAAU 20 473 CFTR-G551D-40 + AUUGUCUUUCUCUGCAAACU 20 483 CFTR-G551D-41 UCUGGAAUUGAAAAAAUCCU 20 478 CFTR-G551D-42 ACUCUCUAAUUUUCUAUUUU 20 472

Table 17A provides exemplary targeting domains for correcting a mutation (e.g., G55D) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 17A 1st Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G551D-43 + GAUUUUUUCAAUUCCAGAAA 20  766 CFTR-G551D-44 + GGAUUUUUUCAAUUCCAGAAA 21 1898 CFTR-G551D-45 + GUCACUUUUAGUAUGCUCAAU 21 1899 CFTR-G551D-46 + GAGUCACUUUUAGUAUGCUCAAU 23 1900 CFTR-G551D-47 GGAGAAGGUGGAAUCACA 18 2160 CFTR-G551D-48 GUUCUUGGAGAAGGUGGAAUCACA 24 2161 CFTR-G551D-49 GCAAGAAUUUCUUUAGCAAG 20  746 CFTR-G551D-50 GAGCAAGAAUUUCUUUAGCAAG 22 1902 CFTR-G551D-51 GACAAUAUAGUUCUUGGAGAAGG 23 2162 CFTR-G551D-52 GUUUUAUGGCUAGUGGGUU 19 1903 CFTR-G551D-53 GGUUUUAUGGCUAGUGGGUU 20  751 CFTR-G551D-54 GGGUUUUAUGGCUAGUGGGUU 21 1904 CFTR-G551D-55 GGGGUUUUAUGGCUAGUGGGUU 22 1905

Table 17B provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G55AD), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 17B 2nd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G551D-56 + UUUUUUCAAUUCCAGAAA 18 1906 CFTR-G551D-57 + AUUUUUUCAAUUCCAGAAA 19 1907 CFTR-G551D-58 + AGGAUUUUUUCAAUUCCAGAAA 22 1908 CFTR-G551D-59 + CAGGAUUUUUUCAAUUCCAGAAA 23 1909 CFTR-G551D-60 + CCAGGAUUUUUUCAAUUCCAGAAA 24 1910 CFTR-G551D-61 + UGUCUGUAAUUUUUUUAC 18 1911 CFTR-G551D-62 + AUGUCUGUAAUUUUUUUAC 19 1912 CFTR-G551D-63 + AAUGUCUGUAAUUUUUUUAC 20  763 CFTR-G551D-64 + CCACUAGCCAUAAAACCC 18 1913 CFTR-G551D-65 + CCCACUAGCCAUAAAACCC 19 1914 CFTR-G551D-66 + ACCCACUAGCCAUAAAACCC 20 1915 CFTR-G551D-67 + AACCCACUAGCCAUAAAACCC 21 1916 CFTR-G551D-68 + UAACCCACUAGCCAUAAAACCC 22 1917 CFTR-G551D-69 + UUAACCCACUAGCCAUAAAACCC 23 1918 CFTR-G551D-70 + CUUAACCCACUAGCCAUAAAACCC 24 1919 CFTR-G551D-71 + ACUUUUAGUAUGCUCAAU 18 1920 CFTR-G551D-72 + CACUUUUAGUAUGCUCAAU 19 1921 CFTR-G551D-73 + UCACUUUUAGUAUGCUCAAU 20  756 CFTR-G551D-74 + AGUCACUUUUAGUAUGCUCAAU 22 1922 CFTR-G551D-75 + AGAGUCACUUUUAGUAUGCUCAAU 24 1923 CFTR-G551D-76 UGGAGAAGGUGGAAUCACA 19 2163 CFTR-G551D-77 UUGGAGAAGGUGGAAUCACA 20  742 CFTR-G551D-78 CUUGGAGAAGGUGGAAUCACA 21 2164 CFTR-G551D-79 UCUUGGAGAAGGUGGAAUCACA 22 2165 CFTR-G551D-80 UUCUUGGAGAAGGUGGAAUCACA 23 2166 CFTR-G551D-81 CCUGGGGUUUUAUGGCUA 18 1924 CFTR-G551D-82 UCCUGGGGUUUUAUGGCUA 19 1925 CFTR-G551D-83 AUCCUGGGGUUUUAUGGCUA 20  750 CFTR-G551D-84 AAUCCUGGGGUUUUAUGGCUA 21 1926 CFTR-G551D-85 AAAUCCUGGGGUUUUAUGGCUA 22 1927 CFTR-G551D-86 AAAAUCCUGGGGUUUUAUGGCUA 23 1928 CFTR-G551D-87 AAAAAUCCUGGGGUUUUAUGGCUA 24 1929 CFTR-G551D-88 UGCUUUAUAUUCUGUUUC 18 1931 CFTR-G551D-89 UUGCUUUAUAUUCUGUUUC 19 1932 CFTR-G551D-36 AUUGCUUUAUAUUCUGUUUC 20  476 CFTR-G551D-90 UAUUGCUUUAUAUUCUGUUUC 21 1933 CFTR-G551D-91 CUAUUGCUUUAUAUUCUGUUUC 22 1934 CFTR-G551D-92 UCUAUUGCUUUAUAUUCUGUUUC 23 1935 CFTR-G551D-93 CUCUAUUGCUUUAUAUUCUGUUUC 24 1936 CFTR-G551D-94 AAGAAUUUCUUUAGCAAG 18 1937 CFTR-G551D-95 CAAGAAUUUCUUUAGCAAG 19 1938 CFTR-G551D-96 AGCAAGAAUUUCUUUAGCAAG 21 1939 CFTR-G551D-97 CGAGCAAGAAUUUCUUUAGCAAG 23 1940 CFTR-G551D-98 ACGAGCAAGAAUUUCUUUAGCAAG 24 1941 CFTR-G551D-99 UAUAGUUCUUGGAGAAGG 18 2167 CFTR-G551D-100 AUAUAGUUCUUGGAGAAGG 19 2168 CFTR-G551D-23 AAUAUAGUUCUUGGAGAAGG 20  474 CFTR-G551D-101 CAAUAUAGUUCUUGGAGAAGG 21 2169 CFTR-G551D-102 ACAAUAUAGUUCUUGGAGAAGG 22 2170 CFTR-G551D-103 AGACAAUAUAGUUCUUGGAGAAGG 24 2171 CFTR-G551D-104 UUUUAUGGCUAGUGGGUU 18 1942 CFTR-G551D-105 UGGGGUUUUAUGGCUAGUGGGUU 23 1943 CFTR-G551D-106 CUGGGGUUUUAUGGCUAGUGGGUU 24 1944

Table 17C provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 17C 3rd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G551D-107 + GAAAUGUCUGUAAUUUUUUUAC 22 1945 CFTR-G551D-108 + GAGAAAUGUCUGUAAUUUUUUUAC 24 1946 CFTR-G551D-109 GUUUCUGGAAUUGAAAAAAUCC 22 1948 CFTR-G551D-110 GAGUGGAGAUCAACGAGC 18 2172

Table 17D provides exemplary targeting domains for correcting a mutation (e.g., G55D) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G555D), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 17D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G551D-111 + ACCAAAAAUAGAAAAUUA 18 1950 CFTR-G551D-112 + UACCAAAAAUAGAAAAUUA 19 1951 CFTR-G551D-113 + UUACCAAAAAUAGAAAAUUA 20 757 CFTR-G551D-114 + AUUACCAAAAAUAGAAAAUUA 21 1952 CFTR-G551D-115 + UAUUACCAAAAAUAGAAAAUUA 22 1953 CFTR-G551D-116 + CUAUUACCAAAAAUAGAAAAUUA 23 1954 CFTR-G551D-117 + CCUAUUACCAAAAAUAGAAAAUUA 24 1955 CFTR-G551D-118 + AAAUGUCUGUAAUUUUUUUAC 21 1956 CFTR-G551D-119 + AGAAAUGUCUGUAAUUUUUUUAC 23 1957 CFTR-G551D-120 CUGGAAUUGAAAAAAUCC 18 1964 CFTR-G551D-121 UCUGGAAUUGAAAAAAUCC 19 1965 CFTR-G551D-22 UUCUGGAAUUGAAAAAAUCC 20 477 CFTR-G551D-122 UUUCUGGAAUUGAAAAAAUCC 21 1966 CFTR-G551D-123 UGUUUCUGGAAUUGAAAAAAUCC 23 1967 CFTR-G551D-124 CUGUUUCUGGAAUUGAAAAAAUCC 24 1968 CFTR-G551D-125 UGAGUGGAGAUCAACGAGC 19 2173 CFTR-G551D-126 CUGAGUGGAGAUCAACGAGC 20 2174 CFTR-G551D-127 ACUGAGUGGAGAUCAACGAGC 21 2175 CFTR-G551D-128 CACUGAGUGGAGAUCAACGAGC 22 2176 CFTR-G551D-129 ACACUGAGUGGAGAUCAACGAGC 23 2177 CFTR-G551D-130 CACACUGAGUGGAGAUCAACGAGC 24 2178

Table 17E provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 17E 5th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G551D-131 + AUGUCCUAUUACCAAAAA 18 1978 CFTR-G551D-132 + GAUGUCCUAUUACCAAAAA 19 1979 CFTR-G551D-133 + AGAUGUCCUAUUACCAAAAA 20 759 CFTR-G551D-134 + GAGAUGUCCUAUUACCAAAAA 21 1980 CFTR-G551D-135 + GGAGAUGUCCUAUUACCAAAAA 22 1981 CFTR-G551D-136 + UGGAGAUGUCCUAUUACCAAAAA 23 1982 CFTR-G551D-137 + UUGGAGAUGUCCUAUUACCAAAAA 24 1983 CFTR-G551D-138 + AAACAGAAUAUAAAGCAA 18 1984 CFTR-G551D-139 + GAAACAGAAUAUAAAGCAA 19 1985 CFTR-G551D-140 + AGAAACAGAAUAUAAAGCAA 20 765 CFTR-G551D-141 + CAGAAACAGAAUAUAAAGCAA 21 1986 CFTR-G551D-142 + CCAGAAACAGAAUAUAAAGCAA 22 1987 CFTR-G551D-143 + UCCAGAAACAGAAUAUAAAGCAA 23 1988 CFTR-G551D-144 + UUCCAGAAACAGAAUAUAAAGCAA 24 1989 CFTR-G551D-145 + ACAGAAUAUAAAGCAAUA 18 1997 CFTR-G551D-146 + AACAGAAUAUAAAGCAAUA 19 1998 CFTR-G551D-147 + AAACAGAAUAUAAAGCAAUA 20 764 CFTR-G551D-148 + GAAACAGAAUAUAAAGCAAUA 21 1999 CFTR-G551D-149 + AGAAACAGAAUAUAAAGCAAUA 22 2000 CFTR-G551D-150 + CAGAAACAGAAUAUAAAGCAAUA 23 2001 CFTR-G551D-151 + CCAGAAACAGAAUAUAAAGCAAUA 24 2002 CFTR-G551D-152 + UAGUUAUUCACCUUGCUA 18 2003 CFTR-G551D-153 + UUAGUUAUUCACCUUGCUA 19 2004 CFTR-G551D-154 + AUUAGUUAUUCACCUUGCUA 20 762 CFTR-G551D-155 + AAUUAGUUAUUCACCUUGCUA 21 2005 CFTR-G551D-156 + UAAUUAGUUAUUCACCUUGCUA 22 2006 CFTR-G551D-157 + AUAAUUAGUUAUUCACCUUGCUA 23 2007 CFTR-G551D-158 + AAUAAUUAGUUAUUCACCUUGCUA 24 2008 CFTR-G551D-159 + UUGUCUUUCUCUGCAAAC 18 2009 CFTR-G551D-160 + AUUGUCUUUCUCUGCAAAC 19 2010 CFTR-G551D-161 + UAUUGUCUUUCUCUGCAAAC 20 760 CFTR-G551D-162 + AUAUUGUCUUUCUCUGCAAAC 21 2011 CFTR-G551D-163 + UAUAUUGUCUUUCUCUGCAAAC 22 2012 CFTR-G551D-164 + CUAUAUUGUCUUUCUCUGCAAAC 23 2013 CFTR-G551D-165 + ACUAUAUUGUCUUUCUCUGCAAAC 24 2014 CFTR-G551D-166 + UGUGAUUCCACCUUCUCC 18 2179 CFTR-G551D-167 + GUGUGAUUCCACCUUCUCC 19 2180 CFTR-G551D-168 + AGUGUGAUUCCACCUUCUCC 20 761 CFTR-G551D-169 + CAGUGUGAUUCCACCUUCUCC 21 2181 CFTR-G551D-170 + UCAGUGUGAUUCCACCUUCUCC 22 2182 CFTR-G551D-171 + CUCAGUGUGAUUCCACCUUCUCC 23 2183 CFTR-G551D-172 + ACUCAGUGUGAUUCCACCUUCUCC 24 2184 CFTR-G551D-173 + CCAGGAUUUUUUCAAUUC 18 2015 CFTR-G551D-174 + CCCAGGAUUUUUUCAAUUC 19 2016 CFTR-G551D-175 + CCCCAGGAUUUUUUCAAUUC 20 767 CFTR-G551D-176 + ACCCCAGGAUUUUUUCAAUUC 21 2017 CFTR-G551D-177 + AACCCCAGGAUUUUUUCAAUUC 22 2018 CFTR-G551D-178 + AAACCCCAGGAUUUUUUCAAUUC 23 2019 CFTR-G551D-179 + AAAACCCCAGGAUUUUUUCAAUUC 24 2020 CFTR-G551D-180 + CUAUUGCUUUAACCACAG 18 2021 CFTR-G551D-181 + ACUAUUGCUUUAACCACAG 19 2022 CFTR-G551D-182 + CACUAUUGCUUUAACCACAG 20 754 CFTR-G551D-183 + ACACUAUUGCUUUAACCACAG 21 2023 CFTR-G551D-184 + CACACUAUUGCUUUAACCACAG 22 2024 CFTR-G551D-185 + UCACACUAUUGCUUUAACCACAG 23 2025 CFTR-G551D-186 + AUCACACUAUUGCUUUAACCACAG 24 2026 CFTR-G551D-187 + UUACCAAAAAUAGAAAAU 18 2027 CFTR-G551D-188 + AUUACCAAAAAUAGAAAAU 19 2028 CFTR-G551D-189 + UAUUACCAAAAAUAGAAAAU 20 758 CFTR-G551D-190 + CUAUUACCAAAAAUAGAAAAU 21 2029 CFTR-G551D-191 + CCUAUUACCAAAAAUAGAAAAU 22 2030 CFTR-G551D-192 + UCCUAUUACCAAAAAUAGAAAAU 23 2031 CFTR-G551D-193 + GUCCUAUUACCAAAAAUAGAAAAU 24 2032 CFTR-G551D-194 + AGUAUGCUCAAUCUGAAU 18 2033 CFTR-G551D-195 + UAGUAUGCUCAAUCUGAAU 19 2034 CFTR-G551D-196 + UUAGUAUGCUCAAUCUGAAU 20 755 CFTR-G551D-197 + UUUAGUAUGCUCAAUCUGAAU 21 2035 CFTR-G551D-198 + UUUUAGUAUGCUCAAUCUGAAU 22 2036 CFTR-G551D-199 + CUUUUAGUAUGCUCAAUCUGAAU 23 2037 CFTR-G551D-200 + ACUUUUAGUAUGCUCAAUCUGAAU 24 2038 CFTR-G551D-201 + UGUCUUUCUCUGCAAACU 18 2039 CFTR-G551D-202 + UUGUCUUUCUCUGCAAACU 19 2040 CFTR-G551D-40 + AUUGUCUUUCUCUGCAAACU 20 483 CFTR-G551D-203 + UAUUGUCUUUCUCUGCAAACU 21 2041 CFTR-G551D-204 + AUAUUGUCUUUCUCUGCAAACU 22 2042 CFTR-G551D-205 + UAUAUUGUCUUUCUCUGCAAACU 23 2043 CFTR-G551D-206 + CUAUAUUGUCUUUCUCUGCAAACU 24 2044 CFTR-G551D-207 + UUAACCACAGUUGAAAUU 18 2045 CFTR-G551D-208 + UUUAACCACAGUUGAAAUU 19 2046 CFTR-G551D-209 + CUUUAACCACAGUUGAAAUU 20 753 CFTR-G551D-210 + GCUUUAACCACAGUUGAAAUU 21 2047 CFTR-G551D-211 + UGCUUUAACCACAGUUGAAAUU 22 2048 CFTR-G551D-212 + UUGCUUUAACCACAGUUGAAAUU 23 2049 CFTR-G551D-213 + AUUGCUUUAACCACAGUUGAAAUU 24 2050 CFTR-G551D-214 UAUAUUCUGUUUCUGGAA 18 2051 CFTR-G551D-215 UUAUAUUCUGUUUCUGGAA 19 2052 CFTR-G551D-216 UUUAUAUUCUGUUUCUGGAA 20 748 CFTR-G551D-217 CUUUAUAUUCUGUUUCUGGAA 21 2053 CFTR-G551D-218 GCUUUAUAUUCUGUUUCUGGAA 22 2054 CFTR-G551D-219 UGCUUUAUAUUCUGUUUCUGGAA 23 2055 CFTR-G551D-220 UUGCUUUAUAUUCUGUUUCUGGAA 24 2056 CFTR-G551D-221 AUUUUCUAUUUUUGGUAA 18 2059 CFTR-G551D-222 AAUUUUCUAUUUUUGGUAA 19 2060 CFTR-G551D-223 UAAUUUUCUAUUUUUGGUAA 20 736 CFTR-G551D-224 CUAAUUUUCUAUUUUUGGUAA 21 2061 CFTR-G551D-225 UCUAAUUUUCUAUUUUUGGUAA 22 2062 CFTR-G551D-226 CUCUAAUUUUCUAUUUUUGGUAA 23 2063 CFTR-G551D-227 UCUCUAAUUUUCUAUUUUUGGUAA 24 2064 CFTR-G551D-228 GACAUCUCCAAGUUUGCA 18 2065 CFTR-G551D-229 GGACAUCUCCAAGUUUGCA 19 2066 CFTR-G551D-230 AGGACAUCUCCAAGUUUGCA 20 738 CFTR-G551D-231 UAGGACAUCUCCAAGUUUGCA 21 2067 CFTR-G551D-232 AUAGGACAUCUCCAAGUUUGCA 22 2068 CFTR-G551D-233 AAUAGGACAUCUCCAAGUUUGCA 23 2069 CFTR-G551D-234 UAAUAGGACAUCUCCAAGUUUGCA 24 2070 CFTR-G551D-235 CACACUGAGUGGAGAUCA 18 2185 CFTR-G551D-236 UCACACUGAGUGGAGAUCA 19 2186 CFTR-G551D-237 AUCACACUGAGUGGAGAUCA 20 2187 CFTR-G551D-238 AAUCACACUGAGUGGAGAUCA 21 2188 CFTR-G551D-239 GAAUCACACUGAGUGGAGAUCA 22 2189 CFTR-G551D-240 GGAAUCACACUGAGUGGAGAUCA 23 2190 CFTR-G551D-241 UGGAAUCACACUGAGUGGAGAUCA 24 2191 CFTR-G551D-242 GUGCCUUUCAAAUUCAGA 18 2077 CFTR-G551D-243 UGUGCCUUUCAAAUUCAGA 19 2078 CFTR-G551D-244 AUGUGCCUUUCAAAUUCAGA 20 735 CFTR-G551D-245 GAUGUGCCUUUCAAAUUCAGA 21 2079 CFTR-G551D-246 AGAUGUGCCUUUCAAAUUCAGA 22 2080 CFTR-G551D-247 AAGAUGUGCCUUUCAAAUUCAGA 23 2081 CFTR-G551D-248 GAAGAUGUGCCUUUCAAAUUCAGA 24 2082 CFTR-G551D-249 AUAUAUGAUUACAUUAGA 18 2083 CFTR-G551D-250 GAUAUAUGAUUACAUUAGA 19 2084 CFTR-G551D-20 UGAUAUAUGAUUACAUUAGA 20 471 CFTR-G551D-251 GUGAUAUAUGAUUACAUUAGA 21 2085 CFTR-G551D-252 UGUGAUAUAUGAUUACAUUAGA 22 2086 CFTR-G551D-253 GUGUGAUAUAUGAUUACAUUAGA 23 2087 CFTR-G551D-254 AGUGUGAUAUAUGAUUACAUUAGA 24 2088 CFTR-G551D-255 AAGGUGGAAUCACACUGA 18 2089 CFTR-G551D-256 GAAGGUGGAAUCACACUGA 19 2090 CFTR-G551D-257 AGAAGGUGGAAUCACACUGA 20 743 CFTR-G551D-258 GAGAAGGUGGAAUCACACUGA 21 2091 CFTR-G551D-259 GGAGAAGGUGGAAUCACACUGA 22 2192 CFTR-G551D-260 UGGAGAAGGUGGAAUCACACUGA 23 2193 CFTR-G551D-261 UUGGAGAAGGUGGAAUCACACUGA 24 2194 CFTR-G551D-262 UCUGGAAUUGAAAAAAUC 18 2098 CFTR-G551D-263 UUCUGGAAUUGAAAAAAUC 19 2099 CFTR-G551D-264 UUUCUGGAAUUGAAAAAAUC 20 749 CFTR-G551D-265 GUUUCUGGAAUUGAAAAAAUC 21 2100 CFTR-G551D-266 UGUUUCUGGAAUUGAAAAAAUC 22 2101 CFTR-G551D-267 CUGUUUCUGGAAUUGAAAAAAUC 23 2102 CFTR-G551D-268 UCUGUUUCUGGAAUUGAAAAAAUC 24 2103 CFTR-G551D-269 AGAAAGACAAUAUAGUUC 18 2195 CFTR-G551D-270 GAGAAAGACAAUAUAGUUC 19 2196 CFTR-G551D-271 AGAGAAAGACAAUAUAGUUC 20 739 CFTR-G551D-272 CAGAGAAAGACAAUAUAGUUC 21 2197 CFTR-G551D-273 GCAGAGAAAGACAAUAUAGUUC 22 2198 CFTR-G551D-274 UGCAGAGAAAGACAAUAUAGUUC 23 2199 CFTR-G551D-275 UUGCAGAGAAAGACAAUAUAGUUC 24 2200 CFTR-G551D-276 AUAUAGUUCUUGGAGAAG 18 2201 CFTR-G551D-277 AAUAUAGUUCUUGGAGAAG 19 2202 CFTR-G551D-278 CAAUAUAGUUCUUGGAGAAG 20 741 CFTR-G551D-279 ACAAUAUAGUUCUUGGAGAAG 21 2203 CFTR-G551D-280 GACAAUAUAGUUCUUGGAGAAG 22 2204 CFTR-G551D-281 AGACAAUAUAGUUCUUGGAGAAG 23 2205 CFTR-G551D-282 AAGACAAUAUAGUUCUUGGAGAAG 24 2206 CFTR-G551D-283 AGGUGGAAUCACACUGAG 18 2111 CFTR-G551D-284 AAGGUGGAAUCACACUGAG 19 2112 CFTR-G551D-8 GAAGGUGGAAUCACACUGAG 20 461 CFTR-G551D-285 AGAAGGUGGAAUCACACUGAG 21 2113 CFTR-G551D-286 GAGAAGGUGGAAUCACACUGAG 22 2114 CFTR-G551D-287 GGAGAAGGUGGAAUCACACUGAG 23 2207 CFTR-G551D-288 UGGAGAAGGUGGAAUCACACUGAG 24 2208 CFTR-G551D-289 GAUAUAUGAUUACAUUAG 18 2117 CFTR-G551D-290 UGAUAUAUGAUUACAUUAG 19 2118 CFTR-G551D-291 GUGAUAUAUGAUUACAUUAG 20 734 CFTR-G551D-292 UGUGAUAUAUGAUUACAUUAG 21 2119 CFTR-G551D-293 GUGUGAUAUAUGAUUACAUUAG 22 2120 CFTR-G551D-294 AGUGUGAUAUAUGAUUACAUUAG 23 2121 CFTR-G551D-295 UAGUGUGAUAUAUGAUUACAUUAG 24 2122 CFTR-G551D-296 AAGACAAUAUAGUUCUUG 18 2209 CFTR-G551D-297 AAAGACAAUAUAGUUCUUG 19 2210 CFTR-G551D-298 GAAAGACAAUAUAGUUCUUG 20 740 CFTR-G551D-299 AGAAAGACAAUAUAGUUCUUG 21 2211 CFTR-G551D-300 GAGAAAGACAAUAUAGUUCUUG 22 2212 CFTR-G551D-301 AGAGAAAGACAAUAUAGUUCUUG 23 2213 CFTR-G551D-302 CAGAGAAAGACAAUAUAGUUCUUG 24 2214 CFTR-G551D-303 AGGACAUCUCCAAGUUUG 18 2123 CFTR-G551D-304 UAGGACAUCUCCAAGUUUG 19 2124 CFTR-G551D-305 AUAGGACAUCUCCAAGUUUG 20 737 CFTR-G551D-306 AAUAGGACAUCUCCAAGUUUG 21 2125 CFTR-G551D-307 UAAUAGGACAUCUCCAAGUUUG 22 2126 CFTR-G551D-308 GUAAUAGGACAUCUCCAAGUUUG 23 2127 CFTR-G551D-309 GGUAAUAGGACAUCUCCAAGUUUG 24 2128 CFTR-G551D-310 UGUGAUAUAUGAUUACAU 18 2129 CFTR-G551D-311 GUGUGAUAUAUGAUUACAU 19 2130 CFTR-G551D-312 AGUGUGAUAUAUGAUUACAU 20 733 CFTR-G551D-313 UAGUGUGAUAUAUGAUUACAU 21 2131 CFTR-G551D-314 AUAGUGUGAUAUAUGAUUACAU 22 2132 CFTR-G551D-315 AAUAGUGUGAUAUAUGAUUACAU 23 2133 CFTR-G551D-316 CAAUAGUGUGAUAUAUGAUUACAU 24 2134 CFTR-G551D-317 GAAAGACAAUAUAGUUCU 18 2135 CFTR-G551D-318 AGAAAGACAAUAUAGUUCU 19 2136 CFTR-G551D-9 GAGAAAGACAAUAUAGUUCU 20 453 CFTR-G551D-319 AGAGAAAGACAAUAUAGUUCU 21 2137 CFTR-G551D-320 CAGAGAAAGACAAUAUAGUUCU 22 2138 CFTR-G551D-321 GCAGAGAAAGACAAUAUAGUUCU 23 2139 CFTR-G551D-322 UGCAGAGAAAGACAAUAUAGUUCU 24 2140 CFTR-G551D-323 GGGUUAAGAAUCACAUUU 18 2215 CFTR-G551D-324 UGGGUUAAGAAUCACAUUU 19 2216 CFTR-G551D-325 GUGGGUUAAGAAUCACAUUU 20 752 CFTR-G551D-326 AGUGGGUUAAGAAUCACAUUU 21 2217 CFTR-G551D-327 UAGUGGGUUAAGAAUCACAUUU 22 2218 CFTR-G551D-328 CUAGUGGGUUAAGAAUCACAUUU 23 2219 CFTR-G551D-329 GCUAGUGGGUUAAGAAUCACAUUU 24 2220 CFTR-G551D-330 UUGCUUUAUAUUCUGUUU 18 2148 CFTR-G551D-331 AUUGCUUUAUAUUCUGUUU 19 2149 CFTR-G551D-332 UAUUGCUUUAUAUUCUGUUU 20 747 CFTR-G551D-333 CUAUUGCUUUAUAUUCUGUUU 21 2150 CFTR-G551D-334 UCUAUUGCUUUAUAUUCUGUUU 22 2151 CFTR-G551D-335 CUCUAUUGCUUUAUAUUCUGUUU 23 2152 CFTR-G551D-336 UCUCUAUUGCUUUAUAUUCUGUUU 24 2153

Table 18A provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 18A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-G551D-337 + GUAAUCAUAUAUCACAC 17 2154 CFTR-G551D-338 GGUUAAAGCAAUAGUGU 20 927 GAU

Table 18B provides exemplary targeting domains for correcting a mutation (e.g., G551D) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G551D) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 18B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G551D-339 + CCACUAGCCAUAAAACC 17 935 CFTR-G551D-340 + UGAAUGACAUUUACAGC 17 2155 CFTR-G551D-341 UAAAGCAAUAGUGUGAU 17 932 CFTR-G551D-342 AGGAAGAUGUGCCUUUCAAA 20 928 CFTR-G551D-343 + AAUGUAAUCAUAUAUCACAC 20 2156 CFTR-G551D-344 + AACCCACUAGCCAUAAAACC 20 930 CFTR-G551D-345 + ACAUGAAUGACAUUUACAGC 20 2157

Table 18C provides exemplary targeting domains for correcting a mutation (e.g., G55D) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., G55D). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 18C 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-G551D-346 AAGAUGUGCCUUUCAAA 17 933 CFTR-G551D-347 + UUAUUUAUAGUUCUUAA 17 936 CFTR-G551D-348 + UCGUUGAUCUCCACUCA 17 2221 CFTR-G551D-349 AAUUACAGACAUUUCUC 17 2158 CFTR-G551D-350 + CCAUUAUUUAUAGUUCUUAA 20 931 CFTR-G551D-351 + UGCUCGUUGAUCUCCACUCA 20 2222 CFTR-G551D-352 AAAAAUUACAGACAUUUCUC 20 2159

Table 19A provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 19A 1st Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-N1303K-1 GGAGUGAUCAAGAAAUA 17 2223 CFTR-N1303K-2 GAGUACCCUAACAUACC 17 2224 CFTR-N1303K-3 GUGUGUGCACAACUUUAA 20 2225 AA CFTR-N1303K-4 GGAAAGUUGCAGAUGAGG 20 2226 UA CFTR-N1303K-5 GAACUUGAUGGUAAGUAC 20 2227 AU CFTR-N1303K-6 + GCUAUAUCAGCCAUUUGU 20 2228 GU

Table 19B provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 19B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-N1303K-7 UGUGCACAACUUUAAAA 17 2229 CFTR-N1303K-8 ACUUGAUGGUAAGUACA 17 2230 CFTR-N1303K-9 AAUUUGAGAGAACUUGA 17 2231 CFTR-N1303K-10 + UCACUCCACUGUUCAUA 17 2232 CFTR-N1303K-11 AAGUUGCAGAUGAGGUA 17 2233 CFTR-N1303K-12 UGGAUCCCUAUGAACAG 17 2234 CFTR-N1303K-13 AUGGAAAGUUGCAGAUG 17 2235 CFTR-N1303K-14 CUUGAUGGUAAGUACAU 17 2236 CFTR-N1303K-15 + AUCACUCCACUGUUCAU 17 2237 CFTR-N1303K-16 + AUAUCAGCCAUUUGUGU 17 2238 CFTR-N1303K-17 AGAACUUGAUGGUAAGUACA 20 2239 CFTR-N1303K-18 AGUGGAGUGAUCAAGAAAUA 20 2240 CFTR-N1303K-19 + UGAUCACUCCACUGUUCAUA 20 2241 CFTR-N1303K-20 AAUAUGGAAAGUUGCAGAUG 20 2242 CFTR-N1303K-21 + UUGAUCACUCCACUGUUCAU 20 2243

Table 19C provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 19C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-N1303K-22 GUAACUCAUACCAACACA 20 2244 AA

Table 19D provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 19D 4th Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-N1303K-23 ACUCAUACCAACACAAA 17 2245 CFTR-N1303K-24 CUGAAAUGAUUUUGAAA 17 2246 CFTR-N1303K-25 ACUGAAAUGAUUUUGAA 17 2247 CFTR-N1303K-26 AUUUUACAAUACAAUAA 17 2248 CFTR-N1303K-27 UAUUUUACAAUACAAUA 17 2249 CFTR-N1303K-28 + UUGCUCCAGGUAUGUUA 17 2250 CFTR-N1303K-29 AAAGUAUUUAUUUUUUC 17 2251 CFTR-N1303K-30 UGAAAUGAUUUUGAAAG 17 2252 CFTR-N1303K-31 AACAUUUAGAAAAAAGU 17 2253 CFTR-N1303K-32 UAACUGAAAUGAUUUUGAAA 20 2254 CFTR-N1303K-33 CUAACUGAAAUGAUUUUGAA 20 2255 CFTR-N1303K-34 AAUAUUUUACAAUACAAUAA 20 2256 CFTR-N1303K-35 UAAAAUUUGAGAGAACUUGA 20 2257 CFTR-N1303K-36 AAAUAUUUUACAAUACAAUA 20 2258 CFTR-N1303K-37 AUGGAGUACCCUAACAUACC 20 2259 CFTR-N1303K-38 UAGAAAGUAUUUAUUUUUUC 20 2260 CFTR-N1303K-39 AACUGAAAUGAUUUUGAAAG 20 2261 CFTR-N1303K-40 AGUUGGAUCCCUAUGAACAG 20 2262 CFTR-N1303K-41 UGGAACAUUUAGAAAAAAGU 20 2263

Table 20A provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 20A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-N1303K-42 + GAUCACUCCACUGUUCAU 18 2264 CFTR-N1303K-43 GUGUGCACAACUUUAAAA 18 2265 CFTR-N1303K-3 GUGUGUGCACAACUUUAAAA 20 2225 CFTR-N1303K-44 GCUAACUGAAAUGAUUUUGAA 21 2266 CFTR-N1303K-45 GCUGCUAACUGAAAUGAUUUUGAA 24 2267 CFTR-N1303K-46 GAACUUGAUGGUAAGUAC 18 2268 CFTR-N1303K-47 GAGAACUUGAUGGUAAGUAC 20 2269 CFTR-N1303K-48 GAGAGAACUUGAUGGUAAGUAC 22 2270

Table 20B provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 20B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-N1303K-49 + UGAUCACUCCACUGUUCAU 19 2271 CFTR-N1303K-21 + UUGAUCACUCCACUGUUCAU 20 2243 CFTR-N1303K-50 + CUUGAUCACUCCACUGUUCAU 21 2272 CFTR-N1303K-51 + UCUUGAUCACUCCACUGUUCAU 22 2273 CFTR-N1303K-52 + UUCUUGAUCACUCCACUGUUCAU 23 2274 CFTR-N1303K-53 + UUUCUUGAUCACUCCACUGUUCAU 24 2275 CFTR-N1303K-54 UGUGUGCACAACUUUAAAA 19 2276 CFTR-N1303K-55 UGCUAACUGAAAUGAUUUUGAA 22 2277 CFTR-N1303K-56 CUGCUAACUGAAAUGAUUUUGAA 23 2278 CFTR-N1303K-57 AGAACUUGAUGGUAAGUAC 19 2279 CFTR-N1303K-58 AGAGAACUUGAUGGUAAGUAC 21 2280 CFTR-N1303K-59 UGAGAGAACUUGAUGGUAAGUAC 23 2281 CFTR-N1303K-60 UUGAGAGAACUUGAUGGUAAGUAC 24 2282

Table 20C provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 20C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-N1303K-61 + GCUAUAUCAGCCAUUUG 24 2283 UGUUGGU CFTR-N1303K-62 GUAUGUGUGUGCACAACU 24 2284 UUAAAA CFTR-N1303K-63 GGAACAUUUAGAAAAAAG 18 2285 CFTR-N1303K-64 GUUGGAUCCCUAUGAAC 19 2286 AG

Table 20D provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 20D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-N1303K-65 + ACAUGCACACAAAGUGUG 18 2287 CFTR-N1303K-66 + UACAUGCACACAAAGUGUG 19 2288 CFTR-N1303K-67 + AUACAUGCACACAAAGUGUG 20 2289 CFTR-N1303K-68 + CAUACAUGCACACAAAGUGUG 21 2290 CFTR-N1303K-69 + ACAUACAUGCACACAAAGUGUG 22 2291 CFTR-N1303K-70 + CACAUACAUGCACACAAAGUGUG 23 2292 CFTR-N1303K-71 + ACACAUACAUGCACACAAAGUGUG 24 2293 CFTR-N1303K-72 + AGAAAAGAAGAAGAAAGU 18 2294 CFTR-N1303K-73 + AAGAAAAGAAGAAGAAAGU 19 2295 CFTR-N1303K-74 + AAAGAAAAGAAGAAGAAAGU 20 2296 CFTR-N1303K-75 + AAAAGAAAAGAAGAAGAAAGU 21 2297 CFTR-N1303K-76 + AAAAAGAAAAGAAGAAGAAAGU 22 2298 CFTR-N1303K-77 + AAAAAAGAAAAGAAGAAGAAAGU 23 2299 CFTR-N1303K-78 + CAAAAAAGAAAAGAAGAAGAAAGU 24 2300 CFTR-N1303K-79 + UCAGCCAUUUGUGUUGGU 18 2301 CFTR-N1303K-80 + AUCAGCCAUUUGUGUUGGU 19 2302 CFTR-N1303K-81 + UAUCAGCCAUUUGUGUUGGU 20 2303 CFTR-N1303K-82 + AUAUCAGCCAUUUGUGUUGGU 21 2304 CFTR-N1303K-83 + UAUAUCAGCCAUUUGUGUUGGU 22 2305 CFTR-N1303K-84 + CUAUAUCAGCCAUUUGUGUUGGU 23 2306 CFTR-N1303K-85 UGUGUGUGCACAACUUUAAAA 21 2307 CFTR-N1303K-86 AUGUGUGUGCACAACUUUAAAA 22 2308 CFTR-N1303K-87 UAUGUGUGUGCACAACUUUAAAA 23 2309 CFTR-N1303K-88 AACUGAAAUGAUUUUGAA 18 2310 CFTR-N1303K-89 UAACUGAAAUGAUUUUGAA 19 2311 CFTR-N1303K-33 CUAACUGAAAUGAUUUUGAA 20 2255 CFTR-N1303K-90 UGGAACAUUUAGAAAAAAG 19 2312 CFTR-N1303K-91 CUGGAACAUUUAGAAAAAAG 20 2313 CFTR-N1303K-92 UCUGGAACAUUUAGAAAAAAG 21 2314 CFTR-N1303K-93 UUCUGGAACAUUUAGAAAAAAG 22 2315 CFTR-N1303K-94 UUUCUGGAACAUUUAGAAAAAAG 23 2316 CFTR-N1303K-95 UUUUCUGGAACAUUUAGAAAAAAG 24 2317 CFTR-N1303K-96 UUGGAUCCCUAUGAACAG 18 2318 CFTR-N1303K-40 AGUUGGAUCCCUAUGAACAG 20 2262 CFTR-N1303K-97 AAGUUGGAUCCCUAUGAACAG 21 2319 CFTR-N1303K-98 AAAGUUGGAUCCCUAUGAACAG 22 2320 CFTR-N1303K-99 AAAAGUUGGAUCCCUAUGAACAG 23 2321 CFTR-N1303K-100 AAAAAGUUGGAUCCCUAUGAACAG 24 2322

Table 20E provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 20E 5th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-N1303K-101 + AUACUUUCUAUAGCAAAA 18 2323 CFTR-N1303K-102 + AAUACUUUCUAUAGCAAAA 19 2324 CFTR-N1303K-103 + AAAUACUUUCUAUAGCAAAA 20 2325 CFTR-N1303K-104 + UAAAUACUUUCUAUAGCAAAA 21 2326 CFTR-N1303K-105 + AUAAAUACUUUCUAUAGCAAAA 22 2327 CFTR-N1303K-106 + AAUAAAUACUUUCUAUAGCAAAA 23 2328 CFTR-N1303K-107 + AAAUAAAUACUUUCUAUAGCAAAA 24 2329 CFTR-N1303K-108 + UUCUAUAGCAAAAAAGAA 18 2330 CFTR-N1303K-109 + UUUCUAUAGCAAAAAAGAA 19 2331 CFTR-N1303K-110 + CUUUCUAUAGCAAAAAAGAA 20 2332 CFTR-N1303K-111 + ACUUUCUAUAGCAAAAAAGAA 21 2333 CFTR-N1303K-112 + UACUUUCUAUAGCAAAAAAGAA 22 2334 CFTR-N1303K-113 + AUACUUUCUAUAGCAAAAAAGAA 23 2335 CFTR-N1303K-114 + AAUACUUUCUAUAGCAAAAAAGAA 24 2336 CFTR-N1303K-115 + UGAUCACUCCACUGUUCA 18 2337 CFTR-N1303K-116 + UUGAUCACUCCACUGUUCA 19 2338 CFTR-N1303K-117 + CUUGAUCACUCCACUGUUCA 20 2339 CFTR-N1303K-118 + UCUUGAUCACUCCACUGUUCA 21 2340 CFTR-N1303K-119 + UUCUUGAUCACUCCACUGUUCA 22 2341 CFTR-N1303K-120 + UUUCUUGAUCACUCCACUGUUCA 23 2342 CFTR-N1303K-121 + AUUUCUUGAUCACUCCACUGUUCA 24 2343 CFTR-N1303K-122 + ACUUUUUUCUAAAUGUUC 18 2344 CFTR-N1303K-123 + AACUUUUUUCUAAAUGUUC 19 2345 CFTR-N1303K-124 + CAACUUUUUUCUAAAUGUUC 20 2346 CFTR-N1303K-125 + CCAACUUUUUUCUAAAUGUUC 21 2347 CFTR-N1303K-126 + UCCAACUUUUUUCUAAAUGUUC 22 2348 CFTR-N1303K-127 + AUCCAACUUUUUUCUAAAUGUUC 23 2349 CFTR-N1303K-128 + GAUCCAACUUUUUUCUAAAUGUUC 24 2350 CFTR-N1303K-129 + UAUAGCAAAAAAGAAAAG 18 2351 CFTR-N1303K-130 + CUAUAGCAAAAAAGAAAAG 19 2352 CFTR-N1303K-131 + UCUAUAGCAAAAAAGAAAAG 20 2353 CFTR-N1303K-132 + UUCUAUAGCAAAAAAGAAAAG 21 2354 CFTR-N1303K-133 + UUUCUAUAGCAAAAAAGAAAAG 22 2355 CFTR-N1303K-134 + CUUUCUAUAGCAAAAAAGAAAAG 23 2356 CFTR-N1303K-135 + ACUUUCUAUAGCAAAAAAGAAAAG 24 2357 CFTR-N1303K-136 + AUUGUAAAAUAUUUCAAG 18 2358 CFTR-N1303K-137 + UAUUGUAAAAUAUUUCAAG 19 2359 CFTR-N1303K-138 + GUAUUGUAAAAUAUUUCAAG 20 2360 CFTR-N1303K-139 + UGUAUUGUAAAAUAUUUCAAG 21 2361 CFTR-N1303K-140 + UUGUAUUGUAAAAUAUUUCAAG 22 2362 CFTR-N1303K-141 + AUUGUAUUGUAAAAUAUUUCAAG 23 2363 CFTR-N1303K-142 + UAUUGUAUUGUAAAAUAUUUCAAG 24 2364 CFTR-N1303K-143 + AGCAAAAAAGAAAAGAAG 18 2365 CFTR-N1303K-144 + UAGCAAAAAAGAAAAGAAG 19 2366 CFTR-N1303K-145 + AUAGCAAAAAAGAAAAGAAG 20 2367 CFTR-N1303K-146 + UAUAGCAAAAAAGAAAAGAAG 21 2368 CFTR-N1303K-147 + CUAUAGCAAAAAAGAAAAGAAG 22 2369 CFTR-N1303K-148 + UCUAUAGCAAAAAAGAAAAGAAG 23 2370 CFTR-N1303K-149 + UUCUAUAGCAAAAAAGAAAAGAAG 24 2371 CFTR-N1303K-150 + GAAAAAUUAUUUUAAAAU 18 2372 CFTR-N1303K-151 + AGAAAAAUUAUUUUAAAAU 19 2373 CFTR-N1303K-152 + UAGAAAAAUUAUUUUAAAAU 20 2374 CFTR-N1303K-153 + GUAGAAAAAUUAUUUUAAAAU 21 2375 CFTR-N1303K-154 + AGUAGAAAAAUUAUUUUAAAAU 22 2376 CFTR-N1303K-155 + AAGUAGAAAAAUUAUUUUAAAAU 23 2377 CFTR-N1303K-156 + CAAGUAGAAAAAUUAUUUUAAAAU 24 2378 CFTR-N1303K-157 UGUGUGCACAACUUUAAA 18 2379 CFTR-N1303K-158 GUGUGUGCACAACUUUAAA 19 2380 CFTR-N1303K-159 UGUGUGUGCACAACUUUAAA 20 2381 CFTR-N1303K-160 AUGUGUGUGCACAACUUUAAA 21 2382 CFTR-N1303K-161 UAUGUGUGUGCACAACUUUAAA 22 2383 CFTR-N1303K-162 GUAUGUGUGUGCACAACUUUAAA 23 2384 CFTR-N1303K-163 UGUAUGUGUGUGCACAACUUUAAA 24 2385 CFTR-N1303K-164 UAUUUUACAAUACAAUAA 18 2386 CFTR-N1303K-165 AUAUUUUACAAUACAAUAA 19 2387 CFTR-N1303K-34 AAUAUUUUACAAUACAAUAA 20 2256 CFTR-N1303K-166 AAAUAUUUUACAAUACAAUAA 21 2388 CFTR-N1303K-167 GAAAUAUUUUACAAUACAAUAA 22 2389 CFTR-N1303K-168 UGAAAUAUUUUACAAUACAAUAA 23 2390 CFTR-N1303K-169 UUGAAAUAUUUUACAAUACAAUAA 24 2391 CFTR-N1303K-170 AUGAGGUAAGGCUGCUAA 18 2392 CFTR-N1303K-171 GAUGAGGUAAGGCUGCUAA 19 2393 CFTR-N1303K-172 AGAUGAGGUAAGGCUGCUAA 20 2394 CFTR-N1303K-173 CAGAUGAGGUAAGGCUGCUAA 21 2395 CFTR-N1303K-174 GCAGAUGAGGUAAGGCUGCUAA 22 2396 CFTR-N1303K-175 UGCAGAUGAGGUAAGGCUGCUAA 23 2397 CFTR-N1303K-176 UUGCAGAUGAGGUAAGGCUGCUAA 24 2398 CFTR-N1303K-177 GUUGGAUCCCUAUGAACA 18 2399 CFTR-N1303K-178 AGUUGGAUCCCUAUGAACA 19 2400 CFTR-N1303K-179 AAGUUGGAUCCCUAUGAACA 20 2401 CFTR-N1303K-180 AAAGUUGGAUCCCUAUGAACA 21 2402 CFTR-N1303K-181 AAAAGUUGGAUCCCUAUGAACA 22 2403 CFTR-N1303K-182 AAAAAGUUGGAUCCCUAUGAACA 23 2404 CFTR-N1303K-183 AAAAAAGUUGGAUCCCUAUGAACA 24 2405 CFTR-N1303K-184 UAAAAUAUUAAAAUUUGA 18 2406 CFTR-N1303K-185 AUAAAAUAUUAAAAUUUGA 19 2407 CFTR-N1303K-186 GAUAAAAUAUUAAAAUUUGA 20 2408 CFTR-N1303K-187 UGAUAAAAUAUUAAAAUUUGA 21 2409 CFTR-N1303K-188 AUGAUAAAAUAUUAAAAUUUGA 22 2410 CFTR-N1303K-189 CAUGAUAAAAUAUUAAAAUUUGA 23 2411 CFTR-N1303K-190 ACAUGAUAAAAUAUUAAAAUUUGA 24 2412 CFTR-N1303K-191 UAACUGAAAUGAUUUUGA 18 2413 CFTR-N1303K-192 CUAACUGAAAUGAUUUUGA 19 2414 CFTR-N1303K-193 GCUAACUGAAAUGAUUUUGA 20 2415 CFTR-N1303K-194 UGCUAACUGAAAUGAUUUUGA 21 2416 CFTR-N1303K-195 CUGCUAACUGAAAUGAUUUUGA 22 2417 CFTR-N1303K-196 GCUGCUAACUGAAAUGAUUUUGA 23 2418 CFTR-N1303K-197 GGCUGCUAACUGAAAUGAUUUUGA 24 2419 CFTR-N1303K-198 UGGAGUGAUCAAGAAAUA 18 2420 CFTR-N1303K-199 GUGGAGUGAUCAAGAAAUA 19 2421 CFTR-N1303K-18 AGUGGAGUGAUCAAGAAAUA 20 2240 CFTR-N1303K-200 CAGUGGAGUGAUCAAGAAAUA 21 2422 CFTR-N1303K-201 ACAGUGGAGUGAUCAAGAAAUA 22 2423 CFTR-N1303K-202 AACAGUGGAGUGAUCAAGAAAUA 23 2424 CFTR-N1303K-203 GAACAGUGGAGUGAUCAAGAAAUA 24 2425 CFTR-N1303K-204 AUAUUUUACAAUACAAUA 18 2426 CFTR-N1303K-205 AAUAUUUUACAAUACAAUA 19 2427 CFTR-N1303K-36 AAAUAUUUUACAAUACAAUA 20 2258 CFTR-N1303K-206 GAAAUAUUUUACAAUACAAUA 21 2428 CFTR-N1303K-207 UGAAAUAUUUUACAAUACAAUA 22 2429 CFTR-N1303K-208 UUGAAAUAUUUUACAAUACAAUA 23 2430 CFTR-N1303K-209 CUUGAAAUAUUUUACAAUACAAUA 24 2431 CFTR-N1303K-210 UUCUUUUCUUUUUUGCUA 18 2432 CFTR-N1303K-211 CUUCUUUUCUUUUUUGCUA 19 2433 CFTR-N1303K-212 UCUUCUUUUCUUUUUUGCUA 20 2434 CFTR-N1303K-213 UUCUUCUUUUCUUUUUUGCUA 21 2435 CFTR-N1303K-214 CUUCUUCUUUUCUUUUUUGCUA 22 2436 CFTR-N1303K-215 UCUUCUUCUUUUCUUUUUUGCUA 23 2437 CFTR-N1303K-216 UUCUUCUUCUUUUCUUUUUUGCUA 24 2438 CFTR-N1303K-217 UGGAGUACCCUAACAUAC 18 2439 CFTR-N1303K-218 AUGGAGUACCCUAACAUAC 19 2440 CFTR-N1303K-219 AAUGGAGUACCCUAACAUAC 20 2441 CFTR-N1303K-220 AAAUGGAGUACCCUAACAUAC 21 2442 CFTR-N1303K-221 AAAAUGGAGUACCCUAACAUAC 22 2443 CFTR-N1303K-222 UAAAAUGGAGUACCCUAACAUAC 23 2444 CFTR-N1303K-223 UUAAAAUGGAGUACCCUAACAUAC 24 2445 CFTR-N1303K-224 UUAAAAUAAUUUUUCUAC 18 2446 CFTR-N1303K-225 UUUAAAAUAAUUUUUCUAC 19 2447 CFTR-N1303K-226 UUUUAAAAUAAUUUUUCUAC 20 2448 CFTR-N1303K-227 AUUUUAAAAUAAUUUUUCUAC 21 2449 CFTR-N1303K-228 UAUUUUAAAAUAAUUUUUCUAC 22 2450 CFTR-N1303K-229 UUAUUUUAAAAUAAUUUUUCUAC 23 2451 CFTR-N1303K-230 CUUAUUUUAAAAUAAUUUUUCUAC 24 2452 CFTR-N1303K-231 GGAGUACCCUAACAUACC 18 2453 CFTR-N1303K-232 UGGAGUACCCUAACAUACC 19 2454 CFTR-N1303K-37 AUGGAGUACCCUAACAUACC 20 2259 CFTR-N1303K-233 AAUGGAGUACCCUAACAUACC 21 2455 CFTR-N1303K-234 AAAUGGAGUACCCUAACAUACC 22 2456 CFTR-N1303K-235 AAAAUGGAGUACCCUAACAUACC 23 2457 CFTR-N1303K-236 UAAAAUGGAGUACCCUAACAUACC 24 2458 CFTR-N1303K-237 AUGAACAGUGGAGUGAUC 18 2459 CFTR-N1303K-238 UAUGAACAGUGGAGUGAUC 19 2460 CFTR-N1303K-239 CUAUGAACAGUGGAGUGAUC 20 2461 CFTR-N1303K-240 CCUAUGAACAGUGGAGUGAUC 21 2462 CFTR-N1303K-241 CCCUAUGAACAGUGGAGUGAUC 22 2463 CFTR-N1303K-242 UCCCUAUGAACAGUGGAGUGAUC 23 2464 CFTR-N1303K-243 AUCCCUAUGAACAGUGGAGUGAUC 24 2465 CFTR-N1303K-244 GAAAGUAUUUAUUUUUUC 18 2466 CFTR-N1303K-245 AGAAAGUAUUUAUUUUUUC 19 2467 CFTR-N1303K-38 UAGAAAGUAUUUAUUUUUUC 20 2260 CFTR-N1303K-246 AUAGAAAGUAUUUAUUUUUUC 21 2468 CFTR-N1303K-247 UAUAGAAAGUAUUUAUUUUUUC 22 2469 CFTR-N1303K-248 CUAUAGAAAGUAUUUAUUUUUUC 23 2470 CFTR-N1303K-249 GCUAUAGAAAGUAUUUAUUUUUUC 24 2471 CFTR-N1303K-250 AAAUAUGGAAAGUUGCAG 18 2472 CFTR-N1303K-251 GAAAUAUGGAAAGUUGCAG 19 2473 CFTR-N1303K-252 AGAAAUAUGGAAAGUUGCAG 20 2474 CFTR-N1303K-253 AAGAAAUAUGGAAAGUUGCAG 21 2475 CFTR-N1303K-254 CAAGAAAUAUGGAAAGUUGCAG 22 2476 CFTR-N1303K-255 UCAAGAAAUAUGGAAAGUUGCAG 23 2477 CFTR-N1303K-256 AUCAAGAAAUAUGGAAAGUUGCAG 24 2478 CFTR-N1303K-257 AUGAUAAAAUAUUAAAAU 18 2479 CFTR-N1303K-258 CAUGAUAAAAUAUUAAAAU 19 2480 CFTR-N1303K-259 ACAUGAUAAAAUAUUAAAAU 20 2481 CFTR-N1303K-260 GUGGAGUGAUCAAGAAAU 18 2482 CFTR-N1303K-261 AGUGGAGUGAUCAAGAAAU 19 2483 CFTR-N1303K-262 CAGUGGAGUGAUCAAGAAAU 20 2484 CFTR-N1303K-263 ACAGUGGAGUGAUCAAGAAAU 21 2485 CFTR-N1303K-264 AACAGUGGAGUGAUCAAGAAAU 22 2486 CFTR-N1303K-265 GAACAGUGGAGUGAUCAAGAAAU 23 2487 CFTR-N1303K-266 UGAACAGUGGAGUGAUCAAGAAAU 24 2488 CFTR-N1303K-267 AAUAUUUUACAAUACAAU 18 2489 CFTR-N1303K-268 AAAUAUUUUACAAUACAAU 19 2490 CFTR-N1303K-269 GAAAUAUUUUACAAUACAAU 20 2491 CFTR-N1303K-270 UGAAAUAUUUUACAAUACAAU 21 2492 CFTR-N1303K-271 UUGAAAUAUUUUACAAUACAAU 22 2493 CFTR-N1303K-272 CUUGAAAUAUUUUACAAUACAAU 23 2494 CFTR-N1303K-273 ACUUGAAAUAUUUUACAAUACAAU 24 2495 CFTR-N1303K-274 GAAAAAAGUUGGAUCCCU 18 2496 CFTR-N1303K-275 AGAAAAAAGUUGGAUCCCU 19 2497 CFTR-N1303K-276 UAGAAAAAAGUUGGAUCCCU 20 2498 CFTR-N1303K-277 UUAGAAAAAAGUUGGAUCCCU 21 2499 CFTR-N1303K-278 UUUAGAAAAAAGUUGGAUCCCU 22 2500 CFTR-N1303K-279 AUUUAGAAAAAAGUUGGAUCCCU 23 2501 CFTR-N1303K-280 CAUUUAGAAAAAAGUUGGAUCCCU 24 2502 CFTR-N1303K-281 UAUUUUUUCUGGAACAUU 18 2503 CFTR-N1303K-282 UUAUUUUUUCUGGAACAUU 19 2504 CFTR-N1303K-283 UUUAUUUUUUCUGGAACAUU 20 2505 CFTR-N1303K-284 AUUUAUUUUUUCUGGAACAUU 21 2506 CFTR-N1303K-285 UAUUUAUUUUUUCUGGAACAUU 22 2507 CFTR-N1303K-286 GUAUUUAUUUUUUCUGGAACAUU 23 2508 CFTR-N1303K-287 AGUAUUUAUUUUUUCUGGAACAUU 24 2509 CFTR-N1303K-288 CUGCUAACUGAAAUGAUU 18 2510 CFTR-N1303K-289 GCUGCUAACUGAAAUGAUU 19 2511 CFTR-N1303K-290 GGCUGCUAACUGAAAUGAUU 20 2512 CFTR-N1303K-291 AGGCUGCUAACUGAAAUGAUU 21 2513 CFTR-N1303K-292 AAGGCUGCUAACUGAAAUGAUU 22 2514 CFTR-N1303K-293 UAAGGCUGCUAACUGAAAUGAUU 23 2515 CFTR-N1303K-294 GUAAGGCUGCUAACUGAAAUGAUU 24 2516 CFTR-N1303K-295 GAUAAAAUAUUAAAAUUU 18 2517 CFTR-N1303K-296 UGAUAAAAUAUUAAAAUUU 19 2518 CFTR-N1303K-297 AUGAUAAAAUAUUAAAAUUU 20 2519 CFTR-N1303K-298 AGAAAGUAUUUAUUUUUU 18 2520 CFTR-N1303K-299 UAGAAAGUAUUUAUUUUUU 19 2521 CFTR-N1303K-300 AUAGAAAGUAUUUAUUUUUU 20 2522 CFTR-N1303K-301 UAUAGAAAGUAUUUAUUUUUU 21 2523 CFTR-N1303K-302 CUAUAGAAAGUAUUUAUUUUUU 22 2524 CFTR-N1303K-303 GCUAUAGAAAGUAUUUAUUUUUU 23 2525 CFTR-N1303K-304 UGCUAUAGAAAGUAUUUAUUUUUU 24 2526

Table 21A provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 21A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-N1303K-305 GGUAAGGCUGCUAACUG 17 2527

Table 21B provides exemplary targeting domains for correcting a mutation (e.g., N1303K) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., N1303K) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 21B 2nd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-N1303K-306 UGAGGUAAGGCUGCUAACUG 20 2528

Table 22A provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 22A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-1 + GUGAUGAAGGCCAAAAA 17 2529 CFTR-R117H-2 + GGUGACUUCCUACAAAA 17 2530 CFTR-R117H-3 + GCCAUGGGGCCUGUGCA 17 2531 CFTR-R117H-4 + GCAUUCCAAUGUGAUGA 17 2532 CFTR-R117H-5 GUAAUACUUCCUUGCAC 17 2533 CFTR-R117H-6 + GUGACUUCCUACAAAAG 17 2534 CFTR-R117H-7 GCCUUCUCUUUAUUGUG 17 2535 CFTR-R117H-8 GCGAUUUAUCUAGGCAU 17 2536 CFTR-R117H-9 GUACAGCCUCUCUUACU 17 2537 CFTR-R117H-10 + GAAGGCCAAAAAUGGCU 17 2538 CFTR-R117H-11 + GAGAGGCUGUACUGCUU 17 2539 CFTR-R117H-12 + GAUACAGAAUAUAUGUGCCA 20 2540 CFTR-R117H-13 GUCUUGUGUUGAAAUUCUCA 20 2541 CFTR-R117H-14 + GUGUCCUCACAAUAAAGAGA 20 2542 CFTR-R117H-15 GCAGUACAGCCUCUCUUACU 20 2543 CFTR-R117H-16 + GAUGAAGGCCAAAAAUGGCU 20 2544 CFTR-R117H-17 + GGCCAAAAAUGGCUGGGUGU 20 2545

Table 22B provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 22B 2nd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-18 + UGGUGACUUCCUACAAA 17 2546 CFTR-R117H-19 CUAUGACCCGGAUAACA 17 2547 CFTR-R117H-20 UUGUGUUGAAAUUCUCA 17 2548 CFTR-R117H-21 UAGUUUGAUUUAUAAGA 17 2549 CFTR-R117H-22 + UCCUCACAAUAAAGAGA 17 2550 CFTR-R117H-23 AGUACAGCCUCUCUUAC 17 2551 CFTR-R117H-24 CAUAGCUUCCUAUGACC 17 2552 CFTR-R117H-25 + UGAAGGCCAAAAAUGGC 17 2553 CFTR-R117H-26 + UGUUCCUCCUUGUUAUC 17 2554 CFTR-R117H-27 CUUGUGUUGAAAUUCUC 17 2555 CFTR-R117H-28 + AUUCUUCCCAGUAAGAG 17 2556 CFTR-R117H-29 + AGACUUUUCAUCUUUAG 17 2557 CFTR-R117H-30 UGACCCGGAUAACAAGG 17 2558 CFTR-R117H-31 UUUGGCCUUCAUCACAU 17 2559 CFTR-R117H-32 + CAGAAUAUAUGUGCCAU 17 2560 CFTR-R117H-33 + CUUGUUAUCCGGGUCAU 17 2561 CFTR-R117H-34 UCUAUCGCGAUUUAUCU 17 2562 CFTR-R117H-35 + CAAAAAUGGCUGGGUGU 17 2563 CFTR-R117H-36 CUACACCCAGCCAUUUU 17 2564 CFTR-R117H-37 + AAUGUGAUGAAGGCCAAAAA 20 2565 CFTR-R117H-38 + UUUGGUGACUUCCUACAAAA 20 2566 CFTR-R117H-39 + CUUUGGUGACUUCCUACAAA 20 2567 CFTR-R117H-40 UUCCUAUGACCCGGAUAACA 20 2568 CFTR-R117H-41 ACUUCCUUGCACAGGCCCCA 20 2569 CFTR-R117H-42 + UGUGCCAUGGGGCCUGUGCA 20 2570 CFTR-R117H-43 + UCUGCAUUCCAAUGUGAUGA 20 2571 CFTR-R117H-44 AAGGUAAUACUUCCUUGCAC 20 2572 CFTR-R117H-45 AGCAGUACAGCCUCUCUUAC 20 2573 CFTR-R117H-46 AAUCAUAGCUUCCUAUGACC 20 2574 CFTR-R117H-47 + UGAUGAAGGCCAAAAAUGGC 20 2575 CFTR-R117H-48 AGUCUUGUGUUGAAAUUCUC 20 2576 CFTR-R117H-49 + UUGGUGACUUCCUACAAAAG 20 2577 CFTR-R117H-50 + AUGAUUCUUCCCAGUAAGAG 20 2578 CFTR-R117H-51 + CUUAAAAUGAGUUUAUAUAG 20 2579 CFTR-R117H-52 + ACAAGACUUUUCAUCUUUAG 20 2580 CFTR-R117H-53 CUAUGACCCGGAUAACAAGG 20 2581 CFTR-R117H-54 + UACAGAAUAUAUGUGCCAUG 20 2582 CFTR-R117H-55 UAUGCCUUCUCUUUAUUGUG 20 2583 CFTR-R117H-56 AUUUUUGGCCUUCAUCACAU 20 2584 CFTR-R117H-57 + AUACAGAAUAUAUGUGCCAU 20 2585 CFTR-R117H-58 AUCGCGAUUUAUCUAGGCAU 20 2586 CFTR-R117H-59 + CUCCUUGUUAUCCGGGUCAU 20 2587 CFTR-R117H-60 + UAAGAGAGGCUGUACUGCUU 20 2588 CFTR-R117H-61 CUCCUACACCCAGCCAUUUU 20 2589

Table 22C provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 22C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-62 + GUUCCUCCUUGUUAUCC 17 2590 CFTR-R117H-63 GUUUAGUUUGAUUUAUAAGA 20 2591 CFTR-R117H-64 + GAGUGUUCCUCCUUGUUAUC 20 2592

Table 22D provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 22D 4th Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-65 UCCUUGCACAGGCCCCA 17 2593 CFTR-R117H-66 + ACAGAAUAUAUGUGCCA 17 2594 CFTR-R117H-67 + AAAUGAGUUUAUAUAGA 17 2595 CFTR-R117H-68 + AAAAUGAGUUUAUAUAG 17 2596 CFTR-R117H-69 + AGAAUAUAUGUGCCAUG 17 2597 CFTR-R117H-70 UGUUUUUCCCCUUUUGU 17 2598 CFTR-R117H-71 + UUAAAAUGAGUUUAUAUAGA 20 2599 CFTR-R117H-72 + AGUGUUCCUCCUUGUUAUCC 20 2600 CFTR-R117H-73 CACUCUAUCGCGAUUUAUCU 20 2601 CFTR-R117H-74 CUCUGUUUUUCCCCUUUUGU 20 2602

Table 23A provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 23A 1st Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-75 + GCCUAUGCCUAGAUAAAUCGCGA 23 2603 CFTR-R117H-76 + GAUGAAGGCCAAAAAUGG 18 2604 CFTR-R117H-77 + GUGAUGAAGGCCAAAAAUGG 20 2605 CFTR-R117H-78 GAAUCAUAGCUUCCUAUGAC 20 2606 CFTR-R117H-79 GAAGAAUCAUAGCUUCCUAUGAC 23 2607 CFTR-R117H-80 GGAAGAAUCAUAGCUUCCUAUGAC 24 2608 CFTR-R117H-81 GUACAGCCUCUCUUACUGGG 20 2609 CFTR-R117H-82 GCAGUACAGCCUCUCUUACUGGG 23 2610 CFTR-R117H-83 GCCAUUUUUGGCCUUCAUCACAU 23 2611 CFTR-R117H-84 GUCUUGUGUUGAAAUUCU 18 2612 CFTR-R117H-85 GAAAAGUCUUGUGUUGAAAUUCU 23 2613

Table 23B provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 23B 2nd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-86 + CUUUAGAGGAGACUUAAA 18 2614 CFTR-R117H-87 + UCUUUAGAGGAGACUUAAA 19 2615 CFTR-R117H-88 + AUCUUUAGAGGAGACUUAAA 20 2616 CFTR-R117H-89 + CAUCUUUAGAGGAGACUUAAA 21 2617 CFTR-R117H-90 + UCAUCUUUAGAGGAGACUUAAA 22 2618 CFTR-R117H-91 + UUCAUCUUUAGAGGAGACUUAAA 23 2619 CFTR-R117H-92 + UUUCAUCUUUAGAGGAGACUUAAA 24 2620 CFTR-R117H-93 + UGCCUAGAUAAAUCGCGA 18 2621 CFTR-R117H-94 + AUGCCUAGAUAAAUCGCGA 19 2622 CFTR-R117H-95 + UAUGCCUAGAUAAAUCGCGA 20 2623 CFTR-R117H-96 + CUAUGCCUAGAUAAAUCGCGA 21 2624 CFTR-R117H-97 + CCUAUGCCUAGAUAAAUCGCGA 22 2625 CFTR-R117H-98 + AGCCUAUGCCUAGAUAAAUCGCGA 24 2626 CFTR-R117H-99 + AUUAAAACAUGUACGAUA 18 2627 CFTR-R117H-100 + CAUUAAAACAUGUACGAUA 19 2628 CFTR-R117H-101 + ACAUUAAAACAUGUACGAUA 20 2629 CFTR-R117H-102 + UUAAAAUGAGUUUAUAUA 18 2630 CFTR-R117H-103 + CUUAAAAUGAGUUUAUAUA 19 2631 CFTR-R117H-104 + ACUUAAAAUGAGUUUAUAUA 20 2632 CFTR-R117H-105 + UGAUGAAGGCCAAAAAUGG 19 2633 CFTR-R117H-106 + UGUGAUGAAGGCCAAAAAUGG 21 2634 CFTR-R117H-107 + AUGUGAUGAAGGCCAAAAAUGG 22 2635 CFTR-R117H-108 + AAUGUGAUGAAGGCCAAAAAUGG 23 2636 CFTR-R117H-109 + CAAUGUGAUGAAGGCCAAAAAUGG 24 2637 CFTR-R117H-110 + UUUCUCAUAAAAUACCCU 18 2638 CFTR-R117H-111 + AUUUCUCAUAAAAUACCCU 19 2639 CFTR-R117H-112 + UAUUUCUCAUAAAAUACCCU 20 2640 CFTR-R117H-113 AUCAUAGCUUCCUAUGAC 18 2641 CFTR-R117H-114 AAUCAUAGCUUCCUAUGAC 19 2642 CFTR-R117H-115 AGAAUCAUAGCUUCCUAUGAC 21 2643 CFTR-R117H-116 AAGAAUCAUAGCUUCCUAUGAC 22 2644 CFTR-R117H-117 ACAGCCUCUCUUACUGGG 18 2645 CFTR-R117H-118 UACAGCCUCUCUUACUGGG 19 2646 CFTR-R117H-119 AGUACAGCCUCUCUUACUGGG 21 2647 CFTR-R117H-120 CAGUACAGCCUCUCUUACUGGG 22 2648 CFTR-R117H-121 AGCAGUACAGCCUCUCUUACUGGG 24 2649 CFTR-R117H-122 UUUUGGCCUUCAUCACAU 18 2650 CFTR-R117H-123 UUUUUGGCCUUCAUCACAU 19 2651 CFTR-R117H-56 AUUUUUGGCCUUCAUCACAU 20 2584 CFTR-R117H-124 CAUUUUUGGCCUUCAUCACAU 21 2652 CFTR-R117H-125 CCAUUUUUGGCCUUCAUCACAU 22 2653 CFTR-R117H-126 AGCCAUUUUUGGCCUUCAUCACAU 24 2654 CFTR-R117H-127 AGUCUUGUGUUGAAAUUCU 19 2655 CFTR-R117H-128 AAGUCUUGUGUUGAAAUUCU 20 2656 CFTR-R117H-129 AAAGUCUUGUGUUGAAAUUCU 21 2657 CFTR-R117H-130 AAAAGUCUUGUGUUGAAAUUCU 22 2658 CFTR-R117H-131 UGAAAAGUCUUGUGUUGAAAUUCU 24 2659

Table 23C provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 23C 3rd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-132 + GACUUAAAAUGAGUUUAUAUA 21 2660 CFTR-R117H-133 + GAGACUUAAAAUGAGUUUAUAUA 23 2661 CFTR-R117H-134 + GGAGACUUAAAAUGAGUUUAUAUA 24 2662 CFTR-R117H-135 + GAGUGUUCCUCCUUGUUAU 19 2663 CFTR-R117H-136 + GAUAGAGUGUUCCUCCUUGUUAU 23 2664

Table 23D provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 23D 4th Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-137 + AGACUUAAAAUGAGUUUAUAUA 22 2665 CFTR-R117H-138 + AGUGUUCCUCCUUGUUAU 18 2666 CFTR-R117H-139 + AGAGUGUUCCUCCUUGUUAU 20 2667 CFTR-R117H-140 + UAGAGUGUUCCUCCUUGUUAU 21 2668 CFTR-R117H-141 + AUAGAGUGUUCCUCCUUGUUAU 22 2669 CFTR-R117H-142 + CGAUAGAGUGUUCCUCCUUGUUAU 24 2670 CFTR-R117H-143 + UUAUUUCUCAUAAAAUACCCU 21 2671 CFTR-R117H-144 + UUUAUUUCUCAUAAAAUACCCU 22 2672 CFTR-R117H-145 + AUUUAUUUCUCAUAAAAUACCCU 23 2673 CFTR-R117H-146 + CAUUUAUUUCUCAUAAAAUACCCU 24 2674 CFTR-R117H-147 UCACAUUGGAAUGCAGAU 18 2675 CFTR-R117H-148 AUCACAUUGGAAUGCAGAU 19 2676 CFTR-R117H-149 CAUCACAUUGGAAUGCAGAU 20 2677 CFTR-R117H-150 UCAUCACAUUGGAAUGCAGAU 21 2678 CFTR-R117H-151 UUCAUCACAUUGGAAUGCAGAU 22 2679 CFTR-R117H-152 CUUCAUCACAUUGGAAUGCAGAU 23 2680 CFTR-R117H-153 CCUUCAUCACAUUGGAAUGCAGAU 24 2681

Table 23E provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 23E 5th Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-154 + CCUACAAAAGGGGAAAAA 18 2682 CFTR-R117H-155 + UCCUACAAAAGGGGAAAAA 19 2683 CFTR-R117H-156 + UUCCUACAAAAGGGGAAAAA 20 2684 CFTR-R117H-157 + CUUCCUACAAAAGGGGAAAAA 21 2685 CFTR-R117H-158 + ACUUCCUACAAAAGGGGAAAAA 22 2686 CFTR-R117H-159 + GACUUCCUACAAAAGGGGAAAAA 23 2687 CFTR-R117H-160 + UGACUUCCUACAAAAGGGGAAAAA 24 2688 CFTR-R117H-161 + UGGUGACUUCCUACAAAA 18 2689 CFTR-R117H-162 + UUGGUGACUUCCUACAAAA 19 2690 CFTR-R117H-38 + UUUGGUGACUUCCUACAAAA 20 2566 CFTR-R117H-163 + CUUUGGUGACUUCCUACAAAA 21 2691 CFTR-R117H-164 + GCUUUGGUGACUUCCUACAAAA 22 2692 CFTR-R117H-165 + UGCUUUGGUGACUUCCUACAAAA 23 2693 CFTR-R117H-166 + CUGCUUUGGUGACUUCCUACAAAA 24 2694 CFTR-R117H-167 + UUGGUGACUUCCUACAAA 18 2695 CFTR-R117H-168 + UUUGGUGACUUCCUACAAA 19 2696 CFTR-R117H-39 + CUUUGGUGACUUCCUACAAA 20 2567 CFTR-R117H-169 + GCUUUGGUGACUUCCUACAAA 21 2697 CFTR-R117H-170 + UGCUUUGGUGACUUCCUACAAA 22 2698 CFTR-R117H-171 + CUGCUUUGGUGACUUCCUACAAA 23 2699 CFTR-R117H-172 + ACUGCUUUGGUGACUUCCUACAAA 24 2700 CFTR-R117H-173 + CAGUGUCCUCACAAUAAA 18 2701 CFTR-R117H-174 + GCAGUGUCCUCACAAUAAA 19 2702 CFTR-R117H-175 + AGCAGUGUCCUCACAAUAAA 20 2703 CFTR-R117H-176 + GAGCAGUGUCCUCACAAUAAA 21 2704 CFTR-R117H-177 + GGAGCAGUGUCCUCACAAUAAA 22 2705 CFTR-R117H-178 + AGGAGCAGUGUCCUCACAAUAAA 23 2706 CFTR-R117H-179 + UAGGAGCAGUGUCCUCACAAUAAA 24 2707 CFTR-R117H-180 + UUUGGUGACUUCCUACAA 18 2708 CFTR-R117H-181 + CUUUGGUGACUUCCUACAA 19 2709 CFTR-R117H-182 + GCUUUGGUGACUUCCUACAA 20 2710 CFTR-R117H-183 + UGCUUUGGUGACUUCCUACAA 21 2711 CFTR-R117H-184 + CUGCUUUGGUGACUUCCUACAA 22 2712 CFTR-R117H-185 + ACUGCUUUGGUGACUUCCUACAA 23 2713 CFTR-R117H-186 + UACUGCUUUGGUGACUUCCUACAA 24 2714 CFTR-R117H-187 + UAUGAUUCUUCCCAGUAA 18 2715 CFTR-R117H-188 + CUAUGAUUCUUCCCAGUAA 19 2716 CFTR-R117H-189 + GCUAUGAUUCUUCCCAGUAA 20 2717 CFTR-R117H-190 + AGCUAUGAUUCUUCCCAGUAA 21 2718 CFTR-R117H-191 + AAGCUAUGAUUCUUCCCAGUAA 22 2719 CFTR-R117H-192 + GAAGCUAUGAUUCUUCCCAGUAA 23 2720 CFTR-R117H-193 + GGAAGCUAUGAUUCUUCCCAGUAA 24 2721 CFTR-R117H-194 + UACAAAAGGGGAAAAACA 18 2722 CFTR-R117H-195 + CUACAAAAGGGGAAAAACA 19 2723 CFTR-R117H-196 + CCUACAAAAGGGGAAAAACA 20 2724 CFTR-R117H-197 + UCCUACAAAAGGGGAAAAACA 21 2725 CFTR-R117H-198 + UUCCUACAAAAGGGGAAAAACA 22 2726 CFTR-R117H-199 + CUUCCUACAAAAGGGGAAAAACA 23 2727 CFTR-R117H-200 + ACUUCCUACAAAAGGGGAAAAACA 24 2728 CFTR-R117H-201 + UACAGAAUAUAUGUGCCA 18 2729 CFTR-R117H-202 + AUACAGAAUAUAUGUGCCA 19 2730 CFTR-R117H-12 + GAUACAGAAUAUAUGUGCCA 20 2540 CFTR-R117H-203 + CGAUACAGAAUAUAUGUGCCA 21 2731 CFTR-R117H-204 + ACGAUACAGAAUAUAUGUGCCA 22 2732 CFTR-R117H-205 + UACGAUACAGAAUAUAUGUGCCA 23 2733 CFTR-R117H-206 + GUACGAUACAGAAUAUAUGUGCCA 24 2734 CFTR-R117H-207 + UGCCAUGGGGCCUGUGCA 18 2735 CFTR-R117H-208 + GUGCCAUGGGGCCUGUGCA 19 2736 CFTR-R117H-42 + UGUGCCAUGGGGCCUGUGCA 20 2570 CFTR-R117H-209 + AUGUGCCAUGGGGCCUGUGCA 21 2737 CFTR-R117H-210 + UAUGUGCCAUGGGGCCUGUGCA 22 2738 CFTR-R117H-211 + AUAUGUGCCAUGGGGCCUGUGCA 23 2739 CFTR-R117H-212 + UAUAUGUGCCAUGGGGCCUGUGCA 24 2740 CFTR-R117H-213 + UCCUUGUUAUCCGGGUCA 18 2741 CFTR-R117H-214 + CUCCUUGUUAUCCGGGUCA 19 2742 CFTR-R117H-215 + CCUCCUUGUUAUCCGGGUCA 20 2743 CFTR-R117H-216 + UCCUCCUUGUUAUCCGGGUCA 21 2744 CFTR-R117H-217 + UUCCUCCUUGUUAUCCGGGUCA 22 2745 CFTR-R117H-218 + GUUCCUCCUUGUUAUCCGGGUCA 23 2746 CFTR-R117H-219 + UGUUCCUCCUUGUUAUCCGGGUCA 24 2747 CFTR-R117H-220 + AGCAGUGUCCUCACAAUA 18 2748 CFTR-R117H-221 + GAGCAGUGUCCUCACAAUA 19 2749 CFTR-R117H-222 + GGAGCAGUGUCCUCACAAUA 20 2750 CFTR-R117H-223 + AGGAGCAGUGUCCUCACAAUA 21 2751 CFTR-R117H-224 + UAGGAGCAGUGUCCUCACAAUA 22 2752 CFTR-R117H-225 + GUAGGAGCAGUGUCCUCACAAUA 23 2753 CFTR-R117H-226 + UGUAGGAGCAGUGUCCUCACAAUA 24 2754 CFTR-R117H-227 + ACUUAAAAUGAGUUUAUA 18 2755 CFTR-R117H-228 + GACUUAAAAUGAGUUUAUA 19 2756 CFTR-R117H-229 + AGACUUAAAAUGAGUUUAUA 20 2757 CFTR-R117H-230 + GAGACUUAAAAUGAGUUUAUA 21 2758 CFTR-R117H-231 + GGAGACUUAAAAUGAGUUUAUA 22 2759 CFTR-R117H-232 + AGGAGACUUAAAAUGAGUUUAUA 23 2760 CFTR-R117H-233 + GAGGAGACUUAAAAUGAGUUUAUA 24 2761 CFTR-R117H-234 + CAAGACUUUUCAUCUUUA 18 2762 CFTR-R117H-235 + ACAAGACUUUUCAUCUUUA 19 2763 CFTR-R117H-236 + CACAAGACUUUUCAUCUUUA 20 2764 CFTR-R117H-237 + ACACAAGACUUUUCAUCUUUA 21 2765 CFTR-R117H-238 + AACACAAGACUUUUCAUCUUUA 22 2766 CFTR-R117H-239 + CAACACAAGACUUUUCAUCUUUA 23 2767 CFTR-R117H-240 + UCAACACAAGACUUUUCAUCUUUA 24 2768 CFTR-R117H-241 + UAUUUCUCAUAAAAUACC 18 2769 CFTR-R117H-242 + UUAUUUCUCAUAAAAUACC 19 2770 CFTR-R117H-243 + UUUAUUUCUCAUAAAAUACC 20 2771 CFTR-R117H-244 + AUUUAUUUCUCAUAAAAUACC 21 2772 CFTR-R117H-245 + CAU UUAUUUCUCAUAAAAUACC 22 2773 CFTR-R117H-246 + UCAUUUAUUUCUCAUAAAAUACC 23 2774 CFTR-R117H-247 + UUCAUUUAUUUCUCAUAAAAUACC 24 2775 CFTR-R117H-248 + AUACAGAAUAUAUGUGCC 18 2776 CFTR-R117H-249 + GAUACAGAAUAUAUGUGCC 19 2777 CFTR-R117H-250 + CGAUACAGAAUAUAUGUGCC 20 2778 CFTR-R117H-251 + ACGAUACAGAAUAUAUGUGCC 21 2779 CFTR-R117H-252 + UACGAUACAGAAUAUAUGUGCC 22 2780 CFTR-R117H-253 + GUACGAUACAGAAUAUAUGUGCC 23 2781 CFTR-R117H-254 + UGUACGAUACAGAAUAUAUGUGCC 24 2782 CFTR-R117H-255 + GUGCCAUGGGGCCUGUGC 18 2783 CFTR-R117H-256 + UGUGCCAUGGGGCCUGUGC 19 2784 CFTR-R117H-257 + AUGUGCCAUGGGGCCUGUGC 20 2785 CFTR-R117H-258 + UAUGUGCCAUGGGGCCUGUGC 21 2786 CFTR-R117H-259 + AUAUGUGCCAUGGGGCCUGUGC 22 2787 CFTR-R117H-260 + UAUAUGUGCCAUGGGGCCUGUGC 23 2788 CFTR-R117H-261 + AUAUAUGUGCCAUGGGGCCUGUGC 24 2789 CFTR-R117H-262 + GGUGACUUCCUACAAAAG 18 2790 CFTR-R117H-263 + UGGUGACUUCCUACAAAAG 19 2791 CFTR-R117H-49 + UUGGUGACUUCCUACAAAAG 20 2577 CFTR-R117H-264 + UUUGGUGACUUCCUACAAAAG 21 2792 CFTR-R117H-265 + CUUUGGUGACUUCCUACAAAAG 22 2793 CFTR-R117H-266 + GCUUUGGUGACUUCCUACAAAAG 23 2794 CFTR-R117H-267 + UGCUUUGGUGACUUCCUACAAAAG 24 2795 CFTR-R117H-268 + AAGACUUUUCAUCUUUAG 18 2796 CFTR-R117H-269 + CAAGACUUUUCAUCUUUAG 19 2797 CFTR-R117H-52 + ACAAGACUUUUCAUCUUUAG 20 2580 CFTR-R117H-270 + CACAAGACUUUUCAUCUUUAG 21 2798 CFTR-R117H-271 + ACACAAGACUUUUCAUCUUUAG 22 2799 CFTR-R117H-272 + AACACAAGACUUUUCAUCUUUAG 23 2800 CFTR-R117H-273 + CAACACAAGACUUUUCAUCUUUAG 24 2801 CFTR-R117H-274 + GCCAAAAAUGGCUGGGUG 18 2802 CFTR-R117H-275 + GGCCAAAAAUGGCUGGGUG 19 2803 CFTR-R117H-276 + AGGCCAAAAAUGGCUGGGUG 20 2804 CFTR-R117H-277 + AAGGCCAAAAAUGGCUGGGUG 21 2805 CFTR-R117H-278 + GAAGGCCAAAAAUGGCUGGGUG 22 2806 CFTR-R117H-279 + UGAAGGCCAAAAAUGGCUGGGUG 23 2807 CFTR-R117H-280 + AUGAAGGCCAAAAAUGGCUGGGUG 24 2808 CFTR-R117H-281 + CAUCUGCAUUCCAAUGUG 18 2809 CFTR-R117H-282 + UCAUCUGCAUUCCAAUGUG 19 2810 CFTR-R117H-283 + CUCAUCUGCAUUCCAAUGUG 20 2811 CFTR-R117H-284 + UCUCAUCUGCAUUCCAAUGUG 21 2812 CFTR-R117H-285 + UUCUCAUCUGCAUUCCAAUGUG 22 2813 CFTR-R117H-286 + AUUCUCAUCUGCAUUCCAAUGUG 23 2814 CFTR-R117H-287 + UAUUCUCAUCUGCAUUCCAAUGUG 24 2815 CFTR-R117H-288 + CCUUGUUAUCCGGGUCAU 18 2816 CFTR-R117H-289 + UCCUUGUUAUCCGGGUCAU 19 2817 CFTR-R117H-59 + CUCCUUGUUAUCCGGGUCAU 20 2587 CFTR-R117H-290 + CCUCCUUGUUAUCCGGGUCAU 21 2818 CFTR-R117H-291 + UCCUCCUUGUUAUCCGGGUCAU 22 2819 CFTR-R117H-292 + UUCCUCCUUGUUAUCCGGGUCAU 23 2820 CFTR-R117H-293 + GUUCCUCCUUGUUAUCCGGGUCAU 24 2821 CFTR-R117H-294 + GCUAUGAUUCUUCCCAGU 18 2822 CFTR-R117H-295 + AGCUAUGAUUCUUCCCAGU 19 2823 CFTR-R117H-296 + AAGCUAUGAUUCUUCCCAGU 20 2824 CFTR-R117H-297 + GAAGCUAUGAUUCUUCCCAGU 21 2825 CFTR-R117H-298 + GGAAGCUAUGAUUCUUCCCAGU 22 2826 CFTR-R117H-299 + AGGAAGCUAUGAUUCUUCCCAGU 23 2827 CFTR-R117H-300 + UAGGAAGCUAUGAUUCUUCCCAGU 24 2828 CFTR-R117H-301 + CCAAAAAUGGCUGGGUGU 18 2829 CFTR-R117H-302 + GCCAAAAAUGGCUGGGUGU 19 2830 CFTR-R117H-17 + GGCCAAAAAUGGCUGGGUGU 20 2545 CFTR-R117H-303 + AGGCCAAAAAUGGCUGGGUGU 21 2831 CFTR-R117H-304 + AAGGCCAAAAAUGGCUGGGUGU 22 2832 CFTR-R117H-305 + GAAGGCCAAAAAUGGCUGGGUGU 23 2833 CFTR-R117H-306 + UGAAGGCCAAAAAUGGCUGGGUGU 24 2834 CFTR-R117H-307 + CACAAGACUUUUCAUCUU 18 2835 CFTR-R117H-308 + ACACAAGACUUUUCAUCUU 19 2836 CFTR-R117H-309 + AACACAAGACUUUUCAUCUU 20 2837 CFTR-R117H-310 + CAACACAAGACUUUUCAUCUU 21 2838 CFTR-R117H-311 + UCAACACAAGACUUUUCAUCUU 22 2839 CFTR-R117H-312 + UUCAACACAAGACUUUUCAUCUU 23 2840 CFTR-R117H-313 + UUUCAACACAAGACUUUUCAUCUU 24 2841 CFTR-R117H-314 GUAUUUUAUGAGAAAUAA 18 2842 CFTR-R117H-315 GGUAUUUUAUGAGAAAUAA 19 2843 CFTR-R117H-316 GGGUAUUUUAUGAGAAAUAA 20 2844 CFTR-R117H-317 AGGGUAUUUUAUGAGAAAUAA 21 2845 CFTR-R117H-318 CAGGGUAUUUUAUGAGAAAUAA 22 2846 CFTR-R117H-319 UCAGGGUAUUUUAUGAGAAAUAA 23 2847 CFTR-R117H-320 CUCAGGGUAUUUUAUGAGAAAUAA 24 2848 CFTR-R117H-321 CCUAUGACCCGGAUAACA 18 2849 CFTR-R117H-322 UCCUAUGACCCGGAUAACA 19 2850 CFTR-R117H-40 UUCCUAUGACCCGGAUAACA 20 2568 CFTR-R117H-323 CUUCCUAUGACCCGGAUAACA 21 2851 CFTR-R117H-324 GCUUCCUAUGACCCGGAUAACA 22 2852 CFTR-R117H-325 AGCUUCCUAUGACCCGGAUAACA 23 2853 CFTR-R117H-326 UAGCUUCCUAUGACCCGGAUAACA 24 2854 CFTR-R117H-327 UUUUUGGCCUUCAUCACA 18 2855 CFTR-R117H-328 AUUUUUGGCCUUCAUCACA 19 2856 CFTR-R117H-329 CAUUUUUGGCCUUCAUCACA 20 2857 CFTR-R117H-330 CCAUUUUUGGCCUUCAUCACA 21 2858 CFTR-R117H-331 GCCAUUUUUGGCCUUCAUCACA 22 2859 CFTR-R117H-332 AGCCAUUUUUGGCCUUCAUCACA 23 2860 CFTR-R117H-333 CAGCCAUUUUUGGCCUUCAUCACA 24 2861 CFTR-R117H-334 GCAGUACAGCCUCUCUUA 18 2862 CFTR-R117H-335 AGCAGUACAGCCUCUCUUA 19 2863 CFTR-R117H-336 AAGCAGUACAGCCUCUCUUA 20 2864 CFTR-R117H-337 AAAGCAGUACAGCCUCUCUUA 21 2865 CFTR-R117H-338 CAAAGCAGUACAGCCUCUCUUA 22 2866 CFTR-R117H-339 CCAAAGCAGUACAGCCUCUCUUA 23 2867 CFTR-R117H-340 ACCAAAGCAGUACAGCCUCUCUUA 24 2868 CFTR-R117H-341 UCCUAUGACCCGGAUAAC 18 2869 CFTR-R117H-342 UUCCUAUGACCCGGAUAAC 19 2870 CFTR-R117H-343 CUUCCUAUGACCCGGAUAAC 20 2871 CFTR-R117H-344 GCUUCCUAUGACCCGGAUAAC 21 2872 CFTR-R117H-345 AGCUUCCUAUGACCCGGAUAAC 22 2873 CFTR-R117H-346 UAGCUUCCUAUGACCCGGAUAAC 23 2874 CFTR-R117H-347 AUAGCUUCCUAUGACCCGGAUAAC 24 2875 CFTR-R117H-348 CAGUACAGCCUCUCUUAC 18 2876 CFTR-R117H-349 GCAGUACAGCCUCUCUUAC 19 2877 CFTR-R117H-45 AGCAGUACAGCCUCUCUUAC 20 2573 CFTR-R117H-350 AAGCAGUACAGCCUCUCUUAC 21 2878 CFTR-R117H-351 AAAGCAGUACAGCCUCUCUUAC 22 2879 CFTR-R117H-352 CAAAGCAGUACAGCCUCUCUUAC 23 2880 CFTR-R117H-353 CCAAAGCAGUACAGCCUCUCUUAC 24 2881 CFTR-R117H-354 UUUAAGUCUCCUCUAAAG 18 2882 CFTR-R117H-355 UUUUAAGUCUCCUCUAAAG 19 2883 CFTR-R117H-356 AUUUUAAGUCUCCUCUAAAG 20 2884 CFTR-R117H-357 CAUUUUAAGUCUCCUCUAAAG 21 2885 CFTR-R117H-358 UCAUUUUAAGUCUCCUCUAAAG 22 2886 CFTR-R117H-359 CUCAUUUUAAGUCUCCUCUAAAG 23 2887 CFTR-R117H-360 ACUCAUUUUAAGUCUCCUCUAAAG 24 2888 CFTR-R117H-361 UAUGACCCGGAUAACAAG 18 2889 CFTR-R117H-362 CUAUGACCCGGAUAACAAG 19 2890 CFTR-R117H-363 CCUAUGACCCGGAUAACAAG 20 2891 CFTR-R117H-364 UCCUAUGACCCGGAUAACAAG 21 2892 CFTR-R117H-365 UUCCUAUGACCCGGAUAACAAG 22 2893 CFTR-R117H-366 CUUCCUAUGACCCGGAUAACAAG 23 2894 CFTR-R117H-367 GCUUCCUAUGACCCGGAUAACAAG 24 2895 CFTR-R117H-368 CAUCACAUUGGAAUGCAG 18 2896 CFTR-R117H-369 UCAUCACAUUGGAAUGCAG 19 2897 CFTR-R117H-370 UUCAUCACAUUGGAAUGCAG 20 2898 CFTR-R117H-371 CUUCAUCACAUUGGAAUGCAG 21 2899 CFTR-R117H-372 CCUUCAUCACAUUGGAAUGCAG 22 2900 CFTR-R117H-373 GCCUUCAUCACAUUGGAAUGCAG 23 2901 CFTR-R117H-374 GGCCUUCAUCACAUUGGAAUGCAG 24 2902 CFTR-R117H-375 AUGACCCGGAUAACAAGG 18 2903 CFTR-R117H-376 UAUGACCCGGAUAACAAGG 19 2904 CFTR-R117H-53 CUAUGACCCGGAUAACAAGG 20 2581 CFTR-R117H-377 CCUAUGACCCGGAUAACAAGG 21 2905 CFTR-R117H-378 UCCUAUGACCCGGAUAACAAGG 22 2906 CFTR-R117H-379 UUCCUAUGACCCGGAUAACAAGG 23 2907 CFTR-R117H-380 CUUCCUAUGACCCGGAUAACAAGG 24 2908 CFTR-R117H-381 AAGAUGAAAAGUCUUGUG 18 2909 CFTR-R117H-382 AAAGAUGAAAAGUCUUGUG 19 2910 CFTR-R117H-383 UAAAGAUGAAAAGUCUUGUG 20 2911 CFTR-R117H-384 CUAAAGAUGAAAAGUCUUGUG 21 2912 CFTR-R117H-385 UCUAAAGAUGAAAAGUCUUGUG 22 2913 CFTR-R117H-386 CUCUAAAGAUGAAAAGUCUUGUG 23 2914 CFTR-R117H-387 CCUCUAAAGAUGAAAAGUCUUGUG 24 2915 CFTR-R117H-388 UCUGUUUUUCCCCUUUUG 18 2916 CFTR-R117H-389 CUCUGUUUUUCCCCUUUUG 19 2917 CFTR-R117H-390 UCUCUGUUUUUCCCCUUUUG 20 2918 CFTR-R117H-391 UUCUCUGUUUUUCCCCUUUUG 21 2919 CFTR-R117H-392 UUUCUCUGUUUUUCCCCUUUUG 22 2920 CFTR-R117H-393 AUUUCUCUGUUUUUCCCCUUUUG 23 2921 CFTR-R117H-394 AAUUUCUCUGUUUUUCCCCUUUUG 24 2922 CFTR-R117H-395 AUGUUUAGUUUGAUUUAU 18 2923 CFTR-R117H-396 UAUGUUUAGUUUGAUUUAU 19 2924 CFTR-R117H-397 CUAUGUUUAGUUUGAUUUAU 20 2925 CFTR-R117H-398 GCUAUGUUUAGUUUGAUUUAU 21 2926 CFTR-R117H-399 AGCUAUGUUUAGUUUGAUUUAU 22 2927 CFTR-R117H-400 UAGCUAUGUUUAGUUUGAUUUAU 23 2928 CFTR-R117H-401 AUAGCUAUGUUUAGUUUGAUUUAU 24 2929 CFTR-R117H-402 AUUCUCAGGGUAUUUUAU 18 2930 CFTR-R117H-403 AAUUCUCAGGGUAUUUUAU 19 2931 CFTR-R117H-404 AAAUUCUCAGGGUAUUUUAU 20 2932 CFTR-R117H-405 GAAAUUCUCAGGGUAUUUUAU 21 2933 CFTR-R117H-406 UGAAAUUCUCAGGGUAUUUUAU 22 2934 CFTR-R117H-407 UUGAAAUUCUCAGGGUAUUUUAU 23 2935 CFTR-R117H-408 GUUGAAAUUCUCAGGGUAUUUUAU 24 2936 CFTR-R117H-409 AGUACAGCCUCUCUUACU 18 2937 CFTR-R117H-410 CAGUACAGCCUCUCUUACU 19 2938 CFTR-R117H-15 GCAGUACAGCCUCUCUUACU 20 2543 CFTR-R117H-411 AGCAGUACAGCCUCUCUUACU 21 2939 CFTR-R117H-412 AAGCAGUACAGCCUCUCUUACU 22 2940 CFTR-R117H-413 AAAGCAGUACAGCCUCUCUUACU 23 2941 CFTR-R117H-414 CAAAGCAGUACAGCCUCUCUUACU 24 2942 CFTR-R117H-415 AUGCCUUCUCUUUAUUGU 18 2943 CFTR-R117H-416 UAUGCCUUCUCUUUAUUGU 19 2944 CFTR-R117H-417 UUAUGCCUUCUCUUUAUUGU 20 2945 CFTR-R117H-418 CUUAUGCCUUCUCUUUAUUGU 21 2946 CFTR-R117H-419 GCUUAUGCCUUCUCUUUAUUGU 22 2947 CFTR-R117H-420 GGCUUAUGCCUUCUCUUUAUUGU 23 2948 CFTR-R117H-421 AGGCUUAUGCCUUCUCUUUAUUGU 24 2949 CFTR-R117H-422 CUGUUUUUCCCCUUUUGU 18 2950 CFTR-R117H-423 UCUGUUUUUCCCCUUUUGU 19 2951 CFTR-R117H-74 CUCUGUUUUUCCCCUUUUGU 20 2602 CFTR-R117H-424 UCUCUGUUUUUCCCCUUUUGU 21 2952 CFTR-R117H-425 UUCUCUGUUUUUCCCCUUUUGU 22 2953 CFTR-R117H-426 UUUCUCUGUUUUUCCCCUUUUGU 23 2954 CFTR-R117H-427 AUUUCUCUGUUUUUCCCCUUUUGU 24 2955 CFTR-R117H-428 UUAUGCCUUCUCUUUAUU 18 2956 CFTR-R117H-429 CUUAUGCCUUCUCUUUAUU 19 2957 CFTR-R117H-430 GCUUAUGCCUUCUCUUUAUU 20 2958 CFTR-R117H-431 GGCUUAUGCCUUCUCUUUAUU 21 2959 CFTR-R117H-432 AGGCUUAUGCCUUCUCUUUAUU 22 2960 CFTR-R117H-433 UAGGCUUAUGCCUUCUCUUUAUU 23 2961 CFTR-R117H-434 AUAGGCUUAUGCCUUCUCUUUAUU 24 2962 CFTR-R117H-435 AAAUUCUCAGGGUAUUUU 18 2963 CFTR-R117H-436 GAAAUUCUCAGGGUAUUUU 19 2964 CFTR-R117H-437 UGAAAUUCUCAGGGUAUUUU 20 2965 CFTR-R117H-438 UUGAAAUUCUCAGGGUAUUUU 21 2966 CFTR-R117H-439 GUUGAAAUUCUCAGGGUAUUUU 22 2967 CFTR-R117H-440 UGUUGAAAUUCUCAGGGUAUUUU 23 2968 CFTR-R117H-441 GUGUUGAAAUUCUCAGGGUAUUUU 24 2969

Table 24A provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 24A 1st Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-442 + GUUAUCCGGGUCAUAGGAAG 20 2970

Table 24B provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 24B 2nd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-443 UCGCGAUUUAUCUAGGC 17 2971 CFTR-R117H-444 + AUCCGGGUCAUAGGAAG 17 2972 CFTR-R117H-445 CUCUUACUGGGAAGAAU 17 2973 CFTR-R117H-446 CUAUCGCGAUUUAUCUAGGC 20 2974 CFTR-R117H-447 + CUUCCCAGUAAGAGAGGCUG 20 2975 CFTR-R117H-448 CCUCUCUUACUGGGAAGAAU 20 2976

Table 24C provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 24C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-R117H-449 GAGAAUAGCUAUGUUUA 17 2977 CFTR-R117H-450 GAUGAGAAUAGCUAUGUUUA 20 2978

Table 24D provides exemplary targeting domains for correcting a mutation (e.g., R117H) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R117H). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 24D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R117H-451 - CAAGGAGGAACACUCUA 17 2979 CFTR-R117H-452 + CCCAGUAAGAGAGGCUG 17 2980 CFTR-R117H-453 UAACAAGGAGGAACACUCUA 20 2981

Table 25A provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 25A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-1 - GCUUUAUAUUCUGUUUC 17 466 CFTR-R553X-2 - GGUGGAAUCACACUGAG 17 456 CFTR-R553X-3 - GGAAUCACACUGAGUGG 17 457 CFTR-R553X-4 - GUUCAAAAUUUCAACUG 17 464 CFTR-R553X-5 - GGUGAAUAACUAAUUAU 17 465 CFTR-R553X-6 - GGGGUUUUAUGGCUAGU 17 458 CFTR-R553X-7 - GAGCAAGAAUUUCUUUAGCA 20 462 CFTR-R553X-8 - GACAAUAUAGUUCUUGGAGA 20 460 CFTR-R553X-9 - GAAGGUGGAAUCACACUGAG 20 461 CFTR-R553X-10 - GGUGGAAUCACACUGAGUGG 20 454 CFTR-R553X-11 - GAGAAAGACAAUAUAGUUCU 20 453

Table 25B provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 25B 2nd Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-R553X-12 + CUCAAUCUGAAUUUGAA 17 496 CFTR-R553X-13 - CAAGAAUUUCUUUAGCA 17 491 CFTR-R553X-14 - AAUAUAGUUCUUGGAGA 17 489 CFTR-R553X-15 - UAUAUGAUUACAUUAGA 17 485 CFTR-R553X-16 - AAAAUCCUGGGGUUUUA 17 493 CFTR-R553X-17 + ACUAGCCAUAAAACCCC 17 459 CFTR-R553X-18 - UGGGGUUUUAUGGCUAG 17 494 CFTR-R553X-19 - AUAGUUCUUGGAGAAGG 17 490 CFTR-R553X-20 - AAAGACAAUAUAGUUCU 17 488 CFTR-R553X-21 + AUGCUCAAUCUGAAUUUGAA 20 484 CFTR-R553X-22 - UGAUAUAUGAUUACAUUAGA 20 471 CFTR-R553X-23 + CCCACUAGCCAUAAAACCCC 20 455 CFTR-R553X-24 - UUCUGGAAUUGAAAAAAUCC 20 477 CFTR-R553X-25 - AAUAUAGUUCUUGGAGAAGG 20 474 CFTR-R553X-26 - CUGGAAUUGAAAAAAUCCUG 20 479 CFTR-R553X-27 - CAAGGUGAAUAACUAAUUAU 20 475 CFTR-R553X-28 - CCUGGGGUUUUAUGGCUAGU 20 481

Table 25C provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 25C 3rd Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-R553X-29 - GAAUUGAAAAAAUCCUG 17 468 CFTR-R553X-30 + GUCUUUCUCUGCAAACU 17 469 CFTR-R553X-31 - GGAAUUGAAAAAAUCCU 17 467 CFTR-R553X-32 - GAAAAAAUCCUGGGGUUUUA 20 463

Table 25D provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 25D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-33 - UUAAGAACUAUAAAUAA 17 495 CFTR-R553X-34 - UGGAAUUGAAAAAAUCC 17 492 CFTR-R553X-35 - UUUCUAUUUUUGGUAAU 17 487 CFTR-R553X-36 - CUCUAAUUUUCUAUUUU 17 486 CFTR-R553X-37 - CAUUUAAGAACUAUAAAUAA 20 482 CFTR-R553X-38 - AUUGCUUUAUAUUCUGUUUC 20 476 CFTR-R553X-39 - UCCUGGGGUUUUAUGGCUAG 20 480 CFTR-R553X-40 - AAUUUUCUAUUUUUGGUAAU 20 473 CFTR-R553X-41 + AUUGUCUUUCUCUGCAAACU 20 483 CFTR-R553X-42 - UCUGGAAUUGAAAAAAUCCU 20 478 CFTR-R553X-43 - ACUCUCUAAUUUUCUAUUUU 20 472

Table 26A provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 26A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-44 + GAUUUUUUCAAUUCCAGAAA 20 766 CFTR-R553X-45 + GGAUUUUUUCAAUUCCAGAAA 21 1898 CFTR-R553X-46 + GUCACUUUUAGUAUGCUCAAU 21 1899 CFTR-R553X-47 + GAGUCACUUUUAGUAUGCUCAAU 23 1900 CFTR-R553X-48 - GGAGAAGGUGGAAUCACA 18 2160 CFTR-R553X-49 - GUUCUUGGAGAAGGUGGAAUCACA 24 2161 CFTR-R553X-50 - GCAAGAAUUUCUUUAGCAAG 20 746 CFTR-R553X-51 - GACAAUAUAGUUCUUGGAGAAGG 23 2162 CFTR-R553X-52 - GUUUUAUGGCUAGUGGGUU 19 1903 CFTR-R553X-53 - GGUUUUAUGGCUAGUGGGUU 20 751 CFTR-R553X-54 - GGGUUUUAUGGCUAGUGGGUU 21 1904 CFTR-R553X-55 - GGGGUUUUAUGGCUAGUGGGUU 22 1905

Table 26B provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 26B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-56 + UUUUUUCAAUUCCAGAAA 18 1906 CFTR-R553X-57 + AUUUUUUCAAUUCCAGAAA 19 1907 CFTR-R553X-58 + AGGAUUUUUUCAAUUCCAGAAA 22 1908 CFTR-R553X-59 + CAGGAUUUUUUCAAUUCCAGAAA 23 1909 CFTR-R553X-60 + CCAGGAUUUUUUCAAUUCCAGAAA 24 1910 CFTR-R553X-61 + UGUCUGUAAUUUUUUUAC 18 1911 CFTR-R553X-62 + AUGUCUGUAAUUUUUUUAC 19 1912 CFTR-R553X-63 + AAUGUCUGUAAUUUUUUUAC 20 763 CFTR-R553X-64 + CCACUAGCCAUAAAACCC 18 1913 CFTR-R553X-65 + CCCACUAGCCAUAAAACCC 19 1914 CFTR-R553X-66 + ACCCACUAGCCAUAAAACCC 20 1915 CFTR-R553X-67 + AACCCACUAGCCAUAAAACCC 21 1916 CFTR-R553X-68 + UAACCCACUAGCCAUAAAACCC 22 1917 CFTR-R553X-69 + UUAACCCACUAGCCAUAAAACCC 23 1918 CFTR-R553X-70 + CUUAACCCACUAGCCAUAAAACCC 24 1919 CFTR-R553X-71 + ACUUUUAGUAUGCUCAAU 18 1920 CFTR-R553X-72 + CACUUUUAGUAUGCUCAAU 19 1921 CFTR-R553X-73 + UCACUUUUAGUAUGCUCAAU 20 756 CFTR-R553X-74 + AGUCACUUUUAGUAUGCUCAAU 22 1922 CFTR-R553X-75 + AGAGUCACUUUUAGUAUGCUCAAU 24 1923 CFTR-R553X-76 - UGGAGAAGGUGGAAUCACA 19 2163 CFTR-R553X-77 - UUGGAGAAGGUGGAAUCACA 20 742 CFTR-R553X-78 - CUUGGAGAAGGUGGAAUCACA 21 2164 CFTR-R553X-79 - UCUUGGAGAAGGUGGAAUCACA 22 2165 CFTR-R553X-80 - UUCUUGGAGAAGGUGGAAUCACA 23 2166 CFTR-R553X-81 - CCUGGGGUUUUAUGGCUA 18 1924 CFTR-R553X-82 - UCCUGGGGUUUUAUGGCUA 19 1925 CFTR-R553X-83 - AUCCUGGGGUUUUAUGGCUA 20 750 CFTR-R553X-84 - AAUCCUGGGGUUUUAUGGCUA 21 1926 CFTR-R553X-85 - AAAUCCUGGGGUUUUAUGGCUA 22 1927 CFTR-R553X-86 - AAAAUCCUGGGGUUUUAUGGCUA 23 1928 CFTR-R553X-87 - AAAAAUCCUGGGGUUUUAUGGCUA 24 1929 CFTR-R553X-88 - UGCUUUAUAUUCUGUUUC 18 1931 CFTR-R553X-89 - UUGCUUUAUAUUCUGUUUC 19 1932 CFTR-R553X-38 - AUUGCUUUAUAUUCUGUUUC 20 476 CFTR-R553X-90 - UAUUGCUUUAUAUUCUGUUUC 21 1933 CFTR-R553X-91 - CUAUUGCUUUAUAUUCUGUUUC 22 1934 CFTR-R553X-92 - UCUAUUGCUUUAUAUUCUGUUUC 23 1935 CFTR-R553X-93 - CUCUAUUGCUUUAUAUUCUGUUUC 24 1936 CFTR-R553X-94 - AAGAAUUUCUUUAGCAAG 18 1937 CFTR-R553X-95 - CAAGAAUUUCUUUAGCAAG 19 1938 CFTR-R553X-96 - UAUAGUUCUUGGAGAAGG 18 2167 CFTR-R553X-97 - AUAUAGUUCUUGGAGAAGG 19 2168 CFTR-R553X-25 - AAUAUAGUUCUUGGAGAAGG 20 474 CFTR-R553X-98 - CAAUAUAGUUCUUGGAGAAGG 21 2169 CFTR-R553X-99 - ACAAUAUAGUUCUUGGAGAAGG 22 2170 CFTR-R553X-100 - AGACAAUAUAGUUCUUGGAGAAGG 24 2171 CFTR-R553X-101 - UUUUAUGGCUAGUGGGUU 18 1942 CFTR-R553X-102 - UGGGGUUUUAUGGCUAGUGGGUU 23 1943 CFTR-R553X-103 - CUGGGGUUUUAUGGCUAGUGGGUU 24 1944

Table 26C provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 26C 3rd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-104 + GAAAUGUCUGUAAUUUUUUUAC 22 1945 CFTR-R553X-105 + GAGAAAUGUCUGUAAUUUUUUUAC 24 1946 CFTR-R553X-106 - GUUUCUGGAAUUGAAAAAAUCC 22 1948 CFTR-R553X-107 - GAGUGGAGGUCAAUGAGC 18 2982 CFTR-R553X-108 - GAGCAAGAAUUUCUUUAGCAAG 22 1902

Table 26D provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 26D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-109 + ACCAAAAAUAGAAAAUUA 18 1950 CFTR-R553X-110 + UACCAAAAAUAGAAAAUUA 19 1951 CFTR-R553X-111 + UUACCAAAAAUAGAAAAUUA 20 757 CFTR-R553X-112 + AUUACCAAAAAUAGAAAAUUA 21 1952 CFTR-R553X-113 + UAUUACCAAAAAUAGAAAAUUA 22 1953 CFTR-R553X-114 + CUAUUACCAAAAAUAGAAAAUUA 23 1954 CFTR-R553X-115 + CCUAUUACCAAAAAUAGAAAAUUA 24 1955 CFTR-R553X-116 + AAAUGUCUGUAAUUUUUUUAC 21 1956 CFTR-R553X-117 + AGAAAUGUCUGUAAUUUUUUUAC 23 1957 CFTR-R553X-118 - CUGGAAUUGAAAAAAUCC 18 1964 CFTR-R553X-119 - UCUGGAAUUGAAAAAAUCC 19 1965 CFTR-R553X-24 - UUCUGGAAUUGAAAAAAUCC 20 477 CFTR-R553X-120 - UUUCUGGAAUUGAAAAAAUCC 21 1966 CFTR-R553X-121 - UGUUUCUGGAAUUGAAAAAAUCC 23 1967 CFTR-R553X-122 - CUGUUUCUGGAAUUGAAAAAAUCC 24 1968 CFTR-R553X-123 - UGAGUGGAGGUCAAUGAGC 19 2983 CFTR-R553X-124 - CUGAGUGGAGGUCAAUGAGC 20 2984 CFTR-R553X-125 - ACUGAGUGGAGGUCAAUGAGC 21 2985 CFTR-R553X-126 - CACUGAGUGGAGGUCAAUGAGC 22 2986 CFTR-R553X-127 - ACACUGAGUGGAGGUCAAUGAGC 23 2987 CFTR-R553X-128 - CACACUGAGUGGAGGUCAAUGAGC 24 2988 CFTR-R553X-129 - AGCAAGAAUUUCUUUAGCAAG 21 1939 CFTR-R553X-130 - UGAGCAAGAAUUUCUUUAGCAAG 23 2989 CFTR-R553X-131 - AUGAGCAAGAAUUUCUUUAGCAAG 24 2990

Table 26E provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 26E 5th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-132 + AUGUCCUAUUACCAAAAA 18 1978 CFTR-R553X-133 + GAUGUCCUAUUACCAAAAA 19 1979 CFTR-R553X-134 + AGAUGUCCUAUUACCAAAAA 20 759 CFTR-R553X-135 + GAGAUGUCCUAUUACCAAAAA 21 1980 CFTR-R553X-136 + GGAGAUGUCCUAUUACCAAAAA 22 1981 CFTR-R553X-137 + UGGAGAUGUCCUAUUACCAAAAA 23 1982 CFTR-R553X-138 + UUGGAGAUGUCCUAUUACCAAAAA 24 1983 CFTR-R553X-139 + AAACAGAAUAUAAAGCAA 18 1984 CFTR-R553X-140 + GAAACAGAAUAUAAAGCAA 19 1985 CFTR-R553X-141 + AGAAACAGAAUAUAAAGCAA 20 765 CFTR-R553X-142 + CAGAAACAGAAUAUAAAGCAA 21 1986 CFTR-R553X-143 + CCAGAAACAGAAUAUAAAGCAA 22 1987 CFTR-R553X-144 + UCCAGAAACAGAAUAUAAAGCAA 23 1988 CFTR-R553X-145 + UUCCAGAAACAGAAUAUAAAGCAA 24 1989 CFTR-R553X-146 + ACAGAAUAUAAAGCAAUA 18 1997 CFTR-R553X-147 + AACAGAAUAUAAAGCAAUA 19 1998 CFTR-R553X-148 + AAACAGAAUAUAAAGCAAUA 20 764 CFTR-R553X-149 + GAAACAGAAUAUAAAGCAAUA 21 1999 CFTR-R553X-150 + AGAAACAGAAUAUAAAGCAAUA 22 2000 CFTR-R553X-151 + CAGAAACAGAAUAUAAAGCAAUA 23 2001 CFTR-R553X-152 + CCAGAAACAGAAUAUAAAGCAAUA 24 2002 CFTR-R553X-153 + UAGUUAUUCACCUUGCUA 18 2003 CFTR-R553X-154 + UUAGUUAUUCACCUUGCUA 19 2004 CFTR-R553X-155 + AUUAGUUAUUCACCUUGCUA 20 762 CFTR-R553X-156 + AAUUAGUUAUUCACCUUGCUA 21 2005 CFTR-R553X-157 + UAAUUAGUUAUUCACCUUGCUA 22 2006 CFTR-R553X-158 + AUAAUUAGUUAUUCACCUUGCUA 23 2007 CFTR-R553X-159 + AAUAAUUAGUUAUUCACCUUGCUA 24 2008 CFTR-R553X-160 + UUGUCUUUCUCUGCAAAC 18 2009 CFTR-R553X-161 + AUUGUCUUUCUCUGCAAAC 19 2010 CFTR-R553X-162 + UAUUGUCUUUCUCUGCAAAC 20 760 CFTR-R553X-163 + AUAUUGUCUUUCUCUGCAAAC 21 2011 CFTR-R553X-164 + UAUAUUGUCUUUCUCUGCAAAC 22 2012 CFTR-R553X-165 + CUAUAUUGUCUUUCUCUGCAAAC 23 2013 CFTR-R553X-166 + ACUAUAUUGUCUUUCUCUGCAAAC 24 2014 CFTR-R553X-167 + UGUGAUUCCACCUUCUCC 18 2179 CFTR-R553X-168 + GUGUGAUUCCACCUUCUCC 19 2180 CFTR-R553X-169 + AGUGUGAUUCCACCUUCUCC 20 761 CFTR-R553X-170 + CAGUGUGAUUCCACCUUCUCC 21 2181 CFTR-R553X-171 + UCAGUGUGAUUCCACCUUCUCC 22 2182 CFTR-R553X-172 + CUCAGUGUGAUUCCACCUUCUCC 23 2183 CFTR-R553X-173 + ACUCAGUGUGAUUCCACCUUCUCC 24 2184 CFTR-R553X-174 + CCAGGAUUUUUUCAAUUC 18 2015 CFTR-R553X-175 + CCCAGGAUUUUUUCAAUUC 19 2016 CFTR-R553X-176 + CCCCAGGAUUUUUUCAAUUC 20 767 CFTR-R553X-177 + ACCCCAGGAUUUUUUCAAUUC 21 2017 CFTR-R553X-178 + AACCCCAGGAUUUUUUCAAUUC 22 2018 CFTR-R553X-179 + AAACCCCAGGAUUUUUUCAAUUC 23 2019 CFTR-R553X-180 + AAAACCCCAGGAUUUUUUCAAUUC 24 2020 CFTR-R553X-181 + CUAUUGCUUUAACCACAG 18 2021 CFTR-R553X-182 + ACUAUUGCUUUAACCACAG 19 2022 CFTR-R553X-183 + CACUAUUGCUUUAACCACAG 20 754 CFTR-R553X-184 + ACACUAUUGCUUUAACCACAG 21 2023 CFTR-R553X-185 + CACACUAUUGCUUUAACCACAG 22 2024 CFTR-R553X-186 + UCACACUAUUGCUUUAACCACAG 23 2025 CFTR-R553X-187 + AUCACACUAUUGCUUUAACCACAG 24 2026 CFTR-R553X-188 + UUACCAAAAAUAGAAAAU 18 2027 CFTR-R553X-189 + AUUACCAAAAAUAGAAAAU 19 2028 CFTR-R553X-190 + UAUUACCAAAAAUAGAAAAU 20 758 CFTR-R553X-191 + CUAUUACCAAAAAUAGAAAAU 21 2029 CFTR-R553X-192 + CCUAUUACCAAAAAUAGAAAAU 22 2030 CFTR-R553X-193 + UCCUAUUACCAAAAAUAGAAAAU 23 2031 CFTR-R553X-194 + GUCCUAUUACCAAAAAUAGAAAAU 24 2032 CFTR-R553X-195 + AGUAUGCUCAAUCUGAAU 18 2033 CFTR-R553X-196 + UAGUAUGCUCAAUCUGAAU 19 2034 CFTR-R553X-197 + UUAGUAUGCUCAAUCUGAAU 20 755 CFTR-R553X-198 + UUUAGUAUGCUCAAUCUGAAU 21 2035 CFTR-R553X-199 + UUUUAGUAUGCUCAAUCUGAAU 22 2036 CFTR-R553X-200 + CUUUUAGUAUGCUCAAUCUGAAU 23 2037 CFTR-R553X-201 + ACUUUUAGUAUGCUCAAUCUGAAU 24 2038 CFTR-R553X-202 + UGUCUUUCUCUGCAAACU 18 2039 CFTR-R553X-203 + UUGUCUUUCUCUGCAAACU 19 2040 CFTR-R553X-41 + AUUGUCUUUCUCUGCAAACU 20 483 CFTR-R553X-204 + UAUUGUCUUUCUCUGCAAACU 21 2041 CFTR-R553X-205 + AUAUUGUCUUUCUCUGCAAACU 22 2042 CFTR-R553X-206 + UAUAUUGUCUUUCUCUGCAAACU 23 2043 CFTR-R553X-207 + CUAUAUUGUCUUUCUCUGCAAACU 24 2044 CFTR-R553X-208 + UUAACCACAGUUGAAAUU 18 2045 CFTR-R553X-209 + UUUAACCACAGUUGAAAUU 19 2046 CFTR-R553X-210 + CUUUAACCACAGUUGAAAUU 20 753 CFTR-R553X-211 + GCUUUAACCACAGUUGAAAUU 21 2047 CFTR-R553X-212 + UGCUUUAACCACAGUUGAAAUU 22 2048 CFTR-R553X-213 + UUGCUUUAACCACAGUUGAAAUU 23 2049 CFTR-R553X-214 + AUUGCUUUAACCACAGUUGAAAUU 24 2050 CFTR-R553X-215 - UAUAUUCUGUUUCUGGAA 18 2051 CFTR-R553X-216 - UUAUAUUCUGUUUCUGGAA 19 2052 CFTR-R553X-217 - UUUAUAUUCUGUUUCUGGAA 20 748 CFTR-R553X-218 - CUUUAUAUUCUGUUUCUGGAA 21 2053 CFTR-R553X-219 - GCUUUAUAUUCUGUUUCUGGAA 22 2054 CFTR-R553X-220 - UGCUUUAUAUUCUGUUUCUGGAA 23 2055 CFTR-R553X-221 - UUGCUUUAUAUUCUGUUUCUGGAA 24 2056 CFTR-R553X-222 - AUUUUCUAUUUUUGGUAA 18 2059 CFTR-R553X-223 - AAUUUUCUAUUUUUGGUAA 19 2060 CFTR-R553X-224 - UAAUUUUCUAUUUUUGGUAA 20 736 CFTR-R553X-225 - CUAAUUUUCUAUUUUUGGUAA 21 2061 CFTR-R553X-226 - UCUAAUUUUCUAUUUUUGGUAA 22 2062 CFTR-R553X-227 - CUCUAAUUUUCUAUUUUUGGUAA 23 2063 CFTR-R553X-228 - UCUCUAAUUUUCUAUUUUUGGUAA 24 2064 CFTR-R553X-229 - GACAUCUCCAAGUUUGCA 18 2065 CFTR-R553X-230 - GGACAUCUCCAAGUUUGCA 19 2066 CFTR-R553X-231 - AGGACAUCUCCAAGUUUGCA 20 738 CFTR-R553X-232 - UAGGACAUCUCCAAGUUUGCA 21 2067 CFTR-R553X-233 - AUAGGACAUCUCCAAGUUUGCA 22 2068 CFTR-R553X-234 - AAUAGGACAUCUCCAAGUUUGCA 23 2069 CFTR-R553X-235 - UAAUAGGACAUCUCCAAGUUUGCA 24 2070 CFTR-R553X-236 - CACACUGAGUGGAGGUCA 18 2071 CFTR-R553X-237 - UCACACUGAGUGGAGGUCA 19 2072 CFTR-R553X-238 - AUCACACUGAGUGGAGGUCA 20 744 CFTR-R553X-239 - AAUCACACUGAGUGGAGGUCA 21 2073 CFTR-R553X-240 - GAAUCACACUGAGUGGAGGUCA 22 2074 CFTR-R553X-241 - GGAAUCACACUGAGUGGAGGUCA 23 2075 CFTR-R553X-242 - UGGAAUCACACUGAGUGGAGGUCA 24 2076 CFTR-R553X-243 - GUGCCUUUCAAAUUCAGA 18 2077 CFTR-R553X-244 - UGUGCCUUUCAAAUUCAGA 19 2078 CFTR-R553X-245 - AUGUGCCUUUCAAAUUCAGA 20 735 CFTR-R553X-246 - GAUGUGCCUUUCAAAUUCAGA 21 2079 CFTR-R553X-247 - AGAUGUGCCUUUCAAAUUCAGA 22 2080 CFTR-R553X-248 - AAGAUGUGCCUUUCAAAUUCAGA 23 2081 CFTR-R553X-249 - GAAGAUGUGCCUUUCAAAUUCAGA 24 2082 CFTR-R553X-250 - AUAUAUGAUUACAUUAGA 18 2083 CFTR-R553X-251 - GAUAUAUGAUUACAUUAGA 19 2084 CFTR-R553X-22 - UGAUAUAUGAUUACAUUAGA 20 471 CFTR-R553X-252 - GUGAUAUAUGAUUACAUUAGA 21 2085 CFTR-R553X-253 - UGUGAUAUAUGAUUACAUUAGA 22 2086 CFTR-R553X-254 - GUGUGAUAUAUGAUUACAUUAGA 23 2087 CFTR-R553X-255 - AGUGUGAUAUAUGAUUACAUUAGA 24 2088 CFTR-R553X-256 - AAGGUGGAAUCACACUGA 18 2089 CFTR-R553X-257 - GAAGGUGGAAUCACACUGA 19 2090 CFTR-R553X-258 - AGAAGGUGGAAUCACACUGA 20 743 CFTR-R553X-259 - GAGAAGGUGGAAUCACACUGA 21 2091 CFTR-R553X-260 - GGAGAAGGUGGAAUCACACUGA 22 2192 CFTR-R553X-261 - UGGAGAAGGUGGAAUCACACUGA 23 2193 CFTR-R553X-262 - UUGGAGAAGGUGGAAUCACACUGA 24 2194 CFTR-R553X-263 - UCUGGAAUUGAAAAAAUC 18 2098 CFTR-R553X-264 - UUCUGGAAUUGAAAAAAUC 19 2099 CFTR-R553X-265 - UUUCUGGAAUUGAAAAAAUC 20 749 CFTR-R553X-266 - GUUUCUGGAAUUGAAAAAAUC 21 2100 CFTR-R553X-267 - UGUUUCUGGAAUUGAAAAAAUC 22 2101 CFTR-R553X-268 - CUGUUUCUGGAAUUGAAAAAAUC 23 2102 CFTR-R553X-269 - UCUGUUUCUGGAAUUGAAAAAAUC 24 2103 CFTR-R553X-270 - AGAAAGACAAUAUAGUUC 18 2195 CFTR-R553X-271 - GAGAAAGACAAUAUAGUUC 19 2196 CFTR-R553X-272 - AGAGAAAGACAAUAUAGUUC 20 739 CFTR-R553X-273 - CAGAGAAAGACAAUAUAGUUC 21 2197 CFTR-R553X-274 - GCAGAGAAAGACAAUAUAGUUC 22 2198 CFTR-R553X-275 - UGCAGAGAAAGACAAUAUAGUUC 23 2199 CFTR-R553X-276 - UUGCAGAGAAAGACAAUAUAGUUC 24 2200 CFTR-R553X-277 - AUAUAGUUCUUGGAGAAG 18 2201 CFTR-R553X-278 - AAUAUAGUUCUUGGAGAAG 19 2202 CFTR-R553X-279 - CAAUAUAGUUCUUGGAGAAG 20 741 CFTR-R553X-280 - ACAAUAUAGUUCUUGGAGAAG 21 2203 CFTR-R553X-281 - GACAAUAUAGUUCUUGGAGAAG 22 2204 CFTR-R553X-282 - AGACAAUAUAGUUCUUGGAGAAG 23 2205 CFTR-R553X-283 - AAGACAAUAUAGUUCUUGGAGAAG 24 2206 CFTR-R553X-284 - AGGUGGAAUCACACUGAG 18 2111 CFTR-R553X-285 - AAGGUGGAAUCACACUGAG 19 2112 CFTR-R553X-9 - GAAGGUGGAAUCACACUGAG 20 461 CFTR-R553X-286 - AGAAGGUGGAAUCACACUGAG 21 2113 CFTR-R553X-287 - GAGAAGGUGGAAUCACACUGAG 22 2114 CFTR-R553X-288 - GGAGAAGGUGGAAUCACACUGAG 23 2207 CFTR-R553X-289 - UGGAGAAGGUGGAAUCACACUGAG 24 2208 CFTR-R553X-290 - GAUAUAUGAUUACAUUAG 18 2117 CFTR-R553X-291 - UGAUAUAUGAUUACAUUAG 19 2118 CFTR-R553X-292 - GUGAUAUAUGAUUACAUUAG 20 734 CFTR-R553X-293 - UGUGAUAUAUGAUUACAUUAG 21 2119 CFTR-R553X-294 - GUGUGAUAUAUGAUUACAUUAG 22 2120 CFTR-R553X-295 - AGUGUGAUAUAUGAUUACAUUAG 23 2121 CFTR-R553X-296 - UAGUGUGAUAUAUGAUUACAUUAG 24 2122 CFTR-R553X-297 - AAGACAAUAUAGUUCUUG 18 2209 CFTR-R553X-298 - AAAGACAAUAUAGUUCUUG 19 2210 CFTR-R553X-299 - GAAAGACAAUAUAGUUCUUG 20 740 CFTR-R553X-300 - AGAAAGACAAUAUAGUUCUUG 21 2211 CFTR-R553X-301 - GAGAAAGACAAUAUAGUUCUUG 22 2212 CFTR-R553X-302 - AGAGAAAGACAAUAUAGUUCUUG 23 2213 CFTR-R553X-303 - CAGAGAAAGACAAUAUAGUUCUUG 24 2214 CFTR-R553X-304 - AGGACAUCUCCAAGUUUG 18 2123 CFTR-R553X-305 - UAGGACAUCUCCAAGUUUG 19 2124 CFTR-R553X-306 - AUAGGACAUCUCCAAGUUUG 20 737 CFTR-R553X-307 - AAUAGGACAUCUCCAAGUUUG 21 2125 CFTR-R553X-308 - UAAUAGGACAUCUCCAAGUUUG 22 2126 CFTR-R553X-309 - GUAAUAGGACAUCUCCAAGUUUG 23 2127 CFTR-R553X-310 - GGUAAUAGGACAUCUCCAAGUUUG 24 2128 CFTR-R553X-311 - UGUGAUAUAUGAUUACAU 18 2129 CFTR-R553X-312 - GUGUGAUAUAUGAUUACAU 19 2130 CFTR-R553X-313 - AGUGUGAUAUAUGAUUACAU 20 733 CFTR-R553X-314 - UAGUGUGAUAUAUGAUUACAU 21 2131 CFTR-R553X-315 - AUAGUGUGAUAUAUGAUUACAU 22 2132 CFTR-R553X-316 - AAUAGUGUGAUAUAUGAUUACAU 23 2133 CFTR-R553X-317 - CAAUAGUGUGAUAUAUGAUUACAU 24 2134 CFTR-R553X-318 - GAAAGACAAUAUAGUUCU 18 2135 CFTR-R553X-319 - AGAAAGACAAUAUAGUUCU 19 2136 CFTR-R553X-11 - GAGAAAGACAAUAUAGUUCU 20 453 CFTR-R553X-320 - AGAGAAAGACAAUAUAGUUCU 21 2137 CFTR-R553X-321 - CAGAGAAAGACAAUAUAGUUCU 22 2138 CFTR-R553X-322 - GCAGAGAAAGACAAUAUAGUUCU 23 2139 CFTR-R553X-323 - UGCAGAGAAAGACAAUAUAGUUCU 24 2140 CFTR-R553X-324 - GGGUUAAGAAUCACAUUU 18 2215 CFTR-R553X-325 - UGGGUUAAGAAUCACAUUU 19 2216 CFTR-R553X-326 - GUGGGUUAAGAAUCACAUUU 20 752 CFTR-R553X-327 - AGUGGGUUAAGAAUCACAUUU 21 2217 CFTR-R553X-328 - UAGUGGGUUAAGAAUCACAUUU 22 2218 CFTR-R553X-329 - CUAGUGGGUUAAGAAUCACAUUU 23 2219 CFTR-R553X-330 - GCUAGUGGGUUAAGAAUCACAUUU 24 2220 CFTR-R553X-331 - UUGCUUUAUAUUCUGUUU 18 2148 CFTR-R553X-332 - AUUGCUUUAUAUUCUGUUU 19 2149 CFTR-R553X-333 - UAUUGCUUUAUAUUCUGUUU 20 747 CFTR-R553X-334 - CUAUUGCUUUAUAUUCUGUUU 21 2150 CFTR-R553X-335 - UCUAUUGCUUUAUAUUCUGUUU 22 2151 CFTR-R553X-336 - CUCUAUUGCUUUAUAUUCUGUUU 23 2152 CFTR-R553X-337 - UCUCUAUUGCUUUAUAUUCUGUUU 24 2153

Table 27A provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 27A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-338 + GUAAUCAUAUAUCACAC 17 2154 CFTR-R553X-339 - GGUUAAAGCAAUAGUGUGAU 20 927

Table 27B provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 27B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-340 + CCACUAGCCAUAAAACC 17 935 CFTR-R553X-341 + UGAAUGACAUUUACAGC 17 2155 CFTR-R553X-342 - UAAAGCAAUAGUGUGAU 17 932 CFTR-R553X-343 - AGGAAGAUGUGCCUUUCAAA 20 928 CFTR-R553X-344 + AAUGUAAUCAUAUAUCACAC 20 2156 CFTR-R553X-345 + AACCCACUAGCCAUAAAACC 20 930 CFTR-R553X-346 + ACAUGAAUGACAUUUACAGC 20 2157

Table 27C provides exemplary targeting domains for correcting a mutation (e.g., R553X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., R553X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 27C 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-R553X-347 - AAGAUGUGCCUUUCAAA 17 933 CFTR-R553X-348 + UUAUUUAUAGUUCUUAA 17 936 CFTR-R553X-349 + UCAUUGACCUCCACUCA 17 2991 CFTR-R553X-350 - AAUUACAGACAUUUCUC 17 2158 CFTR-R553X-351 + CCAUUAUUUAUAGUUCUUAA 20 931 CFTR-R553X-352 + UGCUCAUUGACCUCCACUCA 20 2992 CFTR-R553X-353 - AAAAAUUACAGACAUUUCUC 20 2159

Table 28A provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 28A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-W1282X-1 - GAAUUAUGUUUAUGGCA 17 2993 CFTR-W1282X-2 - GGAGAAAUCCAGAUCGA 17 2994 CFTR-W1282X-3 - GGCCUCUUGGGAAGAAC 17 2995 CFTR-W1282X-4 + GUCCUUUUGCUCACCUG 17 2996 CFTR-W1282X-5 - GAUCGAUGGUGUGUCUU 17 2997 CFTR-W1282X-6 - GAAGGAGAAAUCCAGAUCGA 20 2998 CFTR-W1282X-7 - GUGGGCCUCUUGGGAAGAAC 20 2999

Table 28B provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 28B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-W1282X-8 - UACCACAGGUGAGCAAA 17 3000 CFTR-W1282X-9 + CUGUGGUAUCACUCCAA 17 3001 CFTR-W1282X-10 - AGACUACUGAACACUGA 17 3002 CFTR-W1282X-11 + CUAUAAGGUAAAAGUGA 17 3003 CFTR-W1282X-12 - UAACUUUGCAACAGUGA 17 3004 CFTR-W1282X-13 + CAAGAGGCCCACCUAUA 17 3005 CFTR-W1282X-14 - CUUUGGAGUGAUACCAC 17 3006 CFTR-W1282X-15 + CUAUGAGAAAACUGCAC 17 3007 CFTR-W1282X-16 + AAGACACACCAUCGAUC 17 3008 CFTR-W1282X-17 - UUGGGAAGAACUGGAUC 17 3009 CFTR-W1282X-18 + AUCCAGUUCUUCCCAAG 17 3010 CFTR-W1282X-19 - CACUUUUACCUUAUAGG 17 3011 CFTR-W1282X-20 - CAGUGCAGUUUUCUCAU 17 3012 CFTR-W1282X-21 + UAUAAGGUAAAAGUGAU 17 3013 CFTR-W1282X-22 + UCACUUCUGUGACAUAU 17 3014 CFTR-W1282X-23 - CAUCACUUUUACCUUAU 17 3015 CFTR-W1282X-24 - CUUAUAGGUGGGCCUCU 17 3016 CFTR-W1282X-25 - AGAUCGAUGGUGUGUCU 17 3017 CFTR-W1282X-26 - ACUUUUACCUUAUAGGU 17 3018 CFTR-W1282X-27 - UUAUAGGUGGGCCUCUU 17 3019 CFTR-W1282X-28 - AAAGGACUUAGCCAGAAAAA 20 3020 CFTR-W1282X-29 + CACCUGUGGUAUCACUCCAA 20 3021 CFTR-W1282X-30 - ACUGAAUUAUGUUUAUGGCA 20 3022 CFTR-W1282X-31 - UCUUGGGAAGAACUGGAUCA 20 3023 CFTR-W1282X-32 - UUGAGACUACUGAACACUGA 20 3024 CFTR-W1282X-33 + CACCUAUAAGGUAAAAGUGA 20 3025 CFTR-W1282X-34 + UCCCAAGAGGCCCACCUAUA 20 3026 CFTR-W1282X-35 - ACAAUACUGAAUUAUGUUUA 20 3027 CFTR-W1282X-36 - AGCCUUUGGAGUGAUACCAC 20 3028 CFTR-W1282X-37 + UGCCUAUGAGAAAACUGCAC 20 3029 CFTR-W1282X-38 + CCCAAGACACACCAUCGAUC 20 3030 CFTR-W1282X-39 - CUCUUGGGAAGAACUGGAUC 20 3031 CFTR-W1282X-40 + UAAUUUAGUUGCCUUUUUUC 20 3032 CFTR-W1282X-41 + CUGAUCCAGUUCUUCCCAAG 20 3033 CFTR-W1282X-42 - CAUCACUUUUACCUUAUAGG 20 3034 CFTR-W1282X-43 + UAAGUCCUUUUGCUCACCUG 20 3035 CFTR-W1282X-44 - CUCCAGUGCAGUUUUCUCAU 20 3036 CFTR-W1282X-45 + ACCUAUAAGGUAAAAGUGAU 20 3037 CFTR-W1282X-46 - UCCCAUCACUUUUACCUUAU 20 3038 CFTR-W1282X-47 - UACCUUAUAGGUGGGCCUCU 20 3039 CFTR-W1282X-48 - UCCAGAUCGAUGGUGUGUCU 20 3040 CFTR-W1282X-49 - AUCACUUUUACCUUAUAGGU 20 3041 CFTR-W1282X-50 - CCAGAUCGAUGGUGUGUCUU 20 3042

Table 28C provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 28C  3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length  ID CFTR-W1282X-51 GGACUUAGCCAGAAAAA 17 3043 CFTR-W1282X-52 + GGAUCACUUCUGUGACAUAU 20 3044

Table 28D provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 28D  4th Tier Tar-  get DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-W1282X-53 UGGGAAGAACUGGAUCA 17 3045 CFTR-W1282X-54 AUACUGAAUUAUGUUUA 17 3046 CFTR-W1282X-55 + UUUAGUUGCCUUUUUUC 17 3047 CFTR-W1282X-56 CAGUGAAGGAAAGCCUU 17 3048 CFTR-W1282X-57 UGAUACCACAGGUGAGCAAA 20 3049 CFTR-W1282X-58 CAAUAACUUUGCAACAGUGA 20 3050 CFTR-W1282X-59 CAACAGUGAAGGAAAGCCUU 20 3051 CFTR-W1282X-60 ACCUUAUAGGUGGGCCUCUU 20 3052

Table 29A provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 29A  1st Tier DNA Target Seq  gRNA Name Strand Targeting Domain Site Length ID CFTR-W1282X-61 + GCCCACCUAUAAGGUAAAAGUGA 23 3053 CFTR-W1282X-62 + GGCCCACCUAUAAGGUAAAAGUGA 24 3054 CFTR-W1282X-63 + GCAUAACAAAUAUAUUUUG 19 3055 CFTR-W1282X-64 + GAAUCCCAAGACACACCAUCGAU 23 3056 CFTR-W1282X-65 GUGGGCCUCUUGGGAAGAA 19 3057 CFTR-W1282X-66 GGUGGGCCUCUUGGGAAGAA 20 3058 CFTR-W1282X-67 GGAAGAACUGGAUCAGGG 18 3059 CFTR-W1282X-68 GGGAAGAACUGGAUCAGGG 19 3060 CFTR-W1282X-69 GAAAUCCAGAUCGAUGGUGUGUCU 24 3061

Table 29B provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 29B 2nd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-W1282X-70 + CCUAUAAGGUAAAAGUGA 18 3062 CFTR-W1282X-71 + ACCUAUAAGGUAAAAGUGA 19 3063 CFTR-W1282X-33 + CACCUAUAAGGUAAAAGUGA 20 3025 CFTR-W1282X-72 + CCACCUAUAAGGUAAAAGUGA 21 3064 CFTR-W1282X-73 + CCCACCUAUAAGGUAAAAGUGA 22 3065 CFTR-W1282X-74 + UUGCAGAGUAAUAUGAAUUUC 21 3066 CFTR-W1282X-75 + UUUGCAGAGUAAUAUGAAUUUC 22 3067 CFTR-W1282X-76 + UUUUGCAGAGUAAUAUGAAUUUC 23 3068 CFTR-W1282X-77 + AUUUUGCAGAGUAAUAUGAAUUUC 24 3069 CFTR-W1282X-78 + CAUAACAAAUAUAUUUUG 18 3070 CFTR-W1282X-79 + UGCAUAACAAAUAUAUUUUG 20 3071 CFTR-W1282X-80 + UAUAUUUUGCAGAGUAAU 18 3072 CFTR-W1282X-81 + AUAUAUUUUGCAGAGUAAU 19 3073 CFTR-W1282X-82 + AAUAUAUUUUGCAGAGUAAU 20 3074 CFTR-W1282X-83 + CCAAGACACACCAUCGAU 18 3075 CFTR-W1282X-84 + CCCAAGACACACCAUCGAU 19 3076 CFTR-W1282X-85 + UCCCAAGACACACCAUCGAU 20 3077 CFTR-W1282X-86 + AUCCCAAGACACACCAUCGAU 21 3078 CFTR-W1282X-87 + AAUCCCAAGACACACCAUCGAU 22 3079 CFTR-W1282X-88 + UGAAUCCCAAGACACACCAUCGAU 24 3080 CFTR-W1282X-89 UGGGCCUCUUGGGAAGAA 18 3081 CFTR-W1282X-90 AGGUGGGCCUCUUGGGAAGAA 21 3082 CFTR-W1282X-91 UAGGUGGGCCUCUUGGGAAGAA 22 3083 CFTR-W1282X-92 AUAGGUGGGCCUCUUGGGAAGAA 23 3084 CFTR-W1282X-93 UAUAGGUGGGCCUCUUGGGAAGAA 24 3085 CFTR-W1282X-94 UGGGAAGAACUGGAUCAGGG 20 3086 CFTR-W1282X-95 UUGGGAAGAACUGGAUCAGGG 21 3087 CFTR-W1282X-96 CUUGGGAAGAACUGGAUCAGGG 22 3088 CFTR-W1282X-97 UCUUGGGAAGAACUGGAUCAGGG 23 3089 CFTR-W1282X-98 CUCUUGGGAAGAACUGGAUCAGGG 24 3090 CFTR-W1282X-99 CAGAUCGAUGGUGUGUCU 18 3091 CFTR-W1282X-100 CCAGAUCGAUGGUGUGUCU 19 3092 CFTR-W1282X-48 UCCAGAUCGAUGGUGUGUCU 20 3040 CFTR-W1282X-101 AUCCAGAUCGAUGGUGUGUCU 21 3093 CFTR-W1282X-102 AAUCCAGAUCGAUGGUGUGUCU 22 3094 CFTR-W1282X-103 AAAUCCAGAUCGAUGGUGUGUCU 23 3095

Table 29C provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 29C  3rd Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-W1282X-104 + GCAGAGUAAUAUGAAUUUC 19 3096 CFTR-W1282X-105 + GCAAUGCAUAACAAAUAUAUUUUG 24 3097 CFTR-W1282X-106 - GCAACAGUGAAGGAAAGCCUU 21 3098

Table 29D provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 29D  4th Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-W1282X-107 + UUCACUGUUGCAAAGUUA 18 3099 CFTR-W1282X-108 + CUUCACUGUUGCAAAGUUA 19 3100 CFTR-W1282X-109 + CCUUCACUGUUGCAAAGUUA 20 3101 CFTR-W1282X-110 + UCCUUCACUGUUGCAAAGUUA 21 3102 CFTR-W1282X-111 + UUCCUUCACUGUUGCAAAGUUA 22 3103 CFTR-W1282X-112 + UUUCCUUCACUGUUGCAAAGUUA 23 3104 CFTR-W1282X-113 + CUUUCCUUCACUGUUGCAAAGUUA 24 3105 CFTR-W1282X-114 + CAGAGUAAUAUGAAUUUC 18 3106 CFTR-W1282X-115 + UGCAGAGUAAUAUGAAUUUC 20 3107 CFTR-W1282X-116 + AUGCAUAACAAAUAUAUUUUG 21 3108 CFTR-W1282X-117 + AAUGCAUAACAAAUAUAUUUUG 22 3109 CFTR-W1282X-118 + CAAUGCAUAACAAAUAUAUUUUG 23 3110 CFTR-W1282X-119 + AAAUAUAUUUUGCAGAGUAAU 21 3111 CFTR-W1282X-120 + CAAAUAUAUUUUGCAGAGUAAU 22 3112 CFTR-W1282X-121 + ACAAAUAUAUUUUGCAGAGUAAU 23 3113 CFTR-W1282X-122 + AACAAAUAUAUUUUGCAGAGUAAU 24 3114 CFTR-W1282X-123 - ACAGUGAAGGAAAGCCUU 18 3115 CFTR-W1282X-124 - AACAGUGAAGGAAAGCCUU 19 3116 CFTR-W1282X-59 - CAACAGUGAAGGAAAGCCUU 20 3051 CFTR-W1282X-125 - UGCAACAGUGAAGGAAAGCCUU 22 3117 CFTR-W1282X-126 - UUGCAACAGUGAAGGAAAGCCUU 23 3118 CFTR-W1282X-127 - UUUGCAACAGUGAAGGAAAGCCUU 24 3119

Table 29E provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table lean be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 29E  5th Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-W1282X-128 + GCCUAUGAGAAAACUGCA 18 3120 CFTR-W1282X-129 + UGCCUAUGAGAAAACUGCA 19 3121 CFTR-W1282X-130 + CUGCCUAUGAGAAAACUGCA 20 3122 CFTR-W1282X-131 + UCUGCCUAUGAGAAAACUGCA 21 3123 CFTR-W1282X-132 + UUCUGCCUAUGAGAAAACUGCA 22 3124 CFTR-W1282X-133 + UUUCUGCCUAUGAGAAAACUGCA 23 3125 CFTR-W1282X-134 + UUUUCUGCCUAUGAGAAAACUGCA 24 3126 CFTR-W1282X-135 + CCUAUGAGAAAACUGCAC 18 3127 CFTR-W1282X-136 + GCCUAUGAGAAAACUGCAC 19 3128 CFTR-W1282X-37 + UGCCUAUGAGAAAACUGCAC 20 3029 CFTR-W1282X-137 + CUGCCUAUGAGAAAACUGCAC 21 3129 CFTR-W1282X-138 + UCUGCCUAUGAGAAAACUGCAC 22 3130 CFTR-W1282X-139 + UUCUGCCUAUGAGAAAACUGCAC 23 3131 CFTR-W1282X-140 + UUUCUGCCUAUGAGAAAACUGCAC 24 3132 CFTR-W1282X-141 + CCUGAUCCAGUUCUUCCC 18 3133 CFTR-W1282X-142 + CCCUGAUCCAGUUCUUCCC 19 3134 CFTR-W1282X-143 + UCCCUGAUCCAGUUCUUCCC 20 3135 CFTR-W1282X-144 + UUCCCUGAUCCAGUUCUUCCC 21 3136 CFTR-W1282X-145 + CUUCCCUGAUCCAGUUCUUCCC 22 3137 CFTR-W1282X-146 + UCUUCCCUGAUCCAGUUCUUCCC 23 3138 CFTR-W1282X-147 + CUCUUCCCUGAUCCAGUUCUUCCC 24 3139 CFTR-W1282X-148 + UAUGAGAAAACUGCACUG 18 3140 CFTR-W1282X-149 + CUAUGAGAAAACUGCACUG 19 3141 CFTR-W1282X-150 + CCUAUGAGAAAACUGCACUG 20 3142 CFTR-W1282X-151 + GCCUAUGAGAAAACUGCACUG 21 3143 CFTR-W1282X-152 + UGCCUAUGAGAAAACUGCACUG 22 3144 CFTR-W1282X-153 + CUGCCUAUGAGAAAACUGCACUG 23 3145 CFTR-W1282X-154 + UCUGCCUAUGAGAAAACUGCACUG 24 3146 CFTR-W1282X-155 + ACCUAUAAGGUAAAAGUG 18 3147 CFTR-W1282X-156 + CACCUAUAAGGUAAAAGUG 19 3148 CFTR-W1282X-157 + CCACCUAUAAGGUAAAAGUG 20 3149 CFTR-W1282X-158 + CCCACCUAUAAGGUAAAAGUG 21 3150 CFTR-W1282X-159 + GCCCACCUAUAAGGUAAAAGUG 22 3151 CFTR-W1282X-160 + GGCCCACCUAUAAGGUAAAAGUG 23 3152 CFTR-W1282X-161 + AGGCCCACCUAUAAGGUAAAAGUG 24 3153 CFTR-W1282X-162 + GACAUCUUUUCUGCCUAU 18 3154 CFTR-W1282X-163 + AGACAUCUUUUCUGCCUAU 19 3155 CFTR-W1282X-164 + GAGACAUCUUUUCUGCCUAU 20 3156 CFTR-W1282X-165 + AGAGACAUCUUUUCUGCCUAU 21 3157 CFTR-W1282X-166 + UAGAGACAUCUUUUCUGCCUAU 22 3158 CFTR-W1282X-167 + UUAGAGACAUCUUUUCUGCCUAU 23 3159 CFTR-W1282X-168 + UUUAGAGACAUCUUUUCUGCCUAU 24 3160 CFTR-W1282X-169 + GAGACAUCUUUUCUGCCU 18 3161 CFTR-W1282X-170 + AGAGACAUCUUUUCUGCCU 19 3162 CFTR-W1282X-171 + UAGAGACAUCUUUUCUGCCU 20 3163 CFTR-W1282X-172 + UUAGAGACAUCUUUUCUGCCU 21 3164 CFTR-W1282X-173 + UUUAGAGACAUCUUUUCUGCCU 22 3165 CFTR-W1282X-174 + UUUUAGAGACAUCUUUUCUGCCU 23 3166 CFTR-W1282X-175 + CUUUUAGAGACAUCUUUUCUGCCU 24 3167 CFTR-W1282X-176 - GAUACCACAGGUGAGCAA 18 3168 CFTR-W1282X-177 - UGAUACCACAGGUGAGCAA 19 3169 CFTR-W1282X-178 - GUGAUACCACAGGUGAGCAA 20 3170 CFTR-W1282X-179 - AGUGAUACCACAGGUGAGCAA 21 3171 CFTR-W1282X-180 - GAGUGAUACCACAGGUGAGCAA 22 3172 CFTR-W1282X-181 - GGAGUGAUACCACAGGUGAGCAA 23 3173 CFTR-W1282X-182 - UGGAGUGAUACCACAGGUGAGCAA 24 3174 CFTR-W1282X-183 - UUCAAUAACUUUGCAACA 18 3175 CFTR-W1282X-184 - AUUCAAUAACUUUGCAACA 19 3176 CFTR-W1282X-185 - GAUUCAAUAACUUUGCAACA 20 3177 CFTR-W1282X-186 - GGAUUCAAUAACUUUGCAACA 21 3178 CFTR-W1282X-187 - GGGAUUCAAUAACUUUGCAACA 22 3179 CFTR-W1282X-188 - UGGGAUUCAAUAACUUUGCAACA 23 3180 CFTR-W1282X-189 - UUGGGAUUCAAUAACUUUGCAACA 24 3181 CFTR-W1282X-190 - UUUUGAGACUACUGAACA 18 3182 CFTR-W1282X-191 - UUUUUGAGACUACUGAACA 19 3183 CFTR-W1282X-192 - UUUUUUGAGACUACUGAACA 20 3184 CFTR-W1282X-193 - CUUUUUUGAGACUACUGAACA 21 3185 CFTR-W1282X-194 - GCUUUUUUGAGACUACUGAACA 22 3186 CFTR-W1282X-195 - AGCUUUUUUGAGACUACUGAACA 23 3187 CFTR-W1282X-196 - CAGCUUUUUUGAGACUACUGAACA 24 3188 CFTR-W1282X-197 - UUGGGAAGAACUGGAUCA 18 3189 CFTR-W1282X-198 - CUUGGGAAGAACUGGAUCA 19 3190 CFTR-W1282X-31 - UCUUGGGAAGAACUGGAUCA 20 3023 CFTR-W1282X-199 - CUCUUGGGAAGAACUGGAUCA 21 3191 CFTR-W1282X-200 - CCUCUUGGGAAGAACUGGAUCA 22 3192 CFTR-W1282X-201 - GCCUCUUGGGAAGAACUGGAUCA 23 3193 CFTR-W1282X-202 - GGCCUCUUGGGAAGAACUGGAUCA 24 3194 CFTR-W1282X-203 - CAUGGUACCUAUAUGUCA 18 3195 CFTR-W1282X-204 - GCAUGGUACCUAUAUGUCA 19 3196 CFTR-W1282X-205 - GGCAUGGUACCUAUAUGUCA 20 3197 CFTR-W1282X-206 - UGGCAUGGUACCUAUAUGUCA 21 3198 CFTR-W1282X-207 - AUGGCAUGGUACCUAUAUGUCA 22 3199 CFTR-W1282X-208 - UAUGGCAUGGUACCUAUAUGUCA 23 3200 CFTR-W1282X-209 - UUAUGGCAUGGUACCUAUAUGUCA 24 3201 CFTR-W1282X-210 - GAGACUACUGAACACUGA 18 3202 CFTR-W1282X-211 - UGAGACUACUGAACACUGA 19 3203 CFTR-W1282X-32 - UUGAGACUACUGAACACUGA 20 3024 CFTR-W1282X-212 - UUUGAGACUACUGAACACUGA 21 3204 CFTR-W1282X-213 - UUUUGAGACUACUGAACACUGA 22 3205 CFTR-W1282X-214 - UUUUUGAGACUACUGAACACUGA 23 3206 CFTR-W1282X-215 - UUUUUUGAGACUACUGAACACUGA 24 3207 CFTR-W1282X-216 - AUAACUUUGCAACAGUGA 18 3208 CFTR-W1282X-217 - AAUAACUUUGCAACAGUGA 19 3209 CFTR-W1282X-58 - CAAUAACUUUGCAACAGUGA 20 3050 CFTR-W1282X-218 - UCAAUAACUUUGCAACAGUGA 21 3210 CFTR-W1282X-219 - UUCAAUAACUUUGCAACAGUGA 22 3211 CFTR-W1282X-220 - AUUCAAUAACUUUGCAACAGUGA 23 3212 CFTR-W1282X-221 - GAUUCAAUAACUUUGCAACAGUGA 24 3213 CFTR-W1282X-222 - UCAGCUUUUUUGAGACUA 18 3214 CFTR-W1282X-223 - AUCAGCUUUUUUGAGACUA 19 3215 CFTR-W1282X-224 - UAUCAGCUUUUUUGAGACUA 20 3216 CFTR-W1282X-225 - UUAUCAGCUUUUUUGAGACUA 21 3217 CFTR-W1282X-226 - GUUAUCAGCUUUUUUGAGACUA 22 3218 CFTR-W1282X-227 - UGUUAUCAGCUUUUUUGAGACUA 23 3219 CFTR-W1282X-228 - UUGUUAUCAGCUUUUUUGAGACUA 24 3220 CFTR-W1282X-229 - UGAGCAAAAGGACUUAGC 18 3221 CFTR-W1282X-230 - GUGAGCAAAAGGACUUAGC 19 3222 CFTR-W1282X-231 - GGUGAGCAAAAGGACUUAGC 20 3223 CFTR-W1282X-232 - AGGUGAGCAAAAGGACUUAGC 21 3224 CFTR-W1282X-233 - CAGGUGAGCAAAAGGACUUAGC 22 3225 CFTR-W1282X-234 - ACAGGUGAGCAAAAGGACUUAGC 23 3226 CFTR-W1282X-235 - CACAGGUGAGCAAAAGGACUUAGC 24 3227 CFTR-W1282X-236 - CUUGGGAAGAACUGGAUC 18 3228 CFTR-W1282X-237 - UCUUGGGAAGAACUGGAUC 19 3229 CFTR-W1282X-39 - CUCUUGGGAAGAACUGGAUC 20 3031 CFTR-W1282X-238 - CCUCUUGGGAAGAACUGGAUC 21 3230 CFTR-W1282X-239 - GCCUCUUGGGAAGAACUGGAUC 22 3231 CFTR-W1282X-240 - GGCCUCUUGGGAAGAACUGGAUC 23 3232 CFTR-W1282X-241 - GGGCCUCUUGGGAAGAACUGGAUC 24 3233 CFTR-W1282X-242 - UAUUUGAUACUUGUACUC 18 3234 CFTR-W1282X-243 - CUAUUUGAUACUUGUACUC 19 3235 CFTR-W1282X-244 - GCUAUUUGAUACUUGUACUC 20 3236 CFTR-W1282X-245 - UGCUAUUUGAUACUUGUACUC 21 3237 CFTR-W1282X-246 - CUGCUAUUUGAUACUUGUACUC 22 3238 CFTR-W1282X-247 - ACUGCUAUUUGAUACUUGUACUC 23 3239 CFTR-W1282X-248 - UACUGCUAUUUGAUACUUGUACUC 24 3240 CFTR-W1282X-249 - ACCUUAUAGGUGGGCCUC 18 3241 CFTR-W1282X-250 - UACCUUAUAGGUGGGCCUC 19 3242 CFTR-W1282X-251 - UUACCUUAUAGGUGGGCCUC 20 3243 CFTR-W1282X-252 - UUUACCUUAUAGGUGGGCCUC 21 3244 CFTR-W1282X-253 - UUUUACCUUAUAGGUGGGCCUC 22 3245 CFTR-W1282X-254 - CUUUUACCUUAUAGGUGGGCCUC 23 3246 CFTR-W1282X-255 - ACUUUUACCUUAUAGGUGGGCCUC 24 3247 CFTR-W1282X-256 - CCAGAUCGAUGGUGUGUC 18 3248 CFTR-W1282X-257 - UCCAGAUCGAUGGUGUGUC 19 3249 CFTR-W1282X-258 - AUCCAGAUCGAUGGUGUGUC 20 3250 CFTR-W1282X-259 - AAUCCAGAUCGAUGGUGUGUC 21 3251 CFTR-W1282X-260 - AAAUCCAGAUCGAUGGUGUGUC 22 3252 CFTR-W1282X-261 - GAAAUCCAGAUCGAUGGUGUGUC 23 3253 CFTR-W1282X-262 - AGAAAUCCAGAUCGAUGGUGUGUC 24 3254 CFTR-W1282X-263 - GACUACUGAACACUGAAG 18 3255 CFTR-W1282X-264 - AGACUACUGAACACUGAAG 19 3256 CFTR-W1282X-265 - GAGACUACUGAACACUGAAG 20 3257 CFTR-W1282X-266 - UGAGACUACUGAACACUGAAG 21 3258 CFTR-W1282X-267 - UUGAGACUACUGAACACUGAAG 22 3259 CFTR-W1282X-268 - UUUGAGACUACUGAACACUGAAG 23 3260 CFTR-W1282X-269 - UUUUGAGACUACUGAACACUGAAG 24 3261 CFTR-W1282X-270 - UUUGGAGUGAUACCACAG 18 3262 CFTR-W1282X-271 - CUUUGGAGUGAUACCACAG 19 3263 CFTR-W1282X-272 - CCUUUGGAGUGAUACCACAG 20 3264 CFTR-W1282X-273 - GCCUUUGGAGUGAUACCACAG 21 3265 CFTR-W1282X-274 - AGCCUUUGGAGUGAUACCACAG 22 3266 CFTR-W1282X-275 - AAGCCUUUGGAGUGAUACCACAG 23 3267 CFTR-W1282X-276 - AAAGCCUUUGGAGUGAUACCACAG 24 3268 CFTR-W1282X-277 - AUCACUUUUACCUUAUAG 18 3269 CFTR-W1282X-278 - CAUCACUUUUACCUUAUAG 19 3270 CFTR-W1282X-279 - CCAUCACUUUUACCUUAUAG 20 3271 CFTR-W1282X-280 - CCCAUCACUUUUACCUUAUAG 21 3272 CFTR-W1282X-281 - UCCCAUCACUUUUACCUUAUAG 22 3273 CFTR-W1282X-282 - AUCCCAUCACUUUUACCUUAUAG 23 3274 CFTR-W1282X-283 - GAUCCCAUCACUUUUACCUUAUAG 24 3275 CFTR-W1282X-284 - GUGCAGUUUUCUCAUAGG 18 3276 CFTR-W1282X-285 - AGUGCAGUUUUCUCAUAGG 19 3277 CFTR-W1282X-286 - CAGUGCAGUUUUCUCAUAGG 20 3278 CFTR-W1282X-287 - CCAGUGCAGUUUUCUCAUAGG 21 3279 CFTR-W1282X-288 - UCCAGUGCAGUUUUCUCAUAGG 22 3280 CFTR-W1282X-289 - CUCCAGUGCAGUUUUCUCAUAGG 23 3281 CFTR-W1282X-290 - UCUCCAGUGCAGUUUUCUCAUAGG 24 3282 CFTR-W1282X-291 - AUAGGUGGGCCUCUUGGG 18 3283 CFTR-W1282X-292 - UAUAGGUGGGCCUCUUGGG 19 3284 CFTR-W1282X-293 - UUAUAGGUGGGCCUCUUGGG 20 3285 CFTR-W1282X-294 - CUUAUAGGUGGGCCUCUUGGG 21 3286 CFTR-W1282X-295 - CCUUAUAGGUGGGCCUCUUGGG 22 3287 CFTR-W1282X-296 - ACCUUAUAGGUGGGCCUCUUGGG 23 3288 CFTR-W1282X-297 - UACCUUAUAGGUGGGCCUCUUGGG 24 3289 CFTR-W1282X-298 - UGAGACUACUGAACACUG 18 3290 CFTR-W1282X-299 - UUGAGACUACUGAACACUG 19 3291 CFTR-W1282X-300 - UUUGAGACUACUGAACACUG 20 3292 CFTR-W1282X-301 - UUUUGAGACUACUGAACACUG 21 3293 CFTR-W1282X-302 - UUUUUGAGACUACUGAACACUG 22 3294 CFTR-W1282X-303 - UUUUUUGAGACUACUGAACACUG 23 3295 CFTR-W1282X-304 - CUUUUUUGAGACUACUGAACACUG 24 3296 CFTR-W1282X-305 - AAUAACUUUGCAACAGUG 18 3297 CFTR-W1282X-306 - CAAUAACUUUGCAACAGUG 19 3298 CFTR-W1282X-307 - UCAAUAACUUUGCAACAGUG 20 3299 CFTR-W1282X-308 - UUCAAUAACUUUGCAACAGUG 21 3300 CFTR-W1282X-309 - AUUCAAUAACUUUGCAACAGUG 22 3301 CFTR-W1282X-310 - GAUUCAAUAACUUUGCAACAGUG 23 3302 CFTR-W1282X-311 - GGAUUCAAUAACUUUGCAACAGUG 24 3303 CFTR-W1282X-312 - UCUUGGGAAGAACUGGAU 18 3304 CFTR-W1282X-313 - CUCUUGGGAAGAACUGGAU 19 3305 CFTR-W1282X-314 - CCUCUUGGGAAGAACUGGAU 20 3306 CFTR-W1282X-315 - GCCUCUUGGGAAGAACUGGAU 21 3307 CFTR-W1282X-316 - GGCCUCUUGGGAAGAACUGGAU 22 3308 CFTR-W1282X-317 - GGGCCUCUUGGGAAGAACUGGAU 23 3309 CFTR-W1282X-318 - UGGGCCUCUUGGGAAGAACUGGAU 24 3310 CFTR-W1282X-319 - AACAGUGAAGGAAAGCCU 18 3311 CFTR-W1282X-320 - CAACAGUGAAGGAAAGCCU 19 3312 CFTR-W1282X-321 - GCAACAGUGAAGGAAAGCCU 20 3313 CFTR-W1282X-322 - UGCAACAGUGAAGGAAAGCCU 21 3314 CFTR-W1282X-323 - UUGCAACAGUGAAGGAAAGCCU 22 3315 CFTR-W1282X-324 - UUUGCAACAGUGAAGGAAAGCCU 23 3316 CFTR-W1282X-325 - CUUUGCAACAGUGAAGGAAAGCCU 24 3317 CFTR-W1282X-326 - CCUUAUAGGUGGGCCUCU 18 3318 CFTR-W1282X-327 - ACCUUAUAGGUGGGCCUCU 19 3319 CFTR-W1282X-47 - UACCUUAUAGGUGGGCCUCU 20 3039 CFTR-W1282X-328 - UUACCUUAUAGGUGGGCCUCU 21 3320 CFTR-W1282X-329 - UUUACCUUAUAGGUGGGCCUCU 22 3321 CFTR-W1282X-330 - UUUUACCUUAUAGGUGGGCCUCU 23 3322 CFTR-W1282X-331 - CUUUUACCUUAUAGGUGGGCCUCU 24 3323 CFTR-W1282X-332 - CUUAUAGGUGGGCCUCUU 18 3324 CFTR-W1282X-333 - CCUUAUAGGUGGGCCUCUU 19 3325 CFTR-W1282X-60 - ACCUUAUAGGUGGGCCUCUU 20 3052 CFTR-W1282X-334 - UACCUUAUAGGUGGGCCUCUU 21 3326 CFTR-W1282X-335 - UUACCUUAUAGGUGGGCCUCUU 22 3327 CFTR-W1282X-336 - UUUACCUUAUAGGUGGGCCUCUU 23 3328 CFTR-W1282X-337 - UUUUACCUUAUAGGUGGGCCUCUU 24 3329 CFTR-W1282X-338 - ACUUUGUUAUCAGCUUUU 18 3330 CFTR-W1282X-339 - UACUUUGUUAUCAGCUUUU 19 3331 CFTR-W1282X-340 - GUACUUUGUUAUCAGCUUUU 20 3332 CFTR-W1282X-341 - AGUACUUUGUUAUCAGCUUUU 21 3333 CFTR-W1282X-342 - GAGUACUUUGUUAUCAGCUUUU 22 3334 CFTR-W1282X-343 - AGAGUACUUUGUUAUCAGCUUUU 23 3335 CFTR-W1282X-344 - AAGAGUACUUUGUUAUCAGCUUUU 24 3336

Table 30A provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 30A  1st Tier DNA Target Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-W1282X-345 - GGGAAGAGUACUUUGUU 17 3337

Table 30B provides exemplary targeting domains for correcting a mutation (e.g., W1282X) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., W1282X) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table 1 can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 30B  2nd Tier Target Site Seq gRNA Name DNA Strand Targeting Domain Length ID CFTR-W1282X-346 + CCAAGACACACCAUCGA 17 3338 CFTR-W1282X-347 + ACCUGUGGUAUCACUCC 17 3339 CFTR-W1282X-348 - CAGAUCGAUGGUGUGUC 17 3340 CFTR-W1282X-349 + AUCCCAAGACACACCAUCGA 20 3341 CFTR-W1282X-350 + CUCACCUGUGGUAUCACUCC 20 3342 CFTR-W1282X-258 - AUCCAGAUCGAUGGUGUGUC 20 3250 CFTR-W1282X-351 - UCAGGGAAGAGUACUUUGUU 20 3343

Table 31A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 31A  1st Tier Tar-  DNA get Seq Site gRNA Name Strand Targeting Domain Length ID CFTR-3272-1 + GUAAGGCUGCCGUCCGA 17 1282 CFTR-3272-2 - GGAAAUAUUUCACAGGC 17 1283 CFTR-3272-3 + GUAAAUUCAGAGCUUUG 17 1284 CFTR-3272-4 - GGACACUUCGUGCCUUCGGA 20 1285 CFTR-3272-5 + GGAACCAGCGCAGUGUUGAC 20 1286 CFTR-3272-6 + GUAACAAGAUGAGUGAAAAU 20 1287

Table 31B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 31B  2nd Tier Target DNA Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-3272-7 - CUUGUUACAAGCUUAAA 17 1288 CFTR-3272-8 - CAUAUCUAUUCAAAGAA 17 1289 CFTR-3272-9 + UACUUGGCUACCAGAGA 17 1290 CFTR-3272-10 - CACUUCGUGCCUUCGGA 17 1291 CFTR-3272-11 - CAAGCUUAAAAGGACUA 17 1292 CFTR-3272-12 - AUUUACAUACUGCCAAC 17 1293 CFTR-3272-13 + AAAGCUUUUUUUCACAC 17 1294 CFTR-3272-14 - CUAUGGAAAUAUUUCAC 17 1295 CFTR-3272-15 + ACCAGCGCAGUGUUGAC 17 1296 CFTR-3272-16 - ACCUGUCAACACUGCGC 17 1297 CFTR-3272-17 - CUAAUUUAGUCUUUUUC 17 1298 CFTR-3272-18 + CAUAUCACAAAUGUCAU 17 1299 CFTR-3272-19 + ACUUGGCUACCAGAGAU 17 1300 CFTR-3272-20 + UACCCUCUUUUUUUACU 17 1301 CFTR-3272-21 + CAGGUACAAGAACCAGU 17 1302 CFTR-3272-22 - UGGACACUUCGUGCCUU 17 1303 CFTR-3272-23 - CAUCUUGUUACAAGCUUAAA 20 1304 CFTR-3272-24 - AAUCAUAUCUAUUCAAAGAA 20 1305 CFTR-3272-25 + UUUUACUUGGCUACCAGAGA 20 1306 CFTR-3272-26 + AAAGUAAGGCUGCCGUCCGA 20 1307 CFTR-3272-27 - UUACAAGCUUAAAAGGACUA 20 1308 CFTR-3272-28 + UGGAACAGAGUUUCAAAGUA 20 1309 CFTR-3272-29 - UGAAUUUACAUACUGCCAAC 20 1310 CFTR-3272-30 + UAAAAAGCUUUUUUUCACAC 20 1311 CFTR-3272-31 - UUUCUAUGGAAAUAUUUCAC 20 1312 CFTR-3272-32 - UGUACCUGUCAACACUGCGC 20 1313 CFTR-3272-33 - UAUGGAAAUAUUUCACAGGC 20 1314 CFTR-3272-34 - UGGUAGCCAAGUAAAAAAAG 20 1315 CFTR-3272-35 + UAUGUAAAUUCAGAGCUUUG 20 1316 CFTR-3272-36 + AAUCAUAUCACAAAUGUCAU 20 1317 CFTR-3272-37 + UUUACUUGGCUACCAGAGAU 20 1318 CFTR-3272-38 + AGUUACCCUCUUUUUUUACU 20 1319 CFTR-3272-39 + UGACAGGUACAAGAACCAGU 20 1320 CFTR-3272-40 - CUAUGGACACUUCGUGCCUU 20 1321

Table 31C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 31C  3rd Tier Target  DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272- - GGUAGCCAAGUAAAAAAAGA 20 1322 41 CFTR-3272- - GUUAUUUGCAGUGUUUUCUA 20 1323 42

Table 31D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 31D  4th Tier Target Site Seq  gRNA Name DNA Strand Targeting Domain Length ID CFTR-3272-43 - AGCCAAGUAAAAAAAGA 17 1324 CFTR-3272-44 - AUUUGCAGUGUUUUCUA 17 1325 CFTR-3272-45 + AACAGAGUUUCAAAGUA 17 1326 CFTR-3272-46 - UAGCCAAGUAAAAAAAG 17 1327 CFTR-3272-47 + ACAAGAUGAGUGAAAAU 17 1328 CFTR-3272-48 - AUUCUAAUUUAGUCUUUUUC 20 1329

Table 32A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 32A  1st Tier DNA Target Site Seq  gRNA Name Strand Targeting Domain Length ID CFTR-3272-49 + GUCCUUUUAAGCUUGUAACAAG 22 1330 CFTR-3272-50 + GUACCUGAAAAAGACUAAAU 20 1331 CFTR-3272-51 - GUCAACACUGCGCUGGUUCCAAAU 24 1332

Table 32B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 32B  2nd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3272-52 + UUUUAAGCUUGUAACAAG 18 1333 CFTR-3272-53 + CUUUUAAGCUUGUAACAAG 19 1334 CFTR-3272-54 + CCUUUUAAGCUUGUAACAAG 20 1335 CFTR-3272-55 + UCCUUUUAAGCUUGUAACAAG 21 1336 CFTR-3272-56 + AGUCCUUUUAAGCUUGUAACAAG 23 1337 CFTR-3272-57 + UAGUCCUUUUAAGCUUGUAACAAG 24 1338 CFTR-3272-58 + ACCUGAAAAAGACUAAAU 18 1339 CFTR-3272-59 + UACCUGAAAAAGACUAAAU 19 1340 CFTR-3272-60 + UGUACCUGAAAAAGACUAAAU 21 1341 CFTR-3272-61 + UUGUACCUGAAAAAGACUAAAU 22 1342 CFTR-3272-62 + CUUGUACCUGAAAAAGACUAAAU 23 1343 CFTR-3272-63 + UCUUGUACCUGAAAAAGACUAAAU 24 1344 CFTR-3272-64 + UCACACUGGUGCCAUUCU 18 1345 CFTR-3272-65 + UUCACACUGGUGCCAUUCU 19 1346 CFTR-3272-66 + UUUCACACUGGUGCCAUUCU 20 1347 CFTR-3272-67 + UUUUCACACUGGUGCCAUUCU 21 1348 CFTR-3272-68 + UUUUUCACACUGGUGCCAUUCU 22 1349 CFTR-3272-69 + UUUUUUCACACUGGUGCCAUUCU 23 1350 CFTR-3272-70 + UUUUUUUCACACUGGUGCCAUUCU 24 1351 CFTR-3272-71 - ACAAAUCAUAUCUAUUCA 18 1352 CFTR-3272-72 - AACAAAUCAUAUCUAUUCA 19 1353 CFTR-3272-73 - UAACAAAUCAUAUCUAUUCA 20 1354 CFTR-3272-74 - AUAACAAAUCAUAUCUAUUCA 21 1355 CFTR-3272-75 - AAUAACAAAUCAUAUCUAUUCA 22 1356 CFTR-3272-76 - AAAUAACAAAUCAUAUCUAUUCA 23 1357 CFTR-3272-77 - AAAAUAACAAAUCAUAUCUAUUCA 24 1358 CFTR-3272-78 - UGGAAAUAUUUCACAGGC 18 1359 CFTR-3272-79 - AUGGAAAUAUUUCACAGGC 19 1360 CFTR-3272-33 - UAUGGAAAUAUUUCACAGGC 20 1314 CFTR-3272-80 - ACUGCGCUGGUUCCAAAU 18 1361 CFTR-3272-81 - CACUGCGCUGGUUCCAAAU 19 1362 CFTR-3272-82 - ACACUGCGCUGGUUCCAAAU 20 1363 CFTR-3272-83 - AACACUGCGCUGGUUCCAAAU 21 1364 CFTR-3272-84 - CAACACUGCGCUGGUUCCAAAU 22 1365 CFTR-3272-85 - UCAACACUGCGCUGGUUCCAAAU 23 1366 CFTR-3272-86 - ACUCUGUUCCACAAAGCU 18 1367 CFTR-3272-87 - AACUCUGUUCCACAAAGCU 19 1368 CFTR-3272-88 - AAACUCUGUUCCACAAAGCU 20 1369

Table 32C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 32C 3rd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3272-89 + AUUCAGAGCUUUGUGGAA 18 1374 CFTR-3272-90 + AAUUCAGAGCUUUGUGGAA 19 1375 CFTR-3272-91 + AAAUUCAGAGCUUUGUGGAA 20 1376 CFTR-3272-92 + UAAAUUCAGAGCUUUGUGGAA 21 1377 CFTR-3272-93 + GUAAAUUCAGAGCUUUGUGGAA 22 1370 CFTR-3272-94 + UGUAAAUUCAGAGCUUUGUGGAA 23 1378 CFTR-3272-95 + AUGUAAAUUCAGAGCUUUGUGGAA 24 1379 CFTR-3272-96 + UGAUUUGUUAUUUUAUUA 18 1380 CFTR-3272-97 + AUGAUUUGUUAUUUUAUUA 19 1381 CFTR-3272-98 + UAUGAUUUGUUAUUUUAUUA 20 1382 CFTR-3272-99 + AUAUGAUUUGUUAUUUUAUUA 21 1383 CFTR-3272-100 + GAUAUGAUUUGUUAUUUUAUUA 22 1371 CFTR-3272-101 + AGAUAUGAUUUGUUAUUUUAUUA 23 1384 CFTR-3272-102 + UAGAUAUGAUUUGUUAUUUUAUUA 24 1385 CFTR-3272-103 GGUAGCCAAGUAAAAAAA 18 1372 CFTR-3272-104 UGGUAGCCAAGUAAAAAAA 19 1386 CFTR-3272-105 CUGGUAGCCAAGUAAAAAAA 20 1387 CFTR-3272-106 UCUGGUAGCCAAGUAAAAAAA 21 1388 CFTR-3272-107 CUCUGGUAGCCAAGUAAAAAAA 22 1389 CFTR-3272-108 UCUCUGGUAGCCAAGUAAAAAAA 23 1390 CFTR-3272-109 AUCUCUGGUAGCCAAGUAAAAAAA 24 1391 CFTR-3272-110 CUAUGGAAAUAUUUCACAGGC 21 1392 CFTR-3272-111 UCUAUGGAAAUAUUUCACAGGC 22 1393 CFTR-3272-112 UUCUAUGGAAAUAUUUCACAGGC 23 1394 CFTR-3272-113 UUUCUAUGGAAAUAUUUCACAGGC 24 1395 CFTR-3272-114 GAAACUCUGUUCCACAAAGCU 21 1373 CFTR-3272-115 UGAAACUCUGUUCCACAAAGCU 22 1396 CFTR-3272-116 UUGAAACUCUGUUCCACAAAGCU 23 1397 CFTR-3272-117 UUUGAAACUCUGUUCCACAAAGCU 24 1398

Table 32D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 32D 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3272-118 + UAACAAGAUGAGUGAAAA 18 1399 CFTR-3272-119 + GUAACAAGAUGAGUGAAAA 19 1400 CFTR-3272-120 + UGUAACAAGAUGAGUGAAAA 20 1401 CFTR-3272-121 + UUGUAACAAGAUGAGUGAAAA 21 1402 CFTR-3272-122 + CUUGUAACAAGAUGAGUGAAAA 22 1403 CFTR-3272-123 + GCUUGUAACAAGAUGAGUGAAAA 23 1404 CFTR-3272-124 + AGCUUGUAACAAGAUGAGUGAAAA 24 1405 CFTR-3272-125 + GCCUGUGAAAUAUUUCCA 18 1406 CFTR-3272-126 + UGCCUGUGAAAUAUUUCCA 19 1407 CFTR-3272-127 + CUGCCUGUGAAAUAUUUCCA 20 1408 CFTR-3272-128 + CCUGCCUGUGAAAUAUUUCCA 21 1409 CFTR-3272-129 + UCCUGCCUGUGAAAUAUUUCCA 22 1410 CFTR-3272-130 + CUCCUGCCUGUGAAAUAUUUCCA 23 1411 CFTR-3272-131 + ACUCCUGCCUGUGAAAUAUUUCCA 24 1412 CFTR-3272-132 + UUACUUGGCUACCAGAGA 18 1413 CFTR-3272-133 + UUUACUUGGCUACCAGAGA 19 1414 CFTR-3272-25 + UUUUACUUGGCUACCAGAGA 20 1306 CFTR-3272-134 + UUUUUACUUGGCUACCAGAGA 21 1415 CFTR-3272-135 + UUUUUUACUUGGCUACCAGAGA 22 1416 CFTR-3272-136 + UUUUUUUACUUGGCUACCAGAGA 23 1417 CFTR-3272-137 + CUUUUUUUACUUGGCUACCAGAGA 24 1418 CFTR-3272-138 + AAGCUUGUAACAAGAUGA 18 1419 CFTR-3272-139 + UAAGCUUGUAACAAGAUGA 19 1420 CFTR-3272-140 + UUAAGCUUGUAACAAGAUGA 20 1421 CFTR-3272-141 + UUUAAGCUUGUAACAAGAUGA 21 1422 CFTR-3272-142 + UUUUAAGCUUGUAACAAGAUGA 22 1423 CFTR-3272-143 + CUUUUAAGCUUGUAACAAGAUGA 23 1424 CFTR-3272-144 + CCUUUUAAGCUUGUAACAAGAUGA 24 1425 CFTR-3272-145 + CUUUUUUUACUUGGCUAC 18 1426 CFTR-3272-146 + UCUUUUUUUACUUGGCUAC 19 1427 CFTR-3272-147 + CUCUUUUUUUACUUGGCUAC 20 1428 CFTR-3272-148 + CCUCUUUUUUUACUUGGCUAC 21 1429 CFTR-3272-149 + CCCUCUUUUUUUACUUGGCUAC 22 1430 CFTR-3272-150 + ACCCUCUUUUUUUACUUGGCUAC 23 1431 CFTR-3272-151 + UACCCUCUUUUUUUACUUGGCUAC 24 1432 CFTR-3272-152 + CGCAGUGUUGACAGGUAC 18 1433 CFTR-3272-153 + GCGCAGUGUUGACAGGUAC 19 1434 CFTR-3272-154 + AGCGCAGUGUUGACAGGUAC 20 1435 CFTR-3272-155 + CAGCGCAGUGUUGACAGGUAC 21 1436 CFTR-3272-156 + CCAGCGCAGUGUUGACAGGUAC 22 1437 CFTR-3272-157 + ACCAGCGCAGUGUUGACAGGUAC 23 1438 CFTR-3272-158 + AACCAGCGCAGUGUUGACAGGUAC 24 1439 CFTR-3272-159 + UUUCAUAAUAUCUUGUAC 18 1440 CFTR-3272-160 + AUUUCAUAAUAUCUUGUAC 19 1441 CFTR-3272-161 + AAUUUCAUAAUAUCUUGUAC 20 1442 CFTR-3272-162 + UAAUUUCAUAAUAUCUUGUAC 21 1443 CFTR-3272-163 + GUAAUUUCAUAAUAUCUUGUAC 22 1444 CFTR-3272-164 + UGUAAUUUCAUAAUAUCUUGUAC 23 1445 CFTR-3272-165 + AUGUAAUUUCAUAAUAUCUUGUAC 24 1446 CFTR-3272-166 + AGGCUGCCGUCCGAAGGC 18 1447 CFTR-3272-167 + AAGGCUGCCGUCCGAAGGC 19 1448 CFTR-3272-168 + UAAGGCUGCCGUCCGAAGGC 20 1449 CFTR-3272-169 + GUAAGGCUGCCGUCCGAAGGC 21 1450 CFTR-3272-170 + AGUAAGGCUGCCGUCCGAAGGC 22 1451 CFTR-3272-171 + AAGUAAGGCUGCCGUCCGAAGGC 23 1452 CFTR-3272-172 + AAAGUAAGGCUGCCGUCCGAAGGC 24 1453 CFTR-3272-173 + UUUACUUGGCUACCAGAG 18 1454 CFTR-3272-174 + UUUUACUUGGCUACCAGAG 19 1455 CFTR-3272-175 + UUUUUACUUGGCUACCAGAG 20 1456 CFTR-3272-176 + UUUUUUACUUGGCUACCAGAG 21 1457 CFTR-3272-177 + UUUUUUUACUUGGCUACCAGAG 22 1458 CFTR-3272-178 + CUUUUUUUACUUGGCUACCAGAG 23 1459 CFTR-3272-179 + UCUUUUUUUACUUGGCUACCAGAG 24 1460 CFTR-3272-180 + UGUAAAUUCAGAGCUUUG 18 1461 CFTR-3272-181 + AUGUAAAUUCAGAGCUUUG 19 1462 CFTR-3272-35 + UAUGUAAAUUCAGAGCUUUG 20 1316 CFTR-3272-182 + GUAUGUAAAUUCAGAGCUUUG 21 1463 CFTR-3272-183 + AGUAUGUAAAUUCAGAGCUUUG 22 1464 CFTR-3272-184 + CAGUAUGUAAAUUCAGAGCUUUG 23 1465 CFTR-3272-185 + GCAGUAUGUAAAUUCAGAGCUUUG 24 1466 CFTR-3272-186 + UACUUGGCUACCAGAGAU 18 1467 CFTR-3272-187 + UUACUUGGCUACCAGAGAU 19 1468 CFTR-3272-37 + UUUACUUGGCUACCAGAGAU 20 1318 CFTR-3272-188 + UUUUACUUGGCUACCAGAGAU 21 1469 CFTR-3272-189 + UUUUUACUUGGCUACCAGAGAU 22 1470 CFTR-3272-190 + UUUUUUACUUGGCUACCAGAGAU 23 1471 CFTR-3272-191 + UUUUUUUACUUGGCUACCAGAGAU 24 1472 CFTR-3272-192 + AAAAUUGGACUCCUGCCU 18 1473 CFTR-3272-193 + GAAAAUUGGACUCCUGCCU 19 1474 CFTR-3272-194 + UGAAAAUUGGACUCCUGCCU 20 1475 CFTR-3272-195 + GUGAAAAUUGGACUCCUGCCU 21 1476 CFTR-3272-196 + AGUGAAAAUUGGACUCCUGCCU 22 1477 CFTR-3272-197 + GAGUGAAAAUUGGACUCCUGCCU 23 1478 CFTR-3272-198 + UGAGUGAAAAUUGGACUCCUGCCU 24 1479 CFTR-3272-199 + UCAAAGUAAGGCUGCCGU 18 1480 CFTR-3272-200 + UUCAAAGUAAGGCUGCCGU 19 1481 CFTR-3272-201 + UUUCAAAGUAAGGCUGCCGU 20 1482 CFTR-3272-202 + GUUUCAAAGUAAGGCUGCCGU 21 1483 CFTR-3272-203 + AGUUUCAAAGUAAGGCUGCCGU 22 1484 CFTR-3272-204 + GAGUUUCAAAGUAAGGCUGCCGU 23 1485 CFTR-3272-205 + AGAGUUUCAAAGUAAGGCUGCCGU 24 1486 CFTR-3272-206 + GUUGGCAGUAUGUAAAUU 18 1487 CFTR-3272-207 + AGUUGGCAGUAUGUAAAUU 19 1488 CFTR-3272-208 + CAGUUGGCAGUAUGUAAAUU 20 1489 CFTR-3272-209 + CCAGUUGGCAGUAUGUAAAUU 21 1490 CFTR-3272-210 + ACCAGUUGGCAGUAUGUAAAUU 22 1491 CFTR-3272-211 + AACCAGUUGGCAGUAUGUAAAUU 23 1492 CFTR-3272-212 + GAACCAGUUGGCAGUAUGUAAAUU 24 1493 CFTR-3272-213 + AUGUAAAUUCAGAGCUUU 18 1494 CFTR-3272-214 + UAUGUAAAUUCAGAGCUUU 19 1495 CFTR-3272-215 + GUAUGUAAAUUCAGAGCUUU 20 1496 CFTR-3272-216 + AGUAUGUAAAUUCAGAGCUUU 21 1497 CFTR-3272-217 + CAGUAUGUAAAUUCAGAGCUUU 22 1498 CFTR-3272-218 + GCAGUAUGUAAAUUCAGAGCUUU 23 1499 CFTR-3272-219 + GGCAGUAUGUAAAUUCAGAGCUUU 24 1500 CFTR-3272-220 CUGGUAGCCAAGUAAAAA 18 1501 CFTR-3272-221 UCUGGUAGCCAAGUAAAAA 19 1502 CFTR-3272-222 CUCUGGUAGCCAAGUAAAAA 20 1503 CFTR-3272-223 UCUCUGGUAGCCAAGUAAAAA 21 1504 CFTR-3272-224 AUCUCUGGUAGCCAAGUAAAAA 22 1505 CFTR-3272-225 CAUCUCUGGUAGCCAAGUAAAAA 23 1506 CFTR-3272-226 CCAUCUCUGGUAGCCAAGUAAAAA 24 1507 CFTR-3272-227 ACACUGCGCUGGUUCCAA 18 1508 CFTR-3272-228 AACACUGCGCUGGUUCCAA 19 1509 CFTR-3272-229 CAACACUGCGCUGGUUCCAA 20 1510 CFTR-3272-230 UCAACACUGCGCUGGUUCCAA 21 1511 CFTR-3272-231 GUCAACACUGCGCUGGUUCCAA 22 1512 CFTR-3272-232 UGUCAACACUGCGCUGGUUCCAA 23 1513 CFTR-3272-233 CUGUCAACACUGCGCUGGUUCCAA 24 1514 CFTR-3272-234 GCUGGUUCCAAAUGAGAA 18 1515 CFTR-3272-235 CGCUGGUUCCAAAUGAGAA 19 1516 CFTR-3272-236 GCGCUGGUUCCAAAUGAGAA 20 1517 CFTR-3272-237 UGCGCUGGUUCCAAAUGAGAA 21 1518 CFTR-3272-238 CUGCGCUGGUUCCAAAUGAGAA 22 1519 CFTR-3272-239 ACUGCGCUGGUUCCAAAUGAGAA 23 1520 CFTR-3272-240 CACUGCGCUGGUUCCAAAUGAGAA 24 1521 CFTR-3272-241 AUCUUGUUACAAGCUUAA 18 1522 CFTR-3272-242 CAUCUUGUUACAAGCUUAA 19 1523 CFTR-3272-243 UCAUCUUGUUACAAGCUUAA 20 1524 CFTR-3272-244 CUCAUCUUGUUACAAGCUUAA 21 1525 CFTR-3272-245 ACUCAUCUUGUUACAAGCUUAA 22 1526 CFTR-3272-246 CACUCAUCUUGUUACAAGCUUAA 23 1527 CFTR-3272-247 UCACUCAUCUUGUUACAAGCUUAA 24 1528 CFTR-3272-248 UAUUUGCAGUGUUUUCUA 18 1529 CFTR-3272-249 UUAUUUGCAGUGUUUUCUA 19 1530 CFTR-3272-42 GUUAUUUGCAGUGUUUUCUA 20 1323 CFTR-3272-250 UGUUAUUUGCAGUGUUUUCUA 21 1531 CFTR-3272-251 AUGUUAUUUGCAGUGUUUUCUA 22 1532 CFTR-3272-252 UAUGUUAUUUGCAGUGUUUUCUA 23 1533 CFTR-3272-253 UUAUGUUAUUUGCAGUGUUUUCUA 24 1534 CFTR-3272-254 AUGGAAAUAUUUCACAGG 18 1535 CFTR-3272-255 UAUGGAAAUAUUUCACAGG 19 1536 CFTR-3272-256 CUAUGGAAAUAUUUCACAGG 20 1537 CFTR-3272-257 UCUAUGGAAAUAUUUCACAGG 21 1538 CFTR-3272-258 UUCUAUGGAAAUAUUUCACAGG 22 1539 CFTR-3272-259 UUUCUAUGGAAAUAUUUCACAGG 23 1540 CFTR-3272-260 UUUUCUAUGGAAAUAUUUCACAGG 24 1541 CFTR-3272-261 UACAAGCUUAAAAGGACU 18 1542 CFTR-3272-262 UUACAAGCUUAAAAGGACU 19 1543 CFTR-3272-263 GUUACAAGCUUAAAAGGACU 20 1544 CFTR-3272-264 UGUUACAAGCUUAAAAGGACU 21 1545 CFTR-3272-265 UUGUUACAAGCUUAAAAGGACU 22 1546 CFTR-3272-266 CUUGUUACAAGCUUAAAAGGACU 23 1547 CFTR-3272-267 UCUUGUUACAAGCUUAAAAGGACU 24 1548 CFTR-3272-268 UCGGACGGCAGCCUUACU 18 1549 CFTR-3272-269 UUCGGACGGCAGCCUUACU 19 1550 CFTR-3272-270 CUUCGGACGGCAGCCUUACU 20 1551 CFTR-3272-271 CCUUCGGACGGCAGCCUUACU 21 1552 CFTR-3272-272 GCCUUCGGACGGCAGCCUUACU 22 1553 CFTR-3272-273 UGCCUUCGGACGGCAGCCUUACU 23 1554 CFTR-3272-274 GUGCCUUCGGACGGCAGCCUUACU 24 1555 CFTR-3272-275 UAUGGACACUUCGUGCCU 18 1556 CFTR-3272-276 CUAUGGACACUUCGUGCCU 19 1557 CFTR-3272-277 ACUAUGGACACUUCGUGCCU 20 1558 CFTR-3272-278 GACUAUGGACACUUCGUGCCU 21 1559 CFTR-3272-279 GGACUAUGGACACUUCGUGCCU 22 1560 CFTR-3272-280 AGGACUAUGGACACUUCGUGCCU 23 1561 CFTR-3272-281 AAGGACUAUGGACACUUCGUGCCU 24 1562 CFTR-3272-282 UUAUUUGCAGUGUUUUCU 18 1563 CFTR-3272-283 GUUAUUUGCAGUGUUUUCU 19 1564 CFTR-3272-284 UGUUAUUUGCAGUGUUUUCU 20 1565 CFTR-3272-285 AUGUUAUUUGCAGUGUUUUCU 21 1566 CFTR-3272-286 UAUGUUAUUUGCAGUGUUUUCU 22 1567 CFTR-3272-287 UUAUGUUAUUUGCAGUGUUUUCU 23 1568 CFTR-3272-288 UUUAUGUUAUUUGCAGUGUUUUCU 24 1569 CFTR-3272-289 UCAAAGAAUGGCACCAGU 18 1570 CFTR-3272-290 UUCAAAGAAUGGCACCAGU 19 1571 CFTR-3272-291 AUUCAAAGAAUGGCACCAGU 20 1572 CFTR-3272-292 UAUUCAAAGAAUGGCACCAGU 21 1573 CFTR-3272-293 CUAUUCAAAGAAUGGCACCAGU 22 1574 CFTR-3272-294 UCUAUUCAAAGAAUGGCACCAGU 23 1575 CFTR-3272-295 AUCUAUUCAAAGAAUGGCACCAGU 24 1576 CFTR-3272-296 UUUCAGGUACAAGAUAUU 18 1577 CFTR-3272-297 UUUUCAGGUACAAGAUAUU 19 1578 CFTR-3272-298 UUUUUCAGGUACAAGAUAUU 20 1579 CFTR-3272-299 CUUUUUCAGGUACAAGAUAUU 21 1580 CFTR-3272-300 UCUUUUUCAGGUACAAGAUAUU 22 1581 CFTR-3272-301 GUCUUUUUCAGGUACAAGAUAUU 23 1582 CFTR-3272-302 AGUCUUUUUCAGGUACAAGAUAUU 24 1583

Table 33A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 33A 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3272-303 AUGGCACCAGUGUGAAA 17 1584 CFTR-3272-304 + UGCCAUUCUUUGAAUAG 17 1585 CFTR-3272-305 + UUGGCAGUAUGUAAAUU 17 1586 CFTR-3272-306 + AAGUGUCCAUAGUCCUU 17 1587 CFTR-3272-307 AGAAUGGCACCAGUGUGAAA 20 1588 CFTR-3272-308 + UGGUGCCAUUCUUUGAAUAG 20 1589 CFTR-3272-309 + ACGAAGUGUCCAUAGUCCUU 20 1590

Table 33B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 200 bp from a mutation (e.g., 3272-26->G). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 33B 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3272-310 + ACAAAUGUCAUUGGUUA 17 1591 CFTR-3272-311 AACCAAUGACAUUUGUG 17 1592 CFTR-3272-312 UUUUCACUCAUCUUGUU 17 1593 CFTR-3272-313 + AUCACAAAUGUCAUUGGUUA 20 1594 CFTR-3272-314 UUUAACCAAUGACAUUUGUG 20 1595 CFTR-3272-208 + CAGUUGGCAGUAUGUAAAUU 20 1489 CFTR-3272-315 CAAUUUUCACUCAUCUUGUU 20 1596

Table 34A provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 34A 1st Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-1 GAGUAAGACACCCUGAA 17 3344 CFTR-3849-2 GAUUUCUGGAGACCACA 17 3345 CFTR-3849-3 + GGUUUUAGCUAUUACUC 17 3346 CFTR-3849-4 GUAGUUGAAUCAUUCAG 17 3347 CFTR-3849-5 + GAACUCAGUUUUUAGGU 17 3348 CFTR-3849-6 GAAAGGAAAUGUUCUAUUCA 20 3349 CFTR-3849-7 + GUUUUUAGGUUGGGAAAGAC 20 3350 CFTR-3849-8 + GCACAUAAUAAUUAGUUUCC 20 3351 CFTR-3849-9 + GAGAACUCAGUUUUUAGGUU 20 3352 CFTR-3849-10 GAAAACACUGACUUAGAUUU 20 3353

Table 34B provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+17kbC->T) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 34B 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-11 + UCUGACACAUUUUUCAA 17 3354 CFTR-3849-12 + CUUUGGUUUAGCUUUAA 17 3355 CFTR-3849-13 + UGAAAUUUAGAUCCACA 17 3356 CFTR-3849-14 UUGAUCCAACAUUCUCA 17 3357 CFTR-3849-15 AGGAAAUGUUCUAUUCA 17 3358 CFTR-3849-16 + UUUAAUACUGCAACAGA 17 3359 CFTR-3849-17 + CAGUGAUCUGUUGAAUA 17 3360 CFTR-3849-18 AGCAGUUCAAUGAUAUA 17 3361 CFTR-3849-19 ACACUGACUUAGAUUUA 17 3362 CFTR-3849-20 + CUUCUUGUUUAUAUAAC 17 3363 CFTR-3849-21 + CAAAGGCAAGGAAUCAC 17 3364 CFTR-3849-22 + UUUAGGUUGGGAAAGAC 17 3365 CFTR-3849-23 UGUAUAUAUCACAGUAC 17 3366 CFTR-3849-24 CAGAUCACUGAGAAGCC 17 3367 CFTR-3849-25 + CAUAAUAAUUAGUUUCC 17 3368 CFTR-3849-26 + CCGGGAUUUGUUUUUCC 17 3369 CFTR-3849-27 + UUAUAUCAUUGAACUGC 17 3370 CFTR-3849-28 CUUAAAAGCUUAUUUGC 17 3371 CFTR-3849-29 AUUCUUCAUGAUAAAUC 17 3372 CFTR-3849-30 CUUGAUCCAACAUUCUC 17 3373 CFTR-3849-31 + AUAGAACAUUUCCUUUC 17 3374 CFTR-3849-32 + ACAUAAUAAUUAGUUUC 17 3375 CFTR-3849-33 + AAUAUCUAUUUAAUCAG 17 3376 CFTR-3849-34 CAACAUUCUCAGGGAGG 17 3377 CFTR-3849-35 AUCCAACAUUCUCAGGG 17 3378 CFTR-3849-36 + AUACAAUAUACCAUAUG 17 3379 CFTR-3849-37 CAAUUAUAAUCACCUUG 17 3380 CFTR-3849-38 UCUAUCUUGAUAAACAU 17 3381 CFTR-3849-39 UAGUUGAAUCAUUCAGU 17 3382 CFTR-3849-40 + CUCCUCCCUGAGAAUGU 17 3383 CFTR-3849-41 AAACAAGAAGACUUUGU 17 3384 CFTR-3849-42 + AACUCAGUUUUUAGGUU 17 3385 CFTR-3849-43 AACAAGAAGACUUUGUU 17 3386 CFTR-3849-44 AACACUGACUUAGAUUU 17 3387 CFTR-3849-45 UUUAAGGUCUAUACUUU 17 3388 CFTR-3849-46 CAUCUGUUGCAGUAUUAAAA 20 3389 CFTR-3849-47 + UAUUUUCAAGAGACUACAAA 20 3390 CFTR-3849-48 + AUAUCUGACACAUUUUUCAA 20 3391 CFTR-3849-49 + AAUCUUUGGUUUAGCUUUAA 20 3392 CFTR-3849-50 CUUGAUUUCUGGAGACCACA 20 3393 CFTR-3849-51 + UGACACAUUUUUCAAAGGCA 20 3394 CFTR-3849-52 AUCUUGAUCCAACAUUCUCA 20 3395 CFTR-3849-53 + CAUUUUAAUACUGCAACAGA 20 3396 CFTR-3849-54 + UCUCAGUGAUCUGUUGAAUA 20 3397 CFTR-3849-55 CUUAAUCAAAAUUCCUCAUA 20 3398 CFTR-3849-56 ACCAGCAGUUCAAUGAUAUA 20 3399 CFTR-3849-57 AAAACACUGACUUAGAUUUA 20 3400 CFTR-3849-58 AGAUAUUUGAUAGUACUUUA 20 3401 CFTR-3849-59 + UUUCAAAGGCAAGGAAUCAC 20 3402 CFTR-3849-60 UAUUGUAUAUAUCACAGUAC 20 3403 CFTR-3849-61 CAACAGAUCACUGAGAAGCC 20 3404 CFTR-3849-62 AAGCCUGGAAAAACAAAUCC 20 3405 CFTR-3849-63 + UUUCCGGGAUUUGUUUUUCC 20 3406 CFTR-3849-64 + UCCUUAUAUCAUUGAACUGC 20 3407 CFTR-3849-65 UGUCUUAAAAGCUUAUUUGC 20 3408 CFTR-3849-66 + AAAGGUUUUAGCUAUUACUC 20 3409 CFTR-3849-67 UAUCUUGAUCCAACAUUCUC 20 3410 CFTR-3849-68 UGACUUGUCAUCUUGAUUUC 20 3411 CFTR-3849-69 + UGAAUAGAACAUUUCCUUUC 20 3412 CFTR-3849-70 + UUGGGAAAGACUGGAUGAAG 20 3413 CFTR-3849-71 + UCAAAUAUCUAUUUAAUCAG 20 3414 CFTR-3849-72 AAAGUAGUUGAAUCAUUCAG 20 3415 CFTR-3849-73 AUCCAACAUUCUCAGGGAGG 20 3416 CFTR-3849-74 UUGAUCCAACAUUCUCAGGG 20 3417 CFTR-3849-75 AUUCAAUUAUAAUCACCUUG 20 3418 CFTR-3849-76 AUGUCUUAAAAGCUUAUUUG 20 3419 CFTR-3849-77 UUUUCUAUCUUGAUAAACAU 20 3420 CFTR-3849-78 + AGAGAACUCAGUUUUUAGGU 20 3421 CFTR-3849-79 + CACCUCCUCCCUGAGAAUGU 20 3422 CFTR-3849-80 UAUAAACAAGAAGACUUUGU 20 3423 CFTR-3849-81 + AAGUUAAACAGUGUUGAAUU 20 3424 CFTR-3849-82 AUAAACAAGAAGACUUUGUU 20 3425 CFTR-3849-83 + AACAAAGCAAACAAGUAUUU 20 3426 CFTR-3849-84 UACUUUAAGGUCUAUACUUU 20 3427

Table 34C provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 34C 3rd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-85 + GGAAAGACUGGAUGAAG 17 3428 CFTR-3849-86 + GGCAAUUUGUAAAUCUU 17 3429 CFTR-3849-87 GUAUUUUUUUCUGAAGAAAA 20 3430 CFTR-3849-88 GGUGAGUAAGACACCCUGAA 20 3431 CFTR-3849-89 + GAAUAGAACAUUUCCUUUCA 20 3432 CFTR-3849-90 + GGCACAUAAUAAUUAGUUUC 20 3433

Table 34D provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+35kbC->T). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 34D 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-91 UUUUUUUCUGAAGAAAA 17 3434 CFTR-3849-92 + UUUAUCAAGAUAGAAAA 17 3435 CFTR-3849-93 CUGUUGCAGUAUUAAAA 17 3436 CFTR-3849-94 + UUUCAAGAGACUACAAA 17 3437 CFTR-3849-95 AUUUUUUUCUGAAGAAA 17 3438 CFTR-3849-96 + CACAUUUUUCAAAGGCA 17 3439 CFTR-3849-97 AAUUUAUAAGAAUAUCA 17 3440 CFTR-3849-98 + UAGAACAUUUCCUUUCA 17 3441 CFTR-3849-99 AAUCAAAAUUCCUCAUA 17 3442 CFTR-3849-100 UAUUUGAUAGUACUUUA 17 3443 CFTR-3849-101 CCUGGAAAAACAAAUCC 17 3444 CFTR-3849-102 CUUGUCAUCUUGAUUUC 17 3445 CFTR-3849-103 UUUUUUCUGAAGAAAAG 17 3446 CFTR-3849-104 + UAUUUUUCAUUACCUUG 17 3447 CFTR-3849-105 UCUUAAAAGCUUAUUUG 17 3448 CFTR-3849-106 + UUAUCAAGAUAGAAAAU 17 3449 CFTR-3849-107 + UUAAACAGUGUUGAAUU 17 3450 CFTR-3849-108 + AAAGCAAACAAGUAUUU 17 3451 CFTR-3849-109 + UAGAGAACUCAGUUUUU 17 3452 CFTR-3849-110 + AUGUUUAUCAAGAUAGAAAA 20 3453 CFTR-3849-111 AGUAUUUUUUUCUGAAGAAA 20 3454 CFTR-3849-112 + AACUGAAAUUUAGAUCCACA 20 3455 CFTR-3849-113 AAUAAUUUAUAAGAAUAUCA 20 3456 CFTR-3849-114 + AGUCUUCUUGUUUAUAUAAC 20 3457 CFTR-3849-115 UAUUUUUUUCUGAAGAAAAG 20 3458 CFTR-3849-116 + UAUAUACAAUAUACCAUAUG 20 3459 CFTR-3849-117 + AAUUAUUUUUCAUUACCUUG 20 3460 CFTR-3849-118 + UGUUUAUCAAGAUAGAAAAU 20 3461 CFTR-3849-119 AAGUAGUUGAAUCAUUCAGU 20 3462 CFTR-3849-120 + AGAGGCAAUUUGUAAAUCUU 20 3463 CFTR-3849-121 + UUUUAGAGAACUCAGUUUUU 20 3464

Table 35A provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 35A 1st Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-122 + GUUUAUCAAGAUAGAAAA 18 3465 CFTR-3849-123 + GAUCCACAAGGUGAUUAUAA 20 3466 CFTR-3849-124 + GAAUAUGCUGCUUAUACCCA 20 3467 CFTR-3849-125 + GACACAUUUUUCAAAGGCA 19 3468 CFTR-3849-126 + GUUUUUAGGUUGGGAAAGA 19 3469 CFTR-3849-127 + GCUGUAAUUGCAUUGUACC 19 3470 CFTR-3849-128 + GCUAGCUGUAAUUGCAUUGUACC 23 3471 CFTR-3849-129 + GUGAUCUGUUGAAUAAGGC 19 3472 CFTR-3849-130 + GCACAUAAUAAUUAGUUUC 19 3473 CFTR-3849-90 + GGCACAUAAUAAUUAGUUUC 20 3433 CFTR-3849-131 + GCACCUCCUCCCUGAGAAUG 20 3474 CFTR-3849-132 + GAUUAAGUCCAGAUUUAUCAUG 22 3475 CFTR-3849-133 + GAUAUAUACAAUAUACCAUAUG 22 3476 CFTR-3849-134 + GUGAUAUAUACAAUAUACCAUAUG 24 3477 CFTR-3849-135 + GUUGAAAGUUAAACAGUG 18 3478 CFTR-3849-136 + GUGUUUGUGCUGAUAUGAU 19 3479 CFTR-3849-137 + GGUGUUUGUGCUGAUAUGAU 20 3480 CFTR-3849-138 GUCUUUCCCAACCUAAAAA 19 3481 CFTR-3849-139 GUUCAAUGAUAUAAGGAAAC 20 3482 CFTR-3849-140 GCAGUUCAAUGAUAUAAGGAAAC 23 3483 CFTR-3849-141 GUAAUGAAAAAUAAUUAC 18 3484 CFTR-3849-142 GGUAAUGAAAAAUAAUUAC 19 3485 CFTR-3849-143 GAAAUAAUUUAUAAGAAUAUC 21 3486 CFTR-3849-144 GAUAAACAUUGGUGUAAAGUAG 22 3487 CFTR-3849-145 GUUAUAUAAACAAGAAGACUUUG 23 3488 CFTR-3849-146 GAAAACACUGACUUAGAUU 19 3489 CFTR-3849-147 GUACUUUAAGGUCUAUACUU 20 3490 CFTR-3849-148 GAUAGUACUUUAAGGUCUAUACUU 24 3491 CFTR-3849-149 GAUUCAAUUAUAAUCACCUU 20 3492

Table 35B provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 35B 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-150 + UGUUUAUCAAGAUAGAAAA 19 3493 CFTR-3849-110 + AUGUUUAUCAAGAUAGAAAA 20 3453 CFTR-3849-151 + UCCACAAGGUGAUUAUAA 18 3494 CFTR-3849-152 + AUCCACAAGGUGAUUAUAA 19 3495 CFTR-3849-153 + AUAUGCUGCUUAUACCCA 18 3496 CFTR-3849-154 + AAUAUGCUGCUUAUACCCA 19 3497 CFTR-3849-155 + ACACAUUUUUCAAAGGCA 18 3498 CFTR-3849-51 + UGACACAUUUUUCAAAGGCA 20 3394 CFTR-3849-156 + CUGACACAUUUUUCAAAGGCA 21 3499 CFTR-3849-157 + UCUGACACAUUUUUCAAAGGCA 22 3500 CFTR-3849-158 + AUCUGACACAUUUUUCAAAGGCA 23 3501 CFTR-3849-159 + UAUCUGACACAUUUUUCAAAGGCA 24 3502 CFTR-3849-160 + UUUUUAGGUUGGGAAAGA 18 3503 CFTR-3849-161 + AGUUUUUAGGUUGGGAAAGA 20 3504 CFTR-3849-162 + CAGUUUUUAGGUUGGGAAAGA 21 3505 CFTR-3849-163 + UCAGUUUUUAGGUUGGGAAAGA 22 3506 CFTR-3849-164 + CUCAGUUUUUAGGUUGGGAAAGA 23 3507 CFTR-3849-165 + ACUCAGUUUUUAGGUUGGGAAAGA 24 3508 CFTR-3849-166 + CUGUAAUUGCAUUGUACC 18 3509 CFTR-3849-167 + AGCUGUAAUUGCAUUGUACC 20 3510 CFTR-3849-168 + UAGCUGUAAUUGCAUUGUACC 21 3511 CFTR-3849-169 + CUAGCUGUAAUUGCAUUGUACC 22 3512 CFTR-3849-170 + UGCUAGCUGUAAUUGCAUUGUACC 24 3513 CFTR-3849-171 + UGAUCUGUUGAAUAAGGC 18 3514 CFTR-3849-172 + AGUGAUCUGUUGAAUAAGGC 20 3515 CFTR-3849-173 + CAGUGAUCUGUUGAAUAAGGC 21 3516 CFTR-3849-174 + UCAGUGAUCUGUUGAAUAAGGC 22 3517 CFTR-3849-175 + CUCAGUGAUCUGUUGAAUAAGGC 23 3518 CFTR-3849-176 + UCUCAGUGAUCUGUUGAAUAAGGC 24 3519 CFTR-3849-177 + CACAUAAUAAUUAGUUUC 18 3520 CFTR-3849-178 + UGGCACAUAAUAAUUAGUUUC 21 3521 CFTR-3849-179 + CUGGCACAUAAUAAUUAGUUUC 22 3522 CFTR-3849-180 + ACUGGCACAUAAUAAUUAGUUUC 23 3523 CFTR-3849-181 + AACUGGCACAUAAUAAUUAGUUUC 24 3524 CFTR-3849-182 + ACCUCCUCCCUGAGAAUG 18 3525 CFTR-3849-183 + CACCUCCUCCCUGAGAAUG 19 3526 CFTR-3849-184 + UGCACCUCCUCCCUGAGAAUG 21 3527 CFTR-3849-185 + AUGCACCUCCUCCCUGAGAAUG 22 3528 CFTR-3849-186 + AAUGCACCUCCUCCCUGAGAAUG 23 3529 CFTR-3849-187 + CAAUGCACCUCCUCCCUGAGAAUG 24 3530 CFTR-3849-188 + AAGUCCAGAUUUAUCAUG 18 3531 CFTR-3849-189 + UAAGUCCAGAUUUAUCAUG 19 3532 CFTR-3849-190 + UUAAGUCCAGAUUUAUCAUG 20 3533 CFTR-3849-191 + AUUAAGUCCAGAUUUAUCAUG 21 3534 CFTR-3849-192 + UGAUUAAGUCCAGAUUUAUCAUG 23 3535 CFTR-3849-193 + UUGAUUAAGUCCAGAUUUAUCAUG 24 3536 CFTR-3849-194 + UAUACAAUAUACCAUAUG 18 3537 CFTR-3849-195 + AUAUACAAUAUACCAUAUG 19 3538 CFTR-3849-116 + UAUAUACAAUAUACCAUAUG 20 3459 CFTR-3849-196 + AUAUAUACAAUAUACCAUAUG 21 3539 CFTR-3849-197 + UGAUAUAUACAAUAUACCAUAUG 23 3540 CFTR-3849-198 + AGGCUUCUCAGUGAUCUG 18 3541 CFTR-3849-199 + CAGGCUUCUCAGUGAUCUG 19 3542 CFTR-3849-200 + CCAGGCUUCUCAGUGAUCUG 20 3543 CFTR-3849-201 + UCCAGGCUUCUCAGUGAUCUG 21 3544 CFTR-3849-202 + UUCCAGGCUUCUCAGUGAUCUG 22 3545 CFTR-3849-203 + UUUCCAGGCUUCUCAGUGAUCUG 23 3546 CFTR-3849-204 + UUUUCCAGGCUUCUCAGUGAUCUG 24 3547 CFTR-3849-205 + UGUUGAAAGUUAAACAGUG 19 3548 CFTR-3849-206 + AUGUUGAAAGUUAAACAGUG 20 3549 CFTR-3849-207 + UAUGUUGAAAGUUAAACAGUG 21 3550 CFTR-3849-208 + AUAUGUUGAAAGUUAAACAGUG 22 3551 CFTR-3849-209 + AAUAUGUUGAAAGUUAAACAGUG 23 3552 CFTR-3849-210 + UAAUAUGUUGAAAGUUAAACAGUG 24 3553 CFTR-3849-211 + UGUUUGUGCUGAUAUGAU 18 3554 CFTR-3849-212 + AGGUGUUUGUGCUGAUAUGAU 21 3555 CFTR-3849-213 + UAGGUGUUUGUGCUGAUAUGAU 22 3556 CFTR-3849-214 + UUAGGUGUUUGUGCUGAUAUGAU 23 3557 CFTR-3849-215 + UUUAGGUGUUUGUGCUGAUAUGAU 24 3558 CFTR-3849-216 + UCAAUGCACCUCCUCCCU 18 3559 CFTR-3849-217 + UUCAAUGCACCUCCUCCCU 19 3560 CFTR-3849-218 + CUUCAAUGCACCUCCUCCCU 20 3561 CFTR-3849-219 + ACUUCAAUGCACCUCCUCCCU 21 3562 CFTR-3849-220 + AACUUCAAUGCACCUCCUCCCU 22 3563 CFTR-3849-221 + UAACUUCAAUGCACCUCCUCCCU 23 3564 CFTR-3849-222 + AUAACUUCAAUGCACCUCCUCCCU 24 3565 CFTR-3849-223 + UUAAUGAAACAUAGUAUU 18 3566 CFTR-3849-224 + AUUAAUGAAACAUAGUAUU 19 3567 CFTR-3849-225 + UAUUAAUGAAACAUAGUAUU 20 3568 CFTR-3849-226 + UUAUUAAUGAAACAUAGUAUU 21 3569 CFTR-3849-227 + AUUAUUAAUGAAACAUAGUAUU 22 3570 CFTR-3849-228 + AAUUAUUAAUGAAACAUAGUAUU 23 3571 CFTR-3849-229 + UAAUUAUUAAUGAAACAUAGUAUU 24 3572 CFTR-3849-230 + CAUGAAUAGAACAUUUCCUUU 21 3573 CFTR-3849-231 + CCAUGAAUAGAACAUUUCCUUU 22 3574 CFTR-3849-232 + ACCAUGAAUAGAACAUUUCCUUU 23 3575 CFTR-3849-233 + UACCAUGAAUAGAACAUUUCCUUU 24 3576 CFTR-3849-234 UCUUUCCCAACCUAAAAA 18 3577 CFTR-3849-235 AGUCUUUCCCAACCUAAAAA 20 3578 CFTR-3849-236 CAGUCUUUCCCAACCUAAAAA 21 3579 CFTR-3849-237 CCAGUCUUUCCCAACCUAAAAA 22 3580 CFTR-3849-238 UCCAGUCUUUCCCAACCUAAAAA 23 3581 CFTR-3849-239 AUCCAGUCUUUCCCAACCUAAAAA 24 3582 CFTR-3849-240 AAGUAGUUGAAUCAUUCA 18 3583 CFTR-3849-241 AAAGUAGUUGAAUCAUUCA 19 3584 CFTR-3849-242 UAAAGUAGUUGAAUCAUUCA 20 3585 CFTR-3849-243 AUUGUAUAUAUCACAGUA 18 3586 CFTR-3849-244 UAUUGUAUAUAUCACAGUA 19 3587 CFTR-3849-245 AUAUUGUAUAUAUCACAGUA 20 3588 CFTR-3849-246 UCAAUGAUAUAAGGAAAC 18 3589 CFTR-3849-247 UUCAAUGAUAUAAGGAAAC 19 3590 CFTR-3849-248 AGUUCAAUGAUAUAAGGAAAC 21 3591 CFTR-3849-249 CAGUUCAAUGAUAUAAGGAAAC 22 3592 CFTR-3849-250 AGCAGUUCAAUGAUAUAAGGAAAC 24 3593 CFTR-3849-251 AGGUAAUGAAAAAUAAUUAC 20 3594 CFTR-3849-252 AGAAAUAAUUUAUAAGAAUAUC 22 3595 CFTR-3849-253 CAGAAAUAAUUUAUAAGAAUAUC 23 3596 CFTR-3849-254 UCAGAAAUAAUUUAUAAGAAUAUC 24 3597 CFTR-3849-255 AACAUUGGUGUAAAGUAG 18 3598 CFTR-3849-256 AAACAUUGGUGUAAAGUAG 19 3599 CFTR-3849-257 UAAACAUUGGUGUAAAGUAG 20 3600 CFTR-3849-258 AUAAACAUUGGUGUAAAGUAG 21 3601 CFTR-3849-259 UGAUAAACAUUGGUGUAAAGUAG 23 3602 CFTR-3849-260 UUGAUAAACAUUGGUGUAAAGUAG 24 3603 CFTR-3849-261 UGUUGCAGUAUUAAAAUG 18 3604 CFTR-3849-262 CUGUUGCAGUAUUAAAAUG 19 3605 CFTR-3849-263 UCUGUUGCAGUAUUAAAAUG 20 3606 CFTR-3849-264 AUCUGUUGCAGUAUUAAAAUG 21 3607 CFTR-3849-265 CAUCUGUUGCAGUAUUAAAAUG 22 3608 CFTR-3849-266 CCAUCUGUUGCAGUAUUAAAAUG 23 3609 CFTR-3849-267 UCCAUCUGUUGCAGUAUUAAAAUG 24 3610 CFTR-3849-268 AUAAACAAGAAGACUUUG 18 3611 CFTR-3849-269 UAUAAACAAGAAGACUUUG 19 3612 CFTR-3849-270 AUAUAAACAAGAAGACUUUG 20 3613 CFTR-3849-271 UAUAUAAACAAGAAGACUUUG 21 3614 CFTR-3849-272 UUAUAUAAACAAGAAGACUUUG 22 3615 CFTR-3849-273 AGUUAUAUAAACAAGAAGACUUUG 24 3616 CFTR-3849-274 AAAACACUGACUUAGAUU 18 3617 CFTR-3849-275 AGAAAACACUGACUUAGAUU 20 3618 CFTR-3849-276 UAGAAAACACUGACUUAGAUU 21 3619 CFTR-3849-277 UUAGAAAACACUGACUUAGAUU 22 3620 CFTR-3849-278 AUUAGAAAACACUGACUUAGAUU 23 3621 CFTR-3849-279 UAUUAGAAAACACUGACUUAGAUU 24 3622 CFTR-3849-280 ACUUUAAGGUCUAUACUU 18 3623 CFTR-3849-281 UACUUUAAGGUCUAUACUU 19 3624 CFTR-3849-282 AGUACUUUAAGGUCUAUACUU 21 3625 CFTR-3849-283 UAGUACUUUAAGGUCUAUACUU 22 3626 CFTR-3849-284 AUAGUACUUUAAGGUCUAUACUU 23 3627 CFTR-3849-285 UUCAAUUAUAAUCACCUU 18 3628 CFTR-3849-286 AUUCAAUUAUAAUCACCUU 19 3629 CFTR-3849-287 AGAUUCAAUUAUAAUCACCUU 21 3630 CFTR-3849-288 AAGAUUCAAUUAUAAUCACCUU 22 3631 CFTR-3849-289 AAAGAUUCAAUUAUAAUCACCUU 23 3632 CFTR-3849-290 AAAAGAUUCAAUUAUAAUCACCUU 24 3633

Table 35C provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 35C 3rd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-291 + AAUGUUUAUCAAGAUAGAAAA 21 3634 CFTR-3849-292 + CAAUGUUUAUCAAGAUAGAAAA 22 3635 CFTR-3849-293 + CCAAUGUUUAUCAAGAUAGAAAA 23 3636 CFTR-3849-294 + ACCAAUGUUUAUCAAGAUAGAAAA 24 3637 CFTR-3849-295 + AGAUCCACAAGGUGAUUAUAA 21 3638 CFTR-3849-296 + UAGAUCCACAAGGUGAUUAUAA 22 3639 CFTR-3849-297 + UUAGAUCCACAAGGUGAUUAUAA 23 3640 CFTR-3849-298 + UUUAGAUCCACAAGGUGAUUAUAA 24 3641 CFTR-3849-299 + AGAAUAUGCUGCUUAUACCCA 21 3642 CFTR-3849-300 + GAGAAUAUGCUGCUUAUACCCA 22 3643 CFTR-3849-301 + UGAGAAUAUGCUGCUUAUACCCA 23 3644 CFTR-3849-302 + UUGAGAAUAUGCUGCUUAUACCCA 24 3645 CFTR-3849-303 + GAAUAGAACAUUUCCUUU 18 3646 CFTR-3849-304 + UGAAUAGAACAUUUCCUUU 19 3647 CFTR-3849-305 + AUGAAUAGAACAUUUCCUUU 20 3648 CFTR-3849-306 GUAAAGUAGUUGAAUCAUUCA 21 3649 CFTR-3849-307 UGUAAAGUAGUUGAAUCAUUCA 22 3650 CFTR-3849-308 GUGUAAAGUAGUUGAAUCAUUCA 23 3651 CFTR-3849-309 GGUGUAAAGUAGUUGAAUCAUUCA 24 3652 CFTR-3849-310 UAUAUUGUAUAUAUCACAGUA 21 3653 CFTR-3849-311 GUAUAUUGUAUAUAUCACAGUA 22 3654 CFTR-3849-312 GGUAUAUUGUAUAUAUCACAGUA 23 3655 CFTR-3849-313 UGGUAUAUUGUAUAUAUCACAGUA 24 3656 CFTR-3849-314 AAGGUAAUGAAAAAUAAUUAC 21 3657 CFTR-3849-315 CAAGGUAAUGAAAAAUAAUUAC 22 3658 CFTR-3849-316 ACAAGGUAAUGAAAAAUAAUUAC 23 3659 CFTR-3849-317 CACAAGGUAAUGAAAAAUAAUUAC 24 3660 CFTR-3849-318 AUAAUUUAUAAGAAUAUC 18 3661 CFTR-3849-319 AAUAAUUUAUAAGAAUAUC 19 3662 CFTR-3849-320 AAAUAAUUUAUAAGAAUAUC 20 3663 CFTR-3849-321 AUUUCAGAAAUAAUUUAU 18 3664 CFTR-3849-322 AAUUUCAGAAAUAAUUUAU 19 3665 CFTR-3849-323 AAAUUUCAGAAAUAAUUUAU 20 3666 CFTR-3849-324 GAAAUUUCAGAAAUAAUUUAU 21 3667 CFTR-3849-325 AGAAAUUUCAGAAAUAAUUUAU 22 3668 CFTR-3849-326 CAGAAAUUUCAGAAAUAAUUUAU 23 3669 CFTR-3849-327 ACAGAAAUUUCAGAAAUAAUUUAU 24 3670

Table 35D provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+21kbC->T), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 35D 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-328 + UUUUCAAGAGACUACAAA 18 3671 CFTR-3849-329 + AUUUUCAAGAGACUACAAA 19 3672 CFTR-3849-47 + UAUUUUCAAGAGACUACAAA 20 3390 CFTR-3849-330 + GUAUUUUCAAGAGACUACAAA 21 3673 CFTR-3849-331 + UGUAUUUUCAAGAGACUACAAA 22 3674 CFTR-3849-332 + CUGUAUUUUCAAGAGACUACAAA 23 3675 CFTR-3849-333 + UCUGUAUUUUCAAGAGACUACAAA 24 3676 CFTR-3849-334 + UGUUUAUCAAGAUAGAAA 18 3677 CFTR-3849-335 + AUGUUUAUCAAGAUAGAAA 19 3678 CFTR-3849-336 + AAUGUUUAUCAAGAUAGAAA 20 3679 CFTR-3849-337 + CAAUGUUUAUCAAGAUAGAAA 21 3680 CFTR-3849-338 + CCAAUGUUUAUCAAGAUAGAAA 22 3681 CFTR-3849-339 + ACCAAUGUUUAUCAAGAUAGAAA 23 3682 CFTR-3849-340 + CACCAAUGUUUAUCAAGAUAGAAA 24 3683 CFTR-3849-341 + AUUUUCAAGAGACUACAA 18 3684 CFTR-3849-342 + UAUUUUCAAGAGACUACAA 19 3685 CFTR-3849-343 + GUAUUUUCAAGAGACUACAA 20 3686 CFTR-3849-344 + UGUAUUUUCAAGAGACUACAA 21 3687 CFTR-3849-345 + CUGUAUUUUCAAGAGACUACAA 22 3688 CFTR-3849-346 + UCUGUAUUUUCAAGAGACUACAA 23 3689 CFTR-3849-347 + UUCUGUAUUUUCAAGAGACUACAA 24 3690 CFTR-3849-348 + AUCAAGAUGACAAGUCAA 18 3691 CFTR-3849-349 + AAUCAAGAUGACAAGUCAA 19 3692 CFTR-3849-350 + AAAUCAAGAUGACAAGUCAA 20 3693 CFTR-3849-351 + GAAAUCAAGAUGACAAGUCAA 21 3694 CFTR-3849-352 + AGAAAUCAAGAUGACAAGUCAA 22 3695 CFTR-3849-353 + CAGAAAUCAAGAUGACAAGUCAA 23 3696 CFTR-3849-354 + CCAGAAAUCAAGAUGACAAGUCAA 24 3697 CFTR-3849-355 + AUUGCAUUGUACCAUGAA 18 3698 CFTR-3849-356 + AAUUGCAUUGUACCAUGAA 19 3699 CFTR-3849-357 + UAAUUGCAUUGUACCAUGAA 20 3700 CFTR-3849-358 + GUAAUUGCAUUGUACCAUGAA 21 3701 CFTR-3849-359 + UGUAAUUGCAUUGUACCAUGAA 22 3702 CFTR-3849-360 + CUGUAAUUGCAUUGUACCAUGAA 23 3703 CFTR-3849-361 + GCUGUAAUUGCAUUGUACCAUGAA 24 3704 CFTR-3849-362 + CAAAUAUCUAUUUAAUCA 18 3705 CFTR-3849-363 + UCAAAUAUCUAUUUAAUCA 19 3706 CFTR-3849-364 + AUCAAAUAUCUAUUUAAUCA 20 3707 CFTR-3849-365 + UAUCAAAUAUCUAUUUAAUCA 21 3708 CFTR-3849-366 + CUAUCAAAUAUCUAUUUAAUCA 22 3709 CFTR-3849-367 + ACUAUCAAAUAUCUAUUUAAUCA 23 3710 CFTR-3849-368 + UACUAUCAAAUAUCUAUUUAAUCA 24 3711 CFTR-3849-369 + UCUGGUUUCCUUAUAUCA 18 3712 CFTR-3849-370 + CUCUGGUUUCCUUAUAUCA 19 3713 CFTR-3849-371 + ACUCUGGUUUCCUUAUAUCA 20 3714 CFTR-3849-372 + UACUCUGGUUUCCUUAUAUCA 21 3715 CFTR-3849-373 + UUACUCUGGUUUCCUUAUAUCA 22 3716 CFTR-3849-374 + AUUACUCUGGUUUCCUUAUAUCA 23 3717 CFTR-3849-375 + UAUUACUCUGGUUUCCUUAUAUCA 24 3718 CFTR-3849-376 + CACCAAUGUUUAUCAAGA 18 3719 CFTR-3849-377 + ACACCAAUGUUUAUCAAGA 19 3720 CFTR-3849-378 + UACACCAAUGUUUAUCAAGA 20 3721 CFTR-3849-379 + UUACACCAAUGUUUAUCAAGA 21 3722 CFTR-3849-380 + UUUACACCAAUGUUUAUCAAGA 22 3723 CFTR-3849-381 + CUUUACACCAAUGUUUAUCAAGA 23 3724 CFTR-3849-382 + ACUUUACACCAAUGUUUAUCAAGA 24 3725 CFTR-3849-383 + UUUUAAUACUGCAACAGA 18 3726 CFTR-3849-384 + AUUUUAAUACUGCAACAGA 19 3727 CFTR-3849-53 + CAUUUUAAUACUGCAACAGA 20 3396 CFTR-3849-385 + CCAUUUUAAUACUGCAACAGA 21 3728 CFTR-3849-386 + ACCAUUUUAAUACUGCAACAGA 22 3729 CFTR-3849-387 + CACCAUUUUAAUACUGCAACAGA 23 3730 CFTR-3849-388 + UCACCAUUUUAAUACUGCAACAGA 24 3731 CFTR-3849-389 + UAUUAAUGAAACAUAGUA 18 3732 CFTR-3849-390 + UUAUUAAUGAAACAUAGUA 19 3733 CFTR-3849-391 + AUUAUUAAUGAAACAUAGUA 20 3734 CFTR-3849-392 + AAUUAUUAAUGAAACAUAGUA 21 3735 CFTR-3849-393 + UAAUUAUUAAUGAAACAUAGUA 22 3736 CFTR-3849-394 + UUAAUUAUUAAUGAAACAUAGUA 23 3737 CFTR-3849-395 + AUUAAUUAUUAAUGAAACAUAGUA 24 3738 CFTR-3849-396 + UAUCUCUAUUAAUUAUUA 18 3739 CFTR-3849-397 + AUAUCUCUAUUAAUUAUUA 19 3740 CFTR-3849-398 + UAUAUCUCUAUUAAUUAUUA 20 3741 CFTR-3849-399 + AUAUAUCUCUAUUAAUUAUUA 21 3742 CFTR-3849-400 + CAUAUAUCUCUAUUAAUUAUUA 22 3743 CFTR-3849-401 + UCAUAUAUCUCUAUUAAUUAUUA 23 3744 CFTR-3849-402 + UUCAUAUAUCUCUAUUAAUUAUUA 24 3745 CFTR-3849-403 + AAAAUACUAAAAUUUUUA 18 3746 CFTR-3849-404 + AAAAAUACUAAAAUUUUUA 19 3747 CFTR-3849-405 + AAAAAAUACUAAAAUUUUUA 20 3748 CFTR-3849-406 + AAAAAAAUACUAAAAUUUUUA 21 3749 CFTR-3849-407 + GAAAAAAAUACUAAAAUUUUUA 22 3750 CFTR-3849-408 + AGAAAAAAAUACUAAAAUUUUUA 23 3751 CFTR-3849-409 + CAGAAAAAAAUACUAAAAUUUUUA 24 3752 CFTR-3849-410 + CUUCAAUGCACCUCCUCC 18 3753 CFTR-3849-411 + ACUUCAAUGCACCUCCUCC 19 3754 CFTR-3849-412 + AACUUCAAUGCACCUCCUCC 20 3755 CFTR-3849-413 + UAACUUCAAUGCACCUCCUCC 21 3756 CFTR-3849-414 + AUAACUUCAAUGCACCUCCUCC 22 3757 CFTR-3849-415 + AAUAACUUCAAUGCACCUCCUCC 23 3758 CFTR-3849-416 + UAAUAACUUCAAUGCACCUCCUCC 24 3759 CFTR-3849-417 + GACACAUUUUUCAAAGGC 18 3760 CFTR-3849-418 + UGACACAUUUUUCAAAGGC 19 3761 CFTR-3849-419 + CUGACACAUUUUUCAAAGGC 20 3762 CFTR-3849-420 + UCUGACACAUUUUUCAAAGGC 21 3763 CFTR-3849-421 + AUCUGACACAUUUUUCAAAGGC 22 3764 CFTR-3849-422 + UAUCUGACACAUUUUUCAAAGGC 23 3765 CFTR-3849-423 + AUAUCUGACACAUUUUUCAAAGGC 24 3766 CFTR-3849-424 + AUUAAGUCCAGAUUUAUC 18 3767 CFTR-3849-425 + GAUUAAGUCCAGAUUUAUC 19 3768 CFTR-3849-426 + UGAUUAAGUCCAGAUUUAUC 20 3769 CFTR-3849-427 + UUGAUUAAGUCCAGAUUUAUC 21 3770 CFTR-3849-428 + UUUGAUUAAGUCCAGAUUUAUC 22 3771 CFTR-3849-429 + UUUUGAUUAAGUCCAGAUUUAUC 23 3772 CFTR-3849-430 + AUUUUGAUUAAGUCCAGAUUUAUC 24 3773 CFTR-3849-431 + UCAUUACCUUGUGGUCUC 18 3774 CFTR-3849-432 + UUCAUUACCUUGUGGUCUC 19 3775 CFTR-3849-433 + UUUCAUUACCUUGUGGUCUC 20 3776 CFTR-3849-434 + UUUUCAUUACCUUGUGGUCUC 21 3777 CFTR-3849-435 + UUUUUCAUUACCUUGUGGUCUC 22 3778 CFTR-3849-436 + AUUUUUCAUUACCUUGUGGUCUC 23 3779 CFTR-3849-437 + UAUUUUUCAUUACCUUGUGGUCUC 24 3780 CFTR-3849-438 + UGAAAUUUCUGUAUUUUC 18 3781 CFTR-3849-439 + CUGAAAUUUCUGUAUUUUC 19 3782 CFTR-3849-440 + UCUGAAAUUUCUGUAUUUUC 20 3783 CFTR-3849-441 + UUCUGAAAUUUCUGUAUUUUC 21 3784 CFTR-3849-442 + UUUCUGAAAUUUCUGUAUUUUC 22 3785 CFTR-3849-443 + AUUUCUGAAAUUUCUGUAUUUUC 23 3786 CFTR-3849-444 + UAUUUCUGAAAUUUCUGUAUUUUC 24 3787 CFTR-3849-445 + AUUUUAAUACUGCAACAG 18 3788 CFTR-3849-446 + CAUUUUAAUACUGCAACAG 19 3789 CFTR-3849-447 + CCAUUUUAAUACUGCAACAG 20 3790 CFTR-3849-448 + ACCAUUUUAAUACUGCAACAG 21 3791 CFTR-3849-449 + CACCAUUUUAAUACUGCAACAG 22 3792 CFTR-3849-450 + UCACCAUUUUAAUACUGCAACAG 23 3793 CFTR-3849-451 + CUCACCAUUUUAAUACUGCAACAG 24 3794 CFTR-3849-452 + GAGAACUCAGUUUUUAGG 18 3795 CFTR-3849-453 + AGAGAACUCAGUUUUUAGG 19 3796 CFTR-3849-454 + UAGAGAACUCAGUUUUUAGG 20 3797 CFTR-3849-455 + UUAGAGAACUCAGUUUUUAGG 21 3798 CFTR-3849-456 + UUUAGAGAACUCAGUUUUUAGG 22 3799 CFTR-3849-457 + UUUUAGAGAACUCAGUUUUUAGG 23 3800 CFTR-3849-458 + UUUUUAGAGAACUCAGUUUUUAGG 24 3801 CFTR-3849-459 + UAGGUUGGGAAAGACUGG 18 3802 CFTR-3849-460 + UUAGGUUGGGAAAGACUGG 19 3803 CFTR-3849-461 + UUUAGGUUGGGAAAGACUGG 20 3804 CFTR-3849-462 + UUUUAGGUUGGGAAAGACUGG 21 3805 CFTR-3849-463 + UUUUUAGGUUGGGAAAGACUGG 22 3806 CFTR-3849-464 + GUUUUUAGGUUGGGAAAGACUGG 23 3807 CFTR-3849-465 + AGUUUUUAGGUUGGGAAAGACUGG 24 3808 CFTR-3849-466 + UUCAAGAGACUACAAAUG 18 3809 CFTR-3849-467 + UUUCAAGAGACUACAAAUG 19 3810 CFTR-3849-468 + UUUUCAAGAGACUACAAAUG 20 3811 CFTR-3849-469 + AUUUUCAAGAGACUACAAAUG 21 3812 CFTR-3849-470 + UAUUUUCAAGAGACUACAAAUG 22 3813 CFTR-3849-471 + GUAUUUUCAAGAGACUACAAAUG 23 3814 CFTR-3849-472 + UGUAUUUUCAAGAGACUACAAAUG 24 3815 CFTR-3849-473 + GUUGGGAAAGACUGGAUG 18 3816 CFTR-3849-474 + GGUUGGGAAAGACUGGAUG 19 3817 CFTR-3849-475 + AGGUUGGGAAAGACUGGAUG 20 3818 CFTR-3849-476 + UAGGUUGGGAAAGACUGGAUG 21 3819 CFTR-3849-477 + UUAGGUUGGGAAAGACUGGAUG 22 3820 CFTR-3849-478 + UUUAGGUUGGGAAAGACUGGAUG 23 3821 CFTR-3849-479 + UUUUAGGUUGGGAAAGACUGGAUG 24 3822 CFTR-3849-480 + AUAAAUCAAAAUAAUAUG 18 3823 CFTR-3849-481 + GAUAAAUCAAAAUAAUAUG 19 3824 CFTR-3849-482 + AGAUAAAUCAAAAUAAUAUG 20 3825 CFTR-3849-483 + AAGAUAAAUCAAAAUAAUAUG 21 3826 CFTR-3849-484 + CAAGAUAAAUCAAAAUAAUAUG 22 3827 CFTR-3849-485 + UCAAGAUAAAUCAAAAUAAUAUG 23 3828 CFTR-3849-486 + AUCAAGAUAAAUCAAAAUAAUAUG 24 3829 CFTR-3849-487 + AUCAAAUAUCUAUUUAAU 18 3830 CFTR-3849-488 + UAUCAAAUAUCUAUUUAAU 19 3831 CFTR-3849-489 + CUAUCAAAUAUCUAUUUAAU 20 3832 CFTR-3849-490 + ACUAUCAAAUAUCUAUUUAAU 21 3833 CFTR-3849-491 + UACUAUCAAAUAUCUAUUUAAU 22 3834 CFTR-3849-492 + GUACUAUCAAAUAUCUAUUUAAU 23 3835 CFTR-3849-493 + AGUACUAUCAAAUAUCUAUUUAAU 24 3836 CFTR-3849-494 + AUAUAUACAAUAUACCAU 18 3837 CFTR-3849-495 + GAUAUAUACAAUAUACCAU 19 3838 CFTR-3849-496 + UGAUAUAUACAAUAUACCAU 20 3839 CFTR-3849-497 + GUGAUAUAUACAAUAUACCAU 21 3840 CFTR-3849-498 + UGUGAUAUAUACAAUAUACCAU 22 3841 CFTR-3849-499 + CUGUGAUAUAUACAAUAUACCAU 23 3842 CFTR-3849-500 + ACUGUGAUAUAUACAAUAUACCAU 24 3843 CFTR-3849-501 + AUAUACAAUAUACCAUAU 18 3844 CFTR-3849-502 + UAUAUACAAUAUACCAUAU 19 3845 CFTR-3849-503 + AUAUAUACAAUAUACCAUAU 20 3846 CFTR-3849-504 + GAUAUAUACAAUAUACCAUAU 21 3847 CFTR-3849-505 + UGAUAUAUACAAUAUACCAUAU 22 3848 CFTR-3849-506 + GUGAUAUAUACAAUAUACCAUAU 23 3849 CFTR-3849-507 + UGUGAUAUAUACAAUAUACCAUAU 24 3850 CFTR-3849-508 + AGAACUCAGUUUUUAGGU 18 3851 CFTR-3849-509 + GAGAACUCAGUUUUUAGGU 19 3852 CFTR-3849-78 + AGAGAACUCAGUUUUUAGGU 20 3421 CFTR-3849-510 + UAGAGAACUCAGUUUUUAGGU 21 3853 CFTR-3849-511 + UUAGAGAACUCAGUUUUUAGGU 22 3854 CFTR-3849-512 + UUUAGAGAACUCAGUUUUUAGGU 23 3855 CFTR-3849-513 + UUUUAGAGAACUCAGUUUUUAGGU 24 3856 CFTR-3849-514 + GAACUCAGUUUUUAGGUU 18 3857 CFTR-3849-515 + AGAACUCAGUUUUUAGGUU 19 3858 CFTR-3849-9 + GAGAACUCAGUUUUUAGGUU 20 3352 CFTR-3849-516 + AGAGAACUCAGUUUUUAGGUU 21 3859 CFTR-3849-517 + UAGAGAACUCAGUUUUUAGGUU 22 3860 CFTR-3849-518 + UUAGAGAACUCAGUUUUUAGGUU 23 3861 CFTR-3849-519 + UUUAGAGAACUCAGUUUUUAGGUU 24 3862 CFTR-3849-520 + UAUUCUUAUAAAUUAUUU 18 3863 CFTR-3849-521 + AUAUUCUUAUAAAUUAUUU 19 3864 CFTR-3849-522 + GAUAUUCUUAUAAAUUAUUU 20 3865 CFTR-3849-523 + UGAUAUUCUUAUAAAUUAUUU 21 3866 CFTR-3849-524 + UUGAUAUUCUUAUAAAUUAUUU 22 3867 CFTR-3849-525 + CUUGAUAUUCUUAUAAAUUAUUU 23 3868 CFTR-3849-526 + CCUUGAUAUUCUUAUAAAUUAUUU 24 3869 CFTR-3849-527 + GCACAUAAUAAUUAGUUU 18 3870 CFTR-3849-528 + GGCACAUAAUAAUUAGUUU 19 3871 CFTR-3849-529 + UGGCACAUAAUAAUUAGUUU 20 3872 CFTR-3849-530 + CUGGCACAUAAUAAUUAGUUU 21 3873 CFTR-3849-531 + ACUGGCACAUAAUAAUUAGUUU 22 3874 CFTR-3849-532 + AACUGGCACAUAAUAAUUAGUUU 23 3875 CFTR-3849-533 + UAACUGGCACAUAAUAAUUAGUUU 24 3876 CFTR-3849-534 + AAAAAAUACUAAAAUUUU 18 3877 CFTR-3849-535 + AAAAAAAUACUAAAAUUUU 19 3878 CFTR-3849-536 + GAAAAAAAUACUAAAAUUUU 20 3879 CFTR-3849-537 + AGAAAAAAAUACUAAAAUUUU 21 3880 CFTR-3849-538 + CAGAAAAAAAUACUAAAAUUUU 22 3881 CFTR-3849-539 + UCAGAAAAAAAUACUAAAAUUUU 23 3882 CFTR-3849-540 + UUCAGAAAAAAAUACUAAAAUUUU 24 3883 CFTR-3849-541 AUUUUUUUCUGAAGAAAA 18 3884 CFTR-3849-542 UAUUUUUUUCUGAAGAAAA 19 3885 CFTR-3849-87 GUAUUUUUUUCUGAAGAAAA 20 3430 CFTR-3849-543 AGUAUUUUUUUCUGAAGAAAA 21 3886 CFTR-3849-544 UAGUAUUUUUUUCUGAAGAAAA 22 3887 CFTR-3849-545 UUAGUAUUUUUUUCUGAAGAAAA 23 3888 CFTR-3849-546 UUUAGUAUUUUUUUCUGAAGAAAA 24 3889 CFTR-3849-547 UAUUUUUUUCUGAAGAAA 18 3890 CFTR-3849-548 GUAUUUUUUUCUGAAGAAA 19 3891 CFTR-3849-111 AGUAUUUUUUUCUGAAGAAA 20 3454 CFTR-3849-549 UAGUAUUUUUUUCUGAAGAAA 21 3892 CFTR-3849-550 UUAGUAUUUUUUUCUGAAGAAA 22 3893 CFTR-3849-551 UUUAGUAUUUUUUUCUGAAGAAA 23 3849 CFTR-3849-552 UUUUAGUAUUUUUUUCUGAAGAAA 24 3895 CFTR-3849-553 GUAUUUUUUUCUGAAGAA 18 3896 CFTR-3849-554 AGUAUUUUUUUCUGAAGAA 19 3897 CFTR-3849-555 UAGUAUUUUUUUCUGAAGAA 20 3898 CFTR-3849-556 UUAGUAUUUUUUUCUGAAGAA 21 3899 CFTR-3849-557 UUUAGUAUUUUUUUCUGAAGAA 22 3900 CFTR-3849-558 UUUUAGUAUUUUUUUCUGAAGAA 23 3901 CFTR-3849-559 AUUUUAGUAUUUUUUUCUGAAGAA 24 3902 CFTR-3849-560 UGAGUAAGACACCCUGAA 18 3903 CFTR-3849-561 GUGAGUAAGACACCCUGAA 19 3904 CFTR-3849-88 GGUGAGUAAGACACCCUGAA 20 3431 CFTR-3849-562 UGGUGAGUAAGACACCCUGAA 21 3905 CFTR-3849-563 AUGGUGAGUAAGACACCCUGAA 22 3906 CFTR-3849-564 AAUGGUGAGUAAGACACCCUGAA 23 3907 CFTR-3849-565 AAAUGGUGAGUAAGACACCCUGAA 24 3908 CFTR-3849-566 UGUUUCAUUAAUAAUUAA 18 3909 CFTR-3849-567 AUGUUUCAUUAAUAAUUAA 19 3910 CFTR-3849-568 UAUGUUUCAUUAAUAAUUAA 20 3911 CFTR-3849-569 CUAUGUUUCAUUAAUAAUUAA 21 3912 CFTR-3849-570 ACUAUGUUUCAUUAAUAAUUAA 22 3913 CFTR-3849-571 UACUAUGUUUCAUUAAUAAUUAA 23 3914 CFTR-3849-572 AUACUAUGUUUCAUUAAUAAUUAA 24 3915 CFTR-3849-573 UCUCAGGGAGGAGGUGCA 18 3916 CFTR-3849-574 UUCUCAGGGAGGAGGUGCA 19 3917 CFTR-3849-575 AUUCUCAGGGAGGAGGUGCA 20 3918 CFTR-3849-576 CAUUCUCAGGGAGGAGGUGCA 21 3919 CFTR-3849-577 ACAUUCUCAGGGAGGAGGUGCA 22 3920 CFTR-3849-578 AACAUUCUCAGGGAGGAGGUGCA 23 3921 CFTR-3849-579 CAACAUUCUCAGGGAGGAGGUGCA 24 3922 CFTR-3849-580 GCCUUAUUCAACAGAUCA 18 3923 CFTR-3849-581 AGCCUUAUUCAACAGAUCA 19 3924 CFTR-3849-582 UAGCCUUAUUCAACAGAUCA 20 3925 CFTR-3849-583 CUAGCCUUAUUCAACAGAUCA 21 3926 CFTR-3849-584 UCUAGCCUUAUUCAACAGAUCA 22 3927 CFTR-3849-585 CUCUAGCCUUAUUCAACAGAUCA 23 3928 CFTR-3849-586 ACUCUAGCCUUAUUCAACAGAUCA 24 3929 CFTR-3849-587 CUUGAUCCAACAUUCUCA 18 3930 CFTR-3849-588 UCUUGAUCCAACAUUCUCA 19 3931 CFTR-3849-52 AUCUUGAUCCAACAUUCUCA 20 3395 CFTR-3849-589 UAUCUUGAUCCAACAUUCUCA 21 3932 CFTR-3849-590 UUAUCUUGAUCCAACAUUCUCA 22 3933 CFTR-3849-591 UUUAUCUUGAUCCAACAUUCUCA 23 3934 CFTR-3849-592 AUUUAUCUUGAUCCAACAUUCUCA 24 3935 CFTR-3849-593 GUGAGUAAGACACCCUGA 18 3936 CFTR-3849-594 GGUGAGUAAGACACCCUGA 19 3937 CFTR-3849-595 UGGUGAGUAAGACACCCUGA 20 3938 CFTR-3849-596 AUGGUGAGUAAGACACCCUGA 21 3939 CFTR-3849-597 AAUGGUGAGUAAGACACCCUGA 22 3940 CFTR-3849-598 AAAUGGUGAGUAAGACACCCUGA 23 3941 CFTR-3849-599 AAAAUGGUGAGUAAGACACCCUGA 24 3942 CFTR-3849-600 UGUAGUCUCUUGAAAAUA 18 3943 CFTR-3849-601 UUGUAGUCUCUUGAAAAUA 19 3944 CFTR-3849-602 UUUGUAGUCUCUUGAAAAUA 20 3945 CFTR-3849-603 AUUUGUAGUCUCUUGAAAAUA 21 3946 CFTR-3849-604 CAUUUGUAGUCUCUUGAAAAUA 22 3947 CFTR-3849-605 CCAUUUGUAGUCUCUUGAAAAUA 23 3948 CFTR-3849-606 UCCAUUUGUAGUCUCUUGAAAAUA 24 3949 CFTR-3849-607 CAGCAGUUCAAUGAUAUA 18 3950 CFTR-3849-608 CCAGCAGUUCAAUGAUAUA 19 3951 CFTR-3849-56 ACCAGCAGUUCAAUGAUAUA 20 3399 CFTR-3849-609 UACCAGCAGUUCAAUGAUAUA 21 3952 CFTR-3849-610 UUACCAGCAGUUCAAUGAUAUA 22 3953 CFTR-3849-611 AUUACCAGCAGUUCAAUGAUAUA 23 3954 CFTR-3849-612 CAUUACCAGCAGUUCAAUGAUAUA 24 3955 CFTR-3849-613 UCUGGAGACCACAAGGUA 18 3956 CFTR-3849-614 UUCUGGAGACCACAAGGUA 19 3957 CFTR-3849-615 UUUCUGGAGACCACAAGGUA 20 3958 CFTR-3849-616 AUUUCUGGAGACCACAAGGUA 21 3959 CFTR-3849-617 GAUUUCUGGAGACCACAAGGUA 22 3960 CFTR-3849-618 UGAUUUCUGGAGACCACAAGGUA 23 3961 CFTR-3849-619 UUGAUUUCUGGAGACCACAAGGUA 24 3962 CFTR-3849-620 UGUGCCAGUUAUAUAAAC 18 3963 CFTR-3849-621 AUGUGCCAGUUAUAUAAAC 19 3964 CFTR-3849-622 UAUGUGCCAGUUAUAUAAAC 20 3965 CFTR-3849-623 UUAUGUGCCAGUUAUAUAAAC 21 3966 CFTR-3849-624 AUUAUGUGCCAGUUAUAUAAAC 22 3967 CFTR-3849-625 UAUUAUGUGCCAGUUAUAUAAAC 23 3968 CFTR-3849-626 UUAUUAUGUGCCAGUUAUAUAAAC 24 3969 CFTR-3849-627 AAUGGUGAGUAAGACACC 18 3970 CFTR-3849-628 AAAUGGUGAGUAAGACACC 19 3971 CFTR-3849-629 AAAAUGGUGAGUAAGACACC 20 3972 CFTR-3849-630 UAAAAUGGUGAGUAAGACACC 21 3973 CFTR-3849-631 UUAAAAUGGUGAGUAAGACACC 22 3974 CFTR-3849-632 AUUAAAAUGGUGAGUAAGACACC 23 3975 CFTR-3849-633 UAUUAAAAUGGUGAGUAAGACACC 24 3976 CFTR-3849-634 ACAGAUCACUGAGAAGCC 18 3977 CFTR-3849-635 AACAGAUCACUGAGAAGCC 19 3978 CFTR-3849-61 CAACAGAUCACUGAGAAGCC 20 3404 CFTR-3849-636 UCAACAGAUCACUGAGAAGCC 21 3979 CFTR-3849-637 UUCAACAGAUCACUGAGAAGCC 22 3980 CFTR-3849-638 AU UCAACAGAUCACUGAGAAGCC 23 3981 CFTR-3849-639 UAUUCAACAGAUCACUGAGAAGCC 24 3982 CFTR-3849-640 GCCUGGAAAAACAAAUCC 18 3983 CFTR-3849-641 AGCCUGGAAAAACAAAUCC 19 3984 CFTR-3849-62 AAGCCUGGAAAAACAAAUCC 20 3405 CFTR-3849-642 GAAGCCUGGAAAAACAAAUCC 21 3985 CFTR-3849-643 AGAAGCCUGGAAAAACAAAUCC 22 3986 CFTR-3849-644 GAGAAGCCUGGAAAAACAAAUCC 23 3987 CFTR-3849-645 UGAGAAGCCUGGAAAAACAAAUCC 24 3988 CFTR-3849-646 AACAGAUCACUGAGAAGC 18 3989 CFTR-3849-647 CAACAGAUCACUGAGAAGC 19 3990 CFTR-3849-648 UCAACAGAUCACUGAGAAGC 20 3991 CFTR-3849-649 UUCAACAGAUCACUGAGAAGC 21 3992 CFTR-3849-650 AUUCAACAGAUCACUGAGAAGC 22 3993 CFTR-3849-651 UAUUCAACAGAUCACUGAGAAGC 23 3994 CFTR-3849-652 UUAUUCAACAGAUCACUGAGAAGC 24 3995 CFTR-3849-653 UCUUAAAAGCUUAUUUGC 18 3996 CFTR-3849-654 GUCUUAAAAGCUUAUUUGC 19 3997 CFTR-3849-65 UGUCUUAAAAGCUUAUUUGC 20 3408 CFTR-3849-655 AUGUCUUAAAAGCUUAUUUGC 21 3998 CFTR-3849-656 UAUGUCUUAAAAGCUUAUUUGC 22 3999 CFTR-3849-657 GUAUGUCUUAAAAGCUUAUUUGC 23 4000 CFTR-3849-658 GGUAUGUCUUAAAAGCUUAUUUGC 24 4001 CFTR-3849-659 AGCCUGGAAAAACAAAUC 18 4002 CFTR-3849-660 AAGCCUGGAAAAACAAAUC 19 4003 CFTR-3849-661 GAAGCCUGGAAAAACAAAUC 20 4004 CFTR-3849-662 AGAAGCCUGGAAAAACAAAUC 21 4005 CFTR-3849-663 GAGAAGCCUGGAAAAACAAAUC 22 4006 CFTR-3849-664 UGAGAAGCCUGGAAAAACAAAUC 23 4007 CFTR-3849-665 CUGAGAAGCCUGGAAAAACAAAUC 24 4008 CFTR-3849-666 UUCUCCAUUUGUAGUCUC 18 4009 CFTR-3849-667 UUUCUCCAUUUGUAGUCUC 19 4010 CFTR-3849-668 CUUUCUCCAUUUGUAGUCUC 20 4011 CFTR-3849-669 GCUUUCUCCAUUUGUAGUCUC 21 4012 CFTR-3849-670 UGCUUUCUCCAUUUGUAGUCUC 22 4013 CFTR-3849-671 CUGCUUUCUCCAUUUGUAGUCUC 23 4014 CFTR-3849-672 ACUGCUUUCUCCAUUUGUAGUCUC 24 4015 CFTR-3849-673 UCUUGAUCCAACAUUCUC 18 4016 CFTR-3849-674 AUCUUGAUCCAACAUUCUC 19 4017 CFTR-3849-67 UAUCUUGAUCCAACAUUCUC 20 3410 CFTR-3849-675 UUAUCUUGAUCCAACAUUCUC 21 4018 CFTR-3849-676 UUUAUCUUGAUCCAACAUUCUC 22 4019 CFTR-3849-677 AUUUAUCUUGAUCCAACAUUCUC 23 4020 CFTR-3849-678 GAUUUAUCUUGAUCCAACAUUCUC 24 4021 CFTR-3849-679 ACUUGUCAUCUUGAUUUC 18 4022 CFTR-3849-680 GACUUGUCAUCUUGAUUUC 19 4023 CFTR-3849-68 UGACUUGUCAUCUUGAUUUC 20 3411 CFTR-3849-681 UUGACUUGUCAUCUUGAUUUC 21 4024 CFTR-3849-682 GUUGACUUGUCAUCUUGAUUUC 22 4025 CFTR-3849-683 AGUUGACUUGUCAUCUUGAUUUC 23 4026 CFTR-3849-684 CAGUUGACUUGUCAUCUUGAUUUC 24 4027 CFTR-3849-685 UUUUUUUCUGAAGAAAAG 18 4028 CFTR-3849-686 AUUUUUUUCUGAAGAAAAG 19 4029 CFTR-3849-115 UAUUUUUUUCUGAAGAAAAG 20 3458 CFTR-3849-687 GUAUUUUUUUCUGAAGAAAAG 21 4030 CFTR-3849-688 AGUAUUUUUUUCUGAAGAAAAG 22 4031 CFTR-3849-689 UAGUAUUUUUUUCUGAAGAAAAG 23 4032 CFTR-3849-690 UUAGUAUUUUUUUCUGAAGAAAAG 24 4033 CFTR-3849-691 UGAUCCAACAUUCUCAGG 18 4034 CFTR-3849-692 UUGAUCCAACAUUCUCAGG 19 4035 CFTR-3849-693 CUUGAUCCAACAUUCUCAGG 20 4036 CFTR-3849-694 UCUUGAUCCAACAUUCUCAGG 21 4037 CFTR-3849-695 AUCUUGAUCCAACAUUCUCAGG 22 4038 CFTR-3849-696 UAUCUUGAUCCAACAUUCUCAGG 23 4039 CFTR-3849-697 UUAUCUUGAUCCAACAUUCUCAGG 24 4040 CFTR-3849-698 GAUCCAACAUUCUCAGGG 18 4041 CFTR-3849-699 UGAUCCAACAUUCUCAGGG 19 4042 CFTR-3849-74 UUGAUCCAACAUUCUCAGGG 20 3417 CFTR-3849-700 CUUGAUCCAACAUUCUCAGGG 21 4043 CFTR-3849-701 UCUUGAUCCAACAUUCUCAGGG 22 4044 CFTR-3849-702 AUCUUGAUCCAACAUUCUCAGGG 23 4045 CFTR-3849-703 UAUCUUGAUCCAACAUUCUCAGGG 24 4046 CFTR-3849-704 UAAGGUCUAUACUUUUGG 18 4047 CFTR-3849-705 UUAAGGUCUAUACUUUUGG 19 4048 CFTR-3849-706 UUUAAGGUCUAUACUUUUGG 20 4049 CFTR-3849-707 CUUUAAGGUCUAUACUUUUGG 21 4050 CFTR-3849-708 ACUUUAAGGUCUAUACUUUUGG 22 4051 CFTR-3849-709 UACUUUAAGGUCUAUACUUUUGG 23 4052 CFTR-3849-710 GUACUUUAAGGUCUAUACUUUUGG 24 4053 CFTR-3849-711 UUUUAGUAUUUUUUUCUG 18 4054 CFTR-3849-712 AUUUUAGUAUUUUUUUCUG 19 4055 CFTR-3849-713 AAUUUUAGUAUUUUUUUCUG 20 4056 CFTR-3849-714 AAAUUUUAGUAUUUUUUUCUG 21 4057 CFTR-3849-715 AAAAUUUUAGUAUUUUUUUCUG 22 4058 CFTR-3849-716 AAAAAUUUUAGUAUUUUUUUCUG 23 4059 CFTR-3849-717 UAAAAAUUUUAGUAUUUUUUUCUG 24 4060 CFTR-3849-718 GUCUUAAAAGCUUAUUUG 18 4061 CFTR-3849-719 UGUCUUAAAAGCUUAUUUG 19 4062 CFTR-3849-76 AUGUCUUAAAAGCUUAUUUG 20 3419 CFTR-3849-720 UAUGUCUUAAAAGCUUAUUUG 21 4063 CFTR-3849-721 GUAUGUCUUAAAAGCUUAUUUG 22 4064 CFTR-3849-722 GGUAUGUCUUAAAAGCUUAUUUG 23 4065 CFTR-3849-723 GGGUAUGUCUUAAAAGCUUAUUUG 24 4066 CFTR-3849-724 AAUAAUUAAUAGAGAUAU 18 4067 CFTR-3849-725 UAAUAAUUAAUAGAGAUAU 19 4068 CFTR-3849-726 UUAAUAAUUAAUAGAGAUAU 20 4069 CFTR-3849-727 AUUAAUAAUUAAUAGAGAUAU 21 4070 CFTR-3849-728 CAUUAAUAAUUAAUAGAGAUAU 22 4071 CFTR-3849-729 UCAUUAAUAAUUAAUAGAGAUAU 23 4072 CFTR-3849-730 UUCAUUAAUAAUUAAUAGAGAUAU 24 4073 CFTR-3849-731 CCAGCAGUUCAAUGAUAU 18 4074 CFTR-3849-732 ACCAGCAGUUCAAUGAUAU 19 4075 CFTR-3849-733 UACCAGCAGUUCAAUGAUAU 20 4076 CFTR-3849-734 UUACCAGCAGUUCAAUGAUAU 21 4077 CFTR-3849-735 AUUACCAGCAGUUCAAUGAUAU 22 4078 CFTR-3849-736 CAUUACCAGCAGUUCAAUGAUAU 23 4079 CFTR-3849-737 GCAUUACCAGCAGUUCAAUGAUAU 24 4080 CFTR-3849-738 GAGGUGCAUUGAAGUUAU 18 4081 CFTR-3849-739 GGAGGUGCAUUGAAGUUAU 19 4082 CFTR-3849-740 AGGAGGUGCAUUGAAGUUAU 20 4083 CFTR-3849-741 GAGGAGGUGCAUUGAAGUUAU 21 4084 CFTR-3849-742 GGAGGAGGUGCAUUGAAGUUAU 22 4085 CFTR-3849-743 GGGAGGAGGUGCAUUGAAGUUAU 23 4086 CFTR-3849-744 AGGGAGGAGGUGCAUUGAAGUUAU 24 4087 CFTR-3849-745 CUUAUUCAACAGAUCACU 18 4088 CFTR-3849-746 CCUUAUUCAACAGAUCACU 19 4089 CFTR-3849-747 GCCUUAUUCAACAGAUCACU 20 4090 CFTR-3849-748 AGCCUUAUUCAACAGAUCACU 21 4091 CFTR-3849-749 UAGCCUUAUUCAACAGAUCACU 22 4092 CFTR-3849-750 CUAGCCUUAUUCAACAGAUCACU 23 4093 CFTR-3849-751 UCUAGCCUUAUUCAACAGAUCACU 24 4094 CFTR-3849-752 ACCAGUGAUUCCUUGCCU 18 4095 CFTR-3849-753 AACCAGUGAUUCCUUGCCU 19 4096 CFTR-3849-754 AAACCAGUGAUUCCUUGCCU 20 4097 CFTR-3849-755 CAAACCAGUGAUUCCUUGCCU 21 4098 CFTR-3849-756 ACAAACCAGUGAUUCCUUGCCU 22 4099 CFTR-3849-757 UACAAACCAGUGAUUCCUUGCCU 23 4100 CFTR-3849-758 GUACAAACCAGUGAUUCCUUGCCU 24 4101 CFTR-3849-759 AUCUUGAUCCAACAUUCU 18 4102 CFTR-3849-760 UAUCUUGAUCCAACAUUCU 19 4103 CFTR-3849-761 UUAUCUUGAUCCAACAUUCU 20 4104 CFTR-3849-762 UUUAUCUUGAUCCAACAUUCU 21 4105 CFTR-3849-763 AUUUAUCUUGAUCCAACAUUCU 22 4106 CFTR-3849-764 GAUUUAUCUUGAUCCAACAUUCU 23 4107 CFTR-3849-765 UGAUUUAUCUUGAUCCAACAUUCU 24 4108 CFTR-3849-766 UUGAAAAUACAGAAAUUU 18 4109 CFTR-3849-767 CUUGAAAAUACAGAAAUUU 19 4110 CFTR-3849-768 UCUUGAAAAUACAGAAAUUU 20 4111 CFTR-3849-769 CUCUUGAAAAUACAGAAAUUU 21 4112 CFTR-3849-770 UCUCUUGAAAAUACAGAAAUUU 22 4113 CFTR-3849-771 GUCUCUUGAAAAUACAGAAAUUU 23 4114 CFTR-3849-772 AGUCUCUUGAAAAUACAGAAAUUU 24 4115 CFTR-3849-773 GACUUGUCAUCUUGAUUU 18 4116 CFTR-3849-774 UGACUUGUCAUCUUGAUUU 19 4117 CFTR-3849-775 UUGACUUGUCAUCUUGAUUU 20 4118 CFTR-3849-776 GUUGACUUGUCAUCUUGAUUU 21 4119 CFTR-3849-777 AGUUGACUUGUCAUCUUGAUUU 22 4120 CFTR-3849-778 CAGUUGACUUGUCAUCUUGAUUU 23 4121 CFTR-3849-779 UCAGUUGACUUGUCAUCUUGAUUU 24 4122 CFTR-3849-780 UGUCUUAAAAGCUUAUUU 18 4123 CFTR-3849-781 AUGUCUUAAAAGCUUAUUU 19 4124 CFTR-3849-782 UAUGUCUUAAAAGCUUAUUU 20 4125 CFTR-3849-783 GUAUGUCUUAAAAGCUUAUUU 21 4126 CFTR-3849-784 GGUAUGUCUUAAAAGCUUAUUU 22 4127 CFTR-3849-785 GGGUAUGUCUUAAAAGCUUAUUU 23 4128 CFTR-3849-786 AGGGUAUGUCUUAAAAGCUUAUUU 24 4129 CFTR-3849-787 AAAUUUUAGUAUUUUUUU 18 4130 CFTR-3849-788 AAAAUUUUAGUAUUUUUUU 19 4131 CFTR-3849-789 AAAAAUUUUAGUAUUUUUUU 20 4132 CFTR-3849-790 UAAAAAUUUUAGUAUUUUUUU 21 4133 CFTR-3849-791 CUAAAAAUUUUAGUAUUUUUUU 22 4134 CFTR-3849-792 UCUAAAAAUUUUAGUAUUUUUUU 23 4135 CFTR-3849-793 CUCUAAAAAUUUUAGUAUUUUUUU 24 4136

Table 36A provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 36A 1st Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID CFTR-3849-794 + GAGGAAUUUUGAUUAAG 17 4137 CFTR-3849-795 GAGAUAUAUGAACACAU 17 4138 CFTR-3849-796 GAUUUAGGGUAUGUCUU 17 4139 CFTR-3849-797 + GGCUAGAGUACUUCCCGCAA 20 4140 CFTR-3849-798 + GAAACAUAGUAUUGAGAAUA 20 4141 CFTR-3849-799 GUUUAACUUUCAACAUAUUA 20 4142 CFTR-3849-800 + GGCAAUUUGUAAAUCUUUGG 20 4143 CFTR-3849-801 + GUAUUUAGGUGUUUGUGCUG 20 4144 CFTR-3849-802 GCACAAACACCUAAAUACUU 20 4145

Table 36B provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 36B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-803 + UAGAGUACUUCCCGCAA 17 4146 CFTR-3849-804 + AUAUACCAUAUGAGGAA 17 4147 CFTR-3849-13 + UGAAAUUUAGAUCCACA 17 3356 CFTR-3849-805 UUUCAGUUGACUUGUCA 17 4148 CFTR-3849-806 + ACAUAGUAUUGAGAAUA 17 4149 CFTR-3849-807 UAACUUUCAACAUAUUA 17 4150 CFTR-3849-808 CUUUGUUGGGUACAAAC 17 4151 CFTR-3849-809 AACCUUUAAAGCUAAAC 17 4152 CFTR-3849-810 CACAGUACUGGAUAGUC 17 4153 CFTR-3849-811 + AAUUUGUAAAUCUUUGG 17 4154 CFTR-3849-812 + UUUAGGUGUUUGUGCUG 17 4155 CFTR-3849-813 UACUUUUGGAUGAACUU 17 4156 CFTR-3849-814 + CACAUAAUAAUUAGUUU 17 4157 CFTR-3849-815 + ACAAUAUACCAUAUGAGGAA 20 4158 CFTR-3849-112 + AACUGAAAUUUAGAUCCACA 20 3455 CFTR-3849-816 AAAUUUCAGUUGACUUGUCA 20 4159 CFTR-3849-817 AGACUUUGUUGGGUACAAAC 20 4160 CFTR-3849-818 UAAAACCUUUAAAGCUAAAC 20 4161 CFTR-3849-819 UAUCACAGUACUGGAUAGUC 20 4162 CFTR-3849-820 + UAUGAGGAAUUUUGAUUAAG 20 4163 CFTR-3849-821 AUAGAGAUAUAUGAACACAU 20 4164 CFTR-3849-822 + AUAUGCUGCUUAUACCCACU 20 4165 CFTR-3849-823 CUAUACUUUUGGAUGAACUU 20 4166 CFTR-3849-824 UUAGAUUUAGGGUAUGUCUU 20 4167 CFTR-3849-529 + UGGCACAUAAUAAUUAGUUU 20 3872

Table 36C provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 36C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-3849- GAAAUAAUUUAUAAGAAUAU 20 4168 825

Table 36D provides exemplary targeting domains for correcting a mutation (e.g., 3849+10kbC->T) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp from a mutation (e.g., 3849+10kbC->T). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 36D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-3849-826 UUAUUAGAAAACACUGA 17 4169 CFTR-3849-827 AUAAUUUAUAAGAAUAU 17 4170 CFTR-3849-828 + UGCUGCUUAUACCCACU 17 4171 CFTR-3849-829 CAAACACCUAAAUACUU 17 4172 CFTR-3849-830 + UUCCGGGAUUUGUUUUU 17 4173 CFTR-3849-831 AAGUUAUUAGAAAACACUGA 20 4174 CFTR-3849-832 + AGUUUCCGGGAUUUGUUUUU 20 4175

Table 37A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 37A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-1 + GUACAAAGUACCAAAAA 17 15101 CFTR-Intron2-2 GCCUGAUGCCAGAUAAA 17 15102 CFTR-Intron2-3 + GGUAAACAAUUAGACAA 17 15103 CFTR-Intron2-4 + GACUAUGAGUGGCCCAA 17 15104 CFTR-Intron2-5 GCCUUGCUCUCUAGGAA 17 15105 CFTR-Intron2-6 + GCUCUAAAUCACUCUAA 17 15106 CFTR-Intron2-7 GGGAAGUCUUAAGGUAA 17 15107 CFTR-Intron2-8 + GUUACCAUAAGUAAACA 17 15108 CFTR-Intron2-9 + GCAAAGAGUUCUAACCA 17 15109 CFTR-Intron2-10 GGAACUCAAUGGGACCA 17 15110 CFTR-Intron2-11 GCUCAAUUUUGUGACCA 17 15111 CFTR-Intron2-12 + GCCAGGGUCACUUCCCA 17 15112 CFTR-Intron2-13 + GUAGAGGAUUCAAUCCA 17 15113 CFTR-Intron2-14 + GACCUCAGCUGGAAUCA 17 15114 CFTR-Intron2-15 + GUAGUUACCUGAGGAGA 17 15115 CFTR-Intron2-16 GGAGAAGCAUGUGGGGA 17 15116 CFTR-Intron2-17 + GUCCCAUUGAGUUCCUA 17 15117 CFTR-Intron2-18 GCAAAUGCCAUGAGGUA 17 15118 CFTR-Intron2-19 + GAGGUCUCUAGUGACCC 17 15119 CFTR-Intron2-20 + GCAAUACAGACCUCAGC 17 15120 CFTR-Intron2-21 GAAACCUGUAGCAUUGC 17 15121 CFTR-Intron2-22 + GAUUCAUGUUCUCUAUC 17 15122 CFTR-Intron2-23 GAAUUUGCAGAAUUAUC 17 15123 CFTR-Intron2-24 GACCUUGCCUUCUCCUC 17 15124 CFTR-Intron2-25 GUUCCAAGAUUGUAGUC 17 15125 CFTR-Intron2-26 + GGUUCAAUGUGAAAAAG 17 15126 CFTR-Intron2-27 + GUAAUAGGCCGGGGCAG 17 15127 CFTR-Intron2-28 + GCUUUACGUUUCAUCAG 17 15128 CFTR-Intron2-29 + GAGAGAUUCUUUAUGGG 17 15129 CFTR-Intron2-30 GAUCUGGGCCUGGUAUG 17 15130 CFTR-Intron2-31 GGCCUUAGGAACUCAAU 17 15131 CFTR-Intron2-32 GGUAACUUGACAGUAAU 17 15132 CFTR-Intron2-33 + GAUCCUAACCUUUUGAU 17 15133 CFTR-Intron2-34 + GUGAAACUUGAACAACU 17 15134 CFTR-Intron2-35 GAACUAUGUGAAGACCU 17 15135 CFTR-Intron2-36 + GGUGGCAUUUGAGUCCU 17 15136 CFTR-Intron2-37 GUAUUGCCUUGCUCUCU 17 15137 CFTR-Intron2-38 GAAUGAUUAAUCAGAGU 17 15138 CFTR-Intron2-39 + GGUGAUGUGGUUCUAGU 17 15139 CFTR-Intron2-40 GGUGGAGAACUGGCCUU 17 15140 CFTR-Intron2-41 GAGUGACAUACCAUUUU 17 15141 CFTR-Intron2-42 + GCCUUCAAAAUGCCAAAAAA 20 15142 CFTR-Intron2-43 + GAGGUACAAAGUACCAAAAA 20 15143 CFTR-Intron2-44 + GUGUACAUAAACCAACAAAA 20 15144 CFTR-Intron2-45 GGUAAUUAGGCUUUAUAGAA 20 15145 CFTR-Intron2-46 + GCAAUGUAGUUUUAGGAACA 20 15146 CFTR-Intron2-47 + GGAGCAAAGAGUUCUAACCA 20 15147 CFTR-Intron2-48 + GAAGCCAGGGUCACUUCCCA 20 15148 CFTR-Intron2-49 + GGAUUUUUCACAUUUAGCCA 20 15149 CFTR-Intron2-50 GAUUCACACUUCUAAGAUCA 20 15150 CFTR-Intron2-51 GCCCUCAAGUGGUUGCCAGA 20 15151 CFTR-Intron2-52 + GGGGUAGUUACCUGAGGAGA 20 15152 CFTR-Intron2-53 GGUGGAGAAGCAUGUGGGGA 20 15153 CFTR-Intron2-54 GAGUAACCAAAUGUUAUGGA 20 15154 CFTR-Intron2-55 GGGAAUGAUUAAUCAGAGUA 20 15155 CFTR-Intron2-56 GUACUCCCUGGGAAGUCUUA 20 15156 CFTR-Intron2-57 + GGAAACUGAGAGAUUCUUUA 20 15157 CFTR-Intron2-58 GAGUCUCGUGCCAACAGCAC 20 15158 CFTR-Intron2-59 + GUAAAUUGGGUUUCUGUCAC 20 15159 CFTR-Intron2-60 + GAAAGUGAAGUAGAGAGACC 20 15160 CFTR-Intron2-61 GCACCCUUGGGAAGUGACCC 20 15161 CFTR-Intron2-62 GCUAACAUUCUCUGCUCUCC 20 15162 CFTR-Intron2-63 + GUUAAUGUUCUUCAACCAUC 20 15163 CFTR-Intron2-64 GACCAGCUUUCUACAUAAAG 20 15164 CFTR-Intron2-65 + GUGUUGUUAUAUUUCAUAAG 20 15165 CFTR-Intron2-66 + GGAGUAAUAGGCCGGGGCAG 20 15166 CFTR-Intron2-67 + GUCACUUCCCAAGGGUGCAG 20 15167 CFTR-Intron2-68 GAUAAAAGGGUGAGUGAAGG 20 15168 CFTR-Intron2-69 GAACUAUGUGAAGACCUAGG 20 15169 CFTR-Intron2-70 GUUUACCUAGUUCUUCCUUG 20 15170 CFTR-Intron2-71 + GGUCGGGGAAUUUCUUUAAU 20 15171 CFTR-Intron2-72 + GUCACAAAAUUGAGCCAGAU 20 15172 CFTR-Intron2-73 + GAAACUGAGAGAUUCUUUAU 20 15173 CFTR-Intron2-74 GAGUCAUAGUGCUUACCCCU 20 15174 CFTR-Intron2-75 GCUCUCAUUAGCAAGCUUCU 20 15175 CFTR-Intron2-76 + GUAGGUGAUGUGGUUCUAGU 20 15176 CFTR-Intron2-77 GAAGAGUGACAUACCAUUUU 20 15177

Table 37B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 37B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-78 CCUGAUGCCAGAUAAAA 17 15178 CFTR-Intron2-79 + AUUUAGCCAAGGACAAA 17 15179 CFTR-Intron2-80 + CAUUUAGCCAAGGACAA 17 15180 CFTR-Intron2-81 + CCAGGGUCACUUCCCAA 17 15181 CFTR-Intron2-82 + UGUCAAUAUACCUGCAA 17 15182 CFTR-Intron2-83 + CUCACCUUCUCCAUCAA 17 15183 CFTR-Intron2-84 CACACUUCUAAGAUCAA 17 15184 CFTR-Intron2-85 UGGCCUUAGGAACUCAA 17 15185 CFTR-Intron2-86 + CCAGGCCCAGAUCAGAA 17 15186 CFTR-Intron2-87 AAUUAGGCUUUAUAGAA 17 15187 CFTR-Intron2-88 + ACGGAAGUAAUGUAGAA 17 15188 CFTR-Intron2-89 + UAACCUUUUGAUUGGAA 17 15189 CFTR-Intron2-90 + UGACUACAAUCUUGGAA 17 15190 CFTR-Intron2-91 + CACGAUUUACUUCAUAA 17 15191 CFTR-Intron2-92 UGGUAACUUGACAGUAA 17 15192 CFTR-Intron2-93 + UCGGGGAAUUUCUUUAA 17 15193 CFTR-Intron2-94 + AUGUAGUUUUAGGAACA 17 15194 CFTR-Intron2-95 + AAAUUUCAUGAACCACA 17 15195 CFTR-Intron2-96 + UGAAAAAGUGGUCCACA 17 15196 CFTR-Intron2-97 + UGAGGGCCAUGGUCACA 17 15197 CFTR-Intron2-98 UAACUGCCUUGUGACCA 17 15198 CFTR-Intron2-99 + AGACUAUGAGUGGCCCA 17 15199 CFTR-Intron2-100 UAAAACUACAUUGCCCA 17 15200 CFTR-Intron2-101 + UACCUUAAGACUUCCCA 17 15201 CFTR-Intron2-102 + UUUUUCACAUUUAGCCA 17 15202 CFTR-Intron2-103 + CAACCACUUGAGGGCCA 17 15203 CFTR-Intron2-104 + CUGGCAAUCUCUAAGCA 17 15204 CFTR-Intron2-105 + ACCAUUCCUAGAGAGCA 17 15205 CFTR-Intron2-106 + UACCUGAGGAGAAGGCA 17 15206 CFTR-Intron2-107 UCACACUUCUAAGAUCA 17 15207 CFTR-Intron2-108 + AAAGUAUCCCUACCUCA 17 15208 CFTR-Intron2-109 + UCACAAAAUCCAUCUCA 17 15209 CFTR-Intron2-110 UUAAGGACCACGAAAGA 17 15210 CFTR-Intron2-111 CUCAAGUGGUUGCCAGA 17 15211 CFTR-Intron2-112 + ACCAGGCCCAGAUCAGA 17 15212 CFTR-Intron2-113 UAAUUAGGCUUUAUAGA 17 15213 CFTR-Intron2-114 UAACCAAAUGUUAUGGA 17 15214 CFTR-Intron2-115 UGCCAGUUAAUGAAUGA 17 15215 CFTR-Intron2-116 + AUCUGGCAACCACUUGA 17 15216 CFTR-Intron2-117 UCAUUAGCAAGCUUCUA 17 15217 CFTR-Intron2-118 UCUCAGCUCCUGAAGUA 17 15218 CFTR-Intron2-119 AAUGAUUAAUCAGAGUA 17 15219 CFTR-Intron2-120 AGAGCCAUGUUUACUUA 17 15220 CFTR-Intron2-121 CUCCCUGGGAAGUCUUA 17 15221 CFTR-Intron2-122 UGAGUAACCAAAUGUUA 17 15222 CFTR-Intron2-123 CUUUGCUCCUAUCUUUA 17 15223 CFTR-Intron2-124 + AACUGAGAGAUUCUUUA 17 15224 CFTR-Intron2-125 + UUAAAUAGUCUGAAAAC 17 15225 CFTR-Intron2-126 AGACCUAGGUGGAGAAC 17 15226 CFTR-Intron2-127 + UCUACCUGGCAUGUAAC 17 15227 CFTR-Intron2-128 + CUCCAUCAUUCAUUAAC 17 15228 CFTR-Intron2-129 UCUCGUGCCAACAGCAC 17 15229 CFTR-Intron2-130 CUUAAGGUAAUGGCUAC 17 15230 CFTR-Intron2-131 + CUCUCCAGCAAUGCUAC 17 15231 CFTR-Intron2-132 + AACGUAUGGGUUUGUAC 17 15232 CFTR-Intron2-133 + AGCAAAGAGUUCUAACC 17 15233 CFTR-Intron2-134 + AUAAGGCAAAUGCCACC 17 15234 CFTR-Intron2-135 AGGACUCAAAUGCCACC 17 15235 CFTR-Intron2-136 + AGUGAAGUAGAGAGACC 17 15236 CFTR-Intron2-137 + UAGUAGGACCACAUACC 17 15237 CFTR-Intron2-138 + AGAGGAGAUAUUCUACC 17 15238 CFTR-Intron2-139 CCCUUGGGAAGUGACCC 17 15239 CFTR-Intron2-140 CUAAAACUACAUUGCCC 17 15240 CFTR-Intron2-141 AAUACAAAUGUACUCCC 17 15241 CFTR-Intron2-142 UACAUAAAGUGGGUCCC 17 15242 CFTR-Intron2-143 + UUACCUUAAGACUUCCC 17 15243 CFTR-Intron2-144 + UUAUGAAAUGUGAAGCC 17 15244 CFTR-Intron2-145 + UAAAGGAGUAAUAGGCC 17 15245 CFTR-Intron2-146 CAUGCUUAGAGAUUGCC 17 15246 CFTR-Intron2-147 + ACUUAGAUAUUCAAAGC 17 15247 CFTR-Intron2-148 + CACUUUAUGUAGAAAGC 17 15248 CFTR-Intron2-149 + UGUUCAAUAAUAGAAGC 17 15249 CFTR-Intron2-150 UAAUAAAUACAAUCAGC 17 15250 CFTR-Intron2-151 + CUAAAGGAGUAAUAGGC 17 15251 CFTR-Intron2-152 AUUAAUCAGAGUAGGGC 17 15252 CFTR-Intron2-153 UGGCAUUUGCCUUAUGC 17 15253 CFTR-Intron2-154 UAAACAUAAUCCAUUGC 17 15254 CFTR-Intron2-155 + AAUGUUCUUCAACCAUC 17 15255 CFTR-Intron2-156 + CCCUUUUAUCUGGCAUC 17 15256 CFTR-Intron2-157 AAGAACAUUAACCUAUC 17 15257 CFTR-Intron2-158 + UCACUCACCCUUUUAUC 17 15258 CFTR-Intron2-159 + UAUGACUCAAGAGUCUC 17 15259 CFTR-Intron2-160 + UAUGUAGAAAGCUGGUC 17 15260 CFTR-Intron2-161 + AGGUCUUCACAUAGUUC 17 15261 CFTR-Intron2-162 CAGCUUUCUACAUAAAG 17 15262 CFTR-Intron2-163 + ACUAUGAGUGGCCCAAG 17 15263 CFTR-Intron2-164 UGACCAUGGCCCUCAAG 17 15264 CFTR-Intron2-165 + UUGUUAUAUUUCAUAAG 17 15265 CFTR-Intron2-166 + ACUUCCCAAGGGUGCAG 17 15266 CFTR-Intron2-167 + AUGCUUUCCACUCAGAG 17 15267 CFTR-Intron2-168 + UCAUUCUAGACUAUGAG 17 15268 CFTR-Intron2-169 UCAAAGAAUUAAGCUAG 17 15269 CFTR-Intron2-170 CAUUAGCAAGCUUCUAG 17 15270 CFTR-Intron2-171 + ACACUGCAGUUAUGUAG 17 15271 CFTR-Intron2-172 + AAAGGAGUAAUAGGCCG 17 15272 CFTR-Intron2-173 + AGGAGAAGGCAAGGUCG 17 15273 CFTR-Intron2-174 + AAGGGCUCCUUCUUUCG 17 15274 CFTR-Intron2-175 CUAUGUGAAGACCUAGG 17 15275 CFTR-Intron2-176 + AGAGAUUCUUUAUGGGG 17 15276 CFTR-Intron2-177 UGGAGAAGCAUGUGGGG 17 15277 CFTR-Intron2-178 CAAAUGUUAUGGAUGGG 17 15278 CFTR-Intron2-179 + UAGUUUUAGGAACAUGG 17 15279 CFTR-Intron2-180 + UGAGAGAUUCUUUAUGG 17 15280 CFTR-Intron2-181 ACUCAAAUGCCACCUGG 17 15281 CFTR-Intron2-182 + UAAAUUGAAUCAACAUG 17 15282 CFTR-Intron2-183 UGUGUGCAAAUGCCAUG 17 15283 CFTR-Intron2-184 AAAGGUGGAGAAGCAUG 17 15284 CFTR-Intron2-185 + AAUGGGGUAGUUACCUG 17 15285 CFTR-Intron2-186 AGCCAUGAUUCCAGCUG 17 15286 CFTR-Intron2-187 UCUACAUUACUUCCGUG 17 15287 CFTR-Intron2-188 + AUCUUGGAACGGAUGUG 17 15288 CFTR-Intron2-189 + CAUCUGGCAACCACUUG 17 15289 CFTR-Intron2-190 + CCUAUUCUAGGCACUUG 17 15290 CFTR-Intron2-191 UACCUAGUUCUUCCUUG 17 15291 CFTR-Intron2-192 UUGGUGCUAACAAUUUG 17 15292 CFTR-Intron2-193 + UACUUAAGCUAGUAAAU 17 15293 CFTR-Intron2-194 CCCCAAGUGCCUAGAAU 17 15294 CFTR-Intron2-195 + CACUCUAAAGGAGUAAU 17 15295 CFTR-Intron2-196 + CGGGGAAUUUCUUUAAU 17 15296 CFTR-Intron2-197 + UCGUGGUCCUUAAAGAU 17 15297 CFTR-Intron2-198 + ACAAAAUUGAGCCAGAU 17 15298 CFTR-Intron2-199 UGGGGAGGGAAAUAGAU 17 15299 CFTR-Intron2-200 AACCAAAUGUUAUGGAU 17 15300 CFTR-Intron2-201 + AAAAUAAUAGAACGUAU 17 15301 CFTR-Intron2-202 AAAAGGAACGAAUUUAU 17 15302 CFTR-Intron2-203 + ACUGAGAGAUUCUUUAU 17 15303 CFTR-Intron2-204 + AACCACAAGGAAGAACU 17 15304 CFTR-Intron2-205 AUAGUCUAGAAUGAACU 17 15305 CFTR-Intron2-206 + AGGCCAGUUCUCCACCU 17 15306 CFTR-Intron2-207 UUGUACCUCUGCACCCU 17 15307 CFTR-Intron2-208 + AGGUCUCUAGUGACCCU 17 15308 CFTR-Intron2-209 UCAUAGUGCUUACCCCU 17 15309 CFTR-Intron2-210 AUACAAAUGUACUCCCU 17 15310 CFTR-Intron2-211 UGUACACACCCCUUCCU 17 15311 CFTR-Intron2-212 + CUUAGAUAUUCAAAGCU 17 15312 CFTR-Intron2-213 UUAAUCAGAGUAGGGCU 17 15313 CFTR-Intron2-214 + UAUCCUGACUACAAUCU 17 15314 CFTR-Intron2-215 + UCUCUAAGCAUGGAUCU 17 15315 CFTR-Intron2-216 ACCACAUCACCUACUCU 17 15316 CFTR-Intron2-217 + AUGACUCAAGAGUCUCU 17 15317 CFTR-Intron2-218 CUCAUUAGCAAGCUUCU 17 15318 CFTR-Intron2-219 + UUGUUAGCACCAAGAGU 17 15319 CFTR-Intron2-220 CAAAGAAUUAAGCUAGU 17 15320 CFTR-Intron2-221 AAGGUGGAGAAGCAUGU 17 15321 CFTR-Intron2-222 + CAUCAGGCCUGUGCUGU 17 15322 CFTR-Intron2-223 CAUUGAACCCAUUUUGU 17 15323 CFTR-Intron2-224 + ACUUAAGCUAGUAAAUU 17 15324 CFTR-Intron2-225 + CUCCCAUCCAUAACAUU 17 15325 CFTR-Intron2-226 UGUACCUCUGCACCCUU 17 15326 CFTR-Intron2-227 CAUAGUGCUUACCCCUU 17 15327 CFTR-Intron2-228 UUUCCAAUCAAAAGGUU 17 15328 CFTR-Intron2-229 AGGCCUGAUGCCAGAUAAAA 20 15329 CFTR-Intron2-230 + CUUCUCCAUCAAAGGAGAAA 20 15330 CFTR-Intron2-231 AUCCAUGAUGGAAUGUGAAA 20 15331 CFTR-Intron2-232 CAGGCCUGAUGCCAGAUAAA 20 15332 CFTR-Intron2-233 + AGCCUUUUUUCUCUUCACAA 20 15333 CFTR-Intron2-234 + CUAGGUAAACAAUUAGACAA 20 15334 CFTR-Intron2-235 + UCACAUUUAGCCAAGGACAA 20 15335 CFTR-Intron2-236 + CUAGACUAUGAGUGGCCCAA 20 15336 CFTR-Intron2-237 + AAGCCAGGGUCACUUCCCAA 20 15337 CFTR-Intron2-238 + ACUUGUCAAUAUACCUGCAA 20 15338 CFTR-Intron2-239 + AGACUCACCUUCUCCAUCAA 20 15339 CFTR-Intron2-240 AUUCACACUUCUAAGAUCAA 20 15340 CFTR-Intron2-241 AACUGGCCUUAGGAACUCAA 20 15341 CFTR-Intron2-242 + AUACCAGGCCCAGAUCAGAA 20 15342 CFTR-Intron2-243 UAGCUCUGUGUGUGAGAGAA 20 15343 CFTR-Intron2-244 + CACACGGAAGUAAUGUAGAA 20 15344 CFTR-Intron2-245 AUUGCCUUGCUCUCUAGGAA 20 15345 CFTR-Intron2-246 + UCCUAACCUUUUGAUUGGAA 20 15346 CFTR-Intron2-247 + UCCUGACUACAAUCUUGGAA 20 15347 CFTR-Intron2-248 CAGAUAAAAGGGUGAGUGAA 20 15348 CFTR-Intron2-249 + AUACACGAUUUACUUCAUAA 20 15349 CFTR-Intron2-250 + AUGGCUCUAAAUCACUCUAA 20 15350 CFTR-Intron2-251 UUAUGGUAACUUGACAGUAA 20 15351 CFTR-Intron2-252 CCUGGGAAGUCUUAAGGUAA 20 15352 CFTR-Intron2-253 + CUACUAAAAUCAUGUAUUAA 20 15353 CFTR-Intron2-254 + AGGUCGGGGAAUUUCUUUAA 20 15354 CFTR-Intron2-255 + CAAGUUACCAUAAGUAAACA 20 15355 CFTR-Intron2-256 + AUGUGAAAAAGUGGUCCACA 20 15356 CFTR-Intron2-257 + ACUUGAGGGCCAUGGUCACA 20 15357 CFTR-Intron2-258 UUAGGAACUCAAUGGGACCA 20 15358 CFTR-Intron2-259 UCAUAACUGCCUUGUGACCA 20 15359 CFTR-Intron2-260 CUGGCUCAAUUUUGUGACCA 20 15360 CFTR-Intron2-261 + UCUAGACUAUGAGUGGCCCA 20 15361 CFTR-Intron2-262 UCCUAAAACUACAUUGCCCA 20 15362 CFTR-Intron2-263 + CAUUACCUUAAGACUUCCCA 20 15363 CFTR-Intron2-264 + AGUUAUGAAAUGUGAAGCCA 20 15364 CFTR-Intron2-265 + UGGCAACCACUUGAGGGCCA 20 15365 CFTR-Intron2-266 + UAUGUAGAGGAUUCAAUCCA 20 15366 CFTR-Intron2-267 + AGCCUGGCAAUCUCUAAGCA 20 15367 CFTR-Intron2-268 + ACUACCAUUCCUAGAGAGCA 20 15368 CFTR-Intron2-269 + AGUUACCUGAGGAGAAGGCA 20 15369 CFTR-Intron2-270 + ACAGACCUCAGCUGGAAUCA 20 15370 CFTR-Intron2-271 + AGCCAUUUCACAUUCCAUCA 20 15371 CFTR-Intron2-272 + AACAAAGUAUCCCUACCUCA 20 15372 CFTR-Intron2-273 + UUUUCACAAAAUCCAUCUCA 20 15373 CFTR-Intron2-274 UCUUUAAGGACCACGAAAGA 20 15374 CFTR-Intron2-275 + CAUACCAGGCCCAGAUCAGA 20 15375 CFTR-Intron2-276 + CAAAGGAGAAAUGGAUCAGA 20 15376 CFTR-Intron2-277 UCUUAUUAGAGACCAUGAGA 20 15377 CFTR-Intron2-278 CAUGUGGGGAGGGAAAUAGA 20 15378 CFTR-Intron2-279 AGGUAAUUAGGCUUUAUAGA 20 15379 CFTR-Intron2-280 + UCAGAUGGGAAAGCCAAGGA 20 15380 CFTR-Intron2-281 CUUUGCCAGUUAAUGAAUGA 20 15381 CFTR-Intron2-282 AAGUUUUAAUUGGAUGCUGA 20 15382 CFTR-Intron2-283 CCAGAUAAAAGGGUGAGUGA 20 15383 CFTR-Intron2-284 + ACCAUCUGGCAACCACUUGA 20 15384 CFTR-Intron2-285 CUGAUCCAUUUCUCCUUUGA 20 15385 CFTR-Intron2-286 UCCUUUUUUUGGCAUUUUGA 20 15386 CFTR-Intron2-287 + UCAGAGUAAGAAGCUAAAUA 20 15387 CFTR-Intron2-288 AUCCCCAAGUGCCUAGAAUA 20 15388 CFTR-Intron2-289 + UUGGUCCCAUUGAGUUCCUA 20 15389 CFTR-Intron2-290 CUCUCAUUAGCAAGCUUCUA 20 15390 CFTR-Intron2-291 ACAUCUCAGCUCCUGAAGUA 20 15391 CFTR-Intron2-292 UGUGCAAAUGCCAUGAGGUA 20 15392 CFTR-Intron2-293 UUUAGAGCCAUGUUUACUUA 20 15393 CFTR-Intron2-294 CUCUGAGUAACCAAAUGUUA 20 15394 CFTR-Intron2-295 ACUCUUUGCUCCUAUCUUUA 20 15395 CFTR-Intron2-296 + ACAUUAAAUAGUCUGAAAAC 20 15396 CFTR-Intron2-297 + AUGGGGGAUACAGUGAAAAC 20 15397 CFTR-Intron2-298 UGAAGACCUAGGUGGAGAAC 20 15398 CFTR-Intron2-299 + UAUUCUACCUGGCAUGUAAC 20 15399 CFTR-Intron2-300 + UGGCUCCAUCAUUCAUUAAC 20 15400 CFTR-Intron2-301 CUGGUUUUAUUUUCUCAGAC 20 15401 CFTR-Intron2-302 AGUCUUAAGGUAAUGGCUAC 20 15402 CFTR-Intron2-303 + UAUCUCUCCAGCAAUGCUAC 20 15403 CFTR-Intron2-304 + UAGAACGUAUGGGUUUGUAC 20 15404 CFTR-Intron2-305 + AGGAGCAAAGAGUUCUAACC 20 15405 CFTR-Intron2-306 + AGCAUAAGGCAAAUGCCACC 20 15406 CFTR-Intron2-307 CCAAGGACUCAAAUGCCACC 20 15407 CFTR-Intron2-308 + UUCUAGUAGGACCACAUACC 20 15408 CFTR-Intron2-309 + CUGAGAGGAGAUAUUCUACC 20 15409 CFTR-Intron2-310 + UAAGAGGUCUCUAGUGACCC 20 15410 CFTR-Intron2-311 UUCCUAAAACUACAUUGCCC 20 15411 CFTR-Intron2-312 UUGAAUACAAAUGUACUCCC 20 15412 CFTR-Intron2-313 UUCUACAUAAAGUGGGUCCC 20 15413 CFTR-Intron2-314 + CCAUUACCUUAAGACUUCCC 20 15414 CFTR-Intron2-315 + CAGUUAUGAAAUGUGAAGCC 20 15415 CFTR-Intron2-316 CUUCCCUUCUGAUCUGGGCC 20 15416 CFTR-Intron2-317 AUCCAUGCUUAGAGAUUGCC 20 15417 CFTR-Intron2-318 + AAAACUUAGAUAUUCAAAGC 20 15418 CFTR-Intron2-319 + ACCCACUUUAUGUAGAAAGC 20 15419 CFTR-Intron2-320 + AAGUGUUCAAUAAUAGAAGC 20 15420 CFTR-Intron2-321 ACUUAAUAAAUACAAUCAGC 20 15421 CFTR-Intron2-322 + AAGGCAAUACAGACCUCAGC 20 15422 CFTR-Intron2-323 AUGAUUAAUCAGAGUAGGGC 20 15423 CFTR-Intron2-324 AUAUAAACAUAAUCCAUUGC 20 15424 CFTR-Intron2-325 AUAGAAACCUGUAGCAUUGC 20 15425 CFTR-Intron2-326 AAACUUCUUCCCUUCUGAUC 20 15426 CFTR-Intron2-327 UUGAAGAACAUUAACCUAUC 20 15427 CFTR-Intron2-328 + UCAGAUUCAUGUUCUCUAUC 20 15428 CFTR-Intron2-329 UCUGAAUUUGCAGAAUUAUC 20 15429 CFTR-Intron2-330 CCCGACCUUGCCUUCUCCUC 20 15430 CFTR-Intron2-331 + CACUAUGACUCAAGAGUCUC 20 15431 CFTR-Intron2-332 UCCGUUCCAAGAUUGUAGUC 20 15432 CFTR-Intron2-333 + CCUGAGGAGAAGGCAAGGUC 20 15433 CFTR-Intron2-334 + CUUUAUGUAGAAAGCUGGUC 20 15434 CFTR-Intron2-335 + CCUAGGUCUUCACAUAGUUC 20 15435 CFTR-Intron2-336 + AUGGGUUCAAUGUGAAAAAG 20 15436 CFTR-Intron2-337 + UAGACUAUGAGUGGCCCAAG 20 15437 CFTR-Intron2-338 UUGUGACCAUGGCCCUCAAG 20 15438 CFTR-Intron2-339 CUUUCAUUAACAGAAAUCAG 20 15439 CFTR-Intron2-340 + AAGGCUUUACGUUUCAUCAG 20 15440 CFTR-Intron2-341 + AUGAUGCUUUCCACUCAGAG 20 15441 CFTR-Intron2-342 + AGUUCAUUCUAGACUAUGAG 20 15442 CFTR-Intron2-343 + UUCCACUCAGAGUGGCUGAG 20 15443 CFTR-Intron2-344 CUCCUCUCAGCCACUCUGAG 20 15444 CFTR-Intron2-345 UAUUCAAAGAAUUAAGCUAG 20 15445 CFTR-Intron2-346 UCUCAUUAGCAAGCUUCUAG 20 15446 CFTR-Intron2-347 + UGCACACUGCAGUUAUGUAG 20 15447 CFTR-Intron2-348 + UCUAAAGGAGUAAUAGGCCG 20 15448 CFTR-Intron2-349 + CUGAGGAGAAGGCAAGGUCG 20 15449 CFTR-Intron2-350 + AUAAGGCAAAUGCCACCAGG 20 15450 CFTR-Intron2-351 + CUGAGAGAUUCUUUAUGGGG 20 15451 CFTR-Intron2-352 AACCAAAUGUUAUGGAUGGG 20 15452 CFTR-Intron2-353 + ACUGAGAGAUUCUUUAUGGG 20 15453 CFTR-Intron2-354 + UUUAAAUUGAAUCAACAUGG 20 15454 CFTR-Intron2-355 + AUGUAGUUUUAGGAACAUGG 20 15455 CFTR-Intron2-356 + AACUGAGAGAUUCUUUAUGG 20 15456 CFTR-Intron2-357 AGGACUCAAAUGCCACCUGG 20 15457 CFTR-Intron2-358 + UUUUAAAUUGAAUCAACAUG 20 15458 CFTR-Intron2-359 + AGCACCAAGAGUAGGUGAUG 20 15459 CFTR-Intron2-360 UCUGAUCUGGGCCUGGUAUG 20 15460 CFTR-Intron2-361 + AAACUGAGAGAUUCUUUAUG 20 15461 CFTR-Intron2-362 + UAGAAUGGGGUAGUUACCUG 20 15462 CFTR-Intron2-363 UGGAGCCAUGAUUCCAGCUG 20 15463 CFTR-Intron2-364 UAAGUUUUAAUUGGAUGCUG 20 15464 CFTR-Intron2-365 CUUUCUACAUUACUUCCGUG 20 15465 CFTR-Intron2-366 + ACAAUCUUGGAACGGAUGUG 20 15466 CFTR-Intron2-367 + AACCAUCUGGCAACCACUUG 20 15467 CFTR-Intron2-368 CUCUUGGUGCUAACAAUUUG 20 15468 CFTR-Intron2-369 + UGUACAUAAACCAACAAAAU 20 15469 CFTR-Intron2-370 + AUUUACUUAAGCUAGUAAAU 20 15470 CFTR-Intron2-371 ACUGGCCUUAGGAACUCAAU 20 15471 CFTR-Intron2-372 CAAGUUCAAAAUAAUAUAAU 20 15472 CFTR-Intron2-373 UAUGGUAACUUGACAGUAAU 20 15473 CFTR-Intron2-374 + AAUCACUCUAAAGGAGUAAU 20 15474 CFTR-Intron2-375 + CUUUCGUGGUCCUUAAAGAU 20 15475 CFTR-Intron2-376 + AAAGGAGAAAUGGAUCAGAU 20 15476 CFTR-Intron2-377 AUGUGGGGAGGGAAAUAGAU 20 15477 CFTR-Intron2-378 AGUAACCAAAUGUUAUGGAU 20 15478 CFTR-Intron2-379 + AAGGAUCCUAACCUUUUGAU 20 15479 CFTR-Intron2-380 + ACAAAAAUAAUAGAACGUAU 20 15480 CFTR-Intron2-381 AAUAAAAGGAACGAAUUUAU 20 15481 CFTR-Intron2-382 + UGGGUGAAACUUGAACAACU 20 15482 CFTR-Intron2-383 + AUGAACCACAAGGAAGAACU 20 15483 CFTR-Intron2-384 CUCAUAGUCUAGAAUGAACU 20 15484 CFTR-Intron2-385 AGCUUCUAUUAUUGAACACU 20 15485 CFTR-Intron2-386 + CUAAGGCCAGUUCUCCACCU 20 15486 CFTR-Intron2-387 CCUGAACUAUGUGAAGACCU 20 15487 CFTR-Intron2-388 + AAGAGGUCUCUAGUGACCCU 20 15488 CFTR-Intron2-389 UGAAUACAAAUGUACUCCCU 20 15489 CFTR-Intron2-390 + CCAGGUGGCAUUUGAGUCCU 20 15490 CFTR-Intron2-391 AAGAAGGAGCCCUUUGUCCU 20 15491 CFTR-Intron2-392 UUAUGUACACACCCCUUCCU 20 15492 CFTR-Intron2-393 + AAACUUAGAUAUUCAAAGCU 20 15493 CFTR-Intron2-394 UGAUUAAUCAGAGUAGGGCU 20 15494 CFTR-Intron2-395 + UCAUAUCCUGACUACAAUCU 20 15495 CFTR-Intron2-396 + CAAUCUCUAAGCAUGGAUCU 20 15496 CFTR-Intron2-397 AACUUCUUCCCUUCUGAUCU 20 15497 CFTR-Intron2-398 AGAACCACAUCACCUACUCU 20 15498 CFTR-Intron2-399 UCUGUAUUGCCUUGCUCUCU 20 15499 CFTR-Intron2-400 + ACUAUGACUCAAGAGUCUCU 20 15500 CFTR-Intron2-401 ACCAGCUUUCUACAUAAAGU 20 15501 CFTR-Intron2-402 + AAAUUGUUAGCACCAAGAGU 20 15502 CFTR-Intron2-403 AGGGAAUGAUUAAUCAGAGU 20 15503 CFTR-Intron2-404 AUUCAAAGAAUUAAGCUAGU 20 15504 CFTR-Intron2-405 + ACCUGAGGAGAAGGCAAGGU 20 15505 CFTR-Intron2-406 AGAAAGGUGGAGAAGCAUGU 20 15506 CFTR-Intron2-407 + UGGCAUCAGGCCUGUGCUGU 20 15507 CFTR-Intron2-408 UCACAUUGAACCCAUUUUGU 20 15508 CFTR-Intron2-409 AUAGAUGGGAAAAGGUAAUU 20 15509 CFTR-Intron2-410 + AACCUCCCAUCCAUAACAUU 20 15510 CFTR-Intron2-411 + UCAACUCAAUGUUUUUACUU 20 15511 CFTR-Intron2-412 CUUUGUACCUCUGCACCCUU 20 15512 CFTR-Intron2-413 AGUCAUAGUGCUUACCCCUU 20 15513 CFTR-Intron2-414 CUAGGUGGAGAACUGGCCUU 20 15514 CFTR-Intron2-415 UCCUUUCCAAUCAAAAGGUU 20 15515 CFTR-Intron2-416 + ACCCUGGGCAAUGUAGUUUU 20 15516

Table 37C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 2 and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 37C 3rd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-417 GGGAAAUAGAUGGGAAA 17 15517 CFTR-Intron2-418 + GACCAGCCUGGCCAACA 17 15518 CFTR-Intron2-419 GCUAAUUUUUGUAGAGA 17 15519 CFTR-Intron2-420 GUGGGGAGGGAAAUAGA 17 15520 CFTR-Intron2-421 + GAUGGGAAAGCCAAGGA 17 15521 CFTR-Intron2-422 GUUGAAUGAAUCCAUGA 17 15522 CFTR-Intron2-423 GAUAAAAGGGUGAGUGA 17 15523 CFTR-Intron2-424 + GAGUAAGAAGCUAAAUA 17 15524 CFTR-Intron2-425 GAAUAGGGCCUGGCAUA 17 15525 CFTR-Intron2-426 + GGGGAUACAGUGAAAAC 17 15526 CFTR-Intron2-427 GUUUUAUUUUCUCAGAC 17 15527 CFTR-Intron2-428 + GAGAAUCACUUGAACCC 17 15528 CFTR-Intron2-429 + GAGAUUCGCUUGAACCC 17 15529 CFTR-Intron2-430 GUCUCGCUGUGUCACCC 17 15530 CFTR-Intron2-431 GGCGUGAGCCACUGCCC 17 15531 CFTR-Intron2-432 GUCUUGCUCUGUUGCCC 17 15532 CFTR-Intron2-433 + GGAGUUCAAGACCAGCC 17 15533 CFTR-Intron2-434 GCAUGCACCACCAGGCC 17 15534 CFTR-Intron2-435 GUGCCUAGAAUAGGGCC 17 15535 CFTR-Intron2-436 GUUUUGCUAUGCUGGCC 17 15536 CFTR-Intron2-437 GUUUCGCCAUGUUGGCC 17 15537 CFTR-Intron2-438 GCACUCGCCACAAUGCC 17 15538 CFTR-Intron2-439 + GAGGAGAAGGCAAGGUC 17 15539 CFTR-Intron2-440 + GCAGAUCACUUGAGGUC 17 15540 CFTR-Intron2-441 + GGUGGAAACCAUACUUC 17 15541 CFTR-Intron2-442 + GAAAAGAAGUAACAGGG 17 15542 CFTR-Intron2-443 GUUUUAAUUGGAUGCUG 17 15543 CFTR-Intron2-444 + GGCGGGCAGAUCACUUG 17 15544 CFTR-Intron2-445 + GGUGGGCAGAUCACUUG 17 15545 CFTR-Intron2-446 + GAAAGAAAAAAUAGAAU 17 15546 CFTR-Intron2-447 GUUCAAAAUAAUAUAAU 17 15547 CFTR-Intron2-448 + GGAGAAAUGGAUCAGAU 17 15548 CFTR-Intron2-449 + GCCCUAUUCUAGGCACU 17 15549 CFTR-Intron2-450 GUGGAGUUUCGCCAUGU 17 15550 CFTR-Intron2-451 GAUGGGAAAAGGUAAUU 17 15551 CFTR-Intron2-452 GUUUUUUAUUUUUUAUU 17 15552 CFTR-Intron2-453 GUGUAAUGGUGCAAUUU 17 15553 CFTR-Intron2-454 GGAGGGAAAUAGAUGGGAAA 20 15554 CFTR-Intron2-455 + GAAAAAUUUCAUGAACCACA 20 15555 CFTR-Intron2-456 + GAGAAAAUAAAACCAGCAUA 20 15556 CFTR-Intron2-457 GACUACAGGCAUGCACCACC 20 15557 CFTR-Intron2-458 GGGGUUUUGCUAUGCUGGCC 20 15558 CFTR-Intron2-459 GGAGUUUCGCCAUGUUGGCC 20 15559 CFTR-Intron2-460 GCCUCAGCCUCUCGAGUAGC 20 15560 CFTR-Intron2-461 + GCUACUCGAGAGGCUGAGGC 20 15561 CFTR-Intron2-462 GAGACGGGGUUUUGCUAUGC 20 15562 CFTR-Intron2-463 + GCCUGUAGUCCCAGCUACUC 20 15563 CFTR-Intron2-464 + GACUUUGUUUUUAAAAGUAG 20 15564 CFTR-Intron2-465 GGCUAAUUUUUGUAGAGACG 20 15565 CFTR-Intron2-466 + GAGAUUCGCUUGAACCCAGG 20 15566 CFTR-Intron2-467 GAGAAAGGUGGAGAAGCAUG 20 15567 CFTR-Intron2-468 GAAAGGUGGAGAAGCAUGUG 20 15568 CFTR-Intron2-469 + GGCCCUAUUCUAGGCACUUG 20 15569 CFTR-Intron2-470 + GCACCAUUACACUCCAGCCU 20 15570 CFTR-Intron2-471 + GCAUUUUGGGAGGCCAAGGU 20 15571 CFTR-Intron2-472 GUGUGCAAAUGCCAUGAGGU 20 15572 CFTR-Intron2-473 GAUGUGGAGUUUCGCCAUGU 20 15573 CFTR-Intron2-474 GCCUUGGCCUCCCAAAGUGU 20 15574 CFTR-Intron2-475 GGAGUGUAAUGGUGCAAUUU 20 15575 CFTR-Intron2-476 + GCCACUAAUCCCAACACUUU 20 15576

Table 37D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 2. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 37D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-477 + UUCAAAAUGCCAAAAAA 17 15577 CFTR-Intron2-478 CUUUGUGAAGAGAAAAA 17 15578 CFTR-Intron2-479 + UACAUAAACCAACAAAA 17 15579 CFTR-Intron2-480 UUUCCUUUCCAAUCAAA 17 15580 CFTR-Intron2-481 + UGUCACUGGCAAUCAAA 17 15581 CFTR-Intron2-482 + CUCCAUCAAAGGAGAAA 17 15582 CFTR-Intron2-483 CAUGAUGGAAUGUGAAA 17 15583 CFTR-Intron2-484 UAGCUUAAGUAAAUAAA 17 15584 CFTR-Intron2-485 + CUUUUUUCUCUUCACAA 17 15585 CFTR-Intron2-486 CUCUGUGUGUGAGAGAA 17 15586 CFTR-Intron2-487 + UGAAAGAAAAAAUAGAA 17 15587 CFTR-Intron2-488 + AUGGGAAAGCCAAGGAA 17 15588 CFTR-Intron2-489 AUAAAAGGGUGAGUGAA 17 15589 CFTR-Intron2-490 + ACAAACAAAAAACAUAA 17 15590 CFTR-Intron2-491 + UUUGUAUUCAAAUAUAA 17 15591 CFTR-Intron2-492 AGUUCAAAAUAAUAUAA 17 15592 CFTR-Intron2-493 CCCAGGCUGGAGUGUAA 17 15593 CFTR-Intron2-494 + CUAAAAUCAUGUAUUAA 17 15594 CFTR-Intron2-495 + UUUAAAUUGAAUCAACA 17 15595 CFTR-Intron2-496 + UAAGAAAAGAAGUAACA 17 15596 CFTR-Intron2-497 + AUCAGAUGGGAAAGCCA 17 15597 CFTR-Intron2-498 + UAUGAAAUGUGAAGCCA 17 15598 CFTR-Intron2-499 + AACACUUUGGGAGGCCA 17 15599 CFTR-Intron2-500 + AGCAUUUUGGGAGGCCA 17 15600 CFTR-Intron2-501 + CAUUUCACAUUCCAUCA 17 15601 CFTR-Intron2-502 + AGGAGAAAUGGAUCAGA 17 15602 CFTR-Intron2-503 UUCUCCUUUGAUGGAGA 17 15603 CFTR-Intron2-504 UAUUAGAGACCAUGAGA 17 15604 CFTR-Intron2-505 UUUUAAUUGGAUGCUGA 17 15605 CFTR-Intron2-506 AUCCAUUUCUCCUUUGA 17 15606 CFTR-Intron2-507 UUUUUUUGGCAUUUUGA 17 15607 CFTR-Intron2-508 CCCAAGUGCCUAGAAUA 17 15608 CFTR-Intron2-509 + AAAAUAAAACCAGCAUA 17 15609 CFTR-Intron2-510 + AAAAAUAAUAGAACGUA 17 15610 CFTR-Intron2-511 UGAUACAUUUGUAUUUA 17 15611 CFTR-Intron2-512 + AUAAGAAAAGAAGUAAC 17 15612 CFTR-Intron2-513 + AAUUGGGUUUCUGUCAC 17 15613 CFTR-Intron2-514 CUAAUUUUUGUAGAGAC 17 15614 CFTR-Intron2-515 UGAGUAGCUGGGACUAC 17 15615 CFTR-Intron2-516 CGAGUAGCUGGGUUUAC 17 15616 CFTR-Intron2-517 UACAGGCAUGCACCACC 17 15617 CFTR-Intron2-518 + AGAUUUGAAGACAAGCC 17 15618 CFTR-Intron2-519 + ACCACUACACUCCAGCC 17 15619 CFTR-Intron2-520 + ACCAUUACACUCCAGCC 17 15620 CFTR-Intron2-521 + AAAUACAAAAAUUAGCC 17 15621 CFTR-Intron2-522 + CUCUACAAAAAUUAGCC 17 15622 CFTR-Intron2-523 + CAAAAAUUAGCCAGGCC 17 15623 CFTR-Intron2-524 CCCUUCUGAUCUGGGCC 17 15624 CFTR-Intron2-525 AGUACCUGUUACAUGCC 17 15625 CFTR-Intron2-526 + AGUAUAUACCAUAUGCC 17 15626 CFTR-Intron2-527 CUGCAAACUCUGCCUCC 17 15627 CFTR-Intron2-528 AACAUUCUCUGCUCUCC 17 15628 CFTR-Intron2-529 CUGCAAACUUCGUCUCC 17 15629 CFTR-Intron2-530 UCAGCCUCUCGAGUAGC 17 15630 CFTR-Intron2-531 UCAGUCUCCUGAGUAGC 17 15631 CFTR-Intron2-532 + CUUUGGGAGGCCAAGGC 17 15632 CFTR-Intron2-533 CGCUGUGUCACCCAGGC 17 15633 CFTR-Intron2-534 UGCUCUGUUGCCCAGGC 17 15634 CFTR-Intron2-535 UGCUAUGCUGGCCAGGC 17 15635 CFTR-Intron2-536 CGCCAUGUUGGCCAGGC 17 15636 CFTR-Intron2-537 + ACUCGAGAGGCUGAGGC 17 15637 CFTR-Intron2-538 UUGGCCUCCCAAAAUGC 17 15638 CFTR-Intron2-539 ACGGGGUUUUGCUAUGC 17 15639 CFTR-Intron2-540 CUUCUUCCCUUCUGAUC 17 15640 CFTR-Intron2-541 + UGUAGUCCCAGCUACUC 17 15641 CFTR-Intron2-542 + CCAAAUGUGUAUUUUUC 17 15642 CFTR-Intron2-543 + UGGGAAAGCCAAGGAAG 17 15643 CFTR-Intron2-544 UAAAAGGGUGAGUGAAG 17 15644 CFTR-Intron2-545 UCAUUAACAGAAAUCAG 17 15645 CFTR-Intron2-546 + AAACCCAGCUACUCGAG 17 15646 CFTR-Intron2-547 + CACUCAGAGUGGCUGAG 17 15647 CFTR-Intron2-548 CUCUCAGCCACUCUGAG 17 15648 CFTR-Intron2-549 + UUCAAAGCUGGGCAUAG 17 15649 CFTR-Intron2-550 + UUUGUUUUUAAAAGUAG 17 15650 CFTR-Intron2-551 CCCAGGCUGGAGUGUAG 17 15651 CFTR-Intron2-552 CAAAGUGUUGGGAUUAG 17 15652 CFTR-Intron2-553 UAAUUUUUGUAGAGACG 17 15653 CFTR-Intron2-554 UGUGUGUGAGAGAAAGG 17 15654 CFTR-Intron2-555 + ACUUUGGGAGGCCAAGG 17 15655 CFTR-Intron2-556 + AUUUUGGGAGGCCAAGG 17 15656 CFTR-Intron2-557 AAAAGGGUGAGUGAAGG 17 15657 CFTR-Intron2-558 + AGGCAAAUGCCACCAGG 17 15658 CFTR-Intron2-559 + AUUCGCUUGAACCCAGG 17 15659 CFTR-Intron2-560 + AAUCCCAACACUUUGGG 17 15660 CFTR-Intron2-561 + AAUCCCAGCAUUUUGGG 17 15661 CFTR-Intron2-562 + AAAUUGAAUCAACAUGG 17 15662 CFTR-Intron2-563 + AAAUUAGCCAGGCCUGG 17 15663 CFTR-Intron2-564 + AAAGAAAAAAUAGAAUG 17 15664 CFTR-Intron2-565 UUGUAUUUUAGUAGAUG 17 15665 CFTR-Intron2-566 + ACCAAGAGUAGGUGAUG 17 15666 CFTR-Intron2-567 + CUGAGAGAUUCUUUAUG 17 15667 CFTR-Intron2-568 UACAGAAAAGCAAACUG 17 15668 CFTR-Intron2-569 + AGCUACUCGAGAGGCUG 17 15669 CFTR-Intron2-570 AGGUGGAGAAGCAUGUG 17 15670 CFTR-Intron2-571 + AAAUUAGCCAGGCAUUG 17 15671 CFTR-Intron2-572 + ACAUAAACCAACAAAAU 17 15672 CFTR-Intron2-573 UUCUUUUCUUAUAAAAU 17 15673 CFTR-Intron2-574 + UUGAAUUGAAGUAAAAU 17 15674 CFTR-Intron2-575 AAUAUCUAAGUUUUAAU 17 15675 CFTR-Intron2-576 + UUAAAUUGAAUCAACAU 17 15676 CFTR-Intron2-577 + UUUCUUUUAAAUACUAU 17 15677 CFTR-Intron2-578 CAAAAUGCUGGGAUUAU 17 15678 CFTR-Intron2-579 UGUUUUUUAUUUUUUAU 17 15679 CFTR-Intron2-580 UUCUAUUAUUGAACACU 17 15680 CFTR-Intron2-581 AAGUGAUCUGCCCACCU 17 15681 CFTR-Intron2-582 + CCACUACACUCCAGCCU 17 15682 CFTR-Intron2-583 + CCAUUACACUCCAGCCU 17 15683 CFTR-Intron2-584 AAGUGAUCUGCCCGCCU 17 15684 CFTR-Intron2-585 UGCAAACUCUGCCUCCU 17 15685 CFTR-Intron2-586 UGCAAACUUCGUCUCCU 17 15686 CFTR-Intron2-587 AAGGAGCCCUUUGUCCU 17 15687 CFTR-Intron2-588 CAGCCUCUCGAGUAGCU 17 15688 CFTR-Intron2-589 CAGUCUCCUGAGUAGCU 17 15689 CFTR-Intron2-590 UGGCCUCCCAAAAUGCU 17 15690 CFTR-Intron2-591 UUCUUCCCUUCUGAUCU 17 15691 CFTR-Intron2-592 + AUGCCAGGCCCUAUUCU 17 15692 CFTR-Intron2-593 AGCUUUCUACAUAAAGU 17 15693 CFTR-Intron2-594 + UUUUGGGAGGCCAAGGU 17 15694 CFTR-Intron2-595 + UGAGGAGAAGGCAAGGU 17 15695 CFTR-Intron2-596 UGCAAAUGCCAUGAGGU 17 15696 CFTR-Intron2-597 UUGGCCUCCCAAAGUGU 17 15697 CFTR-Intron2-598 CCUGAAAAAUACACAUU 17 15698 CFTR-Intron2-599 + CACUAAUCCCAACACUU 17 15699 CFTR-Intron2-600 + CCCUAUUCUAGGCACUU 17 15700 CFTR-Intron2-601 + ACUCAAUGUUUUUACUU 17 15701 CFTR-Intron2-602 UGGCCUCCCAAAGUGUU 17 15702 CFTR-Intron2-603 + CUAUAAUCCCAGCAUUU 17 15703 CFTR-Intron2-604 AAUUUAUUGAAAUAUUU 17 15704 CFTR-Intron2-605 + ACUAAUCCCAACACUUU 17 15705 CFTR-Intron2-606 + UAUAAUCCCAGCAUUUU 17 15706 CFTR-Intron2-607 + CUGGGCAAUGUAGUUUU 17 15707 CFTR-Intron2-608 AAUUCAUUUCCUUUUUU 17 15708 CFTR-Intron2-609 UUCCUUUGUGAAGAGAAAAA 20 15709 CFTR-Intron2-610 + CACAUUUAGCCAAGGACAAA 20 15710 CFTR-Intron2-611 CAGUUUCCUUUCCAAUCAAA 20 15711 CFTR-Intron2-612 + UUCUGUCACUGGCAAUCAAA 20 15712 CFTR-Intron2-613 UACUAGCUUAAGUAAAUAAA 20 15713 CFTR-Intron2-614 + CUAUGAAAGAAAAAAUAGAA 20 15714 CFTR-Intron2-615 + CAGAUGGGAAAGCCAAGGAA 20 15715 CFTR-Intron2-616 + CAAACAAACAAAAAACAUAA 20 15716 CFTR-Intron2-617 + ACAUUUGUAUUCAAAUAUAA 20 15717 CFTR-Intron2-618 ACAAGUUCAAAAUAAUAUAA 20 15718 CFTR-Intron2-619 UUGCCCAGGCUGGAGUGUAA 20 15719 CFTR-Intron2-620 + CAAGACCAGCCUGGCCAACA 20 15720 CFTR-Intron2-621 + UUUUUUAAAUUGAAUCAACA 20 15721 CFTR-Intron2-622 + UUAUAAGAAAAGAAGUAACA 20 15722 CFTR-Intron2-623 + UGGAUCAGAUGGGAAAGCCA 20 15723 CFTR-Intron2-624 + CCCAACACUUUGGGAGGCCA 20 15724 CFTR-Intron2-625 + CCCAGCAUUUUGGGAGGCCA 20 15725 CFTR-Intron2-626 CUGGCUAAUUUUUGUAGAGA 20 15726 CFTR-Intron2-627 CAUUUCUCCUUUGAUGGAGA 20 15727 CFTR-Intron2-628 UUUGUUGAAUGAAUCCAUGA 20 15728 CFTR-Intron2-629 CUAGAAUAGGGCCUGGCAUA 20 15729 CFTR-Intron2-630 + AACAAAAAUAAUAGAACGUA 20 15730 CFTR-Intron2-631 AUGUGAUACAUUUGUAUUUA 20 15731 CFTR-Intron2-632 + UUUAUAAGAAAAGAAGUAAC 20 15732 CFTR-Intron2-633 UGGCUAAUUUUUGUAGAGAC 20 15733 CFTR-Intron2-634 UCCUGAGUAGCUGGGACUAC 20 15734 CFTR-Intron2-635 UCUCGAGUAGCUGGGUUUAC 20 15735 CFTR-Intron2-636 + CAGGAGAAUCACUUGAACCC 20 15736 CFTR-Intron2-637 + ACUGAGAUUCGCUUGAACCC 20 15737 CFTR-Intron2-638 AGAGUCUCGCUGUGUCACCC 20 15738 CFTR-Intron2-639 AGUGGCGUGAGCCACUGCCC 20 15739 CFTR-Intron2-640 AGAGUCUUGCUCUGUUGCCC 20 15740 CFTR-Intron2-641 + CUGAGAUUUGAAGACAAGCC 20 15741 CFTR-Intron2-642 + UCAGGAGUUCAAGACCAGCC 20 15742 CFTR-Intron2-643 + CACACCACUACACUCCAGCC 20 15743 CFTR-Intron2-644 + UGCACCAUUACACUCCAGCC 20 15744 CFTR-Intron2-645 + CUAAAAUACAAAAAUUAGCC 20 15745 CFTR-Intron2-646 + CGUCUCUACAAAAAUUAGCC 20 15746 CFTR-Intron2-647 CAGGCAUGCACCACCAGGCC 20 15747 CFTR-Intron2-648 + CUACAAAAAUUAGCCAGGCC 20 15748 CFTR-Intron2-649 + CUCUAAAGGAGUAAUAGGCC 20 15749 CFTR-Intron2-650 CAAGUGCCUAGAAUAGGGCC 20 15750 CFTR-Intron2-651 CAGGCACUCGCCACAAUGCC 20 15751 CFTR-Intron2-652 UUGAGUACCUGUUACAUGCC 20 15752 CFTR-Intron2-653 + UUGAGUAUAUACCAUAUGCC 20 15753 CFTR-Intron2-654 UCACUGCAAACUCUGCCUCC 20 15754 CFTR-Intron2-655 UCACUGCAAACUUCGUCUCC 20 15755 CFTR-Intron2-656 AUCUCAGUCUCCUGAGUAGC 20 15756 CFTR-Intron2-657 + ACACUUUGGGAGGCCAAGGC 20 15757 CFTR-Intron2-658 UCUCGCUGUGUCACCCAGGC 20 15758 CFTR-Intron2-659 UCUUGCUCUGUUGCCCAGGC 20 15759 CFTR-Intron2-660 UUUUGCUAUGCUGGCCAGGC 20 15760 CFTR-Intron2-661 UUUCGCCAUGUUGGCCAGGC 20 15761 CFTR-Intron2-662 + ACUCUAAAGGAGUAAUAGGC 20 15762 CFTR-Intron2-663 ACCUUGGCCUCCCAAAAUGC 20 15763 CFTR-Intron2-664 UGGUGGCAUUUGCCUUAUGC 20 15764 CFTR-Intron2-665 + UCACCCUUUUAUCUGGCAUC 20 15765 CFTR-Intron2-666 + CCUUCACUCACCCUUUUAUC 20 15766 CFTR-Intron2-667 + CGGGCAGAUCACUUGAGGUC 20 15767 CFTR-Intron2-668 + UGGGCAGAUCACUUGAGGUC 20 15768 CFTR-Intron2-669 + CAUGGUGGAAACCAUACUUC 20 15769 CFTR-Intron2-670 + AAACCAAAUGUGUAUUUUUC 20 15770 CFTR-Intron2-671 + AGAUGGGAAAGCCAAGGAAG 20 15771 CFTR-Intron2-672 AGAUAAAAGGGUGAGUGAAG 20 15772 CFTR-Intron2-673 + UGUAAACCCAGCUACUCGAG 20 15773 CFTR-Intron2-674 + AUAUUCAAAGCUGGGCAUAG 20 15774 CFTR-Intron2-675 UCACCCAGGCUGGAGUGUAG 20 15775 CFTR-Intron2-676 UCCCAAAGUGUUGGGAUUAG 20 15776 CFTR-Intron2-677 + ACAAAGGGCUCCUUCUUUCG 20 15777 CFTR-Intron2-678 CUCUGUGUGUGAGAGAAAGG 20 15778 CFTR-Intron2-679 + AACACUUUGGGAGGCCAAGG 20 15779 CFTR-Intron2-680 + AGCAUUUUGGGAGGCCAAGG 20 15780 CFTR-Intron2-681 + UAAGAAAAGAAGUAACAGGG 20 15781 CFTR-Intron2-682 AGGUGGAGAAGCAUGUGGGG 20 15782 CFTR-Intron2-683 + ACUAAUCCCAACACUUUGGG 20 15783 CFTR-Intron2-684 + UAUAAUCCCAGCAUUUUGGG 20 15784 CFTR-Intron2-685 + CAAAAAUUAGCCAGGCCUGG 20 15785 CFTR-Intron2-686 + AUGAAAGAAAAAAUAGAAUG 20 15786 CFTR-Intron2-687 UGGUGUGUGCAAAUGCCAUG 20 15787 CFTR-Intron2-688 UUUUUGUAUUUUAGUAGAUG 20 15788 CFTR-Intron2-689 UUUUACAGAAAAGCAAACUG 20 15789 CFTR-Intron2-690 + CCCAGCUACUCGAGAGGCUG 20 15790 CFTR-Intron2-691 + CAAAAAUUAGCCAGGCAUUG 20 15791 CFTR-Intron2-692 + CAAGGCGGGCAGAUCACUUG 20 15792 CFTR-Intron2-693 + CAAGGUGGGCAGAUCACUUG 20 15793 CFTR-Intron2-694 UACUUCUUUUCUUAUAAAAU 20 15794 CFTR-Intron2-695 + UUGUUGAAUUGAAGUAAAAU 20 15795 CFTR-Intron2-696 + UAUGAAAGAAAAAAUAGAAU 20 15796 CFTR-Intron2-697 UAUCCCCAAGUGCCUAGAAU 20 15797 CFTR-Intron2-698 UUGAAUAUCUAAGUUUUAAU 20 15798 CFTR-Intron2-699 + UUUUUAAAUUGAAUCAACAU 20 15799 CFTR-Intron2-700 + UGUUUUCUUUUAAAUACUAU 20 15800 CFTR-Intron2-701 UCCCAAAAUGCUGGGAUUAU 20 15801 CFTR-Intron2-702 UUUUGUUUUUUAUUUUUUAU 20 15802 CFTR-Intron2-703 + CAGGCCCUAUUCUAGGCACU 20 15803 CFTR-Intron2-704 CUCAAGUGAUCUGCCCACCU 20 15804 CFTR-Intron2-705 ACUUUGUACCUCUGCACCCU 20 15805 CFTR-Intron2-706 + ACACCACUACACUCCAGCCU 20 15806 CFTR-Intron2-707 CUCAAGUGAUCUGCCCGCCU 20 15807 CFTR-Intron2-708 CACUGCAAACUCUGCCUCCU 20 15808 CFTR-Intron2-709 CACUGCAAACUUCGUCUCCU 20 15809 CFTR-Intron2-710 CCUCAGCCUCUCGAGUAGCU 20 15810 CFTR-Intron2-711 UCUCAGUCUCCUGAGUAGCU 20 15811 CFTR-Intron2-712 CCUUGGCCUCCCAAAAUGCU 20 15812 CFTR-Intron2-713 + CAUAUGCCAGGCCCUAUUCU 20 15813 CFTR-Intron2-714 + UUUACUUAAGCUAGUAAAUU 20 15814 CFTR-Intron2-715 UUUCCUGAAAAAUACACAUU 20 15815 CFTR-Intron2-716 UUUGUUUUUUAUUUUUUAUU 20 15816 CFTR-Intron2-717 + CGCCACUAAUCCCAACACUU 20 15817 CFTR-Intron2-718 + AGGCCCUAUUCUAGGCACUU 20 15818 CFTR-Intron2-719 CCUUGGCCUCCCAAAGUGUU 20 15819 CFTR-Intron2-720 + CACCUAUAAUCCCAGCAUUU 20 15820 CFTR-Intron2-721 UGAAAUUUAUUGAAAUAUUU 20 15821 CFTR-Intron2-722 + ACCUAUAAUCCCAGCAUUUU 20 15822 CFTR-Intron2-723 UUAAAUUCAUUUCCUUUUUU 20 15823

Table 38A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 38A 1st Tier DNA Target Site Seq gRNA Name Strand Targeting Domain Length ID CFTR-Intron2-724 + GUUAGCUAUGAAAGAAAAAA 20 15824 CFTR-Intron2-725 + GUGUACAUAAACCAACAAA 19 15825 CFTR-Intron2-726 + GUGUGUACAUAAACCAACAAA 21 15826 CFTR-Intron2-727 + GGUGUGUACAUAAACCAACAAA 22 15827 CFTR-Intron2-728 + GGGUGUGUACAUAAACCAACAAA 23 15828 CFTR-Intron2-729 + GGGGUGUGUACAUAAACCAACAAA 24 15829 CFTR-Intron2-730 + GCCUUUUUUCUCUUCACAA 19 15830 CFTR-Intron2-731 + GAAAGCCUUUUUUCUCUUCACAA 23 15831 CFTR-Intron2-732 + GGCUCUAAAUCACUCUAA 18 15832 CFTR-Intron2-733 + GCAUUUGAGUCCUUGGUCCCA 21 15833 CFTR-Intron2-734 + GGCAUUUGAGUCCUUGGUCCCA 22 15834 CFTR-Intron2-735 + GUGGCAUUUGAGUCCUUGGUCCCA 24 15835 CFTR-Intron2-736 + GCCAUUACCUUAAGACUUCCCA 22 15836 CFTR-Intron2-737 + GUAGAGAGACCAGGAGAGCA 20 15837 CFTR-Intron2-738 + GUCCUUAAAGAUAGGAGCA 19 15838 CFTR-Intron2-739 + GGUCCUUAAAGAUAGGAGCA 20 15839 CFTR-Intron2-740 + GUGGUCCUUAAAGAUAGGAGCA 22 15840 CFTR-Intron2-741 + GAACUUGUCAAUAUACCUGCA 21 15841 CFTR-Intron2-742 + GCACACUGCAGUUAUGUA 18 15842 CFTR-Intron2-743 + GUUUGCACACUGCAGUUAUGUA 22 15843 CFTR-Intron2-744 + GGUUUGCACACUGCAGUUAUGUA 23 15844 CFTR-Intron2-745 + GGUCGGGGAAUUUCUUUA 18 15845 CFTR-Intron2-746 + GCAAGGUCGGGGAAUUUCUUUA 22 15846 CFTR-Intron2-747 + GGCAAGGUCGGGGAAUUUCUUUA 23 15847 CFTR-Intron2-748 + GCCACAAAUUGUUAGCACC 19 15848 CFTR-Intron2-749 + GUGCCACAAAUUGUUAGCACC 21 15849 CFTR-Intron2-750 + GGUGCCACAAAUUGUUAGCACC 22 15850 CFTR-Intron2-751 + GAAGCCAGGGUCACUUCCC 19 15851 CFTR-Intron2-752 + GUGAAGCCAGGGUCACUUCCC 21 15852 CFTR-Intron2-753 + GCAGUUAUGAAAUGUGAAGC 20 15853 CFTR-Intron2-754 + GGCAGUUAUGAAAUGUGAAGC 21 15854 CFTR-Intron2-755 + GCCUGGCAAUCUCUAAGC 18 15855 CFTR-Intron2-756 + GACAAGCCUGGCAAUCUCUAAGC 23 15856 CFTR-Intron2-757 + GGCAAUACAGACCUCAGC 18 15857 CFTR-Intron2-758 + GCAAGGCAAUACAGACCUCAGC 22 15858 CFTR-Intron2-759 + GAGCAAGGCAAUACAGACCUCAGC 24 15859 CFTR-Intron2-760 + GCCAUUUCACAUUCCAUC 18 15860 CFTR-Intron2-761 + GCUAGCCAUUUCACAUUCCAUC 22 15861 CFTR-Intron2-762 + GGGUAAGCACUAUGACUC 18 15862 CFTR-Intron2-763 + GGGGUAAGCACUAUGACUC 19 15863 CFTR-Intron2-764 + GCACUAUGACUCAAGAGUCUC 21 15864 CFTR-Intron2-765 + GAGGAGAAGGCAAGGUCG 18 15865 CFTR-Intron2-766 + GUUUGUACUGGCAUAGCAUUG 21 15866 CFTR-Intron2-767 + GGUUUGUACUGGCAUAGCAUUG 22 15867 CFTR-Intron2-768 + GGGUUUGUACUGGCAUAGCAUUG 23 15868 CFTR-Intron2-769 + GCAAAUGCCACCAGGUGGCAU 21 15869 CFTR-Intron2-770 + GGCAAAUGCCACCAGGUGGCAU 22 15870 CFTR-Intron2-771 + GAUAAUGAUGCUUUCCACU 19 15871 CFTR-Intron2-772 + GCCUAGUUCAUUCUAGACU 19 15872 CFTR-Intron2-773 + GCUACUCCCACUAGCUUAAUUCU 23 15873 CFTR-Intron2-774 + GCCCUUGAUCUUAGAAGU 18 15874 CFTR-Intron2-775 + GGCCCUUGAUCUUAGAAGU 19 15875 CFTR-Intron2-776 + GCUGGCCCUUGAUCUUAGAAGU 22 15876 CFTR-Intron2-777 GACCAGCUUUCUACAUAAA 19 15877 CFTR-Intron2-778 GGACCAGCUUUCUACAUAAA 20 15878 CFTR-Intron2-779 GACCGGACCAGCUUUCUACAUAAA 24 15879 CFTR-Intron2-780 GCACAGGCCUGAUGCCAGAUAA 22 15880 CFTR-Intron2-781 GCUUUGAAUAUCUAAGUUUUAA 22 15881 CFTR-Intron2-782 GAAAAAUACACAUUUGGUUUCA 22 15882 CFTR-Intron2-783 GCUUAAGUAAAUAAAAGGA 19 15883 CFTR-Intron2-784 GCUCAAUUUUGUGACCAUGGA 21 15884 CFTR-Intron2-785 GGCUCAAUUUUGUGACCAUGGA 22 15885 CFTR-Intron2-786 GUUUUAAUUGGAUGCUGA 18 15886 CFTR-Intron2-787 GAAUGGUAGUCCCCCCCAUA 20 15887 CFTR-Intron2-788 GGAAUGGUAGUCCCCCCCAUA 21 15888 CFTR-Intron2-789 GACAAGUUCAAAAUAAUAUA 20 15889 CFTR-Intron2-790 GCUCUCAUUAGCAAGCUUCUA 21 15890 CFTR-Intron2-791 GGCUCUCAUUAGCAAGCUUCUA 22 15891 CFTR-Intron2-792 GGGCUCUCAUUAGCAAGCUUCUA 23 15892 CFTR-Intron2-793 GUUCAAAAUAAUAUAAUGGGUA 22 15893 CFTR-Intron2-794 GAUAAUAUACUUUGCCAGUUA 21 15894 CFTR-Intron2-795 GAGAUAAUAUACUUUGCCAGUUA 23 15895 CFTR-Intron2-796 GUAUUUAUGGCCAGAUAGAGAAC 23 15896 CFTR-Intron2-797 GAUGUAUCCCCAAGUGCC 18 15897 CFTR-Intron2-798 GUUCCUAAAACUACAUUGCC 20 15898 CFTR-Intron2-799 GAAAAAUCCCAGAGACUC 18 15899 CFTR-Intron2-800 GUGAAAAAUCCCAGAGACUC 20 15900 CFTR-Intron2-801 GCCAGAUAAAAGGGUGAGUGAAG 23 15901 CFTR-Intron2-802 GUCUUAUUAGAGACCAUGAG 20 15902 CFTR-Intron2-803 GCCUGAUGCCAGAUAAAAGG 20 15903 CFTR-Intron2-804 GUACCUGUUACAUGCCAGG 19 15904 CFTR-Intron2-805 GAGUACCUGUUACAUGCCAGG 21 15905 CFTR-Intron2-806 GAAUGAUUAAUCAGAGUAGGG 21 15906 CFTR-Intron2-807 GGAAUGAUUAAUCAGAGUAGGG 22 15907 CFTR-Intron2-808 GGGAAUGAUUAAUCAGAGUAGGG 23 15908 CFTR-Intron2-809 GAACAUGAAUCUGAAUUUG 19 15909 CFTR-Intron2-810 GCCAGAUAGAGAACAUGAAU 20 15910 CFTR-Intron2-811 GAUGCUGAGGGAAUGAUUAAU 21 15911 CFTR-Intron2-812 GGAUGCUGAGGGAAUGAUUAAU 22 15912 CFTR-Intron2-813 GCUUUCAAAACCUUUAUAU 19 15913 CFTR-Intron2-814 GAAUAUCUCCUCUCAGCCACU 21 15914 CFTR-Intron2-815 GUAGAAUAUCUCCUCUCAGCCACU 24 15915 CFTR-Intron2-816 GCUCCAUAUUUAGCUUCUUACU 22 15916 CFTR-Intron2-817 GUCUGUAUUGCCUUGCUCUCU 21 15917 CFTR-Intron2-818 GGUCUGUAUUGCCUUGCUCUCU 22 15918 CFTR-Intron2-819 GAGGUCUGUAUUGCCUUGCUCUCU 24 15919 CFTR-Intron2-820 GUUUCCUUUCCAAUCAAAAGGU 22 15920 CFTR-Intron2-821 GCCCCGGCCUAUUACUCCUU 20 15921 CFTR-Intron2-822 GUCAGGAUAUGAACUUUUU 19 15922 CFTR-Intron2-823 GUAGUCAGGAUAUGAACUUUUU 22 15923

Table 38B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 38B 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-824 + UAGCUAUGAAAGAAAAAA 18 15924 CFTR-Intron2-825 + UUAGCUAUGAAAGAAAAAA 19 15925 CFTR-Intron2-826 + UGUACAUAAACCAACAAA 18 15926 CFTR-Intron2-827 + UGUGUACAUAAACCAACAAA 20 15927 CFTR-Intron2-828 + UUAUUUACUUAAGCUAGUAAA 21 15928 CFTR-Intron2-829 + UUUAUUUACUUAAGCUAGUAAA 22 15929 CFTR-Intron2-830 + UUUUAUUUACUUAAGCUAGUAAA 23 15930 CFTR-Intron2-831 + CUUUUAUUUACUUAAGCUAGUAAA 24 15931 CFTR-Intron2-832 + CCUUUUUUCUCUUCACAA 18 15932 CFTR-Intron2-233 + AGCCUUUUUUCUCUUCACAA 20 15333 CFTR-Intron2-833 + AAGCCUUUUUUCUCUUCACAA 21 15933 CFTR-Intron2-834 + AAAGCCUUUUUUCUCUUCACAA 22 15934 CFTR-Intron2-835 + UGAAAGCCUUUUUUCUCUUCACAA 24 15935 CFTR-Intron2-836 + ACCUUCUCCAUCAAAGGAGAA 21 15936 CFTR-Intron2-837 + CACCUUCUCCAUCAAAGGAGAA 22 15937 CFTR-Intron2-838 + UCACCUUCUCCAUCAAAGGAGAA 23 15938 CFTR-Intron2-839 + CUCACCUUCUCCAUCAAAGGAGAA 24 15939 CFTR-Intron2-840 + UGGCUCUAAAUCACUCUAA 19 15940 CFTR-Intron2-250 + AUGGCUCUAAAUCACUCUAA 20 15350 CFTR-Intron2-841 + CAUGGCUCUAAAUCACUCUAA 21 15941 CFTR-Intron2-842 + ACAUGGCUCUAAAUCACUCUAA 22 15942 CFTR-Intron2-843 + AACAUGGCUCUAAAUCACUCUAA 23 15943 CFTR-Intron2-844 + AAACAUGGCUCUAAAUCACUCUAA 24 15944 CFTR-Intron2-845 + UAGACUAUGAGUGGCCCA 18 15945 CFTR-Intron2-846 + CUAGACUAUGAGUGGCCCA 19 15946 CFTR-Intron2-261 + UCUAGACUAUGAGUGGCCCA 20 15361 CFTR-Intron2-847 + UUCUAGACUAUGAGUGGCCCA 21 15947 CFTR-Intron2-848 + AUUCUAGACUAUGAGUGGCCCA 22 15948 CFTR-Intron2-849 + CAUUCUAGACUAUGAGUGGCCCA 23 15949 CFTR-Intron2-850 + UCAUUCUAGACUAUGAGUGGCCCA 24 15950 CFTR-Intron2-851 + UUUGAGUCCUUGGUCCCA 18 15951 CFTR-Intron2-852 + AUUUGAGUCCUUGGUCCCA 19 15952 CFTR-Intron2-853 + CAUUUGAGUCCUUGGUCCCA 20 15953 CFTR-Intron2-854 + UGGCAUUUGAGUCCUUGGUCCCA 23 15954 CFTR-Intron2-855 + UUACCUUAAGACUUCCCA 18 15955 CFTR-Intron2-856 + AUUACCUUAAGACUUCCCA 19 15956 CFTR-Intron2-263 + CAUUACCUUAAGACUUCCCA 20 15363 CFTR-Intron2-857 + CCAUUACCUUAAGACUUCCCA 21 15957 CFTR-Intron2-858 + AGCCAUUACCUUAAGACUUCCCA 23 15958 CFTR-Intron2-859 + UAGCCAUUACCUUAAGACUUCCCA 24 15959 CFTR-Intron2-860 + AGAGAGACCAGGAGAGCA 18 15960 CFTR-Intron2-861 + UAGAGAGACCAGGAGAGCA 19 15961 CFTR-Intron2-862 + UCCUUAAAGAUAGGAGCA 18 15962 CFTR-Intron2-863 + UGGUCCUUAAAGAUAGGAGCA 21 15963 CFTR-Intron2-864 + CGUGGUCCUUAAAGAUAGGAGCA 23 15964 CFTR-Intron2-865 + UCGUGGUCCUUAAAGAUAGGAGCA 24 15965 CFTR-Intron2-866 + CUUGUCAAUAUACCUGCA 18 15966 CFTR-Intron2-867 + ACUUGUCAAUAUACCUGCA 19 15967 CFTR-Intron2-868 + AACUUGUCAAUAUACCUGCA 20 15968 CFTR-Intron2-869 + UGAACUUGUCAAUAUACCUGCA 22 15969 CFTR-Intron2-870 + UUGAACUUGUCAAUAUACCUGCA 23 15970 CFTR-Intron2-871 + UUUGAACUUGUCAAUAUACCUGCA 24 15971 CFTR-Intron2-872 + AGAUGGGAAAGCCAAGGA 18 15972 CFTR-Intron2-873 + CAGAUGGGAAAGCCAAGGA 19 15973 CFTR-Intron2-280 + UCAGAUGGGAAAGCCAAGGA 20 15380 CFTR-Intron2-874 + CCUGACUACAAUCUUGGA 18 15974 CFTR-Intron2-875 + UCCUGACUACAAUCUUGGA 19 15975 CFTR-Intron2-876 + AUCCUGACUACAAUCUUGGA 20 15976 CFTR-Intron2-877 + UAUCCUGACUACAAUCUUGGA 21 15977 CFTR-Intron2-878 + AUAUCCUGACUACAAUCUUGGA 22 15978 CFTR-Intron2-879 + CAUAUCCUGACUACAAUCUUGGA 23 15979 CFTR-Intron2-880 + UCAUAUCCUGACUACAAUCUUGGA 24 15980 CFTR-Intron2-881 + UGCACACUGCAGUUAUGUA 19 15981 CFTR-Intron2-882 + UUGCACACUGCAGUUAUGUA 20 15982 CFTR-Intron2-883 + UUUGCACACUGCAGUUAUGUA 21 15983 CFTR-Intron2-884 + UGGUUUGCACACUGCAGUUAUGUA 24 15984 CFTR-Intron2-885 + AGGUCGGGGAAUUUCUUUA 19 15985 CFTR-Intron2-886 + AAGGUCGGGGAAUUUCUUUA 20 15986 CFTR-Intron2-887 + CAAGGUCGGGGAAUUUCUUUA 21 15987 CFTR-Intron2-888 + AGGCAAGGUCGGGGAAUUUCUUUA 24 15988 CFTR-Intron2-889 + CCACAAAUUGUUAGCACC 18 15989 CFTR-Intron2-890 + UGCCACAAAUUGUUAGCACC 20 15990 CFTR-Intron2-891 + UGGUGCCACAAAUUGUUAGCACC 23 15991 CFTR-Intron2-892 + UUGGUGCCACAAAUUGUUAGCACC 24 15992 CFTR-Intron2-893 + AAGCCAGGGUCACUUCCC 18 15993 CFTR-Intron2-894 + UGAAGCCAGGGUCACUUCCC 20 15994 CFTR-Intron2-895 + UGUGAAGCCAGGGUCACUUCCC 22 15995 CFTR-Intron2-896 + AUGUGAAGCCAGGGUCACUUCCC 23 15996 CFTR-Intron2-897 + AAUGUGAAGCCAGGGUCACUUCCC 24 15997 CFTR-Intron2-898 + AGUUAUGAAAUGUGAAGC 18 15998 CFTR-Intron2-899 + CAGUUAUGAAAUGUGAAGC 19 15999 CFTR-Intron2-900 + AGGCAGUUAUGAAAUGUGAAGC 22 16000 CFTR-Intron2-901 + AAGGCAGUUAUGAAAUGUGAAGC 23 16001 CFTR-Intron2-902 + CAAGGCAGUUAUGAAAUGUGAAGC 24 16002 CFTR-Intron2-903 + AGCCUGGCAAUCUCUAAGC 19 16003 CFTR-Intron2-904 + AAGCCUGGCAAUCUCUAAGC 20 16004 CFTR-Intron2-905 + CAAGCCUGGCAAUCUCUAAGC 21 16005 CFTR-Intron2-906 + ACAAGCCUGGCAAUCUCUAAGC 22 16006 CFTR-Intron2-907 + AGACAAGCCUGGCAAUCUCUAAGC 24 16007 CFTR-Intron2-908 + AGGCAAUACAGACCUCAGC 19 16008 CFTR-Intron2-322 + AAGGCAAUACAGACCUCAGC 20 15422 CFTR-Intron2-909 + CAAGGCAAUACAGACCUCAGC 21 16009 CFTR-Intron2-910 + AGCAAGGCAAUACAGACCUCAGC 23 16010 CFTR-Intron2-911 + AGCCAUUUCACAUUCCAUC 19 16011 CFTR-Intron2-912 + UAGCCAUUUCACAUUCCAUC 20 16012 CFTR-Intron2-913 + CUAGCCAUUUCACAUUCCAUC 21 16013 CFTR-Intron2-914 + UGCUAGCCAUUUCACAUUCCAUC 23 16014 CFTR-Intron2-915 + AUGCUAGCCAUUUCACAUUCCAUC 24 16015 CFTR-Intron2-916 + AGGGGUAAGCACUAUGACUC 20 16016 CFTR-Intron2-917 + AAGGGGUAAGCACUAUGACUC 21 16017 CFTR-Intron2-918 + CAAGGGGUAAGCACUAUGACUC 22 16018 CFTR-Intron2-919 + CCAAGGGGUAAGCACUAUGACUC 23 16019 CFTR-Intron2-920 + CCCAAGGGGUAAGCACUAUGACUC 24 16020 CFTR-Intron2-921 + CUAUGACUCAAGAGUCUC 18 16021 CFTR-Intron2-922 + ACUAUGACUCAAGAGUCUC 19 16022 CFTR-Intron2-331 + CACUAUGACUCAAGAGUCUC 20 15431 CFTR-Intron2-923 + AGCACUAUGACUCAAGAGUCUC 22 16023 CFTR-Intron2-924 + AAGCACUAUGACUCAAGAGUCUC 23 16024 CFTR-Intron2-925 + UAAGCACUAUGACUCAAGAGUCUC 24 16025 CFTR-Intron2-926 + UGAGGAGAAGGCAAGGUCG 19 16026 CFTR-Intron2-349 + CUGAGGAGAAGGCAAGGUCG 20 15449 CFTR-Intron2-927 + UUAAAUUGAAUCAACAUG 18 16027 CFTR-Intron2-928 + UUUAAAUUGAAUCAACAUG 19 16028 CFTR-Intron2-358 + UUUUAAAUUGAAUCAACAUG 20 15458 CFTR-Intron2-929 + UGUACUGGCAUAGCAUUG 18 16029 CFTR-Intron2-930 + UUGUACUGGCAUAGCAUUG 19 16030 CFTR-Intron2-931 + UUUGUACUGGCAUAGCAUUG 20 16031 CFTR-Intron2-932 + UGGGUUUGUACUGGCAUAGCAUUG 24 16032 CFTR-Intron2-933 + AGGCAAAUGCCACCAGGUGGCAU 23 16033 CFTR-Intron2-934 + AAGGCAAAUGCCACCAGGUGGCAU 24 16034 CFTR-Intron2-935 + AUAAUGAUGCUUUCCACU 18 16035 CFTR-Intron2-936 + AGAUAAUGAUGCUUUCCACU 20 16036 CFTR-Intron2-937 + CCUAGUUCAUUCUAGACU 18 16037 CFTR-Intron2-938 + AGCCUAGUUCAUUCUAGACU 20 16038 CFTR-Intron2-939 + CAGCCUAGUUCAUUCUAGACU 21 16039 CFTR-Intron2-940 + UCAGCCUAGUUCAUUCUAGACU 22 16040 CFTR-Intron2-941 + CUCAGCCUAGUUCAUUCUAGACU 23 16041 CFTR-Intron2-942 + ACUCAGCCUAGUUCAUUCUAGACU 24 16042 CFTR-Intron2-943 + CCAUAACAUUUGGUUACU 18 16043 CFTR-Intron2-944 + UCCAUAACAUUUGGUUACU 19 16044 CFTR-Intron2-945 + AUCCAUAACAUUUGGUUACU 20 16045 CFTR-Intron2-946 + CAUCCAUAACAUUUGGUUACU 21 16046 CFTR-Intron2-947 + CCAUCCAUAACAUUUGGUUACU 22 16047 CFTR-Intron2-948 + CCCAUCCAUAACAUUUGGUUACU 23 16048 CFTR-Intron2-949 + UCCCAUCCAUAACAUUUGGUUACU 24 16049 CFTR-Intron2-950 + UCCCACUAGCUUAAUUCU 18 16050 CFTR-Intron2-951 + CUCCCACUAGCUUAAUUCU 19 16051 CFTR-Intron2-952 + ACUCCCACUAGCUUAAUUCU 20 16052 CFTR-Intron2-953 + UACUCCCACUAGCUUAAUUCU 21 16053 CFTR-Intron2-954 + CUACUCCCACUAGCUUAAUUCU 22 16054 CFTR-Intron2-955 + UGCUACUCCCACUAGCUUAAUUCU 24 16055 CFTR-Intron2-956 + UGGCCCUUGAUCUUAGAAGU 20 16056 CFTR-Intron2-957 + CUGGCCCUUGAUCUUAGAAGU 21 16057 CFTR-Intron2-958 + AGCUGGCCCUUGAUCUUAGAAGU 23 16058 CFTR-Intron2-959 + AAGCUGGCCCUUGAUCUUAGAAGU 24 16059 CFTR-Intron2-960 ACCAGCUUUCUACAUAAA 18 16060 CFTR-Intron2-961 CGGACCAGCUUUCUACAUAAA 21 16061 CFTR-Intron2-962 CCGGACCAGCUUUCUACAUAAA 22 16062 CFTR-Intron2-963 ACCGGACCAGCUUUCUACAUAAA 23 16063 CFTR-Intron2-964 AGGCCUGAUGCCAGAUAA 18 16064 CFTR-Intron2-965 CAGGCCUGAUGCCAGAUAA 19 16065 CFTR-Intron2-966 ACAGGCCUGAUGCCAGAUAA 20 16066 CFTR-Intron2-967 CACAGGCCUGAUGCCAGAUAA 21 16067 CFTR-Intron2-968 AGCACAGGCCUGAUGCCAGAUAA 23 16068 CFTR-Intron2-969 CAGCACAGGCCUGAUGCCAGAUAA 24 16069 CFTR-Intron2-970 CUUUGAAUAUCUAAGUUUUAA 21 16070 CFTR-Intron2-971 AGCUUUGAAUAUCUAAGUUUUAA 23 16071 CFTR-Intron2-972 CAGCUUUGAAUAUCUAAGUUUUAA 24 16072 CFTR-Intron2-973 UGCACCAAAGUAAAAACA 18 16073 CFTR-Intron2-974 UUGCACCAAAGUAAAAACA 19 16074 CFTR-Intron2-975 AUUGCACCAAAGUAAAAACA 20 16075 CFTR-Intron2-976 UAUUGCACCAAAGUAAAAACA 21 16076 CFTR-Intron2-977 UUAUUGCACCAAAGUAAAAACA 22 16077 CFTR-Intron2-978 AUUAUUGCACCAAAGUAAAAACA 23 16078 CFTR-Intron2-979 AAUUAUUGCACCAAAGUAAAAACA 24 16079 CFTR-Intron2-980 AAAAAUACACAUUUGGUUUCA 21 16080 CFTR-Intron2-981 UGAAAAAUACACAUUUGGUUUCA 23 16081 CFTR-Intron2-982 CUGAAAAAUACACAUUUGGUUUCA 24 16082 CFTR-Intron2-983 CUUAAGUAAAUAAAAGGA 18 16083 CFTR-Intron2-984 AGCUUAAGUAAAUAAAAGGA 20 16084 CFTR-Intron2-985 CAAUUUUGUGACCAUGGA 18 16085 CFTR-Intron2-986 UCAAUUUUGUGACCAUGGA 19 16086 CFTR-Intron2-987 CUCAAUUUUGUGACCAUGGA 20 16087 CFTR-Intron2-988 UGGCUCAAUUUUGUGACCAUGGA 23 16088 CFTR-Intron2-989 CUGGCUCAAUUUUGUGACCAUGGA 24 16089 CFTR-Intron2-990 AGUUUUAAUUGGAUGCUGA 19 16090 CFTR-Intron2-282 AAGUUUUAAUUGGAUGCUGA 20 15382 CFTR-Intron2-991 UAAGUUUUAAUUGGAUGCUGA 21 16091 CFTR-Intron2-992 CUAAGUUUUAAUUGGAUGCUGA 22 16092 CFTR-Intron2-993 UCUAAGUUUUAAUUGGAUGCUGA 23 16093 CFTR-Intron2-994 AUCUAAGUUUUAAUUGGAUGCUGA 24 16094 CFTR-Intron2-995 AUGGUAGUCCCCCCCAUA 18 16095 CFTR-Intron2-996 AAUGGUAGUCCCCCCCAUA 19 16096 CFTR-Intron2-997 AGGAAUGGUAGUCCCCCCCAUA 22 16097 CFTR-Intron2-998 UAGGAAUGGUAGUCCCCCCCAUA 23 16098 CFTR-Intron2-999 CUAGGAAUGGUAGUCCCCCCCAUA 24 16099 CFTR-Intron2-1000 CAAGUUCAAAAUAAUAUA 18 16100 CFTR-Intron2-1001 ACAAGUUCAAAAUAAUAUA 19 16101 CFTR-Intron2-1002 UGACAAGUUCAAAAUAAUAUA 21 16102 CFTR-Intron2-1003 UUGACAAGUUCAAAAUAAUAUA 22 16103 CFTR-Intron2-1004 AUUGACAAGUUCAAAAUAAUAUA 23 16104 CFTR-Intron2-1005 UAUUGACAAGUUCAAAAUAAUAUA 24 16105 CFTR-Intron2-1006 CUCAUUAGCAAGCUUCUA 18 16106 CFTR-Intron2-1007 UCUCAUUAGCAAGCUUCUA 19 16107 CFTR-Intron2-290 CUCUCAUUAGCAAGCUUCUA 20 15390 CFTR-Intron2-1008 AGGGCUCUCAUUAGCAAGCUUCUA 24 16108 CFTR-Intron2-1009 AAAAUAAUAUAAUGGGUA 18 16109 CFTR-Intron2-1010 CAAAAUAAUAUAAUGGGUA 19 16110 CFTR-Intron2-1011 UCAAAAUAAUAUAAUGGGUA 20 16111 CFTR-Intron2-1012 UUCAAAAUAAUAUAAUGGGUA 21 16112 CFTR-Intron2-1013 AGUUCAAAAUAAUAUAAUGGGUA 23 16113 CFTR-Intron2-1014 AAGUUCAAAAUAAUAUAAUGGGUA 24 16114 CFTR-Intron2-1015 AAUAUACUUUGCCAGUUA 18 16115 CFTR-Intron2-1016 UAAUAUACUUUGCCAGUUA 19 16116 CFTR-Intron2-1017 AUAAUAUACUUUGCCAGUUA 20 16117 CFTR-Intron2-1018 AGAUAAUAUACUUUGCCAGUUA 22 16118 CFTR-Intron2-1019 AGAGAUAAUAUACUUUGCCAGUUA 24 16119 CFTR-Intron2-1020 UAUGGCCAGAUAGAGAAC 18 16120 CFTR-Intron2-1021 UUAUGGCCAGAUAGAGAAC 19 16121 CFTR-Intron2-1022 UUUAUGGCCAGAUAGAGAAC 20 16122 CFTR-Intron2-1023 AUUUAUGGCCAGAUAGAGAAC 21 16123 CFTR-Intron2-1024 UAUUUAUGGCCAGAUAGAGAAC 22 16124 CFTR-Intron2-1025 UGUAUUUAUGGCCAGAUAGAGAAC 24 16125 CFTR-Intron2-1026 UGGCUCAAUUUUGUGACC 18 16126 CFTR-Intron2-1027 CUGGCUCAAUUUUGUGACC 19 16127 CFTR-Intron2-1028 UCUGGCUCAAUUUUGUGACC 20 16128 CFTR-Intron2-1029 AUCUGGCUCAAUUUUGUGACC 21 16129 CFTR-Intron2-1030 UAUCUGGCUCAAUUUUGUGACC 22 16130 CFTR-Intron2-1031 CUAUCUGGCUCAAUUUUGUGACC 23 16131 CFTR-Intron2-1032 CCUAUCUGGCUCAAUUUUGUGACC 24 16132 CFTR-Intron2-1033 UGAUGUAUCCCCAAGUGCC 19 16133 CFTR-Intron2-1034 AUGAUGUAUCCCCAAGUGCC 20 16134 CFTR-Intron2-1035 UCCUAAAACUACAUUGCC 18 16135 CFTR-Intron2-1036 UUCCUAAAACUACAUUGCC 19 16136 CFTR-Intron2-1037 UGUUCCUAAAACUACAUUGCC 21 16137 CFTR-Intron2-1038 AUGUUCCUAAAACUACAUUGCC 22 16138 CFTR-Intron2-1039 CAUGUUCCUAAAACUACAUUGCC 23 16139 CFTR-Intron2-1040 CCAUGUUCCUAAAACUACAUUGCC 24 16140 CFTR-Intron2-1041 UGAAAAAUCCCAGAGACUC 19 16141 CFTR-Intron2-1042 UGUGAAAAAUCCCAGAGACUC 21 16142 CFTR-Intron2-1043 AUGUGAAAAAUCCCAGAGACUC 22 16143 CFTR-Intron2-1044 AAUGUGAAAAAUCCCAGAGACUC 23 16144 CFTR-Intron2-1045 AAAUGUGAAAAAUCCCAGAGACUC 24 16145 CFTR-Intron2-1046 CUUGGGCCACUCAUAGUC 18 16146 CFTR-Intron2-1047 CCUUGGGCCACUCAUAGUC 19 16147 CFTR-Intron2-1048 CCCUUGGGCCACUCAUAGUC 20 16148 CFTR-Intron2-1049 CCCCUUGGGCCACUCAUAGUC 21 16149 CFTR-Intron2-1050 ACCCCUUGGGCCACUCAUAGUC 22 16150 CFTR-Intron2-1051 UACCCCUUGGGCCACUCAUAGUC 23 16151 CFTR-Intron2-1052 UUACCCCUUGGGCCACUCAUAGUC 24 16152 CFTR-Intron2-1053 AUUUCUCCUUUGAUGGAGAAG 21 16153 CFTR-Intron2-1054 CAUUUCUCCUUUGAUGGAGAAG 22 16154 CFTR-Intron2-1055 CCAUUUCUCCUUUGAUGGAGAAG 23 16155 CFTR-Intron2-1056 UCCAUUUCUCCUUUGAUGGAGAAG 24 16156 CFTR-Intron2-1057 CAGAUAAAAGGGUGAGUGAAG 21 16157 CFTR-Intron2-1058 CCAGAUAAAAGGGUGAGUGAAG 22 16158 CFTR-Intron2-1059 UGCCAGAUAAAAGGGUGAGUGAAG 24 16159 CFTR-Intron2-1060 CUUAUUAGAGACCAUGAG 18 16160 CFTR-Intron2-1061 UCUUAUUAGAGACCAUGAG 19 16161 CFTR-Intron2-1062 UGUCUUAUUAGAGACCAUGAG 21 16162 CFTR-Intron2-1063 UUGUCUUAUUAGAGACCAUGAG 22 16163 CFTR-Intron2-1064 UUUGUCUUAUUAGAGACCAUGAG 23 16164 CFTR-Intron2-1065 AUUUGUCUUAUUAGAGACCAUGAG 24 16165 CFTR-Intron2-1066 CUGAUGCCAGAUAAAAGG 18 16166 CFTR-Intron2-1067 CCUGAUGCCAGAUAAAAGG 19 16167 CFTR-Intron2-1068 UACCUGUUACAUGCCAGG 18 16168 CFTR-Intron2-1069 AGUACCUGUUACAUGCCAGG 20 16169 CFTR-Intron2-1070 UGAGUACCUGUUACAUGCCAGG 22 16170 CFTR-Intron2-1071 UUGAGUACCUGUUACAUGCCAGG 23 16171 CFTR-Intron2-1072 UUUGAGUACCUGUUACAUGCCAGG 24 16172 CFTR-Intron2-1073 AGUCUAGAAUGAACUAGG 18 16173 CFTR-Intron2-1074 UAGUCUAGAAUGAACUAGG 19 16174 CFTR-Intron2-1075 AUAGUCUAGAAUGAACUAGG 20 16175 CFTR-Intron2-1076 CAUAGUCUAGAAUGAACUAGG 21 16176 CFTR-Intron2-1077 UCAUAGUCUAGAAUGAACUAGG 22 16177 CFTR-Intron2-1078 CUCAUAGUCUAGAAUGAACUAGG 23 16178 CFTR-Intron2-1079 ACUCAUAGUCUAGAAUGAACUAGG 24 16179 CFTR-Intron2-1080 UGAUUAAUCAGAGUAGGG 18 16180 CFTR-Intron2-1081 AUGAUUAAUCAGAGUAGGG 19 16181 CFTR-Intron2-1082 AAUGAUUAAUCAGAGUAGGG 20 16182 CFTR-Intron2-1083 AGGGAAUGAUUAAUCAGAGUAGGG 24 16183 CFTR-Intron2-1084 UUUAUUGAAAUAUUUUGG 18 16184 CFTR-Intron2-1085 AUUUAUUGAAAUAUUUUGG 19 16185 CFTR-Intron2-1086 AAUUUAUUGAAAUAUUUUGG 20 16186 CFTR-Intron2-1087 AACAUGAAUCUGAAUUUG 18 16187 CFTR-Intron2-1088 AGAACAUGAAUCUGAAUUUG 20 16188 CFTR-Intron2-1089 CAGAUAGAGAACAUGAAU 18 16189 CFTR-Intron2-1090 CCAGAUAGAGAACAUGAAU 19 16190 CFTR-Intron2-1091 UGGUAACUUGACAGUAAU 18 16191 CFTR-Intron2-1092 AUGGUAACUUGACAGUAAU 19 16192 CFTR-Intron2-373 UAUGGUAACUUGACAGUAAU 20 15473 CFTR-Intron2-1093 UUAUGGUAACUUGACAGUAAU 21 16193 CFTR-Intron2-1094 CUUAUGGUAACUUGACAGUAAU 22 16194 CFTR-Intron2-1095 ACUUAUGGUAACUUGACAGUAAU 23 16195 CFTR-Intron2-1096 UACUUAUGGUAACUUGACAGUAAU 24 16196 CFTR-Intron2-1097 UGGAUGCUGAGGGAAUGAUUAAU 23 16197 CFTR-Intron2-1098 UUGGAUGCUGAGGGAAUGAUUAAU 24 16198 CFTR-Intron2-1099 CUUUCAAAACCUUUAUAU 18 16199 CFTR-Intron2-1100 UGCUUUCAAAACCUUUAUAU 20 16200 CFTR-Intron2-1101 UAUCUCCUCUCAGCCACU 18 16201 CFTR-Intron2-1102 AUAUCUCCUCUCAGCCACU 19 16202 CFTR-Intron2-1103 AAUAUCUCCUCUCAGCCACU 20 16203 CFTR-Intron2-1104 AGAAUAUCUCCUCUCAGCCACU 22 16204 CFTR-Intron2-1105 UAGAAUAUCUCCUCUCAGCCACU 23 16205 CFTR-Intron2-1106 CAUAUUUAGCUUCUUACU 18 16206 CFTR-Intron2-1107 CCAUAUUUAGCUUCUUACU 19 16207 CFTR-Intron2-1108 UCCAUAUUUAGCUUCUUACU 20 16208 CFTR-Intron2-1109 CUCCAUAUUUAGCUUCUUACU 21 16209 CFTR-Intron2-1110 UGCUCCAUAUUUAGCUUCUUACU 23 16210 CFTR-Intron2-1111 CUGCUCCAUAUUUAGCUUCUUACU 24 16211 CFTR-Intron2-1112 UGUAUUGCCUUGCUCUCU 18 16212 CFTR-Intron2-1113 CUGUAUUGCCUUGCUCUCU 19 16213 CFTR-Intron2-399 UCUGUAUUGCCUUGCUCUCU 20 15499 CFTR-Intron2-1114 AGGUCUGUAUUGCCUUGCUCUCU 23 16214 CFTR-Intron2-1115 UCAAAGAAUUAAGCUAGU 18 16215 CFTR-Intron2-1116 UUCAAAGAAUUAAGCUAGU 19 16216 CFTR-Intron2-404 AUUCAAAGAAUUAAGCUAGU 20 15504 CFTR-Intron2-1117 UAUUCAAAGAAUUAAGCUAGU 21 16217 CFTR-Intron2-1118 UUAUUCAAAGAAUUAAGCUAGU 22 16218 CFTR-Intron2-1119 UUUAUUCAAAGAAUUAAGCUAGU 23 16219 CFTR-Intron2-1120 UUUUAUUCAAAGAAUUAAGCUAGU 24 16220 CFTR-Intron2-1121 CCGUUCCAAGAUUGUAGU 18 16221 CFTR-Intron2-1122 UCCGUUCCAAGAUUGUAGU 19 16222 CFTR-Intron2-1123 AUCCGUUCCAAGAUUGUAGU 20 16223 CFTR-Intron2-1124 CAUCCGUUCCAAGAUUGUAGU 21 16224 CFTR-Intron2-1125 ACAUCCGUUCCAAGAUUGUAGU 22 16225 CFTR-Intron2-1126 CACAUCCGUUCCAAGAUUGUAGU 23 16226 CFTR-Intron2-1127 ACACAUCCGUUCCAAGAUUGUAGU 24 16227 CFTR-Intron2-1128 CCUUUCCAAUCAAAAGGU 18 16228 CFTR-Intron2-1129 UCCUUUCCAAUCAAAAGGU 19 16229 CFTR-Intron2-1130 UUCCUUUCCAAUCAAAAGGU 20 16230 CFTR-Intron2-1131 UUUCCUUUCCAAUCAAAAGGU 21 16231 CFTR-Intron2-1132 AGUUUCCUUUCCAAUCAAAAGGU 23 16232 CFTR-Intron2-1133 CAGUUUCCUUUCCAAUCAAAAGGU 24 16233 CFTR-Intron2-1134 CCCGGCCUAUUACUCCUU 18 16234 CFTR-Intron2-1135 CCCCGGCCUAUUACUCCUU 19 16235 CFTR-Intron2-1136 UGCCCCGGCCUAUUACUCCUU 21 16236 CFTR-Intron2-1137 CUGCCCCGGCCUAUUACUCCUU 22 16237 CFTR-Intron2-1138 ACUGCCCCGGCCUAUUACUCCUU 23 16238 CFTR-Intron2-1139 CACUGCCCCGGCCUAUUACUCCUU 24 16239 CFTR-Intron2-1140 UCUGAGUAACCAAAUGUU 18 16240 CFTR-Intron2-1141 CUCUGAGUAACCAAAUGUU 19 16241 CFTR-Intron2-1142 ACUCUGAGUAACCAAAUGUU 20 16242 CFTR-Intron2-1143 UACUCUGAGUAACCAAAUGUU 21 16243 CFTR-Intron2-1144 UUACUCUGAGUAACCAAAUGUU 22 16244 CFTR-Intron2-1145 CUUACUCUGAGUAACCAAAUGUU 23 16245 CFTR-Intron2-1146 UCUUACUCUGAGUAACCAAAUGUU 24 16246 CFTR-Intron2-1147 UCAGGAUAUGAACUUUUU 18 16247 CFTR-Intron2-1148 AGUCAGGAUAUGAACUUUUU 20 16248 CFTR-Intron2-1149 UAGUCAGGAUAUGAACUUUUU 21 16249 CFTR-Intron2-1150 UGUAGUCAGGAUAUGAACUUUUU 23 16250 CFTR-Intron2-1151 UUGUAGUCAGGAUAUGAACUUUUU 24 16251

Table 38C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2, start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 38C 3rd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-1152 + GAAUGUUAGCUAUGAAAGAAAAAA 24 16252 CFTR-Intron2-1153 + GUAAAAUAGGUAUAUUUUUUAAA 23 16253 CFTR-Intron2-1154 + GUUUCUGUCACUGGCAAUCAA 21 16254 CFTR-Intron2-1155 + GGUUUCUGUCACUGGCAAUCAA 22 16255 CFTR-Intron2-1156 + GGGUUUCUGUCACUGGCAAUCAA 23 16256 CFTR-Intron2-1157 + GCUAUGAAAGAAAAAAUAGAA 21 16257 CFTR-Intron2-1158 + GAAGUAGAGAGACCAGGAGAGCA 23 16258 CFTR-Intron2-1159 + GAUCAGAUGGGAAAGCCAAGGA 22 16259 CFTR-Intron2-1160 + GGAUCAGAUGGGAAAGCCAAGGA 23 16260 CFTR-Intron2-1161 + GAUUCAUUCAACAAAUAUUUA 21 16261 CFTR-Intron2-1162 + GGAUUCAUUCAACAAAUAUUUA 22 16262 CFTR-Intron2-1163 + GAUCACACCACUACACUCCAGC 22 16263 CFTR-Intron2-1164 + GAGAUCACACCACUACACUCCAGC 24 16264 CFTR-Intron2-1165 + GGCAGAUCACUUGAGGUC 18 16265 CFTR-Intron2-1166 + GGGCAGAUCACUUGAGGUC 19 16266 CFTR-Intron2-1167 + GCGGGCAGAUCACUUGAGGUC 21 16267 CFTR-Intron2-1168 + GGCGGGCAGAUCACUUGAGGUC 22 16268 CFTR-Intron2-1169 + GUGGGCAGAUCACUUGAGGUC 21 16269 CFTR-Intron2-1170 + GGUGGGCAGAUCACUUGAGGUC 22 16270 CFTR-Intron2-1171 + GCUACUCGAGAGGCUGAGGCAG 22 16271 CFTR-Intron2-1172 + GAUUCGCUUGAACCCAGGAGG 21 16272 CFTR-Intron2-1173 + GAGAUUCGCUUGAACCCAGGAGG 23 16273 CFTR-Intron2-1174 + GAGAUAAUGAUGCUUUCCACU 21 16274 CFTR-Intron2-1175 + GCCCUAUUCUAGGCACUU 18 16275 CFTR-Intron2-1176 + GGCCCUAUUCUAGGCACUU 19 16276 CFTR-Intron2-1177 + GCCAGGCCCUAUUCUAGGCACUU 23 16277 CFTR-Intron2-1178 GCAAACUCUGCCUCCUGGGUUCAA 24 16278 CFTR-Intron2-1179 GGCUAAUUUUUGUAGAGA 18 16279 CFTR-Intron2-1180 GCCUGGCUAAUUUUUGUAGAGA 22 16280 CFTR-Intron2-1181 GGCCUGGCUAAUUUUUGUAGAGA 23 16281 CFTR-Intron2-1182 GUUGCUGUUGUUUUUGAGA 19 16282 CFTR-Intron2-1183 GUUGUUGCUGUUGUUUUUGAGA 22 16283 CFTR-Intron2-1184 GUGUUGUUUGUUUUUGAGA 19 16284 CFTR-Intron2-1185 GUUUGUGUUGUUUGUUUUUGAGA 23 16285 CFTR-Intron2-1186 GUUUUGUUUUUUAUUUUUUA 20 16286 CFTR-Intron2-1187 GUUUAUGAUGUAUCCCCAAGUGCC 24 16287 CFTR-Intron2-1188 GUCUCGCUGUGUCACCCAGGC 21 16288 CFTR-Intron2-1189 GAGUCUCGCUGUGUCACCCAGGC 23 16289 CFTR-Intron2-1190 GUCUUGCUCUGUUGCCCAGGC 21 16290 CFTR-Intron2-1191 GAGUCUUGCUCUGUUGCCCAGGC 23 16291 CFTR-Intron2-1192 GCCCACCUUGGCCUCCCAAAAUGC 24 16292 CFTR-Intron2-1193 GAUUCUCCUGCCUCAGCCUC 20 16293 CFTR-Intron2-1194 GUGAUUCUCCUGCCUCAGCCUC 22 16294 CFTR-Intron2-1195 GCUCACUGCAAACUCUGCCUC 21 16295 CFTR-Intron2-1196 GUUCAAGCGAAUCUCAGUCUC 21 16296 CFTR-Intron2-1197 GGUUCAAGCGAAUCUCAGUCUC 22 16297 CFTR-Intron2-1198 GGGUUCAAGCGAAUCUCAGUCUC 23 16298 CFTR-Intron2-1199 GCUCACUGCAAACUUCGUCUC 21 16299 CFTR-Intron2-1200 GGCUCACUGCAAACUUCGUCUC 22 16300 CFTR-Intron2-1201 GAUAAAAGGGUGAGUGAAG 19 16301 CFTR-Intron2-1202 GCCUCAGCCUCUCGAGUAG 19 16302 CFTR-Intron2-1203 GGCCUGAUGCCAGAUAAAAGG 21 16303 CFTR-Intron2-1204 GAAAUUUAUUGAAAUAUUUUGG 22 16304 CFTR-Intron2-1205 GAGAACAUGAAUCUGAAUUUG 21 16305 CFTR-Intron2-1206 GUAUAUACUCAAUAAAUAUUUG 22 16306 CFTR-Intron2-1207 GGUAUAUACUCAAUAAAUAUUUG 23 16307 CFTR-Intron2-1208 GGCCAGAUAGAGAACAUGAAU 21 16308 CFTR-Intron2-1209 GCUGAGGGAAUGAUUAAU 18 16309 CFTR-Intron2-1210 GAGCCACUAUGCCCAGCU 18 16310 CFTR-Intron2-1211 GUGAGCCACUAUGCCCAGCU 20 16311 CFTR-Intron2-1212 GUGUGAGCCACUAUGCCCAGCU 22 16312 CFTR-Intron2-1213 GGUGUGAGCCACUAUGCCCAGCU 23 16313 CFTR-Intron2-1214 GUGCAAAUGCCAUGAGGU 18 16314 CFTR-Intron2-472 GUGUGCAAAUGCCAUGAGGU 20 15572 CFTR-Intron2-1215 GUGUGUGCAAAUGCCAUGAGGU 22 16315 CFTR-Intron2-1216 GGUGUGUGCAAAUGCCAUGAGGU 23 16316 CFTR-Intron2-474 GCCUUGGCCUCCCAAAGUGU 20 15574 CFTR-Intron2-1217 GCCCGCCUUGGCCUCCCAAAGUGU 24 16317

Table 38D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 2, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 38D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-1218 + UGUUAGCUAUGAAAGAAAAAA 21 16318 CFTR-Intron2-1219 + AUGUUAGCUAUGAAAGAAAAAA 22 16319 CFTR-Intron2-1220 + AAUGUUAGCUAUGAAAGAAAAAA 23 16320 CFTR-Intron2-1221 + UUUACUUAAGCUAGUAAA 18 16321 CFTR-Intron2-1222 + AUUUACUUAAGCUAGUAAA 19 16322 CFTR-Intron2-1223 + UAUUUACUUAAGCUAGUAAA 20 16323 CFTR-Intron2-1224 + AUAGGUAUAUUUUUUAAA 18 16324 CFTR-Intron2-1225 + AAUAGGUAUAUUUUUUAAA 19 16325 CFTR-Intron2-1226 + AAAUAGGUAUAUUUUUUAAA 20 16326 CFTR-Intron2-1227 + AAAAUAGGUAUAUUUUUUAAA 21 16327 CFTR-Intron2-1228 + UAAAAUAGGUAUAUUUUUUAAA 22 16328 CFTR-Intron2-1229 + AGUAAAAUAGGUAUAUUUUUUAAA 24 16329 CFTR-Intron2-1230 + UCUGUCACUGGCAAUCAA 18 16330 CFTR-Intron2-1231 + UUCUGUCACUGGCAAUCAA 19 16331 CFTR-Intron2-1232 + UUUCUGUCACUGGCAAUCAA 20 16332 CFTR-Intron2-1233 + UGGGUUUCUGUCACUGGCAAUCAA 24 16333 CFTR-Intron2-1234 + UUCUCCAUCAAAGGAGAA 18 16334 CFTR-Intron2-1235 + CUUCUCCAUCAAAGGAGAA 19 16335 CFTR-Intron2-1236 + CCUUCUCCAUCAAAGGAGAA 20 16336 CFTR-Intron2-1237 + AUGAAAGAAAAAAUAGAA 18 16337 CFTR-Intron2-1238 + UAUGAAAGAAAAAAUAGAA 19 16338 CFTR-Intron2-614 + CUAUGAAAGAAAAAAUAGAA 20 15714 CFTR-Intron2-1239 + AGCUAUGAAAGAAAAAAUAGAA 22 16339 CFTR-Intron2-1240 + UAGCUAUGAAAGAAAAAAUAGAA 23 16340 CFTR-Intron2-1241 + UUAGCUAUGAAAGAAAAAAUAGAA 24 16341 CFTR-Intron2-1242 + AAAUGCCAAAAAAAGGAA 18 16342 CFTR-Intron2-1243 + AAAAUGCCAAAAAAAGGAA 19 16343 CFTR-Intron2-1244 + CAAAAUGCCAAAAAAAGGAA 20 16344 CFTR-Intron2-1245 + UCAAAAUGCCAAAAAAAGGAA 21 16345 CFTR-Intron2-1246 + UUCAAAAUGCCAAAAAAAGGAA 22 16346 CFTR-Intron2-1247 + CUUCAAAAUGCCAAAAAAAGGAA 23 16347 CFTR-Intron2-1248 + CCUUCAAAAUGCCAAAAAAAGGAA 24 16348 CFTR-Intron2-1249 + AACAAACAAAAAACAUAA 18 16349 CFTR-Intron2-1250 + AAACAAACAAAAAACAUAA 19 16350 CFTR-Intron2-616 + CAAACAAACAAAAAACAUAA 20 15716 CFTR-Intron2-1251 + ACAAACAAACAAAAAACAUAA 21 16351 CFTR-Intron2-1252 + CACAAACAAACAAAAAACAUAA 22 16352 CFTR-Intron2-1253 + ACACAAACAAACAAAAAACAUAA 23 16353 CFTR-Intron2-1254 + AACACAAACAAACAAAAAACAUAA 24 16354 CFTR-Intron2-1255 + UUAUAAGAAAAGAAGUAA 18 16355 CFTR-Intron2-1256 + UUUAUAAGAAAAGAAGUAA 19 16356 CFTR-Intron2-1257 + UUUUAUAAGAAAAGAAGUAA 20 16357 CFTR-Intron2-1258 + AUUUUAUAAGAAAAGAAGUAA 21 16358 CFTR-Intron2-1259 + AAUUUUAUAAGAAAAGAAGUAA 22 16359 CFTR-Intron2-1260 + CAAUUUUAUAAGAAAAGAAGUAA 23 16360 CFTR-Intron2-1261 + CCAAUUUUAUAAGAAAAGAAGUAA 24 16361 CFTR-Intron2-1262 + AGUAGAGAGACCAGGAGAGCA 21 16362 CFTR-Intron2-1263 + AAGUAGAGAGACCAGGAGAGCA 22 16363 CFTR-Intron2-1264 + UGAAGUAGAGAGACCAGGAGAGCA 24 16364 CFTR-Intron2-1265 + AUCAGAUGGGAAAGCCAAGGA 21 16365 CFTR-Intron2-1266 + UGGAUCAGAUGGGAAAGCCAAGGA 24 16366 CFTR-Intron2-1267 + UCAUUCAACAAAUAUUUA 18 16367 CFTR-Intron2-1268 + UUCAUUCAACAAAUAUUUA 19 16368 CFTR-Intron2-1269 + AUUCAUUCAACAAAUAUUUA 20 16369 CFTR-Intron2-1270 + UGGAUUCAUUCAACAAAUAUUUA 23 16370 CFTR-Intron2-1271 + AUGGAUUCAUUCAACAAAUAUUUA 24 16371 CFTR-Intron2-1272 + ACACCACUACACUCCAGC 18 16372 CFTR-Intron2-1273 + CACACCACUACACUCCAGC 19 16373 CFTR-Intron2-1274 + UCACACCACUACACUCCAGC 20 16374 CFTR-Intron2-1275 + AUCACACCACUACACUCCAGC 21 16375 CFTR-Intron2-1276 + AGAUCACACCACUACACUCCAGC 23 16376 CFTR-Intron2-667 + CGGGCAGAUCACUUGAGGUC 20 15767 CFTR-Intron2-1277 + AGGCGGGCAGAUCACUUGAGGUC 23 16377 CFTR-Intron2-1278 + AAGGCGGGCAGAUCACUUGAGGUC 24 16378 CFTR-Intron2-668 + UGGGCAGAUCACUUGAGGUC 20 15768 CFTR-Intron2-1279 + AGGUGGGCAGAUCACUUGAGGUC 23 16379 CFTR-Intron2-1280 + AAGGUGGGCAGAUCACUUGAGGUC 24 16380 CFTR-Intron2-1281 + CUCGAGAGGCUGAGGCAG 18 16381 CFTR-Intron2-1282 + ACUCGAGAGGCUGAGGCAG 19 16382 CFTR-Intron2-1283 + UACUCGAGAGGCUGAGGCAG 20 16383 CFTR-Intron2-1284 + CUACUCGAGAGGCUGAGGCAG 21 16384 CFTR-Intron2-1285 + AGCUACUCGAGAGGCUGAGGCAG 23 16385 CFTR-Intron2-1286 + CAGCUACUCGAGAGGCUGAGGCAG 24 16386 CFTR-Intron2-1287 + CCUGAGGAGAAGGCAAGGUCG 21 16387 CFTR-Intron2-1288 + ACCUGAGGAGAAGGCAAGGUCG 22 16388 CFTR-Intron2-1289 + UACCUGAGGAGAAGGCAAGGUCG 23 16389 CFTR-Intron2-1290 + UUACCUGAGGAGAAGGCAAGGUCG 24 16390 CFTR-Intron2-1291 + UCGCUUGAACCCAGGAGG 18 16391 CFTR-Intron2-1292 + UUCGCUUGAACCCAGGAGG 19 16392 CFTR-Intron2-1293 + AUUCGCUUGAACCCAGGAGG 20 16393 CFTR-Intron2-1294 + AGAUUCGCUUGAACCCAGGAGG 22 16394 CFTR-Intron2-1295 + UGAGAUUCGCUUGAACCCAGGAGG 24 16395 CFTR-Intron2-1296 + UUUUUAAAUUGAAUCAACAUG 21 16396 CFTR-Intron2-1297 + UUUUUUAAAUUGAAUCAACAUG 22 16397 CFTR-Intron2-1298 + AUUUUUUAAAUUGAAUCAACAUG 23 16398 CFTR-Intron2-1299 + UAUUUUUUAAAUUGAAUCAACAUG 24 16399 CFTR-Intron2-1300 + AAUUAGCCAGGCAUUGUG 18 16400 CFTR-Intron2-1301 + AAAUUAGCCAGGCAUUGUG 19 16401 CFTR-Intron2-1302 + AAAAUUAGCCAGGCAUUGUG 20 16402 CFTR-Intron2-1303 + AAAAAUUAGCCAGGCAUUGUG 21 16403 CFTR-Intron2-1304 + CAAAAAUUAGCCAGGCAUUGUG 22 16404 CFTR-Intron2-1305 + ACAAAAAUUAGCCAGGCAUUGUG 23 16405 CFTR-Intron2-1306 + UACAAAAAUUAGCCAGGCAUUGUG 24 16406 CFTR-Intron2-1307 + AAUGCCACCAGGUGGCAU 18 16407 CFTR-Intron2-1308 + AAAUGCCACCAGGUGGCAU 19 16408 CFTR-Intron2-1309 + CAAAUGCCACCAGGUGGCAU 20 16409 CFTR-Intron2-1310 + AGAGAUAAUGAUGCUUUCCACU 22 16410 CFTR-Intron2-1311 + UAGAGAUAAUGAUGCUUUCCACU 23 16411 CFTR-Intron2-1312 + AUAGAGAUAAUGAUGCUUUCCACU 24 16412 CFTR-Intron2-1313 + UAUAUUUUCUAUUAUAGU 18 16413 CFTR-Intron2-1314 + AUAUAUUUUCUAUUAUAGU 19 16414 CFTR-Intron2-1315 + UAUAUAUUUUCUAUUAUAGU 20 16415 CFTR-Intron2-1316 + UUAUAUAUUUUCUAUUAUAGU 21 16416 CFTR-Intron2-1317 + AUUAUAUAUUUUCUAUUAUAGU 22 16417 CFTR-Intron2-1318 + AAUUAUAUAUUUUCUAUUAUAGU 23 16418 CFTR-Intron2-1319 + AAAUUAUAUAUUUUCUAUUAUAGU 24 16419 CFTR-Intron2-1320 + ACAAAAAUAAUAGAACGU 18 16420 CFTR-Intron2-1321 + AACAAAAAUAAUAGAACGU 19 16421 CFTR-Intron2-1322 + AAACAAAAAUAAUAGAACGU 20 16422 CFTR-Intron2-1323 + AAAACAAAAAUAAUAGAACGU 21 16423 CFTR-Intron2-1324 + CAAAACAAAAAUAAUAGAACGU 22 16424 CFTR-Intron2-1325 + ACAAAACAAAAAUAAUAGAACGU 23 16425 CFTR-Intron2-1326 + AACAAAACAAAAAUAAUAGAACGU 24 16426 CFTR-Intron2-718 + AGGCCCUAUUCUAGGCACUU 20 15818 CFTR-Intron2-1327 + CAGGCCCUAUUCUAGGCACUU 21 16427 CFTR-Intron2-1328 + CCAGGCCCUAUUCUAGGCACUU 22 16428 CFTR-Intron2-1329 + UGCCAGGCCCUAUUCUAGGCACUU 24 16429 CFTR-Intron2-1330 UCUGCCUCCUGGGUUCAA 18 16430 CFTR-Intron2-1331 CUCUGCCUCCUGGGUUCAA 19 16431 CFTR-Intron2-1332 ACUCUGCCUCCUGGGUUCAA 20 16432 CFTR-Intron2-1333 AACUCUGCCUCCUGGGUUCAA 21 16433 CFTR-Intron2-1334 AAACUCUGCCUCCUGGGUUCAA 22 16434 CFTR-Intron2-1335 CAAACUCUGCCUCCUGGGUUCAA 23 16435 CFTR-Intron2-1336 UGAAUAUCUAAGUUUUAA 18 16436 CFTR-Intron2-1337 UUGAAUAUCUAAGUUUUAA 19 16437 CFTR-Intron2-1338 UUUGAAUAUCUAAGUUUUAA 20 16438 CFTR-Intron2-1339 UUUUAUUGAUUUUAUUCA 18 16439 CFTR-Intron2-1340 UUUUUAUUGAUUUUAUUCA 19 16440 CFTR-Intron2-1341 AUUUUUAUUGAUUUUAUUCA 20 16441 CFTR-Intron2-1342 UAUUUUUAUUGAUUUUAUUCA 21 16442 CFTR-Intron2-1343 UUAUUUUUAUUGAUUUUAUUCA 22 16443 CFTR-Intron2-1344 UUUAUUUUUAUUGAUUUUAUUCA 23 16444 CFTR-Intron2-1345 CUUUAUUUUUAUUGAUUUUAUUCA 24 16445 CFTR-Intron2-1346 AAUACACAUUUGGUUUCA 18 16446 CFTR-Intron2-1347 AAAUACACAUUUGGUUUCA 19 16447 CFTR-Intron2-1348 AAAAUACACAUUUGGUUUCA 20 16448 CFTR-Intron2-1349 UGGCUAAUUUUUGUAGAGA 19 16449 CFTR-Intron2-626 CUGGCUAAUUUUUGUAGAGA 20 15726 CFTR-Intron2-1350 CCUGGCUAAUUUUUGUAGAGA 21 16450 CFTR-Intron2-1351 AGGCCUGGCUAAUUUUUGUAGAGA 24 16451 CFTR-Intron2-1352 UUGCUGUUGUUUUUGAGA 18 16452 CFTR-Intron2-1353 UGUUGCUGUUGUUUUUGAGA 20 16453 CFTR-Intron2-1354 UUGUUGCUGUUGUUUUUGAGA 21 16454 CFTR-Intron2-1355 UGUUGUUGCUGUUGUUUUUGAGA 23 16455 CFTR-Intron2-1356 UUGUUGUUGCUGUUGUUUUUGAGA 24 16456 CFTR-Intron2-1357 UGUUGUUUGUUUUUGAGA 18 16457 CFTR-Intron2-1358 UGUGUUGUUUGUUUUUGAGA 20 16458 CFTR-Intron2-1359 UUGUGUUGUUUGUUUUUGAGA 21 16459 CFTR-Intron2-1360 UUUGUGUUGUUUGUUUUUGAGA 22 16460 CFTR-Intron2-1361 UGUUUGUGUUGUUUGUUUUUGAGA 24 16461 CFTR-Intron2-1362 UAGCUUAAGUAAAUAAAAGGA 21 16462 CFTR-Intron2-1363 CUAGCUUAAGUAAAUAAAAGGA 22 16463 CFTR-Intron2-1364 ACUAGCUUAAGUAAAUAAAAGGA 23 16464 CFTR-Intron2-1365 UACUAGCUUAAGUAAAUAAAAGGA 24 16465 CFTR-Intron2-1366 UGUUGAAUGAAUCCAUGA 18 16466 CFTR-Intron2-1367 UUGUUGAAUGAAUCCAUGA 19 16467 CFTR-Intron2-628 UUUGUUGAAUGAAUCCAUGA 20 15728 CFTR-Intron2-1368 AUUUGUUGAAUGAAUCCAUGA 21 16468 CFTR-Intron2-1369 UAUUUGUUGAAUGAAUCCAUGA 22 16469 CFTR-Intron2-1370 AUAUUUGUUGAAUGAAUCCAUGA 23 16470 CFTR-Intron2-1371 AAUAUUUGUUGAAUGAAUCCAUGA 24 16471 CFTR-Intron2-1372 UCAAUAAAUAUUUGUUGA 18 16472 CFTR-Intron2-1373 CUCAAUAAAUAUUUGUUGA 19 16473 CFTR-Intron2-1374 ACUCAAUAAAUAUUUGUUGA 20 16474 CFTR-Intron2-1375 UACUCAAUAAAUAUUUGUUGA 21 16475 CFTR-Intron2-1376 AUACUCAAUAAAUAUUUGUUGA 22 16476 CFTR-Intron2-1377 UAUACUCAAUAAAUAUUUGUUGA 23 16477 CFTR-Intron2-1378 AUAUACUCAAUAAAUAUUUGUUGA 24 16478 CFTR-Intron2-1379 UUUGUUUUUUAUUUUUUA 18 16479 CFTR-Intron2-1380 UUUUGUUUUUUAUUUUUUA 19 16480 CFTR-Intron2-1381 UGUUUUGUUUUUUAUUUUUUA 21 16481 CFTR-Intron2-1382 UUGUUUUGUUUUUUAUUUUUUA 22 16482 CFTR-Intron2-1383 UUUGUUUUGUUUUUUAUUUUUUA 23 16483 CFTR-Intron2-1384 CUUUGUUUUGUUUUUUAUUUUUUA 24 16484 CFTR-Intron2-1385 UAUGAUGUAUCCCCAAGUGCC 21 16485 CFTR-Intron2-1386 UUAUGAUGUAUCCCCAAGUGCC 22 16486 CFTR-Intron2-1387 UUUAUGAUGUAUCCCCAAGUGCC 23 16487 CFTR-Intron2-1388 UCGCUGUGUCACCCAGGC 18 16488 CFTR-Intron2-1389 CUCGCUGUGUCACCCAGGC 19 16489 CFTR-Intron2-658 UCUCGCUGUGUCACCCAGGC 20 15758 CFTR-Intron2-1390 AGUCUCGCUGUGUCACCCAGGC 22 16490 CFTR-Intron2-1391 AGAGUCUCGCUGUGUCACCCAGGC 24 16491 CFTR-Intron2-1392 UUGCUCUGUUGCCCAGGC 18 16492 CFTR-Intron2-1393 CUUGCUCUGUUGCCCAGGC 19 16493 CFTR-Intron2-659 UCUUGCUCUGUUGCCCAGGC 20 15759 CFTR-Intron2-1394 AGUCUUGCUCUGUUGCCCAGGC 22 16494 CFTR-Intron2-1395 AGAGUCUUGCUCUGUUGCCCAGGC 24 16495 CFTR-Intron2-1396 CUUGGCCUCCCAAAAUGC 18 16496 CFTR-Intron2-1397 CCUUGGCCUCCCAAAAUGC 19 16497 CFTR-Intron2-663 ACCUUGGCCUCCCAAAAUGC 20 15763 CFTR-Intron2-1398 CACCUUGGCCUCCCAAAAUGC 21 16498 CFTR-Intron2-1399 CCACCUUGGCCUCCCAAAAUGC 22 16499 CFTR-Intron2-1400 CCCACCUUGGCCUCCCAAAAUGC 23 16500 CFTR-Intron2-1401 UUCUCCUGCCUCAGCCUC 18 16501 CFTR-Intron2-1402 AUUCUCCUGCCUCAGCCUC 19 16502 CFTR-Intron2-1403 UGAUUCUCCUGCCUCAGCCUC 21 16503 CFTR-Intron2-1404 AGUGAUUCUCCUGCCUCAGCCUC 23 16504 CFTR-Intron2-1405 AAGUGAUUCUCCUGCCUCAGCCUC 24 16505 CFTR-Intron2-1406 CACUGCAAACUCUGCCUC 18 16506 CFTR-Intron2-1407 UCACUGCAAACUCUGCCUC 19 16507 CFTR-Intron2-1408 CUCACUGCAAACUCUGCCUC 20 16508 CFTR-Intron2-1409 AGCUCACUGCAAACUCUGCCUC 22 16509 CFTR-Intron2-1410 CAGCUCACUGCAAACUCUGCCUC 23 16510 CFTR-Intron2-1411 UCAGCUCACUGCAAACUCUGCCUC 24 16511 CFTR-Intron2-1412 CAAGCGAAUCUCAGUCUC 18 16512 CFTR-Intron2-1413 UCAAGCGAAUCUCAGUCUC 19 16513 CFTR-Intron2-1414 UUCAAGCGAAUCUCAGUCUC 20 16514 CFTR-Intron2-1415 UGGGUUCAAGCGAAUCUCAGUCUC 24 16515 CFTR-Intron2-1416 CACUGCAAACUUCGUCUC 18 16516 CFTR-Intron2-1417 UCACUGCAAACUUCGUCUC 19 16517 CFTR-Intron2-1418 CUCACUGCAAACUUCGUCUC 20 16518 CFTR-Intron2-1419 UGGCUCACUGCAAACUUCGUCUC 23 16519 CFTR-Intron2-1420 UUGGCUCACUGCAAACUUCGUCUC 24 16520 CFTR-Intron2-1421 UCUCCUUUGAUGGAGAAG 18 16521 CFTR-Intron2-1422 UUCUCCUUUGAUGGAGAAG 19 16522 CFTR-Intron2-1423 UUUCUCCUUUGAUGGAGAAG 20 16523 CFTR-Intron2-1424 AUAAAAGGGUGAGUGAAG 18 16524 CFTR-Intron2-672 AGAUAAAAGGGUGAGUGAAG 20 15772 CFTR-Intron2-1425 CCUCAGCCUCUCGAGUAG 18 16525 CFTR-Intron2-1426 UGCCUCAGCCUCUCGAGUAG 20 16526 CFTR-Intron2-1427 CUGCCUCAGCCUCUCGAGUAG 21 16527 CFTR-Intron2-1428 CCUGCCUCAGCCUCUCGAGUAG 22 16528 CFTR-Intron2-1429 UCCUGCCUCAGCCUCUCGAGUAG 23 16529 CFTR-Intron2-1430 CUCCUGCCUCAGCCUCUCGAGUAG 24 16530 CFTR-Intron2-1431 AGGCCUGAUGCCAGAUAAAAGG 22 16531 CFTR-Intron2-1432 CAGGCCUGAUGCCAGAUAAAAGG 23 16532 CFTR-Intron2-1433 ACAGGCCUGAUGCCAGAUAAAAGG 24 16533 CFTR-Intron2-1434 AAAUUUAUUGAAAUAUUUUGG 21 16534 CFTR-Intron2-1435 UGAAAUUUAUUGAAAUAUUUUGG 23 16535 CFTR-Intron2-1436 UUGAAAUUUAUUGAAAUAUUUUGG 24 16536 CFTR-Intron2-1437 UUUGUAUUUUAGUAGAUG 18 16537 CFTR-Intron2-1438 UUUUGUAUUUUAGUAGAUG 19 16538 CFTR-Intron2-688 UUUUUGUAUUUUAGUAGAUG 20 15788 CFTR-Intron2-1439 AUUUUUGUAUUUUAGUAGAUG 21 16539 CFTR-Intron2-1440 AAUUUUUGUAUUUUAGUAGAUG 22 16540 CFTR-Intron2-1441 UAAUUUUUGUAUUUUAGUAGAUG 23 16541 CFTR-Intron2-1442 CUAAUUUUUGUAUUUUAGUAGAUG 24 16542 CFTR-Intron2-1443 AGAGAACAUGAAUCUGAAUUUG 22 16543 CFTR-Intron2-1444 UAGAGAACAUGAAUCUGAAUUUG 23 16544 CFTR-Intron2-1445 AUAGAGAACAUGAAUCUGAAUUUG 24 16545 CFTR-Intron2-1446 AUACUCAAUAAAUAUUUG 18 16546 CFTR-Intron2-1447 UAUACUCAAUAAAUAUUUG 19 16547 CFTR-Intron2-1448 AUAUACUCAAUAAAUAUUUG 20 16548 CFTR-Intron2-1449 UAUAUACUCAAUAAAUAUUUG 21 16549 CFTR-Intron2-1450 UGGUAUAUACUCAAUAAAUAUUUG 24 16550 CFTR-Intron2-1451 UGGCCAGAUAGAGAACAUGAAU 22 16551 CFTR-Intron2-1452 AUGGCCAGAUAGAGAACAUGAAU 23 16552 CFTR-Intron2-1453 UAUGGCCAGAUAGAGAACAUGAAU 24 16553 CFTR-Intron2-1454 UGCUGAGGGAAUGAUUAAU 19 16554 CFTR-Intron2-1455 AUGCUGAGGGAAUGAUUAAU 20 16555 CFTR-Intron2-1456 UUGCUUUCAAAACCUUUAUAU 21 16556 CFTR-Intron2-1457 UUUGCUUUCAAAACCUUUAUAU 22 16557 CFTR-Intron2-1458 AUUUGCUUUCAAAACCUUUAUAU 23 16558 CFTR-Intron2-1459 UAUUUGCUUUCAAAACCUUUAUAU 24 16559 CFTR-Intron2-1460 UGAGCCACUAUGCCCAGCU 19 16560 CFTR-Intron2-1461 UGUGAGCCACUAUGCCCAGCU 21 16561 CFTR-Intron2-1462 AGGUGUGAGCCACUAUGCCCAGCU 24 16562 CFTR-Intron2-1463 UGUGCAAAUGCCAUGAGGU 19 16563 CFTR-Intron2-1464 UGUGUGCAAAUGCCAUGAGGU 21 16564 CFTR-Intron2-1465 UGGUGUGUGCAAAUGCCAUGAGGU 24 16565 CFTR-Intron2-1466 CUUGGCCUCCCAAAGUGU 18 16566 CFTR-Intron2-1467 CCUUGGCCUCCCAAAGUGU 19 16567 CFTR-Intron2-1468 CGCCUUGGCCUCCCAAAGUGU 21 16568 CFTR-Intron2-1469 CCGCCUUGGCCUCCCAAAGUGU 22 16569 CFTR-Intron2-1470 CCCGCCUUGGCCUCCCAAAGUGU 23 16570 CFTR-Intron2-1471 UGUAAAAAUUGUAUAUUU 18 16571 CFTR-Intron2-1472 AUGUAAAAAUUGUAUAUUU 19 16572 CFTR-Intron2-1473 AAUGUAAAAAUUGUAUAUUU 20 16573 CFTR-Intron2-1474 AAAUGUAAAAAUUGUAUAUUU 21 16574 CFTR-Intron2-1475 CAAAUGUAAAAAUUGUAUAUUU 22 16575 CFTR-Intron2-1476 ACAAAUGUAAAAAUUGUAUAUUU 23 16576 CFTR-Intron2-1477 AACAAAUGUAAAAAUUGUAUAUUU 24 16577

Table 38E provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within intron 2, and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 38E 5th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-1478 + CUUCAAAAUGCCAAAAAA 18 16578 CFTR-Intron2-1479 + CCUUCAAAAUGCCAAAAAA 19 16579 CFTR-Intron2-42 + GCCUUCAAAAUGCCAAAAAA 20 15142 CFTR-Intron2-1480 + UGCCUUCAAAAUGCCAAAAAA 21 16580 CFTR-Intron2-1481 + UUGCCUUCAAAAUGCCAAAAAA 22 16581 CFTR-Intron2-1482 + UUUGCCUUCAAAAUGCCAAAAAA 23 16582 CFTR-Intron2-1483 + CUUUGCCUUCAAAAUGCCAAAAAA 24 16583 CFTR-Intron2-1484 + CCUUCAAAAUGCCAAAAA 18 16584 CFTR-Intron2-1485 + GCCUUCAAAAUGCCAAAAA 19 16585 CFTR-Intron2-1486 + UGCCUUCAAAAUGCCAAAAA 20 16586 CFTR-Intron2-1487 + UUGCCUUCAAAAUGCCAAAAA 21 16587 CFTR-Intron2-1488 + UUUGCCUUCAAAAUGCCAAAAA 22 16588 CFTR-Intron2-1489 + CUUUGCCUUCAAAAUGCCAAAAA 23 16589 CFTR-Intron2-1490 + ACUUUGCCUUCAAAAUGCCAAAAA 24 16590 CFTR-Intron2-1491 + CAAUCCAUGGUCACAAAA 18 16591 CFTR-Intron2-1492 + UCAAUCCAUGGUCACAAAA 19 16592 CFTR-Intron2-1493 + UUCAAUCCAUGGUCACAAAA 20 16593 CFTR-Intron2-1494 + AUUCAAUCCAUGGUCACAAAA 21 16594 CFTR-Intron2-1495 + GAUUCAAUCCAUGGUCACAAAA 22 16595 CFTR-Intron2-1496 + GGAUUCAAUCCAUGGUCACAAAA 23 16596 CFTR-Intron2-1497 + AGGAUUCAAUCCAUGGUCACAAAA 24 16597 CFTR-Intron2-1498 + UGGGGGAUACAGUGAAAA 18 16598 CFTR-Intron2-1499 + AUGGGGGAUACAGUGAAAA 19 16599 CFTR-Intron2-1500 + CAUGGGGGAUACAGUGAAAA 20 16600 CFTR-Intron2-1501 + ACAUGGGGGAUACAGUGAAAA 21 16601 CFTR-Intron2-1502 + AACAUGGGGGAUACAGUGAAAA 22 16602 CFTR-Intron2-1503 + CAACAUGGGGGAUACAGUGAAAA 23 16603 CFTR-Intron2-1504 + UCAACAUGGGGGAUACAGUGAAAA 24 16604 CFTR-Intron2-1505 + AUUAAAGGUCUUUGAAAA 18 16605 CFTR-Intron2-1506 + UAUUAAAGGUCUUUGAAAA 19 16606 CFTR-Intron2-1507 + GUAUUAAAGGUCUUUGAAAA 20 16607 CFTR-Intron2-1508 + UGUAUUAAAGGUCUUUGAAAA 21 16608 CFTR-Intron2-1509 + AUGUAUUAAAGGUCUUUGAAAA 22 16609 CFTR-Intron2-1510 + CAUGUAUUAAAGGUCUUUGAAAA 23 16610 CFTR-Intron2-1511 + UCAUGUAUUAAAGGUCUUUGAAAA 24 16611 CFTR-Intron2-1512 + GUUUGCUUUUCUGUAAAA 18 16612 CFTR-Intron2-1513 + AGUUUGCUUUUCUGUAAAA 19 16613 CFTR-Intron2-1514 + CAGUUUGCUUUUCUGUAAAA 20 16614 CFTR-Intron2-1515 + UCAGUUUGCUUUUCUGUAAAA 21 16615 CFTR-Intron2-1516 + CUCAGUUUGCUUUUCUGUAAAA 22 16616 CFTR-Intron2-1517 + CCUCAGUUUGCUUUUCUGUAAAA 23 16617 CFTR-Intron2-1518 + GCCUCAGUUUGCUUUUCUGUAAAA 24 16618 CFTR-Intron2-1519 + UUUUGAUUGGAAAGGAAA 18 16619 CFTR-Intron2-1520 + CUUUUGAUUGGAAAGGAAA 19 16620 CFTR-Intron2-1521 + CCUUUUGAUUGGAAAGGAAA 20 16621 CFTR-Intron2-1522 + ACCUUUUGAUUGGAAAGGAAA 21 16622 CFTR-Intron2-1523 + AACCUUUUGAUUGGAAAGGAAA 22 16623 CFTR-Intron2-1524 + UAACCUUUUGAUUGGAAAGGAAA 23 16624 CFTR-Intron2-1525 + CUAACCUUUUGAUUGGAAAGGAAA 24 16625 CFTR-Intron2-1526 + GCUGAGAUGUAAAUGAAA 18 16626 CFTR-Intron2-1527 + AGCUGAGAUGUAAAUGAAA 19 16627 CFTR-Intron2-1528 + GAGCUGAGAUGUAAAUGAAA 20 16628 CFTR-Intron2-1529 + GGAGCUGAGAUGUAAAUGAAA 21 16629 CFTR-Intron2-1530 + AGGAGCUGAGAUGUAAAUGAAA 22 16630 CFTR-Intron2-1531 + CAGGAGCUGAGAUGUAAAUGAAA 23 16631 CFTR-Intron2-1532 + UCAGGAGCUGAGAUGUAAAUGAAA 24 16632 CFTR-Intron2-1533 + GGGAUACAUCAUAAACAA 18 16633 CFTR-Intron2-1534 + GGGGAUACAUCAUAAACAA 19 16634 CFTR-Intron2-1535 + UGGGGAUACAUCAUAAACAA 20 16635 CFTR-Intron2-1536 + UUGGGGAUACAUCAUAAACAA 21 16636 CFTR-Intron2-1537 + CUUGGGGAUACAUCAUAAACAA 22 16637 CFTR-Intron2-1538 + ACUUGGGGAUACAUCAUAAACAA 23 16638 CFTR-Intron2-1539 + CACUUGGGGAUACAUCAUAAACAA 24 16639 CFTR-Intron2-1540 + ACACUCCAGCCUGGGCAA 18 16640 CFTR-Intron2-1541 + UACACUCCAGCCUGGGCAA 19 16641 CFTR-Intron2-1542 + UUACACUCCAGCCUGGGCAA 20 16642 CFTR-Intron2-1543 + AUUACACUCCAGCCUGGGCAA 21 16643 CFTR-Intron2-1544 + CAUUACACUCCAGCCUGGGCAA 22 16644 CFTR-Intron2-1545 + CCAUUACACUCCAGCCUGGGCAA 23 16645 CFTR-Intron2-1546 + ACCAUUACACUCCAGCCUGGGCAA 24 16646 CFTR-Intron2-1547 + ACUCACCUUCUCCAUCAA 18 16647 CFTR-Intron2-1548 + GACUCACCUUCUCCAUCAA 19 16648 CFTR-Intron2-239 + AGACUCACCUUCUCCAUCAA 20 15339 CFTR-Intron2-1549 + CAGACUCACCUUCUCCAUCAA 21 16649 CFTR-Intron2-1550 + GCAGACUCACCUUCUCCAUCAA 22 16650 CFTR-Intron2-1551 + AGCAGACUCACCUUCUCCAUCAA 23 16651 CFTR-Intron2-1552 + GAGCAGACUCACCUUCUCCAUCAA 24 16652 CFTR-Intron2-1553 + AUACCAAUUUUAUAAGAA 18 16653 CFTR-Intron2-1554 + AAUACCAAUUUUAUAAGAA 19 16654 CFTR-Intron2-1555 + AAAUACCAAUUUUAUAAGAA 20 16655 CFTR-Intron2-1556 + CAAAUACCAAUUUUAUAAGAA 21 16656 CFTR-Intron2-1557 + UCAAAUACCAAUUUUAUAAGAA 22 16657 CFTR-Intron2-1558 + UUCAAAUACCAAUUUUAUAAGAA 23 16658 CFTR-Intron2-1559 + UUUCAAAUACCAAUUUUAUAAGAA 24 16659 CFTR-Intron2-1560 + ACCAGGCCCAGAUCAGAA 18 16660 CFTR-Intron2-1561 + UACCAGGCCCAGAUCAGAA 19 16661 CFTR-Intron2-242 + AUACCAGGCCCAGAUCAGAA 20 15342 CFTR-Intron2-1562 + CAUACCAGGCCCAGAUCAGAA 21 16662 CFTR-Intron2-1563 + ACAUACCAGGCCCAGAUCAGAA 22 16663 CFTR-Intron2-1564 + CACAUACCAGGCCCAGAUCAGAA 23 16664 CFTR-Intron2-1565 + CCACAUACCAGGCCCAGAUCAGAA 24 16665 CFTR-Intron2-1566 + CUAACCUUUUGAUUGGAA 18 16666 CFTR-Intron2-1567 + CCUAACCUUUUGAUUGGAA 19 16667 CFTR-Intron2-246 + UCCUAACCUUUUGAUUGGAA 20 15346 CFTR-Intron2-1568 + AUCCUAACCUUUUGAUUGGAA 21 16668 CFTR-Intron2-1569 + GAUCCUAACCUUUUGAUUGGAA 22 16669 CFTR-Intron2-1570 + GGAUCCUAACCUUUUGAUUGGAA 23 16670 CFTR-Intron2-1571 + AGGAUCCUAACCUUUUGAUUGGAA 24 16671 CFTR-Intron2-1572 + UGGCAUAGCAUUGUUGAA 18 16672 CFTR-Intron2-1573 + CUGGCAUAGCAUUGUUGAA 19 16673 CFTR-Intron2-1574 + ACUGGCAUAGCAUUGUUGAA 20 16674 CFTR-Intron2-1575 + UACUGGCAUAGCAUUGUUGAA 21 16675 CFTR-Intron2-1576 + GUACUGGCAUAGCAUUGUUGAA 22 16676 CFTR-Intron2-1577 + UGUACUGGCAUAGCAUUGUUGAA 23 16677 CFTR-Intron2-1578 + UUGUACUGGCAUAGCAUUGUUGAA 24 16678 CFTR-Intron2-1579 + AAAACAAAACAAAAAUAA 18 16679 CFTR-Intron2-1580 + CAAAACAAAACAAAAAUAA 19 16680 CFTR-Intron2-1581 + ACAAAACAAAACAAAAAUAA 20 16681 CFTR-Intron2-1582 + AACAAAACAAAACAAAAAUAA 21 16682 CFTR-Intron2-1583 + AAACAAAACAAAACAAAAAUAA 22 16683 CFTR-Intron2-1584 + AAAACAAAACAAAACAAAAAUAA 23 16684 CFTR-Intron2-1585 + AAAAACAAAACAAAACAAAAAUAA 24 16685 CFTR-Intron2-1586 + ACACCAAGUGUUCAAUAA 18 16686 CFTR-Intron2-1587 + CACACCAAGUGUUCAAUAA 19 16687 CFTR-Intron2-1588 + ACACACCAAGUGUUCAAUAA 20 16688 CFTR-Intron2-1589 + CACACACCAAGUGUUCAAUAA 21 16689 CFTR-Intron2-1590 + GCACACACCAAGUGUUCAAUAA 22 16690 CFTR-Intron2-1591 + UGCACACACCAAGUGUUCAAUAA 23 16691 CFTR-Intron2-1592 + UUGCACACACCAAGUGUUCAAUAA 24 16692 CFTR-Intron2-1593 + UCAGGAGCUGAGAUGUAA 18 16693 CFTR-Intron2-1594 + UUCAGGAGCUGAGAUGUAA 19 16694 CFTR-Intron2-1595 + CUUCAGGAGCUGAGAUGUAA 20 16695 CFTR-Intron2-1596 + ACUUCAGGAGCUGAGAUGUAA 21 16696 CFTR-Intron2-1597 + UACUUCAGGAGCUGAGAUGUAA 22 16697 CFTR-Intron2-1598 + AUACUUCAGGAGCUGAGAUGUAA 23 16698 CFTR-Intron2-1599 + CAUACUUCAGGAGCUGAGAUGUAA 24 16699 CFTR-Intron2-1600 + GGAAAUGAAUUUAAUUAA 18 16700 CFTR-Intron2-1601 + AGGAAAUGAAUUUAAUUAA 19 16701 CFTR-Intron2-1602 + AAGGAAAUGAAUUUAAUUAA 20 16702 CFTR-Intron2-1603 + AAAGGAAAUGAAUUUAAUUAA 21 16703 CFTR-Intron2-1604 + AAAAGGAAAUGAAUUUAAUUAA 22 16704 CFTR-Intron2-1605 + AAAAAGGAAAUGAAUUUAAUUAA 23 16705 CFTR-Intron2-1606 + AAAAAAGGAAAUGAAUUUAAUUAA 24 16706 CFTR-Intron2-1607 + UUUUAAAUUGAAUCAACA 18 16707 CFTR-Intron2-1608 + UUUUUAAAUUGAAUCAACA 19 16708 CFTR-Intron2-621 + UUUUUUAAAUUGAAUCAACA 20 15721 CFTR-Intron2-1609 + AUUUUUUAAAUUGAAUCAACA 21 16709 CFTR-Intron2-1610 + UAUUUUUUAAAUUGAAUCAACA 22 16710 CFTR-Intron2-1611 + AUAUUUUUUAAAUUGAAUCAACA 23 16711 CFTR-Intron2-1612 + UAUAUUUUUUAAAUUGAAUCAACA 24 16712 CFTR-Intron2-1613 + CCACCUUUCUCUCACACA 18 16713 CFTR-Intron2-1614 + UCCACCUUUCUCUCACACA 19 16714 CFTR-Intron2-1615 + CUCCACCUUUCUCUCACACA 20 16715 CFTR-Intron2-1616 + UCUCCACCUUUCUCUCACACA 21 16716 CFTR-Intron2-1617 + UUCUCCACCUUUCUCUCACACA 22 16717 CFTR-Intron2-1618 + CUUCUCCACCUUUCUCUCACACA 23 16718 CFTR-Intron2-1619 + GCUUCUCCACCUUUCUCUCACACA 24 16719 CFTR-Intron2-1620 + UCCAGCCUGGGUGACACA 18 16720 CFTR-Intron2-1621 + CUCCAGCCUGGGUGACACA 19 16721 CFTR-Intron2-1622 + ACUCCAGCCUGGGUGACACA 20 16722 CFTR-Intron2-1623 + CACUCCAGCCUGGGUGACACA 21 16723 CFTR-Intron2-1624 + ACACUCCAGCCUGGGUGACACA 22 16724 CFTR-Intron2-1625 + UACACUCCAGCCUGGGUGACACA 23 16725 CFTR-Intron2-1626 + CUACACUCCAGCCUGGGUGACACA 24 16726 CFTR-Intron2-1627 + AAAAUUUCAUGAACCACA 18 16727 CFTR-Intron2-1628 + AAAAAUUUCAUGAACCACA 19 16728 CFTR-Intron2-455 + GAAAAAUUUCAUGAACCACA 20 15555 CFTR-Intron2-1629 + UGAAAAAUUUCAUGAACCACA 21 16729 CFTR-Intron2-1630 + AUGAAAAAUUUCAUGAACCACA 22 16730 CFTR-Intron2-1631 + GAUGAAAAAUUUCAUGAACCACA 23 16731 CFTR-Intron2-1632 + AGAUGAAAAAUUUCAUGAACCACA 24 16732 CFTR-Intron2-1633 + GUGAAAAAGUGGUCCACA 18 16733 CFTR-Intron2-1634 + UGUGAAAAAGUGGUCCACA 19 16734 CFTR-Intron2-256 + AUGUGAAAAAGUGGUCCACA 20 15356 CFTR-Intron2-1635 + AAUGUGAAAAAGUGGUCCACA 21 16735 CFTR-Intron2-1636 + CAAUGUGAAAAAGUGGUCCACA 22 16736 CFTR-Intron2-1637 + UCAAUGUGAAAAAGUGGUCCACA 23 16737 CFTR-Intron2-1638 + UUCAAUGUGAAAAAGUGGUCCACA 24 16738 CFTR-Intron2-1639 + GCCUUUUUUCUCUUCACA 18 16739 CFTR-Intron2-1640 + AGCCUUUUUUCUCUUCACA 19 16740 CFTR-Intron2-1641 + AAGCCUUUUUUCUCUUCACA 20 16741 CFTR-Intron2-1642 + AAAGCCUUUUUUCUCUUCACA 21 16742 CFTR-Intron2-1643 + GAAAGCCUUUUUUCUCUUCACA 22 16743 CFTR-Intron2-1644 + UGAAAGCCUUUUUUCUCUUCACA 23 16744 CFTR-Intron2-1645 + AUGAAAGCCUUUUUUCUCUUCACA 24 16745 CFTR-Intron2-1646 + CACAUUUAGCCAAGGACA 18 16746 CFTR-Intron2-1647 + UCACAUUUAGCCAAGGACA 19 16747 CFTR-Intron2-1648 + UUCACAUUUAGCCAAGGACA 20 16748 CFTR-Intron2-1649 + UUUCACAUUUAGCCAAGGACA 21 16749 CFTR-Intron2-1650 + UUUUCACAUUUAGCCAAGGACA 22 16750 CFTR-Intron2-1651 + UUUUUCACAUUUAGCCAAGGACA 23 16751 CFTR-Intron2-1652 + AUUUUUCACAUUUAGCCAAGGACA 24 16752 CFTR-Intron2-1653 + AUCAACAUGGGGGAUACA 18 16753 CFTR-Intron2-1654 + AAUCAACAUGGGGGAUACA 19 16754 CFTR-Intron2-1655 + GAAUCAACAUGGGGGAUACA 20 16755 CFTR-Intron2-1656 + UGAAUCAACAUGGGGGAUACA 21 16756 CFTR-Intron2-1657 + UUGAAUCAACAUGGGGGAUACA 22 16757 CFTR-Intron2-1658 + AUUGAAUCAACAUGGGGGAUACA 23 16758 CFTR-Intron2-1659 + AAUUGAAUCAACAUGGGGGAUACA 24 16759 CFTR-Intron2-1660 + GAUCAGAUGGGAAAGCCA 18 16760 CFTR-Intron2-1661 + GGAUCAGAUGGGAAAGCCA 19 16761 CFTR-Intron2-623 + UGGAUCAGAUGGGAAAGCCA 20 15723 CFTR-Intron2-1662 + AUGGAUCAGAUGGGAAAGCCA 21 16762 CFTR-Intron2-1663 + AAUGGAUCAGAUGGGAAAGCCA 22 16763 CFTR-Intron2-1664 + AAAUGGAUCAGAUGGGAAAGCCA 23 16764 CFTR-Intron2-1665 + GAAAUGGAUCAGAUGGGAAAGCCA 24 16765 CFTR-Intron2-1666 + CAGGAGACGAAGUUUGCA 18 16766 CFTR-Intron2-1667 + CCAGGAGACGAAGUUUGCA 19 16767 CFTR-Intron2-1668 + CCCAGGAGACGAAGUUUGCA 20 16768 CFTR-Intron2-1669 + ACCCAGGAGACGAAGUUUGCA 21 16769 CFTR-Intron2-1670 + AACCCAGGAGACGAAGUUUGCA 22 16770 CFTR-Intron2-1671 + GAACCCAGGAGACGAAGUUUGCA 23 16771 CFTR-Intron2-1672 + UGAACCCAGGAGACGAAGUUUGCA 24 16772 CFTR-Intron2-1673 + CAGGAGGCAGAGUUUGCA 18 16773 CFTR-Intron2-1674 + CCAGGAGGCAGAGUUUGCA 19 16774 CFTR-Intron2-1675 + CCCAGGAGGCAGAGUUUGCA 20 16775 CFTR-Intron2-1676 + ACCCAGGAGGCAGAGUUUGCA 21 16776 CFTR-Intron2-1677 + AACCCAGGAGGCAGAGUUUGCA 22 16777 CFTR-Intron2-1678 + GAACCCAGGAGGCAGAGUUUGCA 23 16778 CFTR-Intron2-1679 + UGAACCCAGGAGGCAGAGUUUGCA 24 16779 CFTR-Intron2-1680 + GACUCACCUUCUCCAUCA 18 16780 CFTR-Intron2-1681 + AGACUCACCUUCUCCAUCA 19 16781 CFTR-Intron2-1682 + CAGACUCACCUUCUCCAUCA 20 16782 CFTR-Intron2-1683 + GCAGACUCACCUUCUCCAUCA 21 16783 CFTR-Intron2-1684 + AGCAGACUCACCUUCUCCAUCA 22 16784 CFTR-Intron2-1685 + GAGCAGACUCACCUUCUCCAUCA 23 16785 CFTR-Intron2-1686 + GGAGCAGACUCACCUUCUCCAUCA 24 16786 CFTR-Intron2-1687 + UUUCGUGGUCCUUAAAGA 18 16787 CFTR-Intron2-1688 + CUUUCGUGGUCCUUAAAGA 19 16788 CFTR-Intron2-1689 + UCUUUCGUGGUCCUUAAAGA 20 16789 CFTR-Intron2-1690 + UUCUUUCGUGGUCCUUAAAGA 21 16790 CFTR-Intron2-1691 + CUUCUUUCGUGGUCCUUAAAGA 22 16791 CFTR-Intron2-1692 + CCUUCUUUCGUGGUCCUUAAAGA 23 16792 CFTR-Intron2-1693 + UCCUUCUUUCGUGGUCCUUAAAGA 24 16793 CFTR-Intron2-1694 + UACCAGGCCCAGAUCAGA 18 16794 CFTR-Intron2-1695 + AUACCAGGCCCAGAUCAGA 19 16795 CFTR-Intron2-275 + CAUACCAGGCCCAGAUCAGA 20 15375 CFTR-Intron2-1696 + ACAUACCAGGCCCAGAUCAGA 21 16796 CFTR-Intron2-1697 + CACAUACCAGGCCCAGAUCAGA 22 16797 CFTR-Intron2-1698 + CCACAUACCAGGCCCAGAUCAGA 23 16798 CFTR-Intron2-1699 + ACCACAUACCAGGCCCAGAUCAGA 24 16799 CFTR-Intron2-1700 + AAGGAGAAAUGGAUCAGA 18 16800 CFTR-Intron2-1701 + AAAGGAGAAAUGGAUCAGA 19 16801 CFTR-Intron2-276 + CAAAGGAGAAAUGGAUCAGA 20 15376 CFTR-Intron2-1702 + UCAAAGGAGAAAUGGAUCAGA 21 16802 CFTR-Intron2-1703 + AUCAAAGGAGAAAUGGAUCAGA 22 16803 CFTR-Intron2-1704 + CAUCAAAGGAGAAAUGGAUCAGA 23 16804 CFTR-Intron2-1705 + CCAUCAAAGGAGAAAUGGAUCAGA 24 16805 CFTR-Intron2-1706 + CAUCAUAAACAAAAGAGA 18 16806 CFTR-Intron2-1707 + ACAUCAUAAACAAAAGAGA 19 16807 CFTR-Intron2-1708 + UACAUCAUAAACAAAAGAGA 20 16808 CFTR-Intron2-1709 + AUACAUCAUAAACAAAAGAGA 21 16809 CFTR-Intron2-1710 + GAUACAUCAUAAACAAAAGAGA 22 16810 CFTR-Intron2-1711 + GGAUACAUCAUAAACAAAAGAGA 23 16811 CFTR-Intron2-1712 + GGGAUACAUCAUAAACAAAAGAGA 24 16812 CFTR-Intron2-1713 + UCCCAGCUACUCAGGAGA 18 16813 CFTR-Intron2-1714 + GUCCCAGCUACUCAGGAGA 19 16814 CFTR-Intron2-1715 + AGUCCCAGCUACUCAGGAGA 20 16815 CFTR-Intron2-1716 + UAGUCCCAGCUACUCAGGAGA 21 16816 CFTR-Intron2-1717 + GUAGUCCCAGCUACUCAGGAGA 22 16817 CFTR-Intron2-1718 + UGUAGUCCCAGCUACUCAGGAGA 23 16818 CFTR-Intron2-1719 + CUGUAGUCCCAGCUACUCAGGAGA 24 16819 CFTR-Intron2-1720 + UAUGAAAGAAAAAAUAGA 18 16820 CFTR-Intron2-1721 + CUAUGAAAGAAAAAAUAGA 19 16821 CFTR-Intron2-1722 + GCUAUGAAAGAAAAAAUAGA 20 16822 CFTR-Intron2-1723 + AGCUAUGAAAGAAAAAAUAGA 21 16823 CFTR-Intron2-1724 + UAGCUAUGAAAGAAAAAAUAGA 22 16824 CFTR-Intron2-1725 + UUAGCUAUGAAAGAAAAAAUAGA 23 16825 CFTR-Intron2-1726 + GUUAGCUAUGAAAGAAAAAAUAGA 24 16826 CFTR-Intron2-1727 + GAUACAGUGAAAACUGGA 18 16827 CFTR-Intron2-1728 + GGAUACAGUGAAAACUGGA 19 16828 CFTR-Intron2-1729 + GGGAUACAGUGAAAACUGGA 20 16829 CFTR-Intron2-1730 + GGGGAUACAGUGAAAACUGGA 21 16830 CFTR-Intron2-1731 + GGGGGAUACAGUGAAAACUGGA 22 16831 CFTR-Intron2-1732 + UGGGGGAUACAGUGAAAACUGGA 23 16832 CFTR-Intron2-1733 + AUGGGGGAUACAGUGAAAACUGGA 24 16833 CFTR-Intron2-1734 + CCUAACCUUUUGAUUGGA 18 16834 CFTR-Intron2-1735 + UCCUAACCUUUUGAUUGGA 19 16835 CFTR-Intron2-1736 + AUCCUAACCUUUUGAUUGGA 20 16836 CFTR-Intron2-1737 + GAUCCUAACCUUUUGAUUGGA 21 16837 CFTR-Intron2-1738 + GGAUCCUAACCUUUUGAUUGGA 22 16838 CFTR-Intron2-1739 + AGGAUCCUAACCUUUUGAUUGGA 23 16839 CFTR-Intron2-1740 + AAGGAUCCUAACCUUUUGAUUGGA 24 16840 CFTR-Intron2-1741 + AGAGAAUGUUAGCUAUGA 18 16841 CFTR-Intron2-1742 + CAGAGAAUGUUAGCUAUGA 19 16842 CFTR-Intron2-1743 + GCAGAGAAUGUUAGCUAUGA 20 16843 CFTR-Intron2-1744 + AGCAGAGAAUGUUAGCUAUGA 21 16844 CFTR-Intron2-1745 + GAGCAGAGAAUGUUAGCUAUGA 22 16845 CFTR-Intron2-1746 + AGAGCAGAGAAUGUUAGCUAUGA 23 16846 CFTR-Intron2-1747 + GAGAGCAGAGAAUGUUAGCUAUGA 24 16847 CFTR-Intron2-1748 + UCCACUCAGAGUGGCUGA 18 16848 CFTR-Intron2-1749 + UUCCACUCAGAGUGGCUGA 19 16849 CFTR-Intron2-1750 + UUUCCACUCAGAGUGGCUGA 20 16850 CFTR-Intron2-1751 + CUUUCCACUCAGAGUGGCUGA 21 16851 CFTR-Intron2-1752 + GCUUUCCACUCAGAGUGGCUGA 22 16852 CFTR-Intron2-1753 + UGCUUUCCACUCAGAGUGGCUGA 23 16853 CFTR-Intron2-1754 + AUGCUUUCCACUCAGAGUGGCUGA 24 16854 CFTR-Intron2-1755 + AGGAUCCUAACCUUUUGA 18 16855 CFTR-Intron2-1756 + AAGGAUCCUAACCUUUUGA 19 16856 CFTR-Intron2-1757 + AAAGGAUCCUAACCUUUUGA 20 16857 CFTR-Intron2-1758 + AAAAGGAUCCUAACCUUUUGA 21 16858 CFTR-Intron2-1759 + CAAAAGGAUCCUAACCUUUUGA 22 16859 CFTR-Intron2-1760 + UCAAAAGGAUCCUAACCUUUUGA 23 16860 CFTR-Intron2-1761 + AUCAAAAGGAUCCUAACCUUUUGA 24 16861 CFTR-Intron2-1762 + AGAGUAAGAAGCUAAAUA 18 16862 CFTR-Intron2-1763 + CAGAGUAAGAAGCUAAAUA 19 16863 CFTR-Intron2-287 + UCAGAGUAAGAAGCUAAAUA 20 15387 CFTR-Intron2-1764 + CUCAGAGUAAGAAGCUAAAUA 21 16864 CFTR-Intron2-1765 + ACUCAGAGUAAGAAGCUAAAUA 22 16865 CFTR-Intron2-1766 + UACUCAGAGUAAGAAGCUAAAUA 23 16866 CFTR-Intron2-1767 + UUACUCAGAGUAAGAAGCUAAAUA 24 16867 CFTR-Intron2-1768 + AAACAAACAAAAAACAUA 18 16868 CFTR-Intron2-1769 + CAAACAAACAAAAAACAUA 19 16869 CFTR-Intron2-1770 + ACAAACAAACAAAAAACAUA 20 16870 CFTR-Intron2-1771 + CACAAACAAACAAAAAACAUA 21 16871 CFTR-Intron2-1772 + ACACAAACAAACAAAAAACAUA 22 16872 CFTR-Intron2-1773 + AACACAAACAAACAAAAAACAUA 23 16873 CFTR-Intron2-1774 + CAACACAAACAAACAAAAAACAUA 24 16874 CFTR-Intron2-1775 + GUUUUCUUUUAAAUACUA 18 16875 CFTR-Intron2-1776 + UGUUUUCUUUUAAAUACUA 19 16876 CFTR-Intron2-1777 + CUGUUUUCUUUUAAAUACUA 20 16877 CFTR-Intron2-1778 + UCUGUUUUCUUUUAAAUACUA 21 16878 CFTR-Intron2-1779 + UUCUGUUUUCUUUUAAAUACUA 22 16879 CFTR-Intron2-1780 + UUUCUGUUUUCUUUUAAAUACUA 23 16880 CFTR-Intron2-1781 + CUUUCUGUUUUCUUUUAAAUACUA 24 16881 CFTR-Intron2-1782 + GGGGGACUACCAUUCCUA 18 16882 CFTR-Intron2-1783 + GGGGGGACUACCAUUCCUA 19 16883 CFTR-Intron2-1784 + GGGGGGGACUACCAUUCCUA 20 16884 CFTR-Intron2-1785 + UGGGGGGGACUACCAUUCCUA 21 16885 CFTR-Intron2-1786 + AUGGGGGGGACUACCAUUCCUA 22 16886 CFTR-Intron2-1787 + UAUGGGGGGGACUACCAUUCCUA 23 16887 CFTR-Intron2-1788 + UUAUGGGGGGGACUACCAUUCCUA 24 16888 CFTR-Intron2-1789 + UCCCCUAGAAGCUUGCUA 18 16889 CFTR-Intron2-1790 + AUCCCCUAGAAGCUUGCUA 19 16890 CFTR-Intron2-1791 + CAUCCCCUAGAAGCUUGCUA 20 16891 CFTR-Intron2-1792 + GCAUCCCCUAGAAGCUUGCUA 21 16892 CFTR-Intron2-1793 + GGCAUCCCCUAGAAGCUUGCUA 22 16893 CFTR-Intron2-1794 + UGGCAUCCCCUAGAAGCUUGCUA 23 16894 CFTR-Intron2-1795 + UUGGCAUCCCCUAGAAGCUUGCUA 24 16895 CFTR-Intron2-1796 + UGGCUCUAAAUCACUCUA 18 16896 CFTR-Intron2-1797 + AUGGCUCUAAAUCACUCUA 19 16897 CFTR-Intron2-1798 + CAUGGCUCUAAAUCACUCUA 20 16898 CFTR-Intron2-1799 + ACAUGGCUCUAAAUCACUCUA 21 16899 CFTR-Intron2-1800 + AACAUGGCUCUAAAUCACUCUA 22 16900 CFTR-Intron2-1801 + AAACAUGGCUCUAAAUCACUCUA 23 16901 CFTR-Intron2-1802 + UAAACAUGGCUCUAAAUCACUCUA 24 16902 CFTR-Intron2-1803 + GUAAAUGAAAGUGAAGUA 18 16903 CFTR-Intron2-1804 + UGUAAAUGAAAGUGAAGUA 19 16904 CFTR-Intron2-1805 + AUGUAAAUGAAAGUGAAGUA 20 16905 CFTR-Intron2-1806 + GAUGUAAAUGAAAGUGAAGUA 21 16906 CFTR-Intron2-1807 + AGAUGUAAAUGAAAGUGAAGUA 22 16907 CFTR-Intron2-1808 + GAGAUGUAAAUGAAAGUGAAGUA 23 16908 CFTR-Intron2-1809 + UGAGAUGUAAAUGAAAGUGAAGUA 24 16909 CFTR-Intron2-1810 + CUUAAUUUUCAAACUGUA 18 16910 CFTR-Intron2-1811 + UCUUAAUUUUCAAACUGUA 19 16911 CFTR-Intron2-1812 + AUCUUAAUUUUCAAACUGUA 20 16912 CFTR-Intron2-1813 + CAUCUUAAUUUUCAAACUGUA 21 16913 CFTR-Intron2-1814 + UCAUCUUAAUUUUCAAACUGUA 22 16914 CFTR-Intron2-1815 + AUCAUCUUAAUUUUCAAACUGUA 23 16915 CFTR-Intron2-1816 + UAUCAUCUUAAUUUUCAAACUGUA 24 16916 CFTR-Intron2-1817 + UGCCACUGAUUUCUGUUA 18 16917 CFTR-Intron2-1818 + UUGCCACUGAUUUCUGUUA 19 16918 CFTR-Intron2-1819 + AUUGCCACUGAUUUCUGUUA 20 16919 CFTR-Intron2-1820 + UAUUGCCACUGAUUUCUGUUA 21 16920 CFTR-Intron2-1821 + UUAUUGCCACUGAUUUCUGUUA 22 16921 CFTR-Intron2-1822 + GUUAUUGCCACUGAUUUCUGUUA 23 16922 CFTR-Intron2-1823 + AGUUAUUGCCACUGAUUUCUGUUA 24 16923 CFTR-Intron2-1824 + AAACUGAGAGAUUCUUUA 18 16924 CFTR-Intron2-1825 + GAAACUGAGAGAUUCUUUA 19 16925 CFTR-Intron2-57 + GGAAACUGAGAGAUUCUUUA 20 15157 CFTR-Intron2-1826 + AGGAAACUGAGAGAUUCUUUA 21 16926 CFTR-Intron2-1827 + AAGGAAACUGAGAGAUUCUUUA 22 16927 CFTR-Intron2-1828 + AAAGGAAACUGAGAGAUUCUUUA 23 16928 CFTR-Intron2-1829 + GAAAGGAAACUGAGAGAUUCUUUA 24 16929 CFTR-Intron2-1830 + GGGGGAUACAGUGAAAAC 18 16930 CFTR-Intron2-1831 + UGGGGGAUACAGUGAAAAC 19 16931 CFTR-Intron2-297 + AUGGGGGAUACAGUGAAAAC 20 15397 CFTR-Intron2-1832 + CAUGGGGGAUACAGUGAAAAC 21 16932 CFTR-Intron2-1833 + ACAUGGGGGAUACAGUGAAAAC 22 16933 CFTR-Intron2-1834 + AACAUGGGGGAUACAGUGAAAAC 23 16934 CFTR-Intron2-1835 + CAACAUGGGGGAUACAGUGAAAAC 24 16935 CFTR-Intron2-1836 + UUCUUUAAUGGGUGAAAC 18 16936 CFTR-Intron2-1837 + UUUCUUUAAUGGGUGAAAC 19 16937 CFTR-Intron2-1838 + AUUUCUUUAAUGGGUGAAAC 20 16938 CFTR-Intron2-1839 + AAUUUCUUUAAUGGGUGAAAC 21 16939 CFTR-Intron2-1840 + GAAUUUCUUUAAUGGGUGAAAC 22 16940 CFTR-Intron2-1841 + GGAAUUUCUUUAAUGGGUGAAAC 23 16941 CFTR-Intron2-1842 + GGGAAUUUCUUUAAUGGGUGAAAC 24 16942 CFTR-Intron2-1843 + UUUUUAAAUUGAAUCAAC 18 16943 CFTR-Intron2-1844 + UUUUUUAAAUUGAAUCAAC 19 16944 CFTR-Intron2-1845 + AUUUUUUAAAUUGAAUCAAC 20 16945 CFTR-Intron2-1846 + UAUUUUUUAAAUUGAAUCAAC 21 16946 CFTR-Intron2-1847 + AUAUUUUUUAAAUUGAAUCAAC 22 16947 CFTR-Intron2-1848 + UAUAUUUUUUAAAUUGAAUCAAC 23 16948 CFTR-Intron2-1849 + GUAUAUUUUUUAAAUUGAAUCAAC 24 16949 CFTR-Intron2-1850 + GGAGCAAAGAGUUCUAAC 18 16950 CFTR-Intron2-1851 + AGGAGCAAAGAGUUCUAAC 19 16951 CFTR-Intron2-1852 + UAGGAGCAAAGAGUUCUAAC 20 16952 CFTR-Intron2-1853 + AUAGGAGCAAAGAGUUCUAAC 21 16953 CFTR-Intron2-1854 + GAUAGGAGCAAAGAGUUCUAAC 22 16954 CFTR-Intron2-1855 + AGAUAGGAGCAAAGAGUUCUAAC 23 16955 CFTR-Intron2-1856 + AAGAUAGGAGCAAAGAGUUCUAAC 24 16956 CFTR-Intron2-1857 + CAACCAUCUGGCAACCAC 18 16957 CFTR-Intron2-1858 + UCAACCAUCUGGCAACCAC 19 16958 CFTR-Intron2-1859 + UUCAACCAUCUGGCAACCAC 20 16959 CFTR-Intron2-1860 + CUUCAACCAUCUGGCAACCAC 21 16960 CFTR-Intron2-1861 + UCUUCAACCAUCUGGCAACCAC 22 16961 CFTR-Intron2-1862 + UUCUUCAACCAUCUGGCAACCAC 23 16962 CFTR-Intron2-1863 + GUUCUUCAACCAUCUGGCAACCAC 24 16963 CFTR-Intron2-1864 + AAAAAUUUCAUGAACCAC 18 16964 CFTR-Intron2-1865 + GAAAAAUUUCAUGAACCAC 19 16965 CFTR-Intron2-1866 + UGAAAAAUUUCAUGAACCAC 20 16966 CFTR-Intron2-1867 + AUGAAAAAUUUCAUGAACCAC 21 16967 CFTR-Intron2-1868 + GAUGAAAAAUUUCAUGAACCAC 22 16968 CFTR-Intron2-1869 + AGAUGAAAAAUUUCAUGAACCAC 23 16969 CFTR-Intron2-1870 + GAGAUGAAAAAUUUCAUGAACCAC 24 16970 CFTR-Intron2-1871 + UGUGAAAAAGUGGUCCAC 18 16971 CFTR-Intron2-1872 + AUGUGAAAAAGUGGUCCAC 19 16972 CFTR-Intron2-1873 + AAUGUGAAAAAGUGGUCCAC 20 16973 CFTR-Intron2-1874 + CAAUGUGAAAAAGUGGUCCAC 21 16974 CFTR-Intron2-1875 + UCAAUGUGAAAAAGUGGUCCAC 22 16975 CFTR-Intron2-1876 + UUCAAUGUGAAAAAGUGGUCCAC 23 16976 CFTR-Intron2-1877 + GUUCAAUGUGAAAAAGUGGUCCAC 24 16977 CFTR-Intron2-1878 + AGGCCCUAUUCUAGGCAC 18 16978 CFTR-Intron2-1879 + CAGGCCCUAUUCUAGGCAC 19 16979 CFTR-Intron2-1880 + CCAGGCCCUAUUCUAGGCAC 20 16980 CFTR-Intron2-1881 + GCCAGGCCCUAUUCUAGGCAC 21 16981 CFTR-Intron2-1882 + UGCCAGGCCCUAUUCUAGGCAC 22 16982 CFTR-Intron2-1883 + AUGCCAGGCCCUAUUCUAGGCAC 23 16983 CFTR-Intron2-1884 + UAUGCCAGGCCCUAUUCUAGGCAC 24 16984 CFTR-Intron2-1885 + CUGAGGCAGGAGAAUCAC 18 16985 CFTR-Intron2-1886 + GCUGAGGCAGGAGAAUCAC 19 16986 CFTR-Intron2-1887 + GGCUGAGGCAGGAGAAUCAC 20 16987 CFTR-Intron2-1888 + AGGCUGAGGCAGGAGAAUCAC 21 16988 CFTR-Intron2-1889 + GAGGCUGAGGCAGGAGAAUCAC 22 16989 CFTR-Intron2-1890 + AGAGGCUGAGGCAGGAGAAUCAC 23 16990 CFTR-Intron2-1891 + GAGAGGCUGAGGCAGGAGAAUCAC 24 16991 CFTR-Intron2-1892 + CCAAGGCGGGCAGAUCAC 18 16992 CFTR-Intron2-1893 + GCCAAGGCGGGCAGAUCAC 19 16993 CFTR-Intron2-1894 + GGCCAAGGCGGGCAGAUCAC 20 16994 CFTR-Intron2-1895 + AGGCCAAGGCGGGCAGAUCAC 21 16995 CFTR-Intron2-1896 + GAGGCCAAGGCGGGCAGAUCAC 22 16996 CFTR-Intron2-1897 + GGAGGCCAAGGCGGGCAGAUCAC 23 16997 CFTR-Intron2-1898 + GGGAGGCCAAGGCGGGCAGAUCAC 24 16998 CFTR-Intron2-1899 + CCAAGGUGGGCAGAUCAC 18 16999 CFTR-Intron2-1900 + GCCAAGGUGGGCAGAUCAC 19 17000 CFTR-Intron2-1901 + GGCCAAGGUGGGCAGAUCAC 20 17001 CFTR-Intron2-1902 + AGGCCAAGGUGGGCAGAUCAC 21 17002 CFTR-Intron2-1903 + GAGGCCAAGGUGGGCAGAUCAC 22 17003 CFTR-Intron2-1904 + GGAGGCCAAGGUGGGCAGAUCAC 23 17004 CFTR-Intron2-1905 + GGGAGGCCAAGGUGGGCAGAUCAC 24 17005 CFTR-Intron2-1906 + AAAGUGAAGUAGAGAGAC 18 17006 CFTR-Intron2-1907 + GAAAGUGAAGUAGAGAGAC 19 17007 CFTR-Intron2-1908 + UGAAAGUGAAGUAGAGAGAC 20 17008 CFTR-Intron2-1909 + AUGAAAGUGAAGUAGAGAGAC 21 17009 CFTR-Intron2-1910 + AAUGAAAGUGAAGUAGAGAGAC 22 17010 CFTR-Intron2-1911 + AAAUGAAAGUGAAGUAGAGAGAC 23 17011 CFTR-Intron2-1912 + UAAAUGAAAGUGAAGUAGAGAGAC 24 17012 CFTR-Intron2-1913 + GCCUGUAAACCCAGCUAC 18 17013 CFTR-Intron2-1914 + UGCCUGUAAACCCAGCUAC 19 17014 CFTR-Intron2-1915 + GUGCCUGUAAACCCAGCUAC 20 17015 CFTR-Intron2-1916 + AGUGCCUGUAAACCCAGCUAC 21 17016 CFTR-Intron2-1917 + GAGUGCCUGUAAACCCAGCUAC 22 17017 CFTR-Intron2-1918 + CGAGUGCCUGUAAACCCAGCUAC 23 17018 CFTR-Intron2-1919 + GCGAGUGCCUGUAAACCCAGCUAC 24 17019 CFTR-Intron2-1920 + AUAGAAUGGGGUAGUUAC 18 17020 CFTR-Intron2-1921 + AAUAGAAUGGGGUAGUUAC 19 17021 CFTR-Intron2-1922 + AAAUAGAAUGGGGUAGUUAC 20 17022 CFTR-Intron2-1923 + AAAAUAGAAUGGGGUAGUUAC 21 17023 CFTR-Intron2-1924 + AAAAAUAGAAUGGGGUAGUUAC 22 17024 CFTR-Intron2-1925 + AAAAAAUAGAAUGGGGUAGUUAC 23 17025 CFTR-Intron2-1926 + GAAAAAAUAGAAUGGGGUAGUUAC 24 17026 CFTR-Intron2-1927 + AGGAGAAUCACUUGAACC 18 17027 CFTR-Intron2-1928 + CAGGAGAAUCACUUGAACC 19 17028 CFTR-Intron2-1929 + GCAGGAGAAUCACUUGAACC 20 17029 CFTR-Intron2-1930 + GGCAGGAGAAUCACUUGAACC 21 17030 CFTR-Intron2-1931 + AGGCAGGAGAAUCACUUGAACC 22 17031 CFTR-Intron2-1932 + GAGGCAGGAGAAUCACUUGAACC 23 17032 CFTR-Intron2-1933 + UGAGGCAGGAGAAUCACUUGAACC 24 17033 CFTR-Intron2-1934 + CUGAGAUUCGCUUGAACC 18 17034 CFTR-Intron2-1935 + ACUGAGAUUCGCUUGAACC 19 17035 CFTR-Intron2-1936 + GACUGAGAUUCGCUUGAACC 20 17036 CFTR-Intron2-1937 + AGACUGAGAUUCGCUUGAACC 21 17037 CFTR-Intron2-1938 + GAGACUGAGAUUCGCUUGAACC 22 17038 CFTR-Intron2-1939 + GGAGACUGAGAUUCGCUUGAACC 23 17039 CFTR-Intron2-1940 + AGGAGACUGAGAUUCGCUUGAACC 24 17040 CFTR-Intron2-1941 + GAGCAAAGAGUUCUAACC 18 17041 CFTR-Intron2-1942 + GGAGCAAAGAGUUCUAACC 19 17042 CFTR-Intron2-305 + AGGAGCAAAGAGUUCUAACC 20 15405 CFTR-Intron2-1943 + UAGGAGCAAAGAGUUCUAACC 21 17043 CFTR-Intron2-1944 + AUAGGAGCAAAGAGUUCUAACC 22 17044 CFTR-Intron2-1945 + GAUAGGAGCAAAGAGUUCUAACC 23 17045 CFTR-Intron2-1946 + AGAUAGGAGCAAAGAGUUCUAACC 24 17046 CFTR-Intron2-1947 + AAGUGAAGUAGAGAGACC 18 17047 CFTR-Intron2-1948 + AAAGUGAAGUAGAGAGACC 19 17048 CFTR-Intron2-60 + GAAAGUGAAGUAGAGAGACC 20 15160 CFTR-Intron2-1949 + UGAAAGUGAAGUAGAGAGACC 21 17049 CFTR-Intron2-1950 + AUGAAAGUGAAGUAGAGAGACC 22 17050 CFTR-Intron2-1951 + AAUGAAAGUGAAGUAGAGAGACC 23 17051 CFTR-Intron2-1952 + AAAUGAAAGUGAAGUAGAGAGACC 24 17052 CFTR-Intron2-1953 + AAGAGGUCUCUAGUGACC 18 17053 CFTR-Intron2-1954 + UAAGAGGUCUCUAGUGACC 19 17054 CFTR-Intron2-1955 + AUAAGAGGUCUCUAGUGACC 20 17055 CFTR-Intron2-1956 + CAUAAGAGGUCUCUAGUGACC 21 17056 CFTR-Intron2-1957 + UCAUAAGAGGUCUCUAGUGACC 22 17057 CFTR-Intron2-1958 + UUCAUAAGAGGUCUCUAGUGACC 23 17058 CFTR-Intron2-1959 + UUUCAUAAGAGGUCUCUAGUGACC 24 17059 CFTR-Intron2-1960 + GGAGAAUCACUUGAACCC 18 17060 CFTR-Intron2-1961 + AGGAGAAUCACUUGAACCC 19 17061 CFTR-Intron2-636 + CAGGAGAAUCACUUGAACCC 20 15736 CFTR-Intron2-1962 + GCAGGAGAAUCACUUGAACCC 21 17062 CFTR-Intron2-1963 + GGCAGGAGAAUCACUUGAACCC 22 17063 CFTR-Intron2-1964 + AGGCAGGAGAAUCACUUGAACCC 23 17064 CFTR-Intron2-1965 + GAGGCAGGAGAAUCACUUGAACCC 24 17065 CFTR-Intron2-1966 + UGAGAUUCGCUUGAACCC 18 17066 CFTR-Intron2-1967 + CUGAGAUUCGCUUGAACCC 19 17067 CFTR-Intron2-637 + ACUGAGAUUCGCUUGAACCC 20 15737 CFTR-Intron2-1968 + GACUGAGAUUCGCUUGAACCC 21 17068 CFTR-Intron2-1969 + AGACUGAGAUUCGCUUGAACCC 22 17069 CFTR-Intron2-1970 + GAGACUGAGAUUCGCUUGAACCC 23 17070 CFTR-Intron2-1971 + GGAGACUGAGAUUCGCUUGAACCC 24 17071 CFTR-Intron2-1972 + AUGGAUCUUGGCAUCCCC 18 17072 CFTR-Intron2-1973 + CAUGGAUCUUGGCAUCCCC 19 17073 CFTR-Intron2-1974 + GCAUGGAUCUUGGCAUCCCC 20 17074 CFTR-Intron2-1975 + AGCAUGGAUCUUGGCAUCCCC 21 17075 CFTR-Intron2-1976 + AAGCAUGGAUCUUGGCAUCCCC 22 17076 CFTR-Intron2-1977 + UAAGCAUGGAUCUUGGCAUCCCC 23 17077 CFTR-Intron2-1978 + CUAAGCAUGGAUCUUGGCAUCCCC 24 17078 CFTR-Intron2-1979 + CUAGACUAUGAGUGGCCC 18 17079 CFTR-Intron2-1980 + UCUAGACUAUGAGUGGCCC 19 17080 CFTR-Intron2-1981 + UUCUAGACUAUGAGUGGCCC 20 17081 CFTR-Intron2-1982 + AUUCUAGACUAUGAGUGGCCC 21 17082 CFTR-Intron2-1983 + CAUUCUAGACUAUGAGUGGCCC 22 17083 CFTR-Intron2-1984 + UCAUUCUAGACUAUGAGUGGCCC 23 17084 CFTR-Intron2-1985 + UUCAUUCUAGACUAUGAGUGGCCC 24 17085 CFTR-Intron2-1986 + AUUACCUUAAGACUUCCC 18 17086 CFTR-Intron2-1987 + CAUUACCUUAAGACUUCCC 19 17087 CFTR-Intron2-314 + CCAUUACCUUAAGACUUCCC 20 15414 CFTR-Intron2-1988 + GCCAUUACCUUAAGACUUCCC 21 17088 CFTR-Intron2-1989 + AGCCAUUACCUUAAGACUUCCC 22 17089 CFTR-Intron2-1990 + UAGCCAUUACCUUAAGACUUCCC 23 17090 CFTR-Intron2-1991 + GUAGCCAUUACCUUAAGACUUCCC 24 17091 CFTR-Intron2-1992 + GGAUCAGAUGGGAAAGCC 18 17092 CFTR-Intron2-1993 + UGGAUCAGAUGGGAAAGCC 19 17093 CFTR-Intron2-1994 + AUGGAUCAGAUGGGAAAGCC 20 17094 CFTR-Intron2-1995 + AAUGGAUCAGAUGGGAAAGCC 21 17095 CFTR-Intron2-1996 + AAAUGGAUCAGAUGGGAAAGCC 22 17096 CFTR-Intron2-1997 + GAAAUGGAUCAGAUGGGAAAGCC 23 17097 CFTR-Intron2-1998 + AGAAAUGGAUCAGAUGGGAAAGCC 24 17098 CFTR-Intron2-1999 + GAUUUUUCACAUUUAGCC 18 17099 CFTR-Intron2-2000 + GGAUUUUUCACAUUUAGCC 19 17100 CFTR-Intron2-2001 + GGGAUUUUUCACAUUUAGCC 20 17101 CFTR-Intron2-2002 + UGGGAUUUUUCACAUUUAGCC 21 17102 CFTR-Intron2-2003 + CUGGGAUUUUUCACAUUUAGCC 22 17103 CFTR-Intron2-2004 + UCUGGGAUUUUUCACAUUUAGCC 23 17104 CFTR-Intron2-2005 + CUCUGGGAUUUUUCACAUUUAGCC 24 17105 CFTR-Intron2-2006 + GGGGGGGACUACCAUUCC 18 17106 CFTR-Intron2-2007 + UGGGGGGGACUACCAUUCC 19 17107 CFTR-Intron2-2008 + AUGGGGGGGACUACCAUUCC 20 17108 CFTR-Intron2-2009 + UAUGGGGGGGACUACCAUUCC 21 17109 CFTR-Intron2-2010 + UUAUGGGGGGGACUACCAUUCC 22 17110 CFTR-Intron2-2011 + UUUAUGGGGGGGACUACCAUUCC 23 17111 CFTR-Intron2-2012 + CUUUAUGGGGGGGACUACCAUUCC 24 17112 CFTR-Intron2-2013 + CAUUACCUUAAGACUUCC 18 17113 CFTR-Intron2-2014 + CCAUUACCUUAAGACUUCC 19 17114 CFTR-Intron2-2015 + GCCAUUACCUUAAGACUUCC 20 17115 CFTR-Intron2-2016 + AGCCAUUACCUUAAGACUUCC 21 17116 CFTR-Intron2-2017 + UAGCCAUUACCUUAAGACUUCC 22 17117 CFTR-Intron2-2018 + GUAGCCAUUACCUUAAGACUUCC 23 17118 CFTR-Intron2-2019 + AGUAGCCAUUACCUUAAGACUUCC 24 17119 CFTR-Intron2-2020 + GCACCAUUACACUCCAGC 18 17120 CFTR-Intron2-2021 + UGCACCAUUACACUCCAGC 19 17121 CFTR-Intron2-2022 + UUGCACCAUUACACUCCAGC 20 17122 CFTR-Intron2-2023 + AUUGCACCAUUACACUCCAGC 21 17123 CFTR-Intron2-2024 + AAUUGCACCAUUACACUCCAGC 22 17124 CFTR-Intron2-2025 + AAAUUGCACCAUUACACUCCAGC 23 17125 CFTR-Intron2-2026 + AAAAUUGCACCAUUACACUCCAGC 24 17126 CFTR-Intron2-2027 + CAGGAGACUGAGAUUCGC 18 17127 CFTR-Intron2-2028 + UCAGGAGACUGAGAUUCGC 19 17128 CFTR-Intron2-2029 + CUCAGGAGACUGAGAUUCGC 20 17129 CFTR-Intron2-2030 + ACUCAGGAGACUGAGAUUCGC 21 17130 CFTR-Intron2-2031 + UACUCAGGAGACUGAGAUUCGC 22 17131 CFTR-Intron2-2032 + CUACUCAGGAGACUGAGAUUCGC 23 17132 CFTR-Intron2-2033 + GCUACUCAGGAGACUGAGAUUCGC 24 17133 CFTR-Intron2-2034 + UACUCGAGAGGCUGAGGC 18 17134 CFTR-Intron2-2035 + CUACUCGAGAGGCUGAGGC 19 17135 CFTR-Intron2-461 + GCUACUCGAGAGGCUGAGGC 20 15561 CFTR-Intron2-2036 + AGCUACUCGAGAGGCUGAGGC 21 17136 CFTR-Intron2-2037 + CAGCUACUCGAGAGGCUGAGGC 22 17137 CFTR-Intron2-2038 + CCAGCUACUCGAGAGGCUGAGGC 23 17138 CFTR-Intron2-2039 + CCCAGCUACUCGAGAGGCUGAGGC 24 17139 CFTR-Intron2-2040 + UCUAAAGGAGUAAUAGGC 18 17140 CFTR-Intron2-2041 + CUCUAAAGGAGUAAUAGGC 19 17141 CFTR-Intron2-662 + ACUCUAAAGGAGUAAUAGGC 20 15762 CFTR-Intron2-2042 + CACUCUAAAGGAGUAAUAGGC 21 17142 CFTR-Intron2-2043 + UCACUCUAAAGGAGUAAUAGGC 22 17143 CFTR-Intron2-2044 + AUCACUCUAAAGGAGUAAUAGGC 23 17144 CFTR-Intron2-2045 + AAUCACUCUAAAGGAGUAAUAGGC 24 17145 CFTR-Intron2-2046 + CAGGCCUGUGCUGUUGGC 18 17146 CFTR-Intron2-2047 + UCAGGCCUGUGCUGUUGGC 19 17147 CFTR-Intron2-2048 + AUCAGGCCUGUGCUGUUGGC 20 17148 CFTR-Intron2-2049 + CAUCAGGCCUGUGCUGUUGGC 21 17149 CFTR-Intron2-2050 + GCAUCAGGCCUGUGCUGUUGGC 22 17150 CFTR-Intron2-2051 + GGCAUCAGGCCUGUGCUGUUGGC 23 17151 CFTR-Intron2-2052 + UGGCAUCAGGCCUGUGCUGUUGGC 24 17152 CFTR-Intron2-2053 + CAUAUCCUGACUACAAUC 18 17153 CFTR-Intron2-2054 + UCAUAUCCUGACUACAAUC 19 17154 CFTR-Intron2-2055 + UUCAUAUCCUGACUACAAUC 20 17155 CFTR-Intron2-2056 + GUUCAUAUCCUGACUACAAUC 21 17156 CFTR-Intron2-2057 + AGUUCAUAUCCUGACUACAAUC 22 17157 CFTR-Intron2-2058 + AAGUUCAUAUCCUGACUACAAUC 23 17158 CFTR-Intron2-2059 + AAAGUUCAUAUCCUGACUACAAUC 24 17159 CFTR-Intron2-2060 + CUGUAAACCCAGCUACUC 18 17160 CFTR-Intron2-2061 + CCUGUAAACCCAGCUACUC 19 17161 CFTR-Intron2-2062 + GCCUGUAAACCCAGCUACUC 20 17162 CFTR-Intron2-2063 + UGCCUGUAAACCCAGCUACUC 21 17163 CFTR-Intron2-2064 + GUGCCUGUAAACCCAGCUACUC 22 17164 CFTR-Intron2-2065 + AGUGCCUGUAAACCCAGCUACUC 23 17165 CFTR-Intron2-2066 + GAGUGCCUGUAAACCCAGCUACUC 24 17166 CFTR-Intron2-2067 + CUGUAGUCCCAGCUACUC 18 17167 CFTR-Intron2-2068 + CCUGUAGUCCCAGCUACUC 19 17168 CFTR-Intron2-463 + GCCUGUAGUCCCAGCUACUC 20 15563 CFTR-Intron2-2069 + UGCCUGUAGUCCCAGCUACUC 21 17169 CFTR-Intron2-2070 + AUGCCUGUAGUCCCAGCUACUC 22 17170 CFTR-Intron2-2071 + CAUGCCUGUAGUCCCAGCUACUC 23 17171 CFTR-Intron2-2072 + GCAUGCCUGUAGUCCCAGCUACUC 24 17172 CFTR-Intron2-2073 + UGAGGAGAAGGCAAGGUC 18 17173 CFTR-Intron2-2074 + CUGAGGAGAAGGCAAGGUC 19 17174 CFTR-Intron2-333 + CCUGAGGAGAAGGCAAGGUC 20 15433 CFTR-Intron2-2075 + ACCUGAGGAGAAGGCAAGGUC 21 17175 CFTR-Intron2-2076 + UACCUGAGGAGAAGGCAAGGUC 22 17176 CFTR-Intron2-2077 + UUACCUGAGGAGAAGGCAAGGUC 23 17177 CFTR-Intron2-2078 + GUUACCUGAGGAGAAGGCAAGGUC 24 17178 CFTR-Intron2-2079 + UGGUGGAAACCAUACUUC 18 17179 CFTR-Intron2-2080 + AUGGUGGAAACCAUACUUC 19 17180 CFTR-Intron2-669 + CAUGGUGGAAACCAUACUUC 20 15769 CFTR-Intron2-2081 + ACAUGGUGGAAACCAUACUUC 21 17181 CFTR-Intron2-2082 + AACAUGGUGGAAACCAUACUUC 22 17182 CFTR-Intron2-2083 + GAACAUGGUGGAAACCAUACUUC 23 17183 CFTR-Intron2-2084 + GGAACAUGGUGGAAACCAUACUUC 24 17184 CFTR-Intron2-2085 + UCACAUAGUUCAGGCUUC 18 17185 CFTR-Intron2-2086 + UUCACAUAGUUCAGGCUUC 19 17186 CFTR-Intron2-2087 + CUUCACAUAGUUCAGGCUUC 20 17187 CFTR-Intron2-2088 + UCUUCACAUAGUUCAGGCUUC 21 17188 CFTR-Intron2-2089 + GUCUUCACAUAGUUCAGGCUUC 22 17189 CFTR-Intron2-2090 + GGUCUUCACAUAGUUCAGGCUUC 23 17190 CFTR-Intron2-2091 + AGGUCUUCACAUAGUUCAGGCUUC 24 17191 CFTR-Intron2-2092 + ACAGAGAUGAAAAAUUUC 18 17192 CFTR-Intron2-2093 + UACAGAGAUGAAAAAUUUC 19 17193 CFTR-Intron2-2094 + GUACAGAGAUGAAAAAUUUC 20 17194 CFTR-Intron2-2095 + UGUACAGAGAUGAAAAAUUUC 21 17195 CFTR-Intron2-2096 + CUGUACAGAGAUGAAAAAUUUC 22 17196 CFTR-Intron2-2097 + ACUGUACAGAGAUGAAAAAUUUC 23 17197 CFTR-Intron2-2098 + AACUGUACAGAGAUGAAAAAUUUC 24 17198 CFTR-Intron2-2099 + ACCAAAUGUGUAUUUUUC 18 17199 CFTR-Intron2-2100 + AACCAAAUGUGUAUUUUUC 19 17200 CFTR-Intron2-670 + AAACCAAAUGUGUAUUUUUC 20 15770 CFTR-Intron2-2101 + GAAACCAAAUGUGUAUUUUUC 21 17201 CFTR-Intron2-2102 + UGAAACCAAAUGUGUAUUUUUC 22 17202 CFTR-Intron2-2103 + CUGAAACCAAAUGUGUAUUUUUC 23 17203 CFTR-Intron2-2104 + UCUGAAACCAAAUGUGUAUUUUUC 24 17204 CFTR-Intron2-2105 + UCACCUUCUCCAUCAAAG 18 17205 CFTR-Intron2-2106 + CUCACCUUCUCCAUCAAAG 19 17206 CFTR-Intron2-2107 + ACUCACCUUCUCCAUCAAAG 20 17207 CFTR-Intron2-2108 + GACUCACCUUCUCCAUCAAAG 21 17208 CFTR-Intron2-2109 + AGACUCACCUUCUCCAUCAAAG 22 17209 CFTR-Intron2-2110 + CAGACUCACCUUCUCCAUCAAAG 23 17210 CFTR-Intron2-2111 + GCAGACUCACCUUCUCCAUCAAAG 24 17211 CFTR-Intron2-2112 + AAACUUAGAUAUUCAAAG 18 17212 CFTR-Intron2-2113 + AAAACUUAGAUAUUCAAAG 19 17213 CFTR-Intron2-2114 + UAAAACUUAGAUAUUCAAAG 20 17214 CFTR-Intron2-2115 + UUAAAACUUAGAUAUUCAAAG 21 17215 CFTR-Intron2-2116 + AUUAAAACUUAGAUAUUCAAAG 22 17216 CFTR-Intron2-2117 + AAUUAAAACUUAGAUAUUCAAAG 23 17217 CFTR-Intron2-2118 + CAAUUAAAACUUAGAUAUUCAAAG 24 17218 CFTR-Intron2-2119 + ACACUUUGGGAGGCCAAG 18 17219 CFTR-Intron2-2120 + AACACUUUGGGAGGCCAAG 19 17220 CFTR-Intron2-2121 + CAACACUUUGGGAGGCCAAG 20 17221 CFTR-Intron2-2122 + CCAACACUUUGGGAGGCCAAG 21 17222 CFTR-Intron2-2123 + CCCAACACUUUGGGAGGCCAAG 22 17223 CFTR-Intron2-2124 + UCCCAACACUUUGGGAGGCCAAG 23 17224 CFTR-Intron2-2125 + AUCCCAACACUUUGGGAGGCCAAG 24 17225 CFTR-Intron2-2126 + GCAUUUUGGGAGGCCAAG 18 17226 CFTR-Intron2-2127 + AGCAUUUUGGGAGGCCAAG 19 17227 CFTR-Intron2-2128 + CAGCAUUUUGGGAGGCCAAG 20 17228 CFTR-Intron2-2129 + CCAGCAUUUUGGGAGGCCAAG 21 17229 CFTR-Intron2-2130 + CCCAGCAUUUUGGGAGGCCAAG 22 17230 CFTR-Intron2-2131 + UCCCAGCAUUUUGGGAGGCCAAG 23 17231 CFTR-Intron2-2132 + AUCCCAGCAUUUUGGGAGGCCAAG 24 17232 CFTR-Intron2-2133 + AUGUAAAUGAAAGUGAAG 18 17233 CFTR-Intron2-2134 + GAUGUAAAUGAAAGUGAAG 19 17234 CFTR-Intron2-2135 + AGAUGUAAAUGAAAGUGAAG 20 17235 CFTR-Intron2-2136 + GAGAUGUAAAUGAAAGUGAAG 21 17236 CFTR-Intron2-2137 + UGAGAUGUAAAUGAAAGUGAAG 22 17237 CFTR-Intron2-2138 + CUGAGAUGUAAAUGAAAGUGAAG 23 17238 CFTR-Intron2-2139 + GCUGAGAUGUAAAUGAAAGUGAAG 24 17239 CFTR-Intron2-2140 + UAAAGGAGUAAUACACAG 18 17240 CFTR-Intron2-2141 + AUAAAGGAGUAAUACACAG 19 17241 CFTR-Intron2-2142 + CAUAAAGGAGUAAUACACAG 20 17242 CFTR-Intron2-2143 + ACAUAAAGGAGUAAUACACAG 21 17243 CFTR-Intron2-2144 + AACAUAAAGGAGUAAUACACAG 22 17244 CFTR-Intron2-2145 + AAACAUAAAGGAGUAAUACACAG 23 17245 CFTR-Intron2-2146 + AAAACAUAAAGGAGUAAUACACAG 24 17246 CFTR-Intron2-2147 + GUGAAGUAGAGAGACCAG 18 17247 CFTR-Intron2-2148 + AGUGAAGUAGAGAGACCAG 19 17248 CFTR-Intron2-2149 + AAGUGAAGUAGAGAGACCAG 20 17249 CFTR-Intron2-2150 + AAAGUGAAGUAGAGAGACCAG 21 17250 CFTR-Intron2-2151 + GAAAGUGAAGUAGAGAGACCAG 22 17251 CFTR-Intron2-2152 + UGAAAGUGAAGUAGAGAGACCAG 23 17252 CFTR-Intron2-2153 + AUGAAAGUGAAGUAGAGAGACCAG 24 17253 CFTR-Intron2-2154 + AUACCAGGCCCAGAUCAG 18 17254 CFTR-Intron2-2155 + CAUACCAGGCCCAGAUCAG 19 17255 CFTR-Intron2-2156 + ACAUACCAGGCCCAGAUCAG 20 17256 CFTR-Intron2-2157 + CACAUACCAGGCCCAGAUCAG 21 17257 CFTR-Intron2-2158 + CCACAUACCAGGCCCAGAUCAG 22 17258 CFTR-Intron2-2159 + ACCACAUACCAGGCCCAGAUCAG 23 17259 CFTR-Intron2-2160 + GACCACAUACCAGGCCCAGAUCAG 24 17260 CFTR-Intron2-2161 + AAAGGAGAAAUGGAUCAG 18 17261 CFTR-Intron2-2162 + CAAAGGAGAAAUGGAUCAG 19 17262 CFTR-Intron2-2163 + UCAAAGGAGAAAUGGAUCAG 20 17263 CFTR-Intron2-2164 + AUCAAAGGAGAAAUGGAUCAG 21 17264 CFTR-Intron2-2165 + CAUCAAAGGAGAAAUGGAUCAG 22 17265 CFTR-Intron2-2166 + CCAUCAAAGGAGAAAUGGAUCAG 23 17266 CFTR-Intron2-2167 + UCCAUCAAAGGAGAAAUGGAUCAG 24 17267 CFTR-Intron2-2168 + AGGCAAUACAGACCUCAG 18 17268 CFTR-Intron2-2169 + AAGGCAAUACAGACCUCAG 19 17269 CFTR-Intron2-2170 + CAAGGCAAUACAGACCUCAG 20 17270 CFTR-Intron2-2171 + GCAAGGCAAUACAGACCUCAG 21 17271 CFTR-Intron2-2172 + AGCAAGGCAAUACAGACCUCAG 22 17272 CFTR-Intron2-2173 + GAGCAAGGCAAUACAGACCUCAG 23 17273 CFTR-Intron2-2174 + AGAGCAAGGCAAUACAGACCUCAG 24 17274 CFTR-Intron2-2175 + UUUUCAAACUGUACAGAG 18 17275 CFTR-Intron2-2176 + AUUUUCAAACUGUACAGAG 19 17276 CFTR-Intron2-2177 + AAUUUUCAAACUGUACAGAG 20 17277 CFTR-Intron2-2178 + UAAUUUUCAAACUGUACAGAG 21 17278 CFTR-Intron2-2179 + UUAAUUUUCAAACUGUACAGAG 22 17279 CFTR-Intron2-2180 + CUUAAUUUUCAAACUGUACAGAG 23 17280 CFTR-Intron2-2181 + UCUUAAUUUUCAAACUGUACAGAG 24 17281 CFTR-Intron2-2182 + GUAGAGAGACCAGGAGAG 18 17282 CFTR-Intron2-2183 + AGUAGAGAGACCAGGAGAG 19 17283 CFTR-Intron2-2184 + AAGUAGAGAGACCAGGAGAG 20 17284 CFTR-Intron2-2185 + GAAGUAGAGAGACCAGGAGAG 21 17285 CFTR-Intron2-2186 + UGAAGUAGAGAGACCAGGAGAG 22 17286 CFTR-Intron2-2187 + GUGAAGUAGAGAGACCAGGAGAG 23 17287 CFTR-Intron2-2188 + AGUGAAGUAGAGAGACCAGGAGAG 24 17288 CFTR-Intron2-2189 + AUCACUUGAACCCAGGAG 18 17289 CFTR-Intron2-2190 + AAUCACUUGAACCCAGGAG 19 17290 CFTR-Intron2-2191 + GAAUCACUUGAACCCAGGAG 20 17291 CFTR-Intron2-2192 + AGAAUCACUUGAACCCAGGAG 21 17292 CFTR-Intron2-2193 + GAGAAUCACUUGAACCCAGGAG 22 17293 CFTR-Intron2-2194 + GGAGAAUCACUUGAACCCAGGAG 23 17294 CFTR-Intron2-2195 + AGGAGAAUCACUUGAACCCAGGAG 24 17295 CFTR-Intron2-2196 + GAAACCAUACUUCAGGAG 18 17296 CFTR-Intron2-2197 + GGAAACCAUACUUCAGGAG 19 17297 CFTR-Intron2-2198 + UGGAAACCAUACUUCAGGAG 20 17298 CFTR-Intron2-2199 + GUGGAAACCAUACUUCAGGAG 21 17299 CFTR-Intron2-2200 + GGUGGAAACCAUACUUCAGGAG 22 17300 CFTR-Intron2-2201 + UGGUGGAAACCAUACUUCAGGAG 23 17301 CFTR-Intron2-2202 + AUGGUGGAAACCAUACUUCAGGAG 24 17302 CFTR-Intron2-2203 + AUGGGGUAGUUACCUGAG 18 17303 CFTR-Intron2-2204 + AAUGGGGUAGUUACCUGAG 19 17304 CFTR-Intron2-2205 + GAAUGGGGUAGUUACCUGAG 20 17305 CFTR-Intron2-2206 + AGAAUGGGGUAGUUACCUGAG 21 17306 CFTR-Intron2-2207 + UAGAAUGGGGUAGUUACCUGAG 22 17307 CFTR-Intron2-2208 + AUAGAAUGGGGUAGUUACCUGAG 23 17308 CFTR-Intron2-2209 + AAUAGAAUGGGGUAGUUACCUGAG 24 17309 CFTR-Intron2-2210 + CCACUCAGAGUGGCUGAG 18 17310 CFTR-Intron2-2211 + UCCACUCAGAGUGGCUGAG 19 17311 CFTR-Intron2-343 + UUCCACUCAGAGUGGCUGAG 20 15443 CFTR-Intron2-2212 + UUUCCACUCAGAGUGGCUGAG 21 17312 CFTR-Intron2-2213 + CUUUCCACUCAGAGUGGCUGAG 22 17313 CFTR-Intron2-2214 + GCUUUCCACUCAGAGUGGCUGAG 23 17314 CFTR-Intron2-2215 + UGCUUUCCACUCAGAGUGGCUGAG 24 17315 CFTR-Intron2-2216 + GGCAGAGUUUGCAGUGAG 18 17316 CFTR-Intron2-2217 + AGGCAGAGUUUGCAGUGAG 19 17317 CFTR-Intron2-2218 + GAGGCAGAGUUUGCAGUGAG 20 17318 CFTR-Intron2-2219 + GGAGGCAGAGUUUGCAGUGAG 21 17319 CFTR-Intron2-2220 + AGGAGGCAGAGUUUGCAGUGAG 22 17320 CFTR-Intron2-2221 + CAGGAGGCAGAGUUUGCAGUGAG 23 17321 CFTR-Intron2-2222 + CCAGGAGGCAGAGUUUGCAGUGAG 24 17322 CFTR-Intron2-2223 + UAGGUGAUGUGGUUCUAG 18 17323 CFTR-Intron2-2224 + GUAGGUGAUGUGGUUCUAG 19 17324 CFTR-Intron2-2225 + AGUAGGUGAUGUGGUUCUAG 20 17325 CFTR-Intron2-2226 + GAGUAGGUGAUGUGGUUCUAG 21 17326 CFTR-Intron2-2227 + AGAGUAGGUGAUGUGGUUCUAG 22 17327 CFTR-Intron2-2228 + AAGAGUAGGUGAUGUGGUUCUAG 23 17328 CFTR-Intron2-2229 + CAAGAGUAGGUGAUGUGGUUCUAG 24 17329 CFTR-Intron2-2230 + AUUUCAUGAACCACAAGG 18 17330 CFTR-Intron2-2231 + AAUUUCAUGAACCACAAGG 19 17331 CFTR-Intron2-2232 + AAAUUUCAUGAACCACAAGG 20 17332 CFTR-Intron2-2233 + AAAAUUUCAUGAACCACAAGG 21 17333 CFTR-Intron2-2234 + AAAAAUUUCAUGAACCACAAGG 22 17334 CFTR-Intron2-2235 + GAAAAAUUUCAUGAACCACAAGG 23 17335 CFTR-Intron2-2236 + UGAAAAAUUUCAUGAACCACAAGG 24 17336 CFTR-Intron2-2237 + CAGAUGGGAAAGCCAAGG 18 17337 CFTR-Intron2-2238 + UCAGAUGGGAAAGCCAAGG 19 17338 CFTR-Intron2-2239 + AUCAGAUGGGAAAGCCAAGG 20 17339 CFTR-Intron2-2240 + GAUCAGAUGGGAAAGCCAAGG 21 17340 CFTR-Intron2-2241 + GGAUCAGAUGGGAAAGCCAAGG 22 17341 CFTR-Intron2-2242 + UGGAUCAGAUGGGAAAGCCAAGG 23 17342 CFTR-Intron2-2243 + AUGGAUCAGAUGGGAAAGCCAAGG 24 17343 CFTR-Intron2-2244 + CCUGAGGAGAAGGCAAGG 18 17344 CFTR-Intron2-2245 + ACCUGAGGAGAAGGCAAGG 19 17345 CFTR-Intron2-2246 + UACCUGAGGAGAAGGCAAGG 20 17346 CFTR-Intron2-2247 + UUACCUGAGGAGAAGGCAAGG 21 17347 CFTR-Intron2-2248 + GUUACCUGAGGAGAAGGCAAGG 22 17348 CFTR-Intron2-2249 + AGUUACCUGAGGAGAAGGCAAGG 23 17349 CFTR-Intron2-2250 + UAGUUACCUGAGGAGAAGGCAAGG 24 17350 CFTR-Intron2-2251 + AAGAAAAGAAGUAACAGG 18 17351 CFTR-Intron2-2252 + UAAGAAAAGAAGUAACAGG 19 17352 CFTR-Intron2-2253 + AUAAGAAAAGAAGUAACAGG 20 17353 CFTR-Intron2-2254 + UAUAAGAAAAGAAGUAACAGG 21 17354 CFTR-Intron2-2255 + UUAUAAGAAAAGAAGUAACAGG 22 17355 CFTR-Intron2-2256 + UUUAUAAGAAAAGAAGUAACAGG 23 17356 CFTR-Intron2-2257 + UUUUAUAAGAAAAGAAGUAACAGG 24 17357 CFTR-Intron2-2258 + ACCCAGCUACUCGAGAGG 18 17358 CFTR-Intron2-2259 + AACCCAGCUACUCGAGAGG 19 17359 CFTR-Intron2-2260 + AAACCCAGCUACUCGAGAGG 20 17360 CFTR-Intron2-2261 + UAAACCCAGCUACUCGAGAGG 21 17361 CFTR-Intron2-2262 + GUAAACCCAGCUACUCGAGAGG 22 17362 CFTR-Intron2-2263 + UGUAAACCCAGCUACUCGAGAGG 23 17363 CFTR-Intron2-2264 + CUGUAAACCCAGCUACUCGAGAGG 24 17364 CFTR-Intron2-2265 + CUACUCGAGAGGCUGAGG 18 17365 CFTR-Intron2-2266 + GCUACUCGAGAGGCUGAGG 19 17366 CFTR-Intron2-2267 + AGCUACUCGAGAGGCUGAGG 20 17367 CFTR-Intron2-2268 + CAGCUACUCGAGAGGCUGAGG 21 17368 CFTR-Intron2-2269 + CCAGCUACUCGAGAGGCUGAGG 22 17369 CFTR-Intron2-2270 + CCCAGCUACUCGAGAGGCUGAGG 23 17370 CFTR-Intron2-2271 + ACCCAGCUACUCGAGAGGCUGAGG 24 17371 CFTR-Intron2-2272 + CUCUAAAGGAGUAAUAGG 18 17372 CFTR-Intron2-2273 + ACUCUAAAGGAGUAAUAGG 19 17373 CFTR-Intron2-2274 + CACUCUAAAGGAGUAAUAGG 20 17374 CFTR-Intron2-2275 + UCACUCUAAAGGAGUAAUAGG 21 17375 CFTR-Intron2-2276 + AUCACUCUAAAGGAGUAAUAGG 22 17376 CFTR-Intron2-2277 + AAUCACUCUAAAGGAGUAAUAGG 23 17377 CFTR-Intron2-2278 + AAAUCACUCUAAAGGAGUAAUAGG 24 17378 CFTR-Intron2-2279 + AGGCCCAGAUCAGAAGGG 18 17379 CFTR-Intron2-2280 + CAGGCCCAGAUCAGAAGGG 19 17380 CFTR-Intron2-2281 + CCAGGCCCAGAUCAGAAGGG 20 17381 CFTR-Intron2-2282 + ACCAGGCCCAGAUCAGAAGGG 21 17382 CFTR-Intron2-2283 + UACCAGGCCCAGAUCAGAAGGG 22 17383 CFTR-Intron2-2284 + AUACCAGGCCCAGAUCAGAAGGG 23 17384 CFTR-Intron2-2285 + CAUACCAGGCCCAGAUCAGAAGGG 24 17385 CFTR-Intron2-2286 + AGAAAAGAAGUAACAGGG 18 17386 CFTR-Intron2-2287 + AAGAAAAGAAGUAACAGGG 19 17387 CFTR-Intron2-681 + UAAGAAAAGAAGUAACAGGG 20 15781 CFTR-Intron2-2288 + AUAAGAAAAGAAGUAACAGGG 21 17388 CFTR-Intron2-2289 + UAUAAGAAAAGAAGUAACAGGG 22 17389 CFTR-Intron2-2290 + UUAUAAGAAAAGAAGUAACAGGG 23 17390 CFTR-Intron2-2291 + UUUAUAAGAAAAGAAGUAACAGGG 24 17391 CFTR-Intron2-2292 + UGAGAGAUUCUUUAUGGG 18 17392 CFTR-Intron2-2293 + CUGAGAGAUUCUUUAUGGG 19 17393 CFTR-Intron2-353 + ACUGAGAGAUUCUUUAUGGG 20 15453 CFTR-Intron2-2294 + AACUGAGAGAUUCUUUAUGGG 21 17394 CFTR-Intron2-2295 + AAACUGAGAGAUUCUUUAUGGG 22 17395 CFTR-Intron2-2296 + GAAACUGAGAGAUUCUUUAUGGG 23 17396 CFTR-Intron2-2297 + GGAAACUGAGAGAUUCUUUAUGGG 24 17397 CFTR-Intron2-2298 + GGGGAAUUUCUUUAAUGG 18 17398 CFTR-Intron2-2299 + CGGGGAAUUUCUUUAAUGG 19 17399 CFTR-Intron2-2300 + UCGGGGAAUUUCUUUAAUGG 20 17400 CFTR-Intron2-2301 + GUCGGGGAAUUUCUUUAAUGG 21 17401 CFTR-Intron2-2302 + GGUCGGGGAAUUUCUUUAAUGG 22 17402 CFTR-Intron2-2303 + AGGUCGGGGAAUUUCUUUAAUGG 23 17403 CFTR-Intron2-2304 + AAGGUCGGGGAAUUUCUUUAAUGG 24 17404 CFTR-Intron2-2305 + GUAGUUUUAGGAACAUGG 18 17405 CFTR-Intron2-2306 + UGUAGUUUUAGGAACAUGG 19 17406 CFTR-Intron2-355 + AUGUAGUUUUAGGAACAUGG 20 15455 CFTR-Intron2-2307 + AAUGUAGUUUUAGGAACAUGG 21 17407 CFTR-Intron2-2308 + CAAUGUAGUUUUAGGAACAUGG 22 17408 CFTR-Intron2-2309 + GCAAUGUAGUUUUAGGAACAUGG 23 17409 CFTR-Intron2-2310 + GGCAAUGUAGUUUUAGGAACAUGG 24 17410 CFTR-Intron2-2311 + CUGAGAGAUUCUUUAUGG 18 17411 CFTR-Intron2-2312 + ACUGAGAGAUUCUUUAUGG 19 17412 CFTR-Intron2-356 + AACUGAGAGAUUCUUUAUGG 20 15456 CFTR-Intron2-2313 + AAACUGAGAGAUUCUUUAUGG 21 17413 CFTR-Intron2-2314 + GAAACUGAGAGAUUCUUUAUGG 22 17414 CFTR-Intron2-2315 + GGAAACUGAGAGAUUCUUUAUGG 23 17415 CFTR-Intron2-2316 + AGGAAACUGAGAGAUUCUUUAUGG 24 17416 CFTR-Intron2-2317 + AAAUAGUCUGAAAACUGG 18 17417 CFTR-Intron2-2318 + UAAAUAGUCUGAAAACUGG 19 17418 CFTR-Intron2-2319 + UUAAAUAGUCUGAAAACUGG 20 17419 CFTR-Intron2-2320 + AUUAAAUAGUCUGAAAACUGG 21 17420 CFTR-Intron2-2321 + CAUUAAAUAGUCUGAAAACUGG 22 17421 CFTR-Intron2-2322 + ACAUUAAAUAGUCUGAAAACUGG 23 17422 CFTR-Intron2-2323 + GACAUUAAAUAGUCUGAAAACUGG 24 17423 CFTR-Intron2-2324 + GCUUUCCACUCAGAGUGG 18 17424 CFTR-Intron2-2325 + UGCUUUCCACUCAGAGUGG 19 17425 CFTR-Intron2-2326 + AUGCUUUCCACUCAGAGUGG 20 17426 CFTR-Intron2-2327 + GAUGCUUUCCACUCAGAGUGG 21 17427 CFTR-Intron2-2328 + UGAUGCUUUCCACUCAGAGUGG 22 17428 CFTR-Intron2-2329 + AUGAUGCUUUCCACUCAGAGUGG 23 17429 CFTR-Intron2-2330 + AAUGAUGCUUUCCACUCAGAGUGG 24 17430 CFTR-Intron2-2331 + GUCCACACGGAAGUAAUG 18 17431 CFTR-Intron2-2332 + GGUCCACACGGAAGUAAUG 19 17432 CFTR-Intron2-2333 + UGGUCCACACGGAAGUAAUG 20 17433 CFTR-Intron2-2334 + GUGGUCCACACGGAAGUAAUG 21 17434 CFTR-Intron2-2335 + AGUGGUCCACACGGAAGUAAUG 22 17435 CFTR-Intron2-2336 + AAGUGGUCCACACGGAAGUAAUG 23 17436 CFTR-Intron2-2337 + AAAGUGGUCCACACGGAAGUAAUG 24 17437 CFTR-Intron2-2338 + ACCAGCCUGGCCAACAUG 18 17438 CFTR-Intron2-2339 + GACCAGCCUGGCCAACAUG 19 17439 CFTR-Intron2-2340 + AGACCAGCCUGGCCAACAUG 20 17440 CFTR-Intron2-2341 + AAGACCAGCCUGGCCAACAUG 21 17441 CFTR-Intron2-2342 + CAAGACCAGCCUGGCCAACAUG 22 17442 CFTR-Intron2-2343 + UCAAGACCAGCCUGGCCAACAUG 23 17443 CFTR-Intron2-2344 + UUCAAGACCAGCCUGGCCAACAUG 24 17444 CFTR-Intron2-2345 + UGUAGUUUUAGGAACAUG 18 17445 CFTR-Intron2-2346 + AUGUAGUUUUAGGAACAUG 19 17446 CFTR-Intron2-2347 + AAUGUAGUUUUAGGAACAUG 20 17447 CFTR-Intron2-2348 + CAAUGUAGUUUUAGGAACAUG 21 17448 CFTR-Intron2-2349 + GCAAUGUAGUUUUAGGAACAUG 22 17449 CFTR-Intron2-2350 + GGCAAUGUAGUUUUAGGAACAUG 23 17450 CFTR-Intron2-2351 + GGGCAAUGUAGUUUUAGGAACAUG 24 17451 CFTR-Intron2-2352 + UUGCACACUGCAGUUAUG 18 17452 CFTR-Intron2-2353 + UUUGCACACUGCAGUUAUG 19 17453 CFTR-Intron2-2354 + GUUUGCACACUGCAGUUAUG 20 17454 CFTR-Intron2-2355 + GGUUUGCACACUGCAGUUAUG 21 17455 CFTR-Intron2-2356 + UGGUUUGCACACUGCAGUUAUG 22 17456 CFTR-Intron2-2357 + GUGGUUUGCACACUGCAGUUAUG 23 17457 CFTR-Intron2-2358 + UGUGGUUUGCACACUGCAGUUAUG 24 17458 CFTR-Intron2-2359 + CCAGGGACCCACUUUAUG 18 17459 CFTR-Intron2-2360 + ACCAGGGACCCACUUUAUG 19 17460 CFTR-Intron2-2361 + AACCAGGGACCCACUUUAUG 20 17461 CFTR-Intron2-2362 + UAACCAGGGACCCACUUUAUG 21 17462 CFTR-Intron2-2363 + CUAACCAGGGACCCACUUUAUG 22 17463 CFTR-Intron2-2364 + UCUAACCAGGGACCCACUUUAUG 23 17464 CFTR-Intron2-2365 + UUCUAACCAGGGACCCACUUUAUG 24 17465 CFTR-Intron2-2366 + ACUGAGAGAUUCUUUAUG 18 17466 CFTR-Intron2-2367 + AACUGAGAGAUUCUUUAUG 19 17467 CFTR-Intron2-361 + AAACUGAGAGAUUCUUUAUG 20 15461 CFTR-Intron2-2368 + GAAACUGAGAGAUUCUUUAUG 21 17468 CFTR-Intron2-2369 + GGAAACUGAGAGAUUCUUUAUG 22 17469 CFTR-Intron2-2370 + AGGAAACUGAGAGAUUCUUUAUG 23 17470 CFTR-Intron2-2371 + AAGGAAACUGAGAGAUUCUUUAUG 24 17471 CFTR-Intron2-2372 + GAAUGGGGUAGUUACCUG 18 17472 CFTR-Intron2-2373 + AGAAUGGGGUAGUUACCUG 19 17473 CFTR-Intron2-362 + UAGAAUGGGGUAGUUACCUG 20 15462 CFTR-Intron2-2374 + AUAGAAUGGGGUAGUUACCUG 21 17474 CFTR-Intron2-2375 + AAUAGAAUGGGGUAGUUACCUG 22 17475 CFTR-Intron2-2376 + AAAUAGAAUGGGGUAGUUACCUG 23 17476 CFTR-Intron2-2377 + AAAAUAGAAUGGGGUAGUUACCUG 24 17477 CFTR-Intron2-2378 + GGUCACUUCCCAAGGGUG 18 17478 CFTR-Intron2-2379 + GGGUCACUUCCCAAGGGUG 19 17479 CFTR-Intron2-2380 + AGGGUCACUUCCCAAGGGUG 20 17480 CFTR-Intron2-2381 + CAGGGUCACUUCCCAAGGGUG 21 17481 CFTR-Intron2-2382 + CCAGGGUCACUUCCCAAGGGUG 22 17482 CFTR-Intron2-2383 + GCCAGGGUCACUUCCCAAGGGUG 23 17483 CFTR-Intron2-2384 + AGCCAGGGUCACUUCCCAAGGGUG 24 17484 CFTR-Intron2-2385 + UAAAGGUCUUUGAAAAAU 18 17485 CFTR-Intron2-2386 + UUAAAGGUCUUUGAAAAAU 19 17486 CFTR-Intron2-2387 + AUUAAAGGUCUUUGAAAAAU 20 17487 CFTR-Intron2-2388 + UAUUAAAGGUCUUUGAAAAAU 21 17488 CFTR-Intron2-2389 + GUAUUAAAGGUCUUUGAAAAAU 22 17489 CFTR-Intron2-2390 + UGUAUUAAAGGUCUUUGAAAAAU 23 17490 CFTR-Intron2-2391 + AUGUAUUAAAGGUCUUUGAAAAAU 24 17491 CFTR-Intron2-2392 + ACAAGGCAGUUAUGAAAU 18 17492 CFTR-Intron2-2393 + CACAAGGCAGUUAUGAAAU 19 17493 CFTR-Intron2-2394 + UCACAAGGCAGUUAUGAAAU 20 17494 CFTR-Intron2-2395 + GUCACAAGGCAGUUAUGAAAU 21 17495 CFTR-Intron2-2396 + GGUCACAAGGCAGUUAUGAAAU 22 17496 CFTR-Intron2-2397 + UGGUCACAAGGCAGUUAUGAAAU 23 17497 CFTR-Intron2-2398 + AUGGUCACAAGGCAGUUAUGAAAU 24 17498 CFTR-Intron2-2399 + CAGAGUAAGAAGCUAAAU 18 17499 CFTR-Intron2-2400 + UCAGAGUAAGAAGCUAAAU 19 17500 CFTR-Intron2-2401 + CUCAGAGUAAGAAGCUAAAU 20 17501 CFTR-Intron2-2402 + ACUCAGAGUAAGAAGCUAAAU 21 17502 CFTR-Intron2-2403 + UACUCAGAGUAAGAAGCUAAAU 22 17503 CFTR-Intron2-2404 + UUACUCAGAGUAAGAAGCUAAAU 23 17504 CFTR-Intron2-2405 + GUUACUCAGAGUAAGAAGCUAAAU 24 17505 CFTR-Intron2-2406 + CAACAAAAUGGGUUCAAU 18 17506 CFTR-Intron2-2407 + CCAACAAAAUGGGUUCAAU 19 17507 CFTR-Intron2-2408 + ACCAACAAAAUGGGUUCAAU 20 17508 CFTR-Intron2-2409 + AACCAACAAAAUGGGUUCAAU 21 17509 CFTR-Intron2-2410 + AAACCAACAAAAUGGGUUCAAU 22 17510 CFTR-Intron2-2411 + UAAACCAACAAAAUGGGUUCAAU 23 17511 CFTR-Intron2-2412 + AUAAACCAACAAAAUGGGUUCAAU 24 17512 CFTR-Intron2-2413 + CCCUAGAAGCUUGCUAAU 18 17513 CFTR-Intron2-2414 + CCCCUAGAAGCUUGCUAAU 19 17514 CFTR-Intron2-2415 + UCCCCUAGAAGCUUGCUAAU 20 17515 CFTR-Intron2-2416 + AUCCCCUAGAAGCUUGCUAAU 21 17516 CFTR-Intron2-2417 + CAUCCCCUAGAAGCUUGCUAAU 22 17517 CFTR-Intron2-2418 + GCAUCCCCUAGAAGCUUGCUAAU 23 17518 CFTR-Intron2-2419 + GGCAUCCCCUAGAAGCUUGCUAAU 24 17519 CFTR-Intron2-2420 + UUUAAAUUGAAUCAACAU 18 17520 CFTR-Intron2-2421 + UUUUAAAUUGAAUCAACAU 19 17521 CFTR-Intron2-699 + UUUUUAAAUUGAAUCAACAU 20 15799 CFTR-Intron2-2422 + UUUUUUAAAUUGAAUCAACAU 21 17522 CFTR-Intron2-2423 + AUUUUUUAAAUUGAAUCAACAU 22 17523 CFTR-Intron2-2424 + UAUUUUUUAAAUUGAAUCAACAU 23 17524 CFTR-Intron2-2425 + AUAUUUUUUAAAUUGAAUCAACAU 24 17525 CFTR-Intron2-2426 + GGUGUUGUUAUAUUUCAU 18 17526 CFTR-Intron2-2427 + AGGUGUUGUUAUAUUUCAU 19 17527 CFTR-Intron2-2428 + AAGGUGUUGUUAUAUUUCAU 20 17528 CFTR-Intron2-2429 + AAAGGUGUUGUUAUAUUUCAU 21 17529 CFTR-Intron2-2430 + GAAAGGUGUUGUUAUAUUUCAU 22 17530 CFTR-Intron2-2431 + AGAAAGGUGUUGUUAUAUUUCAU 23 17531 CFTR-Intron2-2432 + UAGAAAGGUGUUGUUAUAUUUCAU 24 17532 CFTR-Intron2-2433 + UUCGUGGUCCUUAAAGAU 18 17533 CFTR-Intron2-2434 + UUUCGUGGUCCUUAAAGAU 19 17534 CFTR-Intron2-375 + CUUUCGUGGUCCUUAAAGAU 20 15475 CFTR-Intron2-2435 + UCUUUCGUGGUCCUUAAAGAU 21 17535 CFTR-Intron2-2436 + UUCUUUCGUGGUCCUUAAAGAU 22 17536 CFTR-Intron2-2437 + CUUCUUUCGUGGUCCUUAAAGAU 23 17537 CFTR-Intron2-2438 + CCUUCUUUCGUGGUCCUUAAAGAU 24 17538 CFTR-Intron2-2439 + CACAUACCAGGCCCAGAU 18 17539 CFTR-Intron2-2440 + CCACAUACCAGGCCCAGAU 19 17540 CFTR-Intron2-2441 + ACCACAUACCAGGCCCAGAU 20 17541 CFTR-Intron2-2442 + GACCACAUACCAGGCCCAGAU 21 17542 CFTR-Intron2-2443 + GGACCACAUACCAGGCCCAGAU 22 17543 CFTR-Intron2-2444 + AGGACCACAUACCAGGCCCAGAU 23 17544 CFTR-Intron2-2445 + UAGGACCACAUACCAGGCCCAGAU 24 17545 CFTR-Intron2-2446 + AGGAGAAAUGGAUCAGAU 18 17546 CFTR-Intron2-2447 + AAGGAGAAAUGGAUCAGAU 19 17547 CFTR-Intron2-376 + AAAGGAGAAAUGGAUCAGAU 20 15476 CFTR-Intron2-2448 + CAAAGGAGAAAUGGAUCAGAU 21 17548 CFTR-Intron2-2449 + UCAAAGGAGAAAUGGAUCAGAU 22 17549 CFTR-Intron2-2450 + AUCAAAGGAGAAAUGGAUCAGAU 23 17550 CFTR-Intron2-2451 + CAUCAAAGGAGAAAUGGAUCAGAU 24 17551 CFTR-Intron2-2452 + GUAAUACACAGCUGAGAU 18 17552 CFTR-Intron2-2453 + AGUAAUACACAGCUGAGAU 19 17553 CFTR-Intron2-2454 + GAGUAAUACACAGCUGAGAU 20 17554 CFTR-Intron2-2455 + GGAGUAAUACACAGCUGAGAU 21 17555 CFTR-Intron2-2456 + AGGAGUAAUACACAGCUGAGAU 22 17556 CFTR-Intron2-2457 + AAGGAGUAAUACACAGCUGAGAU 23 17557 CFTR-Intron2-2458 + AAAGGAGUAAUACACAGCUGAGAU 24 17558 CFTR-Intron2-2459 + GGAUCCUAACCUUUUGAU 18 17559 CFTR-Intron2-2460 + AGGAUCCUAACCUUUUGAU 19 17560 CFTR-Intron2-379 + AAGGAUCCUAACCUUUUGAU 20 15479 CFTR-Intron2-2461 + AAAGGAUCCUAACCUUUUGAU 21 17561 CFTR-Intron2-2462 + AAAAGGAUCCUAACCUUUUGAU 22 17562 CFTR-Intron2-2463 + CAAAAGGAUCCUAACCUUUUGAU 23 17563 CFTR-Intron2-2464 + UCAAAAGGAUCCUAACCUUUUGAU 24 17564 CFTR-Intron2-2465 + UUUUCUUUUAAAUACUAU 18 17565 CFTR-Intron2-2466 + GUUUUCUUUUAAAUACUAU 19 17566 CFTR-Intron2-700 + UGUUUUCUUUUAAAUACUAU 20 15800 CFTR-Intron2-2467 + CUGUUUUCUUUUAAAUACUAU 21 17567 CFTR-Intron2-2468 + UCUGUUUUCUUUUAAAUACUAU 22 17568 CFTR-Intron2-2469 + UUCUGUUUUCUUUUAAAUACUAU 23 17569 CFTR-Intron2-2470 + UUUCUGUUUUCUUUUAAAUACUAU 24 17570 CFTR-Intron2-2471 + AACUGAGAGAUUCUUUAU 18 17571 CFTR-Intron2-2472 + AAACUGAGAGAUUCUUUAU 19 17572 CFTR-Intron2-73 + GAAACUGAGAGAUUCUUUAU 20 15173 CFTR-Intron2-2473 + GGAAACUGAGAGAUUCUUUAU 21 17573 CFTR-Intron2-2474 + AGGAAACUGAGAGAUUCUUUAU 22 17574 CFTR-Intron2-2475 + AAGGAAACUGAGAGAUUCUUUAU 23 17575 CFTR-Intron2-2476 + AAAGGAAACUGAGAGAUUCUUUAU 24 17576 CFTR-Intron2-2477 + UUCAAAUACCAAUUUUAU 18 17577 CFTR-Intron2-2478 + UUUCAAAUACCAAUUUUAU 19 17578 CFTR-Intron2-2479 + AUUUCAAAUACCAAUUUUAU 20 17579 CFTR-Intron2-2480 + AAUUUCAAAUACCAAUUUUAU 21 17580 CFTR-Intron2-2481 + AAAUUUCAAAUACCAAUUUUAU 22 17581 CFTR-Intron2-2482 + UAAAUUUCAAAUACCAAUUUUAU 23 17582 CFTR-Intron2-2483 + AUAAAUUUCAAAUACCAAUUUUAU 24 17583 CFTR-Intron2-2484 + UUGAUUGGAAAGGAAACU 18 17584 CFTR-Intron2-2485 + UUUGAUUGGAAAGGAAACU 19 17585 CFTR-Intron2-2486 + UUUUGAUUGGAAAGGAAACU 20 17586 CFTR-Intron2-2487 + CUUUUGAUUGGAAAGGAAACU 21 17587 CFTR-Intron2-2488 + CCUUUUGAUUGGAAAGGAAACU 22 17588 CFTR-Intron2-2489 + ACCUUUUGAUUGGAAAGGAAACU 23 17589 CFTR-Intron2-2490 + AACCUUUUGAUUGGAAAGGAAACU 24 17590 CFTR-Intron2-2491 + GCCACUAAUCCCAACACU 18 17591 CFTR-Intron2-2492 + CGCCACUAAUCCCAACACU 19 17592 CFTR-Intron2-2493 + ACGCCACUAAUCCCAACACU 20 17593 CFTR-Intron2-2494 + CACGCCACUAAUCCCAACACU 21 17594 CFTR-Intron2-2495 + UCACGCCACUAAUCCCAACACU 22 17595 CFTR-Intron2-2496 + CUCACGCCACUAAUCCCAACACU 23 17596 CFTR-Intron2-2497 + GCUCACGCCACUAAUCCCAACACU 24 17597 CFTR-Intron2-2498 + GGCCCUAUUCUAGGCACU 18 17598 CFTR-Intron2-2499 + AGGCCCUAUUCUAGGCACU 19 17599 CFTR-Intron2-703 + CAGGCCCUAUUCUAGGCACU 20 15803 CFTR-Intron2-2500 + CCAGGCCCUAUUCUAGGCACU 21 17600 CFTR-Intron2-2501 + GCCAGGCCCUAUUCUAGGCACU 22 17601 CFTR-Intron2-2502 + UGCCAGGCCCUAUUCUAGGCACU 23 17602 CFTR-Intron2-2503 + AUGCCAGGCCCUAUUCUAGGCACU 24 17603 CFTR-Intron2-2504 + CCUGUAGUCCCAGCUACU 18 17604 CFTR-Intron2-2505 + GCCUGUAGUCCCAGCUACU 19 17605 CFTR-Intron2-2506 + UGCCUGUAGUCCCAGCUACU 20 17606 CFTR-Intron2-2507 + AUGCCUGUAGUCCCAGCUACU 21 17607 CFTR-Intron2-2508 + CAUGCCUGUAGUCCCAGCUACU 22 17608 CFTR-Intron2-2509 + GCAUGCCUGUAGUCCCAGCUACU 23 17609 CFTR-Intron2-2510 + UGCAUGCCUGUAGUCCCAGCUACU 24 17610 CFTR-Intron2-2511 + AGAAUGGGGUAGUUACCU 18 17611 CFTR-Intron2-2512 + UAGAAUGGGGUAGUUACCU 19 17612 CFTR-Intron2-2513 + AUAGAAUGGGGUAGUUACCU 20 17613 CFTR-Intron2-2514 + AAUAGAAUGGGGUAGUUACCU 21 17614 CFTR-Intron2-2515 + AAAUAGAAUGGGGUAGUUACCU 22 17615 CFTR-Intron2-2516 + AAAAUAGAAUGGGGUAGUUACCU 23 17616 CFTR-Intron2-2517 + AAAAAUAGAAUGGGGUAGUUACCU 24 17617 CFTR-Intron2-2518 + GAGCAGAGAAUGUUAGCU 18 17618 CFTR-Intron2-2519 + AGAGCAGAGAAUGUUAGCU 19 17619 CFTR-Intron2-2520 + GAGAGCAGAGAAUGUUAGCU 20 17620 CFTR-Intron2-2521 + GGAGAGCAGAGAAUGUUAGCU 21 17621 CFTR-Intron2-2522 + AGGAGAGCAGAGAAUGUUAGCU 22 17622 CFTR-Intron2-2523 + CAGGAGAGCAGAGAAUGUUAGCU 23 17623 CFTR-Intron2-2524 + CCAGGAGAGCAGAGAAUGUUAGCU 24 17624 CFTR-Intron2-2525 + UUUCCACUCAGAGUGGCU 18 17625 CFTR-Intron2-2526 + CUUUCCACUCAGAGUGGCU 19 17626 CFTR-Intron2-2527 + GCUUUCCACUCAGAGUGGCU 20 17627 CFTR-Intron2-2528 + UGCUUUCCACUCAGAGUGGCU 21 17628 CFTR-Intron2-2529 + AUGCUUUCCACUCAGAGUGGCU 22 17629 CFTR-Intron2-2530 + GAUGCUUUCCACUCAGAGUGGCU 23 17630 CFTR-Intron2-2531 + UGAUGCUUUCCACUCAGAGUGGCU 24 17631 CFTR-Intron2-2532 + AUAUCCUGACUACAAUCU 18 17632 CFTR-Intron2-2533 + CAUAUCCUGACUACAAUCU 19 17633 CFTR-Intron2-395 + UCAUAUCCUGACUACAAUCU 20 15495 CFTR-Intron2-2534 + UUCAUAUCCUGACUACAAUCU 21 17634 CFTR-Intron2-2535 + GUUCAUAUCCUGACUACAAUCU 22 17635 CFTR-Intron2-2536 + AGUUCAUAUCCUGACUACAAUCU 23 17636 CFTR-Intron2-2537 + AAGUUCAUAUCCUGACUACAAUCU 24 17637 CFTR-Intron2-2538 + GAAGCUGGCCCUUGAUCU 18 17638 CFTR-Intron2-2539 + AGAAGCUGGCCCUUGAUCU 19 17639 CFTR-Intron2-2540 + UAGAAGCUGGCCCUUGAUCU 20 17640 CFTR-Intron2-2541 + AUAGAAGCUGGCCCUUGAUCU 21 17641 CFTR-Intron2-2542 + AAUAGAAGCUGGCCCUUGAUCU 22 17642 CFTR-Intron2-2543 + UAAUAGAAGCUGGCCCUUGAUCU 23 17643 CFTR-Intron2-2544 + AUAAUAGAAGCUGGCCCUUGAUCU 24 17644 CFTR-Intron2-2545 + GCAAAGUAUAUUAUCUCU 18 17645 CFTR-Intron2-2546 + GGCAAAGUAUAUUAUCUCU 19 17646 CFTR-Intron2-2547 + UGGCAAAGUAUAUUAUCUCU 20 17647 CFTR-Intron2-2548 + CUGGCAAAGUAUAUUAUCUCU 21 17648 CFTR-Intron2-2549 + ACUGGCAAAGUAUAUUAUCUCU 22 17649 CFTR-Intron2-2550 + AACUGGCAAAGUAUAUUAUCUCU 23 17650 CFTR-Intron2-2551 + UAACUGGCAAAGUAUAUUAUCUCU 24 17651 CFTR-Intron2-2552 + ACUAUGACUCAAGAGUCU 18 17652 CFTR-Intron2-2553 + CACUAUGACUCAAGAGUCU 19 17653 CFTR-Intron2-2554 + GCACUAUGACUCAAGAGUCU 20 17654 CFTR-Intron2-2555 + AGCACUAUGACUCAAGAGUCU 21 17655 CFTR-Intron2-2556 + AAGCACUAUGACUCAAGAGUCU 22 17656 CFTR-Intron2-2557 + UAAGCACUAUGACUCAAGAGUCU 23 17657 CFTR-Intron2-2558 + GUAAGCACUAUGACUCAAGAGUCU 24 17658 CFTR-Intron2-2559 + AUCAUGUAUUAAAGGUCU 18 17659 CFTR-Intron2-2560 + AAUCAUGUAUUAAAGGUCU 19 17660 CFTR-Intron2-2561 + AAAUCAUGUAUUAAAGGUCU 20 17661 CFTR-Intron2-2562 + AAAAUCAUGUAUUAAAGGUCU 21 17662 CFTR-Intron2-2563 + UAAAAUCAUGUAUUAAAGGUCU 22 17663 CFTR-Intron2-2564 + CUAAAAUCAUGUAUUAAAGGUCU 23 17664 CFTR-Intron2-2565 + ACUAAAAUCAUGUAUUAAAGGUCU 24 17665 CFTR-Intron2-2566 + AGAAAGCUGGUCCGGUCU 18 17666 CFTR-Intron2-2567 + UAGAAAGCUGGUCCGGUCU 19 17667 CFTR-Intron2-2568 + GUAGAAAGCUGGUCCGGUCU 20 17668 CFTR-Intron2-2569 + UGUAGAAAGCUGGUCCGGUCU 21 17669 CFTR-Intron2-2570 + AUGUAGAAAGCUGGUCCGGUCU 22 17670 CFTR-Intron2-2571 + UAUGUAGAAAGCUGGUCCGGUCU 23 17671 CFTR-Intron2-2572 + UUAUGUAGAAAGCUGGUCCGGUCU 24 17672 CFTR-Intron2-2573 + UCUAAUAAGACAAAUUCU 18 17673 CFTR-Intron2-2574 + CUCUAAUAAGACAAAUUCU 19 17674 CFTR-Intron2-2575 + UCUCUAAUAAGACAAAUUCU 20 17675 CFTR-Intron2-2576 + GUCUCUAAUAAGACAAAUUCU 21 17676 CFTR-Intron2-2577 + GGUCUCUAAUAAGACAAAUUCU 22 17677 CFTR-Intron2-2578 + UGGUCUCUAAUAAGACAAAUUCU 23 17678 CFTR-Intron2-2579 + AUGGUCUCUAAUAAGACAAAUUCU 24 17679 CFTR-Intron2-2580 + CAUUUGGUUACUCAGAGU 18 17680 CFTR-Intron2-2581 + ACAUUUGGUUACUCAGAGU 19 17681 CFTR-Intron2-2582 + AACAUUUGGUUACUCAGAGU 20 17682 CFTR-Intron2-2583 + UAACAUUUGGUUACUCAGAGU 21 17683 CFTR-Intron2-2584 + AUAACAUUUGGUUACUCAGAGU 22 17684 CFTR-Intron2-2585 + CAUAACAUUUGGUUACUCAGAGU 23 17685 CFTR-Intron2-2586 + CCAUAACAUUUGGUUACUCAGAGU 24 17686 CFTR-Intron2-2587 + GAAUAGACAUUAAAUAGU 18 17687 CFTR-Intron2-2588 + AGAAUAGACAUUAAAUAGU 19 17688 CFTR-Intron2-2589 + AAGAAUAGACAUUAAAUAGU 20 17689 CFTR-Intron2-2590 + UAAGAAUAGACAUUAAAUAGU 21 17690 CFTR-Intron2-2591 + GUAAGAAUAGACAUUAAAUAGU 22 17691 CFTR-Intron2-2592 + AGUAAGAAUAGACAUUAAAUAGU 23 17692 CFTR-Intron2-2593 + UAGUAAGAAUAGACAUUAAAUAGU 24 17693 CFTR-Intron2-2594 + CUGAGGAGAAGGCAAGGU 18 17694 CFTR-Intron2-2595 + CCUGAGGAGAAGGCAAGGU 19 17695 CFTR-Intron2-405 + ACCUGAGGAGAAGGCAAGGU 20 15505 CFTR-Intron2-2596 + UACCUGAGGAGAAGGCAAGGU 21 17696 CFTR-Intron2-2597 + UUACCUGAGGAGAAGGCAAGGU 22 17697 CFTR-Intron2-2598 + GUUACCUGAGGAGAAGGCAAGGU 23 17698 CFTR-Intron2-2599 + AGUUACCUGAGGAGAAGGCAAGGU 24 17699 CFTR-Intron2-2600 + GGGCAGAUCACUUGAGGU 18 17700 CFTR-Intron2-2601 + CGGGCAGAUCACUUGAGGU 19 17701 CFTR-Intron2-2602 + GCGGGCAGAUCACUUGAGGU 20 17702 CFTR-Intron2-2603 + GGCGGGCAGAUCACUUGAGGU 21 17703 CFTR-Intron2-2604 + AGGCGGGCAGAUCACUUGAGGU 22 17704 CFTR-Intron2-2605 + AAGGCGGGCAGAUCACUUGAGGU 23 17705 CFTR-Intron2-2606 + CAAGGCGGGCAGAUCACUUGAGGU 24 17706 CFTR-Intron2-2607 + UGGGCAGAUCACUUGAGGU 19 17707 CFTR-Intron2-2608 + GUGGGCAGAUCACUUGAGGU 20 17708 CFTR-Intron2-2609 + GGUGGGCAGAUCACUUGAGGU 21 17709 CFTR-Intron2-2610 + AGGUGGGCAGAUCACUUGAGGU 22 17710 CFTR-Intron2-2611 + AAGGUGGGCAGAUCACUUGAGGU 23 17711 CFTR-Intron2-2612 + CAAGGUGGGCAGAUCACUUGAGGU 24 17712 CFTR-Intron2-2613 + GUAGAAAGCUGGUCCGGU 18 17713 CFTR-Intron2-2614 + UGUAGAAAGCUGGUCCGGU 19 17714 CFTR-Intron2-2615 + AUGUAGAAAGCUGGUCCGGU 20 17715 CFTR-Intron2-2616 + UAUGUAGAAAGCUGGUCCGGU 21 17716 CFTR-Intron2-2617 + UUAUGUAGAAAGCUGGUCCGGU 22 17717 CFTR-Intron2-2618 + UUUAUGUAGAAAGCUGGUCCGGU 23 17718 CFTR-Intron2-2619 + CUUUAUGUAGAAAGCUGGUCCGGU 24 17719 CFTR-Intron2-2620 + ACCUAUAAUCCCAGCAUU 18 17720 CFTR-Intron2-2621 + CACCUAUAAUCCCAGCAUU 19 17721 CFTR-Intron2-2622 + ACACCUAUAAUCCCAGCAUU 20 17722 CFTR-Intron2-2623 + CACACCUAUAAUCCCAGCAUU 21 17723 CFTR-Intron2-2624 + UCACACCUAUAAUCCCAGCAUU 22 17724 CFTR-Intron2-2625 + CUCACACCUAUAAUCCCAGCAUU 23 17725 CFTR-Intron2-2626 + GCUCACACCUAUAAUCCCAGCAUU 24 17726 CFTR-Intron2-2627 + AAUACCCAUUAUAUUAUU 18 17727 CFTR-Intron2-2628 + CAAUACCCAUUAUAUUAUU 19 17728 CFTR-Intron2-2629 + UCAAUACCCAUUAUAUUAUU 20 17729 CFTR-Intron2-2630 + UUCAAUACCCAUUAUAUUAUU 21 17730 CFTR-Intron2-2631 + AUUCAAUACCCAUUAUAUUAUU 22 17731 CFTR-Intron2-2632 + UAUUCAAUACCCAUUAUAUUAUU 23 17732 CFTR-Intron2-2633 + AUAUUCAAUACCCAUUAUAUUAUU 24 17733 CFTR-Intron2-2634 + CCACUAAUCCCAACACUU 18 17734 CFTR-Intron2-2635 + GCCACUAAUCCCAACACUU 19 17735 CFTR-Intron2-717 + CGCCACUAAUCCCAACACUU 20 15817 CFTR-Intron2-2636 + ACGCCACUAAUCCCAACACUU 21 17736 CFTR-Intron2-2637 + CACGCCACUAAUCCCAACACUU 22 17737 CFTR-Intron2-2638 + UCACGCCACUAAUCCCAACACUU 23 17738 CFTR-Intron2-2639 + CUCACGCCACUAAUCCCAACACUU 24 17739 CFTR-Intron2-2640 + ACCAUCUGGCAACCACUU 18 17740 CFTR-Intron2-2641 + AACCAUCUGGCAACCACUU 19 17741 CFTR-Intron2-2642 + CAACCAUCUGGCAACCACUU 20 17742 CFTR-Intron2-2643 + UCAACCAUCUGGCAACCACUU 21 17743 CFTR-Intron2-2644 + UUCAACCAUCUGGCAACCACUU 22 17744 CFTR-Intron2-2645 + CUUCAACCAUCUGGCAACCACUU 23 17745 CFTR-Intron2-2646 + UCUUCAACCAUCUGGCAACCACUU 24 17746 CFTR-Intron2-2647 + AUGGUGGAAACCAUACUU 18 17747 CFTR-Intron2-2648 + CAUGGUGGAAACCAUACUU 19 17748 CFTR-Intron2-2649 + ACAUGGUGGAAACCAUACUU 20 17749 CFTR-Intron2-2650 + AACAUGGUGGAAACCAUACUU 21 17750 CFTR-Intron2-2651 + GAACAUGGUGGAAACCAUACUU 22 17751 CFTR-Intron2-2652 + GGAACAUGGUGGAAACCAUACUU 23 17752 CFTR-Intron2-2653 + AGGAACAUGGUGGAAACCAUACUU 24 17753 CFTR-Intron2-2654 + CAUGGUCACAAGGCAGUU 18 17754 CFTR-Intron2-2655 + CCAUGGUCACAAGGCAGUU 19 17755 CFTR-Intron2-2656 + GCCAUGGUCACAAGGCAGUU 20 17756 CFTR-Intron2-2657 + GGCCAUGGUCACAAGGCAGUU 21 17757 CFTR-Intron2-2658 + GGGCCAUGGUCACAAGGCAGUU 22 17758 CFTR-Intron2-2659 + AGGGCCAUGGUCACAAGGCAGUU 23 17759 CFTR-Intron2-2660 + GAGGGCCAUGGUCACAAGGCAGUU 24 17760 CFTR-Intron2-2661 + UAUUCAAAUAUAAAGGUU 18 17761 CFTR-Intron2-2662 + GUAUUCAAAUAUAAAGGUU 19 17762 CFTR-Intron2-2663 + UGUAUUCAAAUAUAAAGGUU 20 17763 CFTR-Intron2-2664 + UUGUAUUCAAAUAUAAAGGUU 21 17764 CFTR-Intron2-2665 + UUUGUAUUCAAAUAUAAAGGUU 22 17765 CFTR-Intron2-2666 + AUUUGUAUUCAAAUAUAAAGGUU 23 17766 CFTR-Intron2-2667 + CAUUUGUAUUCAAAUAUAAAGGUU 24 17767 CFTR-Intron2-2668 + CCUAUAAUCCCAGCAUUU 18 17768 CFTR-Intron2-2669 + ACCUAUAAUCCCAGCAUUU 19 17769 CFTR-Intron2-720 + CACCUAUAAUCCCAGCAUUU 20 15820 CFTR-Intron2-2670 + ACACCUAUAAUCCCAGCAUUU 21 17770 CFTR-Intron2-2671 + CACACCUAUAAUCCCAGCAUUU 22 17771 CFTR-Intron2-2672 + UCACACCUAUAAUCCCAGCAUUU 23 17772 CFTR-Intron2-2673 + CUCACACCUAUAAUCCCAGCAUUU 24 17773 CFTR-Intron2-2674 + CACUAAUCCCAACACUUU 18 17774 CFTR-Intron2-2675 + CCACUAAUCCCAACACUUU 19 17775 CFTR-Intron2-476 + GCCACUAAUCCCAACACUUU 20 15576 CFTR-Intron2-2676 + CGCCACUAAUCCCAACACUUU 21 17776 CFTR-Intron2-2677 + ACGCCACUAAUCCCAACACUUU 22 17777 CFTR-Intron2-2678 + CACGCCACUAAUCCCAACACUUU 23 17778 CFTR-Intron2-2679 + UCACGCCACUAAUCCCAACACUUU 24 17779 CFTR-Intron2-2680 + GAAACUGAGAGAUUCUUU 18 17780 CFTR-Intron2-2681 + GGAAACUGAGAGAUUCUUU 19 17781 CFTR-Intron2-2682 + AGGAAACUGAGAGAUUCUUU 20 17782 CFTR-Intron2-2683 + AAGGAAACUGAGAGAUUCUUU 21 17783 CFTR-Intron2-2684 + AAAGGAAACUGAGAGAUUCUUU 22 17784 CFTR-Intron2-2685 + GAAAGGAAACUGAGAGAUUCUUU 23 17785 CFTR-Intron2-2686 + GGAAAGGAAACUGAGAGAUUCUUU 24 17786 CFTR-Intron2-2687 + CCCUGGGCAAUGUAGUUU 18 17787 CFTR-Intron2-2688 + ACCCUGGGCAAUGUAGUUU 19 17788 CFTR-Intron2-2689 + GACCCUGGGCAAUGUAGUUU 20 17789 CFTR-Intron2-2690 + UGACCCUGGGCAAUGUAGUUU 21 17790 CFTR-Intron2-2691 + GUGACCCUGGGCAAUGUAGUUU 22 17791 CFTR-Intron2-2692 + AGUGACCCUGGGCAAUGUAGUUU 23 17792 CFTR-Intron2-2693 + UAGUGACCCUGGGCAAUGUAGUUU 24 17793 CFTR-Intron2-2694 + CUAUAAUCCCAGCAUUUU 18 17794 CFTR-Intron2-2695 + CCUAUAAUCCCAGCAUUUU 19 17795 CFTR-Intron2-722 + ACCUAUAAUCCCAGCAUUUU 20 15822 CFTR-Intron2-2696 + CACCUAUAAUCCCAGCAUUUU 21 17796 CFTR-Intron2-2697 + ACACCUAUAAUCCCAGCAUUUU 22 17797 CFTR-Intron2-2698 + CACACCUAUAAUCCCAGCAUUUU 23 17798 CFTR-Intron2-2699 + UCACACCUAUAAUCCCAGCAUUUU 24 17799 CFTR-Intron2-2700 + CCUGGGCAAUGUAGUUUU 18 17800 CFTR-Intron2-2701 + CCCUGGGCAAUGUAGUUUU 19 17801 CFTR-Intron2-416 + ACCCUGGGCAAUGUAGUUUU 20 15516 CFTR-Intron2-2702 + GACCCUGGGCAAUGUAGUUUU 21 17802 CFTR-Intron2-2703 + UGACCCUGGGCAAUGUAGUUUU 22 17803 CFTR-Intron2-2704 + GUGACCCUGGGCAAUGUAGUUUU 23 17804 CFTR-Intron2-2705 + AGUGACCCUGGGCAAUGUAGUUUU 24 17805 CFTR-Intron2-2706 + AACCAAAUGUGUAUUUUU 18 17806 CFTR-Intron2-2707 + AAACCAAAUGUGUAUUUUU 19 17807 CFTR-Intron2-2708 + GAAACCAAAUGUGUAUUUUU 20 17808 CFTR-Intron2-2709 + UGAAACCAAAUGUGUAUUUUU 21 17809 CFTR-Intron2-2710 + CUGAAACCAAAUGUGUAUUUUU 22 17810 CFTR-Intron2-2711 + UCUGAAACCAAAUGUGUAUUUUU 23 17811 CFTR-Intron2-2712 + CUCUGAAACCAAAUGUGUAUUUUU 24 17812 CFTR-Intron2-2713 AUAGUAUUUAAAAGAAAA 18 17813 CFTR-Intron2-2714 UAUAGUAUUUAAAAGAAAA 19 17814 CFTR-Intron2-2715 CUAUAGUAUUUAAAAGAAAA 20 17815 CFTR-Intron2-2716 CCUAUAGUAUUUAAAAGAAAA 21 17816 CFTR-Intron2-2717 UCCUAUAGUAUUUAAAAGAAAA 22 17817 CFTR-Intron2-2718 UUCCUAUAGUAUUUAAAAGAAAA 23 17818 CFTR-Intron2-2719 GUUCCUAUAGUAUUUAAAAGAAAA 24 17819 CFTR-Intron2-2720 AUUUUACAGAAAAGCAAA 18 17820 CFTR-Intron2-2721 UAUUUUACAGAAAAGCAAA 19 17821 CFTR-Intron2-2722 CUAUUUUACAGAAAAGCAAA 20 17822 CFTR-Intron2-2723 UCUAUUUUACAGAAAAGCAAA 21 17823 CFTR-Intron2-2724 CUCUAUUUUACAGAAAAGCAAA 22 17824 CFTR-Intron2-2725 UCUCUAUUUUACAGAAAAGCAAA 23 17825 CFTR-Intron2-2726 AUCUCUAUUUUACAGAAAAGCAAA 24 17826 CFTR-Intron2-2727 UGAUUUUAGUAGUUGAAA 18 17827 CFTR-Intron2-2728 AUGAUUUUAGUAGUUGAAA 19 17828 CFTR-Intron2-2729 CAUGAUUUUAGUAGUUGAAA 20 17829 CFTR-Intron2-2730 ACAUGAUUUUAGUAGUUGAAA 21 17830 CFTR-Intron2-2731 UACAUGAUUUUAGUAGUUGAAA 22 17831 CFTR-Intron2-2732 AUACAUGAUUUUAGUAGUUGAAA 23 17832 CFTR-Intron2-2733 AAUACAUGAUUUUAGUAGUUGAAA 24 17833 CFTR-Intron2-2734 CUAGCUUAAGUAAAUAAA 18 17834 CFTR-Intron2-2735 ACUAGCUUAAGUAAAUAAA 19 17835 CFTR-Intron2-613 UACUAGCUUAAGUAAAUAAA 20 15713 CFTR-Intron2-2736 UUACUAGCUUAAGUAAAUAAA 21 17836 CFTR-Intron2-2737 UUUACUAGCUUAAGUAAAUAAA 22 17837 CFTR-Intron2-2738 AUUUACUAGCUUAAGUAAAUAAA 23 17838 CFTR-Intron2-2739 AAUUUACUAGCUUAAGUAAAUAAA 24 17839 CFTR-Intron2-2740 CUGGCCUUAGGAACUCAA 18 17840 CFTR-Intron2-2741 ACUGGCCUUAGGAACUCAA 19 17841 CFTR-Intron2-241 AACUGGCCUUAGGAACUCAA 20 15341 CFTR-Intron2-2742 GAACUGGCCUUAGGAACUCAA 21 17842 CFTR-Intron2-2743 AGAACUGGCCUUAGGAACUCAA 22 17843 CFTR-Intron2-2744 GAGAACUGGCCUUAGGAACUCAA 23 17844 CFTR-Intron2-2745 GGAGAACUGGCCUUAGGAACUCAA 24 17845 CFTR-Intron2-2746 AUCCCCAAGUGCCUAGAA 18 17846 CFTR-Intron2-2747 UAUCCCCAAGUGCCUAGAA 19 17847 CFTR-Intron2-2748 GUAUCCCCAAGUGCCUAGAA 20 17848 CFTR-Intron2-2749 UGUAUCCCCAAGUGCCUAGAA 21 17849 CFTR-Intron2-2750 AUGUAUCCCCAAGUGCCUAGAA 22 17850 CFTR-Intron2-2751 GAUGUAUCCCCAAGUGCCUAGAA 23 17851 CFTR-Intron2-2752 UGAUGUAUCCCCAAGUGCCUAGAA 24 17852 CFTR-Intron2-2753 GAUAAAAGGGUGAGUGAA 18 17853 CFTR-Intron2-2754 AGAUAAAAGGGUGAGUGAA 19 17854 CFTR-Intron2-248 CAGAUAAAAGGGUGAGUGAA 20 15348 CFTR-Intron2-2755 CCAGAUAAAAGGGUGAGUGAA 21 17855 CFTR-Intron2-2756 GCCAGAUAAAAGGGUGAGUGAA 22 17856 CFTR-Intron2-2757 UGCCAGAUAAAAGGGUGAGUGAA 23 17857 CFTR-Intron2-2758 AUGCCAGAUAAAAGGGUGAGUGAA 24 17858 CFTR-Intron2-2759 AUUUUAUUCCUUUGUGAA 18 17859 CFTR-Intron2-2760 UAUUUUAUUCCUUUGUGAA 19 17860 CFTR-Intron2-2761 AUAUUUUAUUCCUUUGUGAA 20 17861 CFTR-Intron2-2762 GAUAUUUUAUUCCUUUGUGAA 21 17862 CFTR-Intron2-2763 AGAUAUUUUAUUCCUUUGUGAA 22 17863 CFTR-Intron2-2764 GAGAUAUUUUAUUCCUUUGUGAA 23 17864 CFTR-Intron2-2765 AGAGAUAUUUUAUUCCUUUGUGAA 24 17865 CFTR-Intron2-2766 ACUAGCUUAAGUAAAUAA 18 17866 CFTR-Intron2-2767 UACUAGCUUAAGUAAAUAA 19 17867 CFTR-Intron2-2768 UUACUAGCUUAAGUAAAUAA 20 17868 CFTR-Intron2-2769 UUUACUAGCUUAAGUAAAUAA 21 17869 CFTR-Intron2-2770 AUUUACUAGCUUAAGUAAAUAA 22 17870 CFTR-Intron2-2771 AAUUUACUAGCUUAAGUAAAUAA 23 17871 CFTR-Intron2-2772 CAAUUUACUAGCUUAAGUAAAUAA 24 17872 CFTR-Intron2-2773 UGUCUAUUCUUACUAUAA 18 17873 CFTR-Intron2-2774 AUGUCUAUUCUUACUAUAA 19 17874 CFTR-Intron2-2775 AAUGUCUAUUCUUACUAUAA 20 17875 CFTR-Intron2-2776 UAAUGUCUAUUCUUACUAUAA 21 17876 CFTR-Intron2-2777 UUAAUGUCUAUUCUUACUAUAA 22 17877 CFTR-Intron2-2778 UUUAAUGUCUAUUCUUACUAUAA 23 17878 CFTR-Intron2-2779 AUUUAAUGUCUAUUCUUACUAUAA 24 17879 CFTR-Intron2-2780 AUGGUAACUUGACAGUAA 18 17880 CFTR-Intron2-2781 UAUGGUAACUUGACAGUAA 19 17881 CFTR-Intron2-251 UUAUGGUAACUUGACAGUAA 20 15351 CFTR-Intron2-2782 CUUAUGGUAACUUGACAGUAA 21 17882 CFTR-Intron2-2783 ACUUAUGGUAACUUGACAGUAA 22 17883 CFTR-Intron2-2784 UACUUAUGGUAACUUGACAGUAA 23 17884 CFTR-Intron2-2785 UUACUUAUGGUAACUUGACAGUAA 24 17885 CFTR-Intron2-2786 AAAAAAGGCUUUCAUUAA 18 17886 CFTR-Intron2-2787 GAAAAAAGGCUUUCAUUAA 19 17887 CFTR-Intron2-2788 AGAAAAAAGGCUUUCAUUAA 20 17888 CFTR-Intron2-2789 GAGAAAAAAGGCUUUCAUUAA 21 17889 CFTR-Intron2-2790 AGAGAAAAAAGGCUUUCAUUAA 22 17890 CFTR-Intron2-2791 AAGAGAAAAAAGGCUUUCAUUAA 23 17891 CFTR-Intron2-2792 GAAGAGAAAAAAGGCUUUCAUUAA 24 17892 CFTR-Intron2-2793 AGAGUAGGGCUGGGUUAA 18 17893 CFTR-Intron2-2794 CAGAGUAGGGCUGGGUUAA 19 17894 CFTR-Intron2-2795 UCAGAGUAGGGCUGGGUUAA 20 17895 CFTR-Intron2-2796 AUCAGAGUAGGGCUGGGUUAA 21 17896 CFTR-Intron2-2797 AAUCAGAGUAGGGCUGGGUUAA 22 17897 CFTR-Intron2-2798 UAAUCAGAGUAGGGCUGGGUUAA 23 17898 CFTR-Intron2-2799 UUAAUCAGAGUAGGGCUGGGUUAA 24 17899 CFTR-Intron2-2800 UGUUCCUAUAGUAUUUAA 18 17900 CFTR-Intron2-2801 GUGUUCCUAUAGUAUUUAA 19 17901 CFTR-Intron2-2802 GGUGUUCCUAUAGUAUUUAA 20 17902 CFTR-Intron2-2803 UGGUGUUCCUAUAGUAUUUAA 21 17903 CFTR-Intron2-2804 CUGGUGUUCCUAUAGUAUUUAA 22 17904 CFTR-Intron2-2805 GCUGGUGUUCCUAUAGUAUUUAA 23 17905 CFTR-Intron2-2806 AGCUGGUGUUCCUAUAGUAUUUAA 24 17906 CFTR-Intron2-2807 GUGGACCACUUUUUCACA 18 17907 CFTR-Intron2-2808 UGUGGACCACUUUUUCACA 19 17908 CFTR-Intron2-2809 GUGUGGACCACUUUUUCACA 20 17909 CFTR-Intron2-2810 CGUGUGGACCACUUUUUCACA 21 17910 CFTR-Intron2-2811 CCGUGUGGACCACUUUUUCACA 22 17911 CFTR-Intron2-2812 UCCGUGUGGACCACUUUUUCACA 23 17912 CFTR-Intron2-2813 UUCCGUGUGGACCACUUUUUCACA 24 17913 CFTR-Intron2-2814 GAAAUGGCUAGCAUUACA 18 17914 CFTR-Intron2-2815 UGAAAUGGCUAGCAUUACA 19 17915 CFTR-Intron2-2816 GUGAAAUGGCUAGCAUUACA 20 17916 CFTR-Intron2-2817 UGUGAAAUGGCUAGCAUUACA 21 17917 CFTR-Intron2-2818 AUGUGAAAUGGCUAGCAUUACA 22 17918 CFTR-Intron2-2819 AAUGUGAAAUGGCUAGCAUUACA 23 17919 CFTR-Intron2-2820 GAAUGUGAAAUGGCUAGCAUUACA 24 17920 CFTR-Intron2-2821 ACUGGCCUUAGGAACUCA 18 17921 CFTR-Intron2-2822 AACUGGCCUUAGGAACUCA 19 17922 CFTR-Intron2-2823 GAACUGGCCUUAGGAACUCA 20 17923 CFTR-Intron2-2824 AGAACUGGCCUUAGGAACUCA 21 17924 CFTR-Intron2-2825 GAGAACUGGCCUUAGGAACUCA 22 17925 CFTR-Intron2-2826 GGAGAACUGGCCUUAGGAACUCA 23 17926 CFTR-Intron2-2827 UGGAGAACUGGCCUUAGGAACUCA 24 17927 CFTR-Intron2-2828 AAAGCAAACUGAGGCUCA 18 17928 CFTR-Intron2-2829 AAAAGCAAACUGAGGCUCA 19 17929 CFTR-Intron2-2830 GAAAAGCAAACUGAGGCUCA 20 17930 CFTR-Intron2-2831 AGAAAAGCAAACUGAGGCUCA 21 17931 CFTR-Intron2-2832 CAGAAAAGCAAACUGAGGCUCA 22 17932 CFTR-Intron2-2833 ACAGAAAAGCAAACUGAGGCUCA 23 17933 CFTR-Intron2-2834 UACAGAAAAGCAAACUGAGGCUCA 24 17934 CFTR-Intron2-2835 UUUAAGGACCACGAAAGA 18 17935 CFTR-Intron2-2836 CUUUAAGGACCACGAAAGA 19 17936 CFTR-Intron2-274 UCUUUAAGGACCACGAAAGA 20 15374 CFTR-Intron2-2837 AUCUUUAAGGACCACGAAAGA 21 17937 CFTR-Intron2-2838 UAUCUUUAAGGACCACGAAAGA 22 17938 CFTR-Intron2-2839 CUAUCUUUAAGGACCACGAAAGA 23 17939 CFTR-Intron2-2840 CCUAUCUUUAAGGACCACGAAAGA 24 17940 CFTR-Intron2-2841 UUUGUAUUUAUGGCCAGA 18 17941 CFTR-Intron2-2842 AUUUGUAUUUAUGGCCAGA 19 17942 CFTR-Intron2-2843 CAUUUGUAUUUAUGGCCAGA 20 17943 CFTR-Intron2-2844 ACAUUUGUAUUUAUGGCCAGA 21 17944 CFTR-Intron2-2845 UACAUUUGUAUUUAUGGCCAGA 22 17945 CFTR-Intron2-2846 AUACAUUUGUAUUUAUGGCCAGA 23 17946 CFTR-Intron2-2847 GAUACAUUUGUAUUUAUGGCCAGA 24 17947 CFTR-Intron2-2848 UGGUUUUAUUUUCUCAGA 18 17948 CFTR-Intron2-2849 CUGGUUUUAUUUUCUCAGA 19 17949 CFTR-Intron2-2850 GCUGGUUUUAUUUUCUCAGA 20 17950 CFTR-Intron2-2851 UGCUGGUUUUAUUUUCUCAGA 21 17951 CFTR-Intron2-2852 AUGCUGGUUUUAUUUUCUCAGA 22 17952 CFTR-Intron2-2853 UAUGCUGGUUUUAUUUUCUCAGA 23 17953 CFTR-Intron2-2854 UUAUGCUGGUUUUAUUUUCUCAGA 24 17954 CFTR-Intron2-2855 UGUGGGGAGGGAAAUAGA 18 17955 CFTR-Intron2-2856 AUGUGGGGAGGGAAAUAGA 19 17956 CFTR-Intron2-278 CAUGUGGGGAGGGAAAUAGA 20 15378 CFTR-Intron2-2857 GCAUGUGGGGAGGGAAAUAGA 21 17957 CFTR-Intron2-2858 AGCAUGUGGGGAGGGAAAUAGA 22 17958 CFTR-Intron2-2859 AAGCAUGUGGGGAGGGAAAUAGA 23 17959 CFTR-Intron2-2860 GAAGCAUGUGGGGAGGGAAAUAGA 24 17960 CFTR-Intron2-2861 GGCCACUCAUAGUCUAGA 18 17961 CFTR-Intron2-2862 GGGCCACUCAUAGUCUAGA 19 17962 CFTR-Intron2-2863 UGGGCCACUCAUAGUCUAGA 20 17963 CFTR-Intron2-2864 UUGGGCCACUCAUAGUCUAGA 21 17964 CFTR-Intron2-2865 CUUGGGCCACUCAUAGUCUAGA 22 17965 CFTR-Intron2-2866 CCUUGGGCCACUCAUAGUCUAGA 23 17966 CFTR-Intron2-2867 CCCUUGGGCCACUCAUAGUCUAGA 24 17967 CFTR-Intron2-2868 UAUCUUUAAGGACCACGA 18 17968 CFTR-Intron2-2869 CUAUCUUUAAGGACCACGA 19 17969 CFTR-Intron2-2870 CCUAUCUUUAAGGACCACGA 20 17970 CFTR-Intron2-2871 UCCUAUCUUUAAGGACCACGA 21 17971 CFTR-Intron2-2872 CUCCUAUCUUUAAGGACCACGA 22 17972 CFTR-Intron2-2873 GCUCCUAUCUUUAAGGACCACGA 23 17973 CFTR-Intron2-2874 UGCUCCUAUCUUUAAGGACCACGA 24 17974 CFTR-Intron2-2875 UGGAGAAGCAUGUGGGGA 18 17975 CFTR-Intron2-2876 GUGGAGAAGCAUGUGGGGA 19 17976 CFTR-Intron2-53 GGUGGAGAAGCAUGUGGGGA 20 15153 CFTR-Intron2-2877 AGGUGGAGAAGCAUGUGGGGA 21 17977 CFTR-Intron2-2878 AAGGUGGAGAAGCAUGUGGGGA 22 17978 CFTR-Intron2-2879 AAAGGUGGAGAAGCAUGUGGGGA 23 17979 CFTR-Intron2-2880 GAAAGGUGGAGAAGCAUGUGGGGA 24 17980 CFTR-Intron2-2881 GUAACCAAAUGUUAUGGA 18 17981 CFTR-Intron2-2882 AGUAACCAAAUGUUAUGGA 19 17982 CFTR-Intron2-54 GAGUAACCAAAUGUUAUGGA 20 15154 CFTR-Intron2-2883 UGAGUAACCAAAUGUUAUGGA 21 17983 CFTR-Intron2-2884 CUGAGUAACCAAAUGUUAUGGA 22 17984 CFTR-Intron2-2885 UCUGAGUAACCAAAUGUUAUGGA 23 17985 CFTR-Intron2-2886 CUCUGAGUAACCAAAUGUUAUGGA 24 17986 CFTR-Intron2-2887 UUGCCAGUUAAUGAAUGA 18 17987 CFTR-Intron2-2888 UUUGCCAGUUAAUGAAUGA 19 17988 CFTR-Intron2-281 CUUUGCCAGUUAAUGAAUGA 20 15381 CFTR-Intron2-2889 ACUUUGCCAGUUAAUGAAUGA 21 17989 CFTR-Intron2-2890 UACUUUGCCAGUUAAUGAAUGA 22 17990 CFTR-Intron2-2891 AUACUUUGCCAGUUAAUGAAUGA 23 17991 CFTR-Intron2-2892 UAUACUUUGCCAGUUAAUGAAUGA 24 17992 CFTR-Intron2-2893 UCCUCUCAGCCACUCUGA 18 17993 CFTR-Intron2-2894 CUCCUCUCAGCCACUCUGA 19 17994 CFTR-Intron2-2895 UCUCCUCUCAGCCACUCUGA 20 17995 CFTR-Intron2-2896 AUCUCCUCUCAGCCACUCUGA 21 17996 CFTR-Intron2-2897 UAUCUCCUCUCAGCCACUCUGA 22 17997 CFTR-Intron2-2898 AUAUCUCCUCUCAGCCACUCUGA 23 17998 CFTR-Intron2-2899 AAUAUCUCCUCUCAGCCACUCUGA 24 17999 CFTR-Intron2-2900 CCUUUUGAUUGCCAGUGA 18 18000 CFTR-Intron2-2901 UCCUUUUGAUUGCCAGUGA 19 18001 CFTR-Intron2-2902 AUCCUUUUGAUUGCCAGUGA 20 18002 CFTR-Intron2-2903 GAUCCUUUUGAUUGCCAGUGA 21 18003 CFTR-Intron2-2904 GGAUCCUUUUGAUUGCCAGUGA 22 18004 CFTR-Intron2-2905 AGGAUCCUUUUGAUUGCCAGUGA 23 18005 CFTR-Intron2-2906 UAGGAUCCUUUUGAUUGCCAGUGA 24 18006 CFTR-Intron2-2907 AGAUAAAAGGGUGAGUGA 18 18007 CFTR-Intron2-2908 CAGAUAAAAGGGUGAGUGA 19 18008 CFTR-Intron2-283 CCAGAUAAAAGGGUGAGUGA 20 15383 CFTR-Intron2-2909 GCCAGAUAAAAGGGUGAGUGA 21 18009 CFTR-Intron2-2910 UGCCAGAUAAAAGGGUGAGUGA 22 18010 CFTR-Intron2-2911 AUGCCAGAUAAAAGGGUGAGUGA 23 18011 CFTR-Intron2-2912 GAUGCCAGAUAAAAGGGUGAGUGA 24 18012 CFTR-Intron2-2913 UGCCAGAUAAAAGGGUGA 18 18013 CFTR-Intron2-2914 AUGCCAGAUAAAAGGGUGA 19 18014 CFTR-Intron2-2915 GAUGCCAGAUAAAAGGGUGA 20 18015 CFTR-Intron2-2916 UGAUGCCAGAUAAAAGGGUGA 21 18016 CFTR-Intron2-2917 CUGAUGCCAGAUAAAAGGGUGA 22 18017 CFTR-Intron2-2918 CCUGAUGCCAGAUAAAAGGGUGA 23 18018 CFTR-Intron2-2919 GCCUGAUGCCAGAUAAAAGGGUGA 24 18019 CFTR-Intron2-2920 GGUUAGCUCUGUGUGUGA 18 18020 CFTR-Intron2-2921 AGGUUAGCUCUGUGUGUGA 19 18021 CFTR-Intron2-2922 GAGGUUAGCUCUGUGUGUGA 20 18022 CFTR-Intron2-2923 GGAGGUUAGCUCUGUGUGUGA 21 18023 CFTR-Intron2-2924 GGGAGGUUAGCUCUGUGUGUGA 22 18024 CFTR-Intron2-2925 UGGGAGGUUAGCUCUGUGUGUGA 23 18025 CFTR-Intron2-2926 AUGGGAGGUUAGCUCUGUGUGUGA 24 18026 CFTR-Intron2-2927 GAUCCAUUUCUCCUUUGA 18 18027 CFTR-Intron2-2928 UGAUCCAUUUCUCCUUUGA 19 18028 CFTR-Intron2-285 CUGAUCCAUUUCUCCUUUGA 20 15385 CFTR-Intron2-2929 UCUGAUCCAUUUCUCCUUUGA 21 18029 CFTR-Intron2-2930 AUCUGAUCCAUUUCUCCUUUGA 22 18030 CFTR-Intron2-2931 CAUCUGAUCCAUUUCUCCUUUGA 23 18031 CFTR-Intron2-2932 CCAUCUGAUCCAUUUCUCCUUUGA 24 18032 CFTR-Intron2-2933 UGUAUUUAUGGCCAGAUA 18 18033 CFTR-Intron2-2934 UUGUAUUUAUGGCCAGAUA 19 18034 CFTR-Intron2-2935 UUUGUAUUUAUGGCCAGAUA 20 18035 CFTR-Intron2-2936 AUUUGUAUUUAUGGCCAGAUA 21 18036 CFTR-Intron2-2937 CAUUUGUAUUUAUGGCCAGAUA 22 18037 CFTR-Intron2-2938 ACAUUUGUAUUUAUGGCCAGAUA 23 18038 CFTR-Intron2-2939 UACAUUUGUAUUUAUGGCCAGAUA 24 18039 CFTR-Intron2-2940 AUUCAAAGAAUUAAGCUA 18 18040 CFTR-Intron2-2941 UAUUCAAAGAAUUAAGCUA 19 18041 CFTR-Intron2-2942 UUAUUCAAAGAAUUAAGCUA 20 18042 CFTR-Intron2-2943 UUUAUUCAAAGAAUUAAGCUA 21 18043 CFTR-Intron2-2944 UUUUAUUCAAAGAAUUAAGCUA 22 18044 CFTR-Intron2-2945 AUUUUAUUCAAAGAAUUAAGCUA 23 18045 CFTR-Intron2-2946 GAUUUUAUUCAAAGAAUUAAGCUA 24 18046 CFTR-Intron2-2947 UAUGGUAACUUGACAGUA 18 18047 CFTR-Intron2-2948 UUAUGGUAACUUGACAGUA 19 18048 CFTR-Intron2-2949 CUUAUGGUAACUUGACAGUA 20 18049 CFTR-Intron2-2950 ACUUAUGGUAACUUGACAGUA 21 18050 CFTR-Intron2-2951 UACUUAUGGUAACUUGACAGUA 22 18051 CFTR-Intron2-2952 UUACUUAUGGUAACUUGACAGUA 23 18052 CFTR-Intron2-2953 UUUACUUAUGGUAACUUGACAGUA 24 18053 CFTR-Intron2-2954 UUCAAGUUUCACCCAUUA 18 18054 CFTR-Intron2-2955 GUUCAAGUUUCACCCAUUA 19 18055 CFTR-Intron2-2956 UGUUCAAGUUUCACCCAUUA 20 18056 CFTR-Intron2-2957 UUGUUCAAGUUUCACCCAUUA 21 18057 CFTR-Intron2-2958 GUUGUUCAAGUUUCACCCAUUA 22 18058 CFTR-Intron2-2959 AGUUGUUCAAGUUUCACCCAUUA 23 18059 CFTR-Intron2-2960 AAGUUGUUCAAGUUUCACCCAUUA 24 18060 CFTR-Intron2-2961 AAGGGCCAGCUUCUAUUA 18 18061 CFTR-Intron2-2962 CAAGGGCCAGCUUCUAUUA 19 18062 CFTR-Intron2-2963 UCAAGGGCCAGCUUCUAUUA 20 18063 CFTR-Intron2-2964 AUCAAGGGCCAGCUUCUAUUA 21 18064 CFTR-Intron2-2965 GAUCAAGGGCCAGCUUCUAUUA 22 18065 CFTR-Intron2-2966 AGAUCAAGGGCCAGCUUCUAUUA 23 18066 CFTR-Intron2-2967 AAGAUCAAGGGCCAGCUUCUAUUA 24 18067 CFTR-Intron2-2968 AUUGGUAUUUGAAAUUUA 18 18068 CFTR-Intron2-2969 AAUUGGUAUUUGAAAUUUA 19 18069 CFTR-Intron2-2970 AAAUUGGUAUUUGAAAUUUA 20 18070 CFTR-Intron2-2971 AAAAUUGGUAUUUGAAAUUUA 21 18071 CFTR-Intron2-2972 UAAAAUUGGUAUUUGAAAUUUA 22 18072 CFTR-Intron2-2973 AUAAAAUUGGUAUUUGAAAUUUA 23 18073 CFTR-Intron2-2974 UAUAAAAUUGGUAUUUGAAAUUUA 24 18074 CFTR-Intron2-2975 AAAGGUAAUUAGGCUUUA 18 18075 CFTR-Intron2-2976 AAAAGGUAAUUAGGCUUUA 19 18076 CFTR-Intron2-2977 GAAAAGGUAAUUAGGCUUUA 20 18077 CFTR-Intron2-2978 GGAAAAGGUAAUUAGGCUUUA 21 18078 CFTR-Intron2-2979 GGGAAAAGGUAAUUAGGCUUUA 22 18079 CFTR-Intron2-2980 UGGGAAAAGGUAAUUAGGCUUUA 23 18080 CFTR-Intron2-2981 AUGGGAAAAGGUAAUUAGGCUUUA 24 18081 CFTR-Intron2-2982 AUCAUUAUCUCUAUUUUA 18 18082 CFTR-Intron2-2983 CAUCAUUAUCUCUAUUUUA 19 18083 CFTR-Intron2-2984 GCAUCAUUAUCUCUAUUUUA 20 18084 CFTR-Intron2-2985 AGCAUCAUUAUCUCUAUUUUA 21 18085 CFTR-Intron2-2986 AAGCAUCAUUAUCUCUAUUUUA 22 18086 CFTR-Intron2-2987 AAAGCAUCAUUAUCUCUAUUUUA 23 18087 CFTR-Intron2-2988 GAAAGCAUCAUUAUCUCUAUUUUA 24 18088 CFTR-Intron2-2989 UACAUUGCCCAGGGUCAC 18 18089 CFTR-Intron2-2990 CUACAUUGCCCAGGGUCAC 19 18090 CFTR-Intron2-2991 ACUACAUUGCCCAGGGUCAC 20 18091 CFTR-Intron2-2992 AACUACAUUGCCCAGGGUCAC 21 18092 CFTR-Intron2-2993 AAACUACAUUGCCCAGGGUCAC 22 18093 CFTR-Intron2-2994 AAAACUACAUUGCCCAGGGUCAC 23 18094 CFTR-Intron2-2995 UAAAACUACAUUGCCCAGGGUCAC 24 18095 CFTR-Intron2-2996 CCUGGUAUGUGGUCCUAC 18 18096 CFTR-Intron2-2997 GCCUGGUAUGUGGUCCUAC 19 18097 CFTR-Intron2-2998 GGCCUGGUAUGUGGUCCUAC 20 18098 CFTR-Intron2-2999 GGGCCUGGUAUGUGGUCCUAC 21 18099 CFTR-Intron2-3000 UGGGCCUGGUAUGUGGUCCUAC 22 18100 CFTR-Intron2-3001 CUGGGCCUGGUAUGUGGUCCUAC 23 18101 CFTR-Intron2-3002 UCUGGGCCUGGUAUGUGGUCCUAC 24 18102 CFTR-Intron2-3003 UUUGUCUUAUUAGAGACC 18 18103 CFTR-Intron2-3004 AUUUGUCUUAUUAGAGACC 19 18104 CFTR-Intron2-3005 AAUUUGUCUUAUUAGAGACC 20 18105 CFTR-Intron2-3006 GAAUUUGUCUUAUUAGAGACC 21 18106 CFTR-Intron2-3007 AGAAUUUGUCUUAUUAGAGACC 22 18107 CFTR-Intron2-3008 GAGAAUUUGUCUUAUUAGAGACC 23 18108 CFTR-Intron2-3009 AGAGAAUUUGUCUUAUUAGAGACC 24 18109 CFTR-Intron2-3010 CUCCUAUCUUUAAGGACC 18 18110 CFTR-Intron2-3011 GCUCCUAUCUUUAAGGACC 19 18111 CFTR-Intron2-3012 UGCUCCUAUCUUUAAGGACC 20 18112 CFTR-Intron2-3013 UUGCUCCUAUCUUUAAGGACC 21 18113 CFTR-Intron2-3014 UUUGCUCCUAUCUUUAAGGACC 22 18114 CFTR-Intron2-3015 CUUUGCUCCUAUCUUUAAGGACC 23 18115 CFTR-Intron2-3016 UCUUUGCUCCUAUCUUUAAGGACC 24 18116 CFTR-Intron2-3017 UAGGAACUCAAUGGGACC 18 18117 CFTR-Intron2-3018 UUAGGAACUCAAUGGGACC 19 18118 CFTR-Intron2-3019 CUUAGGAACUCAAUGGGACC 20 18119 CFTR-Intron2-3020 CCUUAGGAACUCAAUGGGACC 21 18120 CFTR-Intron2-3021 GCCUUAGGAACUCAAUGGGACC 22 18121 CFTR-Intron2-3022 GGCCUUAGGAACUCAAUGGGACC 23 18122 CFTR-Intron2-3023 UGGCCUUAGGAACUCAAUGGGACC 24 18123 CFTR-Intron2-3024 CUUUGUACCUCUGCACCC 18 18124 CFTR-Intron2-3025 ACUUUGUACCUCUGCACCC 19 18125 CFTR-Intron2-3026 UACUUUGUACCUCUGCACCC 20 18126 CFTR-Intron2-3027 GUACUUUGUACCUCUGCACCC 21 18127 CFTR-Intron2-3028 GGUACUUUGUACCUCUGCACCC 22 18128 CFTR-Intron2-3029 UGGUACUUUGUACCUCUGCACCC 23 18129 CFTR-Intron2-3030 UUGGUACUUUGUACCUCUGCACCC 24 18130 CFTR-Intron2-3031 AGUCAUAGUGCUUACCCC 18 18131 CFTR-Intron2-3032 GAGUCAUAGUGCUUACCCC 19 18132 CFTR-Intron2-3033 UGAGUCAUAGUGCUUACCCC 20 18133 CFTR-Intron2-3034 UUGAGUCAUAGUGCUUACCCC 21 18134 CFTR-Intron2-3035 CUUGAGUCAUAGUGCUUACCCC 22 18135 CFTR-Intron2-3036 UCUUGAGUCAUAGUGCUUACCCC 23 18136 CFTR-Intron2-3037 CUCUUGAGUCAUAGUGCUUACCCC 24 18137 CFTR-Intron2-3038 GAAUACAAAUGUACUCCC 18 18138 CFTR-Intron2-3039 UGAAUACAAAUGUACUCCC 19 18139 CFTR-Intron2-312 UUGAAUACAAAUGUACUCCC 20 15412 CFTR-Intron2-3040 UUUGAAUACAAAUGUACUCCC 21 18140 CFTR-Intron2-3041 AUUUGAAUACAAAUGUACUCCC 22 18141 CFTR-Intron2-3042 UAUUUGAAUACAAAUGUACUCCC 23 18142 CFTR-Intron2-3043 AUAUUUGAAUACAAAUGUACUCCC 24 18143 CFTR-Intron2-3044 UUGGUGUGUGCAAAUGCC 18 18144 CFTR-Intron2-3045 CUUGGUGUGUGCAAAUGCC 19 18145 CFTR-Intron2-3046 ACUUGGUGUGUGCAAAUGCC 20 18146 CFTR-Intron2-3047 CACUUGGUGUGUGCAAAUGCC 21 18147 CFTR-Intron2-3048 ACACUUGGUGUGUGCAAAUGCC 22 18148 CFTR-Intron2-3049 AACACUUGGUGUGUGCAAAUGCC 23 18149 CFTR-Intron2-3050 GAACACUUGGUGUGUGCAAAUGCC 24 18150 CFTR-Intron2-3051 GCUAAAUGUGAAAAAUCC 18 18151 CFTR-Intron2-3052 GGCUAAAUGUGAAAAAUCC 19 18152 CFTR-Intron2-3053 UGGCUAAAUGUGAAAAAUCC 20 18153 CFTR-Intron2-3054 UUGGCUAAAUGUGAAAAAUCC 21 18154 CFTR-Intron2-3055 CUUGGCUAAAUGUGAAAAAUCC 22 18155 CFTR-Intron2-3056 CCUUGGCUAAAUGUGAAAAAUCC 23 18156 CFTR-Intron2-3057 UCCUUGGCUAAAUGUGAAAAAUCC 24 18157 CFTR-Intron2-3058 UGAAUACAAAUGUACUCC 18 18158 CFTR-Intron2-3059 UUGAAUACAAAUGUACUCC 19 18159 CFTR-Intron2-3060 UUUGAAUACAAAUGUACUCC 20 18160 CFTR-Intron2-3061 AUUUGAAUACAAAUGUACUCC 21 18161 CFTR-Intron2-3062 UAUUUGAAUACAAAUGUACUCC 22 18162 CFTR-Intron2-3063 AUAUUUGAAUACAAAUGUACUCC 23 18163 CFTR-Intron2-3064 UAUAUUUGAAUACAAAUGUACUCC 24 18164 CFTR-Intron2-3065 UUUAUUGGCUCAUGAAGC 18 18165 CFTR-Intron2-3066 AUUUAUUGGCUCAUGAAGC 19 18166 CFTR-Intron2-3067 AAUUUAUUGGCUCAUGAAGC 20 18167 CFTR-Intron2-3068 GAAUUUAUUGGCUCAUGAAGC 21 18168 CFTR-Intron2-3069 CGAAUUUAUUGGCUCAUGAAGC 22 18169 CFTR-Intron2-3070 ACGAAUUUAUUGGCUCAUGAAGC 23 18170 CFTR-Intron2-3071 AACGAAUUUAUUGGCUCAUGAAGC 24 18171 CFTR-Intron2-3072 CUCAGUCUCCUGAGUAGC 18 18172 CFTR-Intron2-3073 UCUCAGUCUCCUGAGUAGC 19 18173 CFTR-Intron2-656 AUCUCAGUCUCCUGAGUAGC 20 15756 CFTR-Intron2-3074 AAUCUCAGUCUCCUGAGUAGC 21 18174 CFTR-Intron2-3075 GAAUCUCAGUCUCCUGAGUAGC 22 18175 CFTR-Intron2-3076 CGAAUCUCAGUCUCCUGAGUAGC 23 18176 CFTR-Intron2-3077 GCGAAUCUCAGUCUCCUGAGUAGC 24 18177 CFTR-Intron2-3078 AGUGUUGGGAUUAGUGGC 18 18178 CFTR-Intron2-3079 AAGUGUUGGGAUUAGUGGC 19 18179 CFTR-Intron2-3080 AAAGUGUUGGGAUUAGUGGC 20 18180 CFTR-Intron2-3081 CAAAGUGUUGGGAUUAGUGGC 21 18181 CFTR-Intron2-3082 CCAAAGUGUUGGGAUUAGUGGC 22 18182 CFTR-Intron2-3083 CCCAAAGUGUUGGGAUUAGUGGC 23 18183 CFTR-Intron2-3084 UCCCAAAGUGUUGGGAUUAGUGGC 24 18184 CFTR-Intron2-3085 AGAAACCUGUAGCAUUGC 18 18185 CFTR-Intron2-3086 UAGAAACCUGUAGCAUUGC 19 18186 CFTR-Intron2-325 AUAGAAACCUGUAGCAUUGC 20 15425 CFTR-Intron2-3087 CAUAGAAACCUGUAGCAUUGC 21 18187 CFTR-Intron2-3088 ACAUAGAAACCUGUAGCAUUGC 22 18188 CFTR-Intron2-3089 UACAUAGAAACCUGUAGCAUUGC 23 18189 CFTR-Intron2-3090 UUACAUAGAAACCUGUAGCAUUGC 24 18190 CFTR-Intron2-3091 AUUCACACUUCUAAGAUC 18 18191 CFTR-Intron2-3092 GAUUCACACUUCUAAGAUC 19 18192 CFTR-Intron2-3093 AGAUUCACACUUCUAAGAUC 20 18193 CFTR-Intron2-3094 CAGAUUCACACUUCUAAGAUC 21 18194 CFTR-Intron2-3095 GCAGAUUCACACUUCUAAGAUC 22 18195 CFTR-Intron2-3096 AGCAGAUUCACACUUCUAAGAUC 23 18196 CFTR-Intron2-3097 UAGCAGAUUCACACUUCUAAGAUC 24 18197 CFTR-Intron2-3098 UCAUUUACAUCUCAGCUC 18 18198 CFTR-Intron2-3099 UUCAUUUACAUCUCAGCUC 19 18199 CFTR-Intron2-3100 UUUCAUUUACAUCUCAGCUC 20 18200 CFTR-Intron2-3101 CUUUCAUUUACAUCUCAGCUC 21 18201 CFTR-Intron2-3102 ACUUUCAUUUACAUCUCAGCUC 22 18202 CFTR-Intron2-3103 CACUUUCAUUUACAUCUCAGCUC 23 18203 CFTR-Intron2-3104 UCACUUUCAUUUACAUCUCAGCUC 24 18204 CFTR-Intron2-3105 GAACGAAUUUAUUGGCUC 18 18205 CFTR-Intron2-3106 GGAACGAAUUUAUUGGCUC 19 18206 CFTR-Intron2-3107 AGGAACGAAUUUAUUGGCUC 20 18207 CFTR-Intron2-3108 AAGGAACGAAUUUAUUGGCUC 21 18208 CFTR-Intron2-3109 AAAGGAACGAAUUUAUUGGCUC 22 18209 CFTR-Intron2-3110 AAAAGGAACGAAUUUAUUGGCUC 23 18210 CFTR-Intron2-3111 UAAAAGGAACGAAUUUAUUGGCUC 24 18211 CFTR-Intron2-3112 CUGUAUUGCCUUGCUCUC 18 18212 CFTR-Intron2-3113 UCUGUAUUGCCUUGCUCUC 19 18213 CFTR-Intron2-3114 GUCUGUAUUGCCUUGCUCUC 20 18214 CFTR-Intron2-3115 GGUCUGUAUUGCCUUGCUCUC 21 18215 CFTR-Intron2-3116 AGGUCUGUAUUGCCUUGCUCUC 22 18216 CFTR-Intron2-3117 GAGGUCUGUAUUGCCUUGCUCUC 23 18217 CFTR-Intron2-3118 UGAGGUCUGUAUUGCCUUGCUCUC 24 18218 CFTR-Intron2-3119 AUGCUGGCCAGGCUGGUC 18 18219 CFTR-Intron2-3120 UAUGCUGGCCAGGCUGGUC 19 18220 CFTR-Intron2-3121 CUAUGCUGGCCAGGCUGGUC 20 18221 CFTR-Intron2-3122 GCUAUGCUGGCCAGGCUGGUC 21 18222 CFTR-Intron2-3123 UGCUAUGCUGGCCAGGCUGGUC 22 18223 CFTR-Intron2-3124 UUGCUAUGCUGGCCAGGCUGGUC 23 18224 CFTR-Intron2-3125 UUUGCUAUGCUGGCCAGGCUGGUC 24 18225 CFTR-Intron2-3126 AUGUUGGCCAGGCUGGUC 18 18226 CFTR-Intron2-3127 CAUGUUGGCCAGGCUGGUC 19 18227 CFTR-Intron2-3128 CCAUGUUGGCCAGGCUGGUC 20 18228 CFTR-Intron2-3129 GCCAUGUUGGCCAGGCUGGUC 21 18229 CFTR-Intron2-3130 CGCCAUGUUGGCCAGGCUGGUC 22 18230 CFTR-Intron2-3131 UCGCCAUGUUGGCCAGGCUGGUC 23 18231 CFTR-Intron2-3132 UUCGCCAUGUUGGCCAGGCUGGUC 24 18232 CFTR-Intron2-3133 CUCUCAUUAGCAAGCUUC 18 18233 CFTR-Intron2-3134 GCUCUCAUUAGCAAGCUUC 19 18234 CFTR-Intron2-3135 GGCUCUCAUUAGCAAGCUUC 20 18235 CFTR-Intron2-3136 GGGCUCUCAUUAGCAAGCUUC 21 18236 CFTR-Intron2-3137 AGGGCUCUCAUUAGCAAGCUUC 22 18237 CFTR-Intron2-3138 AAGGGCUCUCAUUAGCAAGCUUC 23 18238 CFTR-Intron2-3139 GAAGGGCUCUCAUUAGCAAGCUUC 24 18239 CFTR-Intron2-3140 AGUUCUUCCUUGUGGUUC 18 18240 CFTR-Intron2-3141 UAGUUCUUCCUUGUGGUUC 19 18241 CFTR-Intron2-3142 CUAGUUCUUCCUUGUGGUUC 20 18242 CFTR-Intron2-3143 CCUAGUUCUUCCUUGUGGUUC 21 18243 CFTR-Intron2-3144 ACCUAGUUCUUCCUUGUGGUUC 22 18244 CFTR-Intron2-3145 UACCUAGUUCUUCCUUGUGGUUC 23 18245 CFTR-Intron2-3146 UUACCUAGUUCUUCCUUGUGGUUC 24 18246 CFTR-Intron2-3147 UCUGUGUGUGAGAGAAAG 18 18247 CFTR-Intron2-3148 CUCUGUGUGUGAGAGAAAG 19 18248 CFTR-Intron2-3149 GCUCUGUGUGUGAGAGAAAG 20 18249 CFTR-Intron2-3150 AGCUCUGUGUGUGAGAGAAAG 21 18250 CFTR-Intron2-3151 UAGCUCUGUGUGUGAGAGAAAG 22 18251 CFTR-Intron2-3152 UUAGCUCUGUGUGUGAGAGAAAG 23 18252 CFTR-Intron2-3153 GUUAGCUCUGUGUGUGAGAGAAAG 24 18253 CFTR-Intron2-3154 CUUUAAGGACCACGAAAG 18 18254 CFTR-Intron2-3155 UCUUUAAGGACCACGAAAG 19 18255 CFTR-Intron2-3156 AUCUUUAAGGACCACGAAAG 20 18256 CFTR-Intron2-3157 UAUCUUUAAGGACCACGAAAG 21 18257 CFTR-Intron2-3158 CUAUCUUUAAGGACCACGAAAG 22 18258 CFTR-Intron2-3159 CCUAUCUUUAAGGACCACGAAAG 23 18259 CFTR-Intron2-3160 UCCUAUCUUUAAGGACCACGAAAG 24 18260 CFTR-Intron2-3161 AUGGAGCCAUGAUUCCAG 18 18261 CFTR-Intron2-3162 GAUGGAGCCAUGAUUCCAG 19 18262 CFTR-Intron2-3163 UGAUGGAGCCAUGAUUCCAG 20 18263 CFTR-Intron2-3164 AUGAUGGAGCCAUGAUUCCAG 21 18264 CFTR-Intron2-3165 AAUGAUGGAGCCAUGAUUCCAG 22 18265 CFTR-Intron2-3166 GAAUGAUGGAGCCAUGAUUCCAG 23 18266 CFTR-Intron2-3167 UGAAUGAUGGAGCCAUGAUUCCAG 24 18267 CFTR-Intron2-3168 GGGAAUGAUUAAUCAGAG 18 18268 CFTR-Intron2-3169 AGGGAAUGAUUAAUCAGAG 19 18269 CFTR-Intron2-3170 GAGGGAAUGAUUAAUCAGAG 20 18270 CFTR-Intron2-3171 UGAGGGAAUGAUUAAUCAGAG 21 18271 CFTR-Intron2-3172 CUGAGGGAAUGAUUAAUCAGAG 22 18272 CFTR-Intron2-3173 GCUGAGGGAAUGAUUAAUCAGAG 23 18273 CFTR-Intron2-3174 UGCUGAGGGAAUGAUUAAUCAGAG 24 18274 CFTR-Intron2-3175 UGGCUAAUUUUUGUAGAG 18 18275 CFTR-Intron2-3176 CUGGCUAAUUUUUGUAGAG 19 18276 CFTR-Intron2-3177 CCUGGCUAAUUUUUGUAGAG 20 18277 CFTR-Intron2-3178 GCCUGGCUAAUUUUUGUAGAG 21 18278 CFTR-Intron2-3179 GGCCUGGCUAAUUUUUGUAGAG 22 18279 CFTR-Intron2-3180 AGGCCUGGCUAAUUUUUGUAGAG 23 18280 CFTR-Intron2-3181 CAGGCCUGGCUAAUUUUUGUAGAG 24 18281 CFTR-Intron2-3182 CCUCUCAGCCACUCUGAG 18 18282 CFTR-Intron2-3183 UCCUCUCAGCCACUCUGAG 19 18283 CFTR-Intron2-344 CUCCUCUCAGCCACUCUGAG 20 15444 CFTR-Intron2-3184 UCUCCUCUCAGCCACUCUGAG 21 18284 CFTR-Intron2-3185 AUCUCCUCUCAGCCACUCUGAG 22 18285 CFTR-Intron2-3186 UAUCUCCUCUCAGCCACUCUGAG 23 18286 CFTR-Intron2-3187 AUAUCUCCUCUCAGCCACUCUGAG 24 18287 CFTR-Intron2-3188 AUGUGGGGAGGGAAAUAG 18 18288 CFTR-Intron2-3189 CAUGUGGGGAGGGAAAUAG 19 18289 CFTR-Intron2-3190 GCAUGUGGGGAGGGAAAUAG 20 18290 CFTR-Intron2-3191 AGCAUGUGGGGAGGGAAAUAG 21 18291 CFTR-Intron2-3192 AAGCAUGUGGGGAGGGAAAUAG 22 18292 CFTR-Intron2-3193 GAAGCAUGUGGGGAGGGAAAUAG 23 18293 CFTR-Intron2-3194 AGAAGCAUGUGGGGAGGGAAAUAG 24 18294 CFTR-Intron2-3195 GGUAAUUAGGCUUUAUAG 18 18295 CFTR-Intron2-3196 AGGUAAUUAGGCUUUAUAG 19 18296 CFTR-Intron2-3197 AAGGUAAUUAGGCUUUAUAG 20 18297 CFTR-Intron2-3198 AAAGGUAAUUAGGCUUUAUAG 21 18298 CFTR-Intron2-3199 AAAAGGUAAUUAGGCUUUAUAG 22 18299 CFTR-Intron2-3200 GAAAAGGUAAUUAGGCUUUAUAG 23 18300 CFTR-Intron2-3201 GGAAAAGGUAAUUAGGCUUUAUAG 24 18301 CFTR-Intron2-3202 AACUAUGUGAAGACCUAG 18 18302 CFTR-Intron2-3203 GAACUAUGUGAAGACCUAG 19 18303 CFTR-Intron2-3204 UGAACUAUGUGAAGACCUAG 20 18304 CFTR-Intron2-3205 CUGAACUAUGUGAAGACCUAG 21 18305 CFTR-Intron2-3206 CCUGAACUAUGUGAAGACCUAG 22 18306 CFTR-Intron2-3207 GCCUGAACUAUGUGAAGACCUAG 23 18307 CFTR-Intron2-3208 AGCCUGAACUAUGUGAAGACCUAG 24 18308 CFTR-Intron2-3209 UUCAAAGAAUUAAGCUAG 18 18309 CFTR-Intron2-3210 AUUCAAAGAAUUAAGCUAG 19 18310 CFTR-Intron2-345 UAUUCAAAGAAUUAAGCUAG 20 15445 CFTR-Intron2-3211 UUAUUCAAAGAAUUAAGCUAG 21 18311 CFTR-Intron2-3212 UUUAUUCAAAGAAUUAAGCUAG 22 18312 CFTR-Intron2-3213 UUUUAUUCAAAGAAUUAAGCUAG 23 18313 CFTR-Intron2-3214 AUUUUAUUCAAAGAAUUAAGCUAG 24 18314 CFTR-Intron2-3215 UCUCAGUCUCCUGAGUAG 18 18315 CFTR-Intron2-3216 AUCUCAGUCUCCUGAGUAG 19 18316 CFTR-Intron2-3217 AAUCUCAGUCUCCUGAGUAG 20 18317 CFTR-Intron2-3218 GAAUCUCAGUCUCCUGAGUAG 21 18318 CFTR-Intron2-3219 CGAAUCUCAGUCUCCUGAGUAG 22 18319 CFTR-Intron2-3220 GCGAAUCUCAGUCUCCUGAGUAG 23 18320 CFTR-Intron2-3221 AGCGAAUCUCAGUCUCCUGAGUAG 24 18321 CFTR-Intron2-3222 AAUACAUGAUUUUAGUAG 18 18322 CFTR-Intron2-3223 UAAUACAUGAUUUUAGUAG 19 18323 CFTR-Intron2-3224 UUAAUACAUGAUUUUAGUAG 20 18324 CFTR-Intron2-3225 UUUAAUACAUGAUUUUAGUAG 21 18325 CFTR-Intron2-3226 CUUUAAUACAUGAUUUUAGUAG 22 18326 CFTR-Intron2-3227 CCUUUAAUACAUGAUUUUAGUAG 23 18327 CFTR-Intron2-3228 ACCUUUAAUACAUGAUUUUAGUAG 24 18328 CFTR-Intron2-3229 CUGUGUGUGAGAGAAAGG 18 18329 CFTR-Intron2-3230 UCUGUGUGUGAGAGAAAGG 19 18330 CFTR-Intron2-678 CUCUGUGUGUGAGAGAAAGG 20 15778 CFTR-Intron2-3231 GCUCUGUGUGUGAGAGAAAGG 21 18331 CFTR-Intron2-3232 AGCUCUGUGUGUGAGAGAAAGG 22 18332 CFTR-Intron2-3233 UAGCUCUGUGUGUGAGAGAAAGG 23 18333 CFTR-Intron2-3234 UUAGCUCUGUGUGUGAGAGAAAGG 24 18334 CFTR-Intron2-3235 CUCGCUGUGUCACCCAGG 18 18335 CFTR-Intron2-3236 UCUCGCUGUGUCACCCAGG 19 18336 CFTR-Intron2-3237 GUCUCGCUGUGUCACCCAGG 20 18337 CFTR-Intron2-3238 AGUCUCGCUGUGUCACCCAGG 21 18338 CFTR-Intron2-3239 GAGUCUCGCUGUGUCACCCAGG 22 18339 CFTR-Intron2-3240 AGAGUCUCGCUGUGUCACCCAGG 23 18340 CFTR-Intron2-3241 CAGAGUCUCGCUGUGUCACCCAGG 24 18341 CFTR-Intron2-3242 CUUGCUCUGUUGCCCAGG 18 18342 CFTR-Intron2-3243 UCUUGCUCUGUUGCCCAGG 19 18343 CFTR-Intron2-3244 GUCUUGCUCUGUUGCCCAGG 20 18344 CFTR-Intron2-3245 AGUCUUGCUCUGUUGCCCAGG 21 18345 CFTR-Intron2-3246 GAGUCUUGCUCUGUUGCCCAGG 22 18346 CFTR-Intron2-3247 AGAGUCUUGCUCUGUUGCCCAGG 23 18347 CFTR-Intron2-3248 CAGAGUCUUGCUCUGUUGCCCAGG 24 18348 CFTR-Intron2-3249 UGUGCAAAUGCCAUGAGG 18 18349 CFTR-Intron2-3250 GUGUGCAAAUGCCAUGAGG 19 18350 CFTR-Intron2-3251 UGUGUGCAAAUGCCAUGAGG 20 18351 CFTR-Intron2-3252 GUGUGUGCAAAUGCCAUGAGG 21 18352 CFTR-Intron2-3253 GGUGUGUGCAAAUGCCAUGAGG 22 18353 CFTR-Intron2-3254 UGGUGUGUGCAAAUGCCAUGAGG 23 18354 CFTR-Intron2-3255 UUGGUGUGUGCAAAUGCCAUGAGG 24 18355 CFTR-Intron2-3256 ACUAUGUGAAGACCUAGG 18 18356 CFTR-Intron2-3257 AACUAUGUGAAGACCUAGG 19 18357 CFTR-Intron2-69 GAACUAUGUGAAGACCUAGG 20 15169 CFTR-Intron2-3258 UGAACUAUGUGAAGACCUAGG 21 18358 CFTR-Intron2-3259 CUGAACUAUGUGAAGACCUAGG 22 18359 CFTR-Intron2-3260 CCUGAACUAUGUGAAGACCUAGG 23 18360 CFTR-Intron2-3261 GCCUGAACUAUGUGAAGACCUAGG 24 18361 CFTR-Intron2-3262 GUGGAGAAGCAUGUGGGG 18 18362 CFTR-Intron2-3263 GGUGGAGAAGCAUGUGGGG 19 18363 CFTR-Intron2-682 AGGUGGAGAAGCAUGUGGGG 20 15782 CFTR-Intron2-3264 AAGGUGGAGAAGCAUGUGGGG 21 18364 CFTR-Intron2-3265 AAAGGUGGAGAAGCAUGUGGGG 22 18365 CFTR-Intron2-3266 GAAAGGUGGAGAAGCAUGUGGGG 23 18366 CFTR-Intron2-3267 AGAAAGGUGGAGAAGCAUGUGGGG 24 18367 CFTR-Intron2-3268 GGUGGAGAAGCAUGUGGG 18 18368 CFTR-Intron2-3269 AGGUGGAGAAGCAUGUGGG 19 18369 CFTR-Intron2-3270 AAGGUGGAGAAGCAUGUGGG 20 18370 CFTR-Intron2-3271 AAAGGUGGAGAAGCAUGUGGG 21 18371 CFTR-Intron2-3272 GAAAGGUGGAGAAGCAUGUGGG 22 18372 CFTR-Intron2-3273 AGAAAGGUGGAGAAGCAUGUGGG 23 18373 CFTR-Intron2-3274 GAGAAAGGUGGAGAAGCAUGUGGG 24 18374 CFTR-Intron2-3275 CAAGUGGUUGCCAGAUGG 18 18375 CFTR-Intron2-3276 UCAAGUGGUUGCCAGAUGG 19 18376 CFTR-Intron2-3277 CUCAAGUGGUUGCCAGAUGG 20 18377 CFTR-Intron2-3278 CCUCAAGUGGUUGCCAGAUGG 21 18378 CFTR-Intron2-3279 CCCUCAAGUGGUUGCCAGAUGG 22 18379 CFTR-Intron2-3280 GCCCUCAAGUGGUUGCCAGAUGG 23 18380 CFTR-Intron2-3281 GGCCCUCAAGUGGUUGCCAGAUGG 24 18381 CFTR-Intron2-3282 AGUAACCAAAUGUUAUGG 18 18382 CFTR-Intron2-3283 GAGUAACCAAAUGUUAUGG 19 18383 CFTR-Intron2-3284 UGAGUAACCAAAUGUUAUGG 20 18384 CFTR-Intron2-3285 CUGAGUAACCAAAUGUUAUGG 21 18385 CFTR-Intron2-3286 UCUGAGUAACCAAAUGUUAUGG 22 18386 CFTR-Intron2-3287 CUCUGAGUAACCAAAUGUUAUGG 23 18387 CFTR-Intron2-3288 ACUCUGAGUAACCAAAUGUUAUGG 24 18388 CFTR-Intron2-3289 CCUUGGCCUCCCAAAAUG 18 18389 CFTR-Intron2-3290 ACCUUGGCCUCCCAAAAUG 19 18390 CFTR-Intron2-3291 CACCUUGGCCUCCCAAAAUG 20 18391 CFTR-Intron2-3292 CCACCUUGGCCUCCCAAAAUG 21 18392 CFTR-Intron2-3293 CCCACCUUGGCCUCCCAAAAUG 22 18393 CFTR-Intron2-3294 GCCCACCUUGGCCUCCCAAAAUG 23 18394 CFTR-Intron2-3295 UGCCCACCUUGGCCUCCCAAAAUG 24 18395 CFTR-Intron2-3296 UUUGCCAGUUAAUGAAUG 18 18396 CFTR-Intron2-3297 CUUUGCCAGUUAAUGAAUG 19 18397 CFTR-Intron2-3298 ACUUUGCCAGUUAAUGAAUG 20 18398 CFTR-Intron2-3299 UACUUUGCCAGUUAAUGAAUG 21 18399 CFTR-Intron2-3300 AUACUUUGCCAGUUAAUGAAUG 22 18400 CFTR-Intron2-3301 UAUACUUUGCCAGUUAAUGAAUG 23 18401 CFTR-Intron2-3302 AUAUACUUUGCCAGUUAAUGAAUG 24 18402 CFTR-Intron2-3303 UUGUUGAAUGAAUCCAUG 18 18403 CFTR-Intron2-3304 UUUGUUGAAUGAAUCCAUG 19 18404 CFTR-Intron2-3305 AUUUGUUGAAUGAAUCCAUG 20 18405 CFTR-Intron2-3306 UAUUUGUUGAAUGAAUCCAUG 21 18406 CFTR-Intron2-3307 AUAUUUGUUGAAUGAAUCCAUG 22 18407 CFTR-Intron2-3308 AAUAUUUGUUGAAUGAAUCCAUG 23 18408 CFTR-Intron2-3309 AAAUAUUUGUUGAAUGAAUCCAUG 24 18409 CFTR-Intron2-3310 GAAAGGUGGAGAAGCAUG 18 18410 CFTR-Intron2-3311 AGAAAGGUGGAGAAGCAUG 19 18411 CFTR-Intron2-467 GAGAAAGGUGGAGAAGCAUG 20 15567 CFTR-Intron2-3312 AGAGAAAGGUGGAGAAGCAUG 21 18412 CFTR-Intron2-3313 GAGAGAAAGGUGGAGAAGCAUG 22 18413 CFTR-Intron2-3314 UGAGAGAAAGGUGGAGAAGCAUG 23 18414 CFTR-Intron2-3315 GUGAGAGAAAGGUGGAGAAGCAUG 24 18415 CFTR-Intron2-3316 CUAAGUUUUAAUUGGAUG 18 18416 CFTR-Intron2-3317 UCUAAGUUUUAAUUGGAUG 19 18417 CFTR-Intron2-3318 AUCUAAGUUUUAAUUGGAUG 20 18418 CFTR-Intron2-3319 UAUCUAAGUUUUAAUUGGAUG 21 18419 CFTR-Intron2-3320 AUAUCUAAGUUUUAAUUGGAUG 22 18420 CFTR-Intron2-3321 AAUAUCUAAGUUUUAAUUGGAUG 23 18421 CFTR-Intron2-3322 GAAUAUCUAAGUUUUAAUUGGAUG 24 18422 CFTR-Intron2-3323 UCCAUUUCUCCUUUGAUG 18 18423 CFTR-Intron2-3324 AUCCAUUUCUCCUUUGAUG 19 18424 CFTR-Intron2-3325 GAUCCAUUUCUCCUUUGAUG 20 18425 CFTR-Intron2-3326 UGAUCCAUUUCUCCUUUGAUG 21 18426 CFTR-Intron2-3327 CUGAUCCAUUUCUCCUUUGAUG 22 18427 CFTR-Intron2-3328 UCUGAUCCAUUUCUCCUUUGAUG 23 18428 CFTR-Intron2-3329 AUCUGAUCCAUUUCUCCUUUGAUG 24 18429 CFTR-Intron2-3330 UAAUGGGAAUAACCACUG 18 18430 CFTR-Intron2-3331 GUAAUGGGAAUAACCACUG 19 18431 CFTR-Intron2-3332 AGUAAUGGGAAUAACCACUG 20 18432 CFTR-Intron2-3333 CAGUAAUGGGAAUAACCACUG 21 18433 CFTR-Intron2-3334 ACAGUAAUGGGAAUAACCACUG 22 18434 CFTR-Intron2-3335 GACAGUAAUGGGAAUAACCACUG 23 18435 CFTR-Intron2-3336 UGACAGUAAUGGGAAUAACCACUG 24 18436 CFTR-Intron2-3337 AGUUUUAAUUGGAUGCUG 18 18437 CFTR-Intron2-3338 AAGUUUUAAUUGGAUGCUG 19 18438 CFTR-Intron2-364 UAAGUUUUAAUUGGAUGCUG 20 15464 CFTR-Intron2-3339 CUAAGUUUUAAUUGGAUGCUG 21 18439 CFTR-Intron2-3340 UCUAAGUUUUAAUUGGAUGCUG 22 18440 CFTR-Intron2-3341 AUCUAAGUUUUAAUUGGAUGCUG 23 18441 CFTR-Intron2-3342 UAUCUAAGUUUUAAUUGGAUGCUG 24 18442 CFTR-Intron2-3343 AAACCUGUAGCAUUGCUG 18 18443 CFTR-Intron2-3344 GAAACCUGUAGCAUUGCUG 19 18444 CFTR-Intron2-3345 AGAAACCUGUAGCAUUGCUG 20 18445 CFTR-Intron2-3346 UAGAAACCUGUAGCAUUGCUG 21 18446 CFTR-Intron2-3347 AUAGAAACCUGUAGCAUUGCUG 22 18447 CFTR-Intron2-3348 CAUAGAAACCUGUAGCAUUGCUG 23 18448 CFTR-Intron2-3349 ACAUAGAAACCUGUAGCAUUGCUG 24 18449 CFTR-Intron2-3350 CCUUGGCCUCCCAAAGUG 18 18450 CFTR-Intron2-3351 GCCUUGGCCUCCCAAAGUG 19 18451 CFTR-Intron2-3352 CGCCUUGGCCUCCCAAAGUG 20 18452 CFTR-Intron2-3353 CCGCCUUGGCCUCCCAAAGUG 21 18453 CFTR-Intron2-3354 CCCGCCUUGGCCUCCCAAAGUG 22 18454 CFTR-Intron2-3355 GCCCGCCUUGGCCUCCCAAAGUG 23 18455 CFTR-Intron2-3356 UGCCCGCCUUGGCCUCCCAAAGUG 24 18456 CFTR-Intron2-3357 CAGAUAAAAGGGUGAGUG 18 18457 CFTR-Intron2-3358 CCAGAUAAAAGGGUGAGUG 19 18458 CFTR-Intron2-3359 GCCAGAUAAAAGGGUGAGUG 20 18459 CFTR-Intron2-3360 UGCCAGAUAAAAGGGUGAGUG 21 18460 CFTR-Intron2-3361 AUGCCAGAUAAAAGGGUGAGUG 22 18461 CFTR-Intron2-3362 GAUGCCAGAUAAAAGGGUGAGUG 23 18462 CFTR-Intron2-3363 UGAUGCCAGAUAAAAGGGUGAGUG 24 18463 CFTR-Intron2-3364 GUGUGUGAGAGAAAGGUG 18 18464 CFTR-Intron2-3365 UGUGUGUGAGAGAAAGGUG 19 18465 CFTR-Intron2-3366 CUGUGUGUGAGAGAAAGGUG 20 18466 CFTR-Intron2-3367 UCUGUGUGUGAGAGAAAGGUG 21 18467 CFTR-Intron2-3368 CUCUGUGUGUGAGAGAAAGGUG 22 18468 CFTR-Intron2-3369 GCUCUGUGUGUGAGAGAAAGGUG 23 18469 CFTR-Intron2-3370 AGCUCUGUGUGUGAGAGAAAGGUG 24 18470 CFTR-Intron2-3371 UAUGUGAAGACCUAGGUG 18 18471 CFTR-Intron2-3372 CUAUGUGAAGACCUAGGUG 19 18472 CFTR-Intron2-3373 ACUAUGUGAAGACCUAGGUG 20 18473 CFTR-Intron2-3374 AACUAUGUGAAGACCUAGGUG 21 18474 CFTR-Intron2-3375 GAACUAUGUGAAGACCUAGGUG 22 18475 CFTR-Intron2-3376 UGAACUAUGUGAAGACCUAGGUG 23 18476 CFTR-Intron2-3377 CUGAACUAUGUGAAGACCUAGGUG 24 18477 CFTR-Intron2-3378 AAGGUGGAGAAGCAUGUG 18 18478 CFTR-Intron2-3379 AAAGGUGGAGAAGCAUGUG 19 18479 CFTR-Intron2-468 GAAAGGUGGAGAAGCAUGUG 20 15568 CFTR-Intron2-3380 AGAAAGGUGGAGAAGCAUGUG 21 18480 CFTR-Intron2-3381 GAGAAAGGUGGAGAAGCAUGUG 22 18481 CFTR-Intron2-3382 AGAGAAAGGUGGAGAAGCAUGUG 23 18482 CFTR-Intron2-3383 GAGAGAAAGGUGGAGAAGCAUGUG 24 18483 CFTR-Intron2-3384 AUAUUUUAUUCCUUUGUG 18 18484 CFTR-Intron2-3385 GAUAUUUUAUUCCUUUGUG 19 18485 CFTR-Intron2-3386 AGAUAUUUUAUUCCUUUGUG 20 18486 CFTR-Intron2-3387 GAGAUAUUUUAUUCCUUUGUG 21 18487 CFTR-Intron2-3388 AGAGAUAUUUUAUUCCUUUGUG 22 18488 CFTR-Intron2-3389 UAGAGAUAUUUUAUUCCUUUGUG 23 18489 CFTR-Intron2-3390 UUAGAGAUAUUUUAUUCCUUUGUG 24 18490 CFTR-Intron2-3391 UAGAAACCUGUAGCAUUG 18 18491 CFTR-Intron2-3392 AUAGAAACCUGUAGCAUUG 19 18492 CFTR-Intron2-3393 CAUAGAAACCUGUAGCAUUG 20 18493 CFTR-Intron2-3394 ACAUAGAAACCUGUAGCAUUG 21 18494 CFTR-Intron2-3395 UACAUAGAAACCUGUAGCAUUG 22 18495 CFTR-Intron2-3396 UUACAUAGAAACCUGUAGCAUUG 23 18496 CFTR-Intron2-3397 AUUACAUAGAAACCUGUAGCAUUG 24 18497 CFTR-Intron2-3398 GUGGUUGCCAGAUGGUUG 18 18498 CFTR-Intron2-3399 AGUGGUUGCCAGAUGGUUG 19 18499 CFTR-Intron2-3400 AAGUGGUUGCCAGAUGGUUG 20 18500 CFTR-Intron2-3401 CAAGUGGUUGCCAGAUGGUUG 21 18501 CFTR-Intron2-3402 UCAAGUGGUUGCCAGAUGGUUG 22 18502 CFTR-Intron2-3403 CUCAAGUGGUUGCCAGAUGGUUG 23 18503 CFTR-Intron2-3404 CCUCAAGUGGUUGCCAGAUGGUUG 24 18504 CFTR-Intron2-3405 UGAUCCAUUUCUCCUUUG 18 18505 CFTR-Intron2-3406 CUGAUCCAUUUCUCCUUUG 19 18506 CFTR-Intron2-3407 UCUGAUCCAUUUCUCCUUUG 20 18507 CFTR-Intron2-3408 AUCUGAUCCAUUUCUCCUUUG 21 18508 CFTR-Intron2-3409 CAUCUGAUCCAUUUCUCCUUUG 22 18509 CFTR-Intron2-3410 CCAUCUGAUCCAUUUCUCCUUUG 23 18510 CFTR-Intron2-3411 CCCAUCUGAUCCAUUUCUCCUUUG 24 18511 CFTR-Intron2-3412 AGGCCUGGCUAAUUUUUG 18 18512 CFTR-Intron2-3413 CAGGCCUGGCUAAUUUUUG 19 18513 CFTR-Intron2-3414 CCAGGCCUGGCUAAUUUUUG 20 18514 CFTR-Intron2-3415 ACCAGGCCUGGCUAAUUUUUG 21 18515 CFTR-Intron2-3416 CACCAGGCCUGGCUAAUUUUUG 22 18516 CFTR-Intron2-3417 CCACCAGGCCUGGCUAAUUUUUG 23 18517 CFTR-Intron2-3418 ACCACCAGGCCUGGCUAAUUUUUG 24 18518 CFTR-Intron2-3419 CUUUGUCCUUGGCUAAAU 18 18519 CFTR-Intron2-3420 CCUUUGUCCUUGGCUAAAU 19 18520 CFTR-Intron2-3421 CCCUUUGUCCUUGGCUAAAU 20 18521 CFTR-Intron2-3422 GCCCUUUGUCCUUGGCUAAAU 21 18522 CFTR-Intron2-3423 AGCCCUUUGUCCUUGGCUAAAU 22 18523 CFTR-Intron2-3424 GAGCCCUUUGUCCUUGGCUAAAU 23 18524 CFTR-Intron2-3425 GGAGCCCUUUGUCCUUGGCUAAAU 24 18525 CFTR-Intron2-3426 AUGAAUCCAUGAUGGAAU 18 18526 CFTR-Intron2-3427 AAUGAAUCCAUGAUGGAAU 19 18527 CFTR-Intron2-3428 GAAUGAAUCCAUGAUGGAAU 20 18528 CFTR-Intron2-3429 UGAAUGAAUCCAUGAUGGAAU 21 18529 CFTR-Intron2-3430 UUGAAUGAAUCCAUGAUGGAAU 22 18530 CFTR-Intron2-3431 GUUGAAUGAAUCCAUGAUGGAAU 23 18531 CFTR-Intron2-3432 UGUUGAAUGAAUCCAUGAUGGAAU 24 18532 CFTR-Intron2-3433 AGAAAGGUGGAGAAGCAU 18 18533 CFTR-Intron2-3434 GAGAAAGGUGGAGAAGCAU 19 18534 CFTR-Intron2-3435 AGAGAAAGGUGGAGAAGCAU 20 18535 CFTR-Intron2-3436 GAGAGAAAGGUGGAGAAGCAU 21 18536 CFTR-Intron2-3437 UGAGAGAAAGGUGGAGAAGCAU 22 18537 CFTR-Intron2-3438 GUGAGAGAAAGGUGGAGAAGCAU 23 18538 CFTR-Intron2-3439 UGUGAGAGAAAGGUGGAGAAGCAU 24 18539 CFTR-Intron2-3440 GUGGGGAGGGAAAUAGAU 18 18540 CFTR-Intron2-3441 UGUGGGGAGGGAAAUAGAU 19 18541 CFTR-Intron2-377 AUGUGGGGAGGGAAAUAGAU 20 15477 CFTR-Intron2-3442 CAUGUGGGGAGGGAAAUAGAU 21 18542 CFTR-Intron2-3443 GCAUGUGGGGAGGGAAAUAGAU 22 18543 CFTR-Intron2-3444 AGCAUGUGGGGAGGGAAAUAGAU 23 18544 CFTR-Intron2-3445 AAGCAUGUGGGGAGGGAAAUAGAU 24 18545 CFTR-Intron2-3446 UUUUGUAUUUUAGUAGAU 18 18546 CFTR-Intron2-3447 UUUUUGUAUUUUAGUAGAU 19 18547 CFTR-Intron2-3448 AUUUUUGUAUUUUAGUAGAU 20 18548 CFTR-Intron2-3449 AAUUUUUGUAUUUUAGUAGAU 21 18549 CFTR-Intron2-3450 UAAUUUUUGUAUUUUAGUAGAU 22 18550 CFTR-Intron2-3451 CUAAUUUUUGUAUUUUAGUAGAU 23 18551 CFTR-Intron2-3452 GCUAAUUUUUGUAUUUUAGUAGAU 24 18552 CFTR-Intron2-3453 CAAGAUUGUAGUCAGGAU 18 18553 CFTR-Intron2-3454 CCAAGAUUGUAGUCAGGAU 19 18554 CFTR-Intron2-3455 UCCAAGAUUGUAGUCAGGAU 20 18555 CFTR-Intron2-3456 UUCCAAGAUUGUAGUCAGGAU 21 18556 CFTR-Intron2-3457 GUUCCAAGAUUGUAGUCAGGAU 22 18557 CFTR-Intron2-3458 CGUUCCAAGAUUGUAGUCAGGAU 23 18558 CFTR-Intron2-3459 CCGUUCCAAGAUUGUAGUCAGGAU 24 18559 CFTR-Intron2-3460 UAACCAAAUGUUAUGGAU 18 18560 CFTR-Intron2-3461 GUAACCAAAUGUUAUGGAU 19 18561 CFTR-Intron2-378 AGUAACCAAAUGUUAUGGAU 20 15478 CFTR-Intron2-3462 GAGUAACCAAAUGUUAUGGAU 21 18562 CFTR-Intron2-3463 UGAGUAACCAAAUGUUAUGGAU 22 18563 CFTR-Intron2-3464 CUGAGUAACCAAAUGUUAUGGAU 23 18564 CFTR-Intron2-3465 UCUGAGUAACCAAAUGUUAUGGAU 24 18565 CFTR-Intron2-3466 AACUUCUUCCCUUCUGAU 18 18566 CFTR-Intron2-3467 AAACUUCUUCCCUUCUGAU 19 18567 CFTR-Intron2-3468 AAAACUUCUUCCCUUCUGAU 20 18568 CFTR-Intron2-3469 UAAAACUUCUUCCCUUCUGAU 21 18569 CFTR-Intron2-3470 AUAAAACUUCUUCCCUUCUGAU 22 18570 CFTR-Intron2-3471 AAUAAAACUUCUUCCCUUCUGAU 23 18571 CFTR-Intron2-3472 GAAUAAAACUUCUUCCCUUCUGAU 24 18572 CFTR-Intron2-3473 UCAUGAAGCCUGAACUAU 18 18573 CFTR-Intron2-3474 CUCAUGAAGCCUGAACUAU 19 18574 CFTR-Intron2-3475 GCUCAUGAAGCCUGAACUAU 20 18575 CFTR-Intron2-3476 GGCUCAUGAAGCCUGAACUAU 21 18576 CFTR-Intron2-3477 UGGCUCAUGAAGCCUGAACUAU 22 18577 CFTR-Intron2-3478 UUGGCUCAUGAAGCCUGAACUAU 23 18578 CFTR-Intron2-3479 AUUGGCUCAUGAAGCCUGAACUAU 24 18579 CFTR-Intron2-3480 UUCUUAUAAAAUUGGUAU 18 18580 CFTR-Intron2-3481 UUUCUUAUAAAAUUGGUAU 19 18581 CFTR-Intron2-3482 UUUUCUUAUAAAAUUGGUAU 20 18582 CFTR-Intron2-3483 CUUUUCUUAUAAAAUUGGUAU 21 18583 CFTR-Intron2-3484 UCUUUUCUUAUAAAAUUGGUAU 22 18584 CFTR-Intron2-3485 UUCUUUUCUUAUAAAAUUGGUAU 23 18585 CFTR-Intron2-3486 CUUCUUUUCUUAUAAAAUUGGUAU 24 18586 CFTR-Intron2-3487 UCAGAGAAUUUGUCUUAU 18 18587 CFTR-Intron2-3488 UUCAGAGAAUUUGUCUUAU 19 18588 CFTR-Intron2-3489 UUUCAGAGAAUUUGUCUUAU 20 18589 CFTR-Intron2-3490 GUUUCAGAGAAUUUGUCUUAU 21 18590 CFTR-Intron2-3491 GGUUUCAGAGAAUUUGUCUUAU 22 18591 CFTR-Intron2-3492 UGGUUUCAGAGAAUUUGUCUUAU 23 18592 CFTR-Intron2-3493 UUGGUUUCAGAGAAUUUGUCUUAU 24 18593 CFTR-Intron2-3494 UUUGUACCUCUGCACCCU 18 18594 CFTR-Intron2-3495 CUUUGUACCUCUGCACCCU 19 18595 CFTR-Intron2-705 ACUUUGUACCUCUGCACCCU 20 15805 CFTR-Intron2-3496 UACUUUGUACCUCUGCACCCU 21 18596 CFTR-Intron2-3497 GUACUUUGUACCUCUGCACCCU 22 18597 CFTR-Intron2-3498 GGUACUUUGUACCUCUGCACCCU 23 18598 CFTR-Intron2-3499 UGGUACUUUGUACCUCUGCACCCU 24 18599 CFTR-Intron2-3500 AAUACAAAUGUACUCCCU 18 18600 CFTR-Intron2-3501 GAAUACAAAUGUACUCCCU 19 18601 CFTR-Intron2-389 UGAAUACAAAUGUACUCCCU 20 15489 CFTR-Intron2-3502 UUGAAUACAAAUGUACUCCCU 21 18602 CFTR-Intron2-3503 UUUGAAUACAAAUGUACUCCCU 22 18603 CFTR-Intron2-3504 AUUUGAAUACAAAUGUACUCCCU 23 18604 CFTR-Intron2-3505 UAUUUGAAUACAAAUGUACUCCCU 24 18605 CFTR-Intron2-3506 UAGGUGGAGAACUGGCCU 18 18606 CFTR-Intron2-3507 CUAGGUGGAGAACUGGCCU 19 18607 CFTR-Intron2-3508 CCUAGGUGGAGAACUGGCCU 20 18608 CFTR-Intron2-3509 ACCUAGGUGGAGAACUGGCCU 21 18609 CFTR-Intron2-3510 GACCUAGGUGGAGAACUGGCCU 22 18610 CFTR-Intron2-3511 AGACCUAGGUGGAGAACUGGCCU 23 18611 CFTR-Intron2-3512 AAGACCUAGGUGGAGAACUGGCCU 24 18612 CFTR-Intron2-3513 GAAAAGCAAACUGAGGCU 18 18613 CFTR-Intron2-3514 AGAAAAGCAAACUGAGGCU 19 18614 CFTR-Intron2-3515 CAGAAAAGCAAACUGAGGCU 20 18615 CFTR-Intron2-3516 ACAGAAAAGCAAACUGAGGCU 21 18616 CFTR-Intron2-3517 UACAGAAAAGCAAACUGAGGCU 22 18617 CFTR-Intron2-3518 UUACAGAAAAGCAAACUGAGGCU 23 18618 CFTR-Intron2-3519 UUUACAGAAAAGCAAACUGAGGCU 24 18619 CFTR-Intron2-3520 GAUGCCAAGAUCCAUGCU 18 18620 CFTR-Intron2-3521 GGAUGCCAAGAUCCAUGCU 19 18621 CFTR-Intron2-3522 GGGAUGCCAAGAUCCAUGCU 20 18622 CFTR-Intron2-3523 GGGGAUGCCAAGAUCCAUGCU 21 18623 CFTR-Intron2-3524 AGGGGAUGCCAAGAUCCAUGCU 22 18624 CFTR-Intron2-3525 UAGGGGAUGCCAAGAUCCAUGCU 23 18625 CFTR-Intron2-3526 CUAGGGGAUGCCAAGAUCCAUGCU 24 18626 CFTR-Intron2-3527 AAGUUUUAAUUGGAUGCU 18 18627 CFTR-Intron2-3528 UAAGUUUUAAUUGGAUGCU 19 18628 CFTR-Intron2-3529 CUAAGUUUUAAUUGGAUGCU 20 18629 CFTR-Intron2-3530 UCUAAGUUUUAAUUGGAUGCU 21 18630 CFTR-Intron2-3531 AUCUAAGUUUUAAUUGGAUGCU 22 18631 CFTR-Intron2-3532 UAUCUAAGUUUUAAUUGGAUGCU 23 18632 CFTR-Intron2-3533 AUAUCUAAGUUUUAAUUGGAUGCU 24 18633 CFTR-Intron2-3534 UCUCAUUAGCAAGCUUCU 18 18634 CFTR-Intron2-3535 CUCUCAUUAGCAAGCUUCU 19 18635 CFTR-Intron2-75 GCUCUCAUUAGCAAGCUUCU 20 15175 CFTR-Intron2-3536 GGCUCUCAUUAGCAAGCUUCU 21 18636 CFTR-Intron2-3537 GGGCUCUCAUUAGCAAGCUUCU 22 18637 CFTR-Intron2-3538 AGGGCUCUCAUUAGCAAGCUUCU 23 18638 CFTR-Intron2-3539 AAGGGCUCUCAUUAGCAAGCUUCU 24 18639 CFTR-Intron2-3540 UUUUCAUCUCUGUACAGU 18 18640 CFTR-Intron2-3541 UUUUUCAUCUCUGUACAGU 19 18641 CFTR-Intron2-3542 AUUUUUCAUCUCUGUACAGU 20 18642 CFTR-Intron2-3543 AAUUUUUCAUCUCUGUACAGU 21 18643 CFTR-Intron2-3544 AAAUUUUUCAUCUCUGUACAGU 22 18644 CFTR-Intron2-3545 GAAAUUUUUCAUCUCUGUACAGU 23 18645 CFTR-Intron2-3546 UGAAAUUUUUCAUCUCUGUACAGU 24 18646 CFTR-Intron2-3547 UUUCUACAUUACUUCCGU 18 18647 CFTR-Intron2-3548 CUUUCUACAUUACUUCCGU 19 18648 CFTR-Intron2-3549 CCUUUCUACAUUACUUCCGU 20 18649 CFTR-Intron2-3550 ACCUUUCUACAUUACUUCCGU 21 18650 CFTR-Intron2-3551 CACCUUUCUACAUUACUUCCGU 22 18651 CFTR-Intron2-3552 ACACCUUUCUACAUUACUUCCGU 23 18652 CFTR-Intron2-3553 AACACCUUUCUACAUUACUUCCGU 24 18653 CFTR-Intron2-3554 AAUGCUGGGAUUAUAGGU 18 18654 CFTR-Intron2-3555 AAAUGCUGGGAUUAUAGGU 19 18655 CFTR-Intron2-3556 AAAAUGCUGGGAUUAUAGGU 20 18656 CFTR-Intron2-3557 CAAAAUGCUGGGAUUAUAGGU 21 18657 CFTR-Intron2-3558 CCAAAAUGCUGGGAUUAUAGGU 22 18658 CFTR-Intron2-3559 CCCAAAAUGCUGGGAUUAUAGGU 23 18659 CFTR-Intron2-3560 UCCCAAAAUGCUGGGAUUAUAGGU 24 18660 CFTR-Intron2-3561 AUAAAGUGGGUCCCUGGU 18 18661 CFTR-Intron2-3562 CAUAAAGUGGGUCCCUGGU 19 18662 CFTR-Intron2-3563 ACAUAAAGUGGGUCCCUGGU 20 18663 CFTR-Intron2-3564 UACAUAAAGUGGGUCCCUGGU 21 18664 CFTR-Intron2-3565 CUACAUAAAGUGGGUCCCUGGU 22 18665 CFTR-Intron2-3566 UCUACAUAAAGUGGGUCCCUGGU 23 18666 CFTR-Intron2-3567 UUCUACAUAAAGUGGGUCCCUGGU 24 18667 CFTR-Intron2-3568 AAAGGUGGAGAAGCAUGU 18 18668 CFTR-Intron2-3569 GAAAGGUGGAGAAGCAUGU 19 18669 CFTR-Intron2-406 AGAAAGGUGGAGAAGCAUGU 20 15506 CFTR-Intron2-3570 GAGAAAGGUGGAGAAGCAUGU 21 18670 CFTR-Intron2-3571 AGAGAAAGGUGGAGAAGCAUGU 22 18671 CFTR-Intron2-3572 GAGAGAAAGGUGGAGAAGCAUGU 23 18672 CFTR-Intron2-3573 UGAGAGAAAGGUGGAGAAGCAUGU 24 18673 CFTR-Intron2-3574 GGGAGGUUAGCUCUGUGU 18 18674 CFTR-Intron2-3575 UGGGAGGUUAGCUCUGUGU 19 18675 CFTR-Intron2-3576 AUGGGAGGUUAGCUCUGUGU 20 18676 CFTR-Intron2-3577 GAUGGGAGGUUAGCUCUGUGU 21 18677 CFTR-Intron2-3578 GGAUGGGAGGUUAGCUCUGUGU 22 18678 CFTR-Intron2-3579 UGGAUGGGAGGUUAGCUCUGUGU 23 18679 CFTR-Intron2-3580 AUGGAUGGGAGGUUAGCUCUGUGU 24 18680 CFTR-Intron2-3581 GAGGUUAGCUCUGUGUGU 18 18681 CFTR-Intron2-3582 GGAGGUUAGCUCUGUGUGU 19 18682 CFTR-Intron2-3583 GGGAGGUUAGCUCUGUGUGU 20 18683 CFTR-Intron2-3584 UGGGAGGUUAGCUCUGUGUGU 21 18684 CFTR-Intron2-3585 AUGGGAGGUUAGCUCUGUGUGU 22 18685 CFTR-Intron2-3586 GAUGGGAGGUUAGCUCUGUGUGU 23 18686 CFTR-Intron2-3587 GGAUGGGAGGUUAGCUCUGUGUGU 24 18687 CFTR-Intron2-3588 AACUAAAGUAACACCAUU 18 18688 CFTR-Intron2-3589 AAACUAAAGUAACACCAUU 19 18689 CFTR-Intron2-3590 AAAACUAAAGUAACACCAUU 20 18690 CFTR-Intron2-3591 GAAAACUAAAGUAACACCAUU 21 18691 CFTR-Intron2-3592 UGAAAACUAAAGUAACACCAUU 22 18692 CFTR-Intron2-3593 GUGAAAACUAAAGUAACACCAUU 23 18693 CFTR-Intron2-3594 UGUGAAAACUAAAGUAACACCAUU 24 18694 CFTR-Intron2-3595 UUUCCUUUUUUUGGCAUU 18 18695 CFTR-Intron2-3596 AUUUCCUUUUUUUGGCAUU 19 18696 CFTR-Intron2-3597 CAUUUCCUUUUUUUGGCAUU 20 18697 CFTR-Intron2-3598 UCAUUUCCUUUUUUUGGCAUU 21 18698 CFTR-Intron2-3599 UUCAUUUCCUUUUUUUGGCAUU 22 18699 CFTR-Intron2-3600 AUUCAUUUCCUUUUUUUGGCAUU 23 18700 CFTR-Intron2-3601 AAUUCAUUUCCUUUUUUUGGCAUU 24 18701 CFTR-Intron2-3602 UACUCCUUUAGAGUGAUU 18 18702 CFTR-Intron2-3603 UUACUCCUUUAGAGUGAUU 19 18703 CFTR-Intron2-3604 AUUACUCCUUUAGAGUGAUU 20 18704 CFTR-Intron2-3605 UAUUACUCCUUUAGAGUGAUU 21 18705 CFTR-Intron2-3606 CUAUUACUCCUUUAGAGUGAUU 22 18706 CFTR-Intron2-3607 CCUAUUACUCCUUUAGAGUGAUU 23 18707 CFTR-Intron2-3608 GCCUAUUACUCCUUUAGAGUGAUU 24 18708 CFTR-Intron2-3609 GAAAUUUAUUGAAAUAUU 18 18709 CFTR-Intron2-3610 UGAAAUUUAUUGAAAUAUU 19 18710 CFTR-Intron2-3611 UUGAAAUUUAUUGAAAUAUU 20 18711 CFTR-Intron2-3612 UUUGAAAUUUAUUGAAAUAUU 21 18712 CFTR-Intron2-3613 AUUUGAAAUUUAUUGAAAUAUU 22 18713 CFTR-Intron2-3614 UAUUUGAAAUUUAUUGAAAUAUU 23 18714 CFTR-Intron2-3615 GUAUUUGAAAUUUAUUGAAAUAUU 24 18715 CFTR-Intron2-3616 AAUUAAGAUGAUAAUAUU 18 18716 CFTR-Intron2-3617 AAAUUAAGAUGAUAAUAUU 19 18717 CFTR-Intron2-3618 AAAAUUAAGAUGAUAAUAUU 20 18718 CFTR-Intron2-3619 GAAAAUUAAGAUGAUAAUAUU 21 18719 CFTR-Intron2-3620 UGAAAAUUAAGAUGAUAAUAUU 22 18720 CFTR-Intron2-3621 UUGAAAAUUAAGAUGAUAAUAUU 23 18721 CFTR-Intron2-3622 UUUGAAAAUUAAGAUGAUAAUAUU 24 18722 CFTR-Intron2-3623 UUGUACCUCUGCACCCUU 18 18723 CFTR-Intron2-3624 UUUGUACCUCUGCACCCUU 19 18724 CFTR-Intron2-412 CUUUGUACCUCUGCACCCUU 20 15512 CFTR-Intron2-3625 ACUUUGUACCUCUGCACCCUU 21 18725 CFTR-Intron2-3626 UACUUUGUACCUCUGCACCCUU 22 18726 CFTR-Intron2-3627 GUACUUUGUACCUCUGCACCCUU 23 18727 CFTR-Intron2-3628 GGUACUUUGUACCUCUGCACCCUU 24 18728 CFTR-Intron2-3629 AGGUGGAGAACUGGCCUU 18 18729 CFTR-Intron2-3630 UAGGUGGAGAACUGGCCUU 19 18730 CFTR-Intron2-414 CUAGGUGGAGAACUGGCCUU 20 15514 CFTR-Intron2-3631 CCUAGGUGGAGAACUGGCCUU 21 18731 CFTR-Intron2-3632 ACCUAGGUGGAGAACUGGCCUU 22 18732 CFTR-Intron2-3633 GACCUAGGUGGAGAACUGGCCUU 23 18733 CFTR-Intron2-3634 AGACCUAGGUGGAGAACUGGCCUU 24 18734 CFTR-Intron2-3635 GGUCACUAGAGACCUCUU 18 18735 CFTR-Intron2-3636 GGGUCACUAGAGACCUCUU 19 18736 CFTR-Intron2-3637 AGGGUCACUAGAGACCUCUU 20 18737 CFTR-Intron2-3638 CAGGGUCACUAGAGACCUCUU 21 18738 CFTR-Intron2-3639 CCAGGGUCACUAGAGACCUCUU 22 18739 CFTR-Intron2-3640 CCCAGGGUCACUAGAGACCUCUU 23 18740 CFTR-Intron2-3641 GCCCAGGGUCACUAGAGACCUCUU 24 18741 CFTR-Intron2-3642 AAAUUUAUUGAAAUAUUU 18 18742 CFTR-Intron2-3643 GAAAUUUAUUGAAAUAUUU 19 18743 CFTR-Intron2-721 UGAAAUUUAUUGAAAUAUUU 20 15821 CFTR-Intron2-3644 UUGAAAUUUAUUGAAAUAUUU 21 18744 CFTR-Intron2-3645 UUUGAAAUUUAUUGAAAUAUUU 22 18745 CFTR-Intron2-3646 AUUUGAAAUUUAUUGAAAUAUUU 23 18746 CFTR-Intron2-3647 UAUUUGAAAUUUAUUGAAAUAUUU 24 18747 CFTR-Intron2-3648 GAGAUAUUUUAUUCCUUU 18 18748 CFTR-Intron2-3649 AGAGAUAUUUUAUUCCUUU 19 18749 CFTR-Intron2-3650 UAGAGAUAUUUUAUUCCUUU 20 18750 CFTR-Intron2-3651 UUAGAGAUAUUUUAUUCCUUU 21 18751 CFTR-Intron2-3652 UUUAGAGAUAUUUUAUUCCUUU 22 18752 CFTR-Intron2-3653 AUUUAGAGAUAUUUUAUUCCUUU 23 18753 CFTR-Intron2-3654 UAUUUAGAGAUAUUUUAUUCCUUU 24 18754 CFTR-Intron2-3655 CUCUUUGCUCCUAUCUUU 18 18755 CFTR-Intron2-3656 ACUCUUUGCUCCUAUCUUU 19 18756 CFTR-Intron2-3657 AACUCUUUGCUCCUAUCUUU 20 18757 CFTR-Intron2-3658 GAACUCUUUGCUCCUAUCUUU 21 18758 CFTR-Intron2-3659 AGAACUCUUUGCUCCUAUCUUU 22 18759 CFTR-Intron2-3660 UAGAACUCUUUGCUCCUAUCUUU 23 18760 CFTR-Intron2-3661 UUAGAACUCUUUGCUCCUAUCUUU 24 18761 CFTR-Intron2-3662 AAAAUACACAUUUGGUUU 18 18762 CFTR-Intron2-3663 AAAAAUACACAUUUGGUUU 19 18763 CFTR-Intron2-3664 GAAAAAUACACAUUUGGUUU 20 18764 CFTR-Intron2-3665 UGAAAAAUACACAUUUGGUUU 21 18765 CFTR-Intron2-3666 CUGAAAAAUACACAUUUGGUUU 22 18766 CFTR-Intron2-3667 CCUGAAAAAUACACAUUUGGUUU 23 18767 CFTR-Intron2-3668 UCCUGAAAAAUACACAUUUGGUUU 24 18768 CFTR-Intron2-3669 UUGUUGUUGCUGUUGUUU 18 18769 CFTR-Intron2-3670 GUUGUUGUUGCUGUUGUUU 19 18770 CFTR-Intron2-3671 UGUUGUUGUUGCUGUUGUUU 20 18771 CFTR-Intron2-3672 UUGUUGUUGUUGCUGUUGUUU 21 18772 CFTR-Intron2-3673 GUUGUUGUUGUUGCUGUUGUUU 22 18773 CFTR-Intron2-3674 UGUUGUUGUUGUUGCUGUUGUUU 23 18774 CFTR-Intron2-3675 UUGUUGUUGUUGUUGCUGUUGUUU 24 18775 CFTR-Intron2-3676 UGUUUGUGUUGUUUGUUU 18 18776 CFTR-Intron2-3677 UUGUUUGUGUUGUUUGUUU 19 18777 CFTR-Intron2-3678 UUUGUUUGUGUUGUUUGUUU 20 18778 CFTR-Intron2-3679 GUUUGUUUGUGUUGUUUGUUU 21 18779 CFTR-Intron2-3680 UGUUUGUUUGUGUUGUUUGUUU 22 18780 CFTR-Intron2-3681 UUGUUUGUUUGUGUUGUUUGUUU 23 18781 CFTR-Intron2-3682 UUUGUUUGUUUGUGUUGUUUGUUU 24 18782 CFTR-Intron2-3683 GACCAUGAGAUGGAUUUU 18 18783 CFTR-Intron2-3684 AGACCAUGAGAUGGAUUUU 19 18784 CFTR-Intron2-3685 GAGACCAUGAGAUGGAUUUU 20 18785 CFTR-Intron2-3686 AGAGACCAUGAGAUGGAUUUU 21 18786 CFTR-Intron2-3687 UAGAGACCAUGAGAUGGAUUUU 22 18787 CFTR-Intron2-3688 UUAGAGACCAUGAGAUGGAUUUU 23 18788 CFTR-Intron2-3689 AUUAGAGACCAUGAGAUGGAUUUU 24 18789

Table 39A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 2, have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 39A 1st Tier Target  DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-3690 GGUGAGUCUGCUCCAUA 17 18790 CFTR-Intron2-3691 GGCCUAUUACUCCUUUA 17 18791 CFTR-Intron2-3692 + GUGAAUCUGCUACUCCC 17 18792 CFTR-Intron2-3693 + GUUUUGAAAGCAAAUAU 17 18793 CFTR-Intron2-3694 + GGAUCUUGGCAUCCCCU 17 18794 CFTR-Intron2-3695 + GCACACUGCAGUUAUGU 17 18795 CFTR-Intron2-3696 GAAGGUGAGUCUGCUCCAUA 20 18796 CFTR-Intron2-3697 + GAACUUGUCAAUAUACCUGC 20 18797 CFTR-Intron2-3698 GUUUAUGUACACACCCCUUC 20 18798 CFTR-Intron2-3699 GUUUUAAUUGGAUGCUGAGG 20 18799 CFTR-Intron2-3700 GUUUUAUUUUCUCAGACCGG 20 18800 CFTR-Intron2-3522 GGGAUGCCAAGAUCCAUGCU 20 18622 CFTR-Intron2-2554 + GCACUAUGACUCAAGAGUCU 20 17654 CFTR-Intron2-3701 GUGCAAACCACACAUCCGUU 20 18801

Table 39B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 2 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 39B 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-3702 UAGAUGGGAAAAGGUAA 17 18802 CFTR-Intron2-3703 CUUAUUAGAGACCAUGA 17 18803 CFTR-Intron2-3704 + CAAUUAACCCAGCCCUA 17 18804 CFTR-Intron2-3705 CUGAAUUUGCAGAAUUA 17 18805 CFTR-Intron2-3706 + UAGGUAAACAAUUAGAC 17 18806 CFTR-Intron2-3707 CACCCUUGGGAAGUGAC 17 18807 CFTR-Intron2-3708 UGGCUCAAUUUUGUGAC 17 18808 CFTR-Intron2-3709 + UCAAAAGGAUCCUAACC 17 18809 CFTR-Intron2-3710 + AAUACUAUAGGAACACC 17 18810 CFTR-Intron2-3711 + CAUCUAUUUCCCUCCCC 17 18811 CFTR-Intron2-3712 UCAAAAGGUUAGGAUCC 17 18812 CFTR-Intron2-3713 + CUUGUCAAUAUACCUGC 17 18813 CFTR-Intron2-3714 + AUUUAUUAAGUUAUUGC 17 18814 CFTR-Intron2-3715 UAUGUACACACCCCUUC 17 18815 CFTR-Intron2-3716 + AAAGGAGUAAUACACAG 17 18816 CFTR-Intron2-3717 CACUUCUAAGAUCAAGG 17 18817 CFTR-Intron2-3718 UUAAUUGGAUGCUGAGG 17 18818 CFTR-Intron2-3719 UUAUUUUCUCAGACCGG 17 18819 CFTR-Intron2-3720 UCCAUGCUUAGAGAUUG 17 18820 CFTR-Intron2-3721 UUUCAAAGACCUUUAAU 17 18821 CFTR-Intron2-3722 CUAGGGGAUGCCAAGAU 17 18822 CFTR-Intron2-3723 UGAAGUAAAUCGUGUAU 17 18823 CFTR-Intron2-3724 + UGAUUGGAAAGGAAACU 17 18824 CFTR-Intron2-3725 AUGCCAAGAUCCAUGCU 17 18825 CFTR-Intron2-3726 AUUAAGCUAGUGGGAGU 17 18826 CFTR-Intron2-3727 + CUAGGUCUUCACAUAGU 17 18827 CFTR-Intron2-3728 CAAACCACACAUCCGUU 17 18828 CFTR-Intron2-3729 AAAUAGAUGGGAAAAGGUAA 20 18829 CFTR-Intron2-3730 AGUUUUCACUGUAUCCCCCA 20 18830 CFTR-Intron2-3731 UCCCAGAGACUCUUGAGUCA 20 18831 CFTR-Intron2-3732 UGUCUUAUUAGAGACCAUGA 20 18832 CFTR-Intron2-3733 + UUUCAAUUAACCCAGCCCUA 20 18833 CFTR-Intron2-3734 AAUCUGAAUUUGCAGAAUUA 20 18834 CFTR-Intron2-3735 CCCGGCCUAUUACUCCUUUA 20 18835 CFTR-Intron2-3736 + AACUAGGUAAACAAUUAGAC 20 18836 CFTR-Intron2-3737 CUGCACCCUUGGGAAGUGAC 20 18837 CFTR-Intron2-3738 AUCUGGCUCAAUUUUGUGAC 20 18838 CFTR-Intron2-3739 + CAAUCAAAAGGAUCCUAACC 20 18839 CFTR-Intron2-3740 + UUAAAUACUAUAGGAACACC 20 18840 CFTR-Intron2-3741 + AGUGUGAAUCUGCUACUCCC 20 18841 CFTR-Intron2-3742 CAAUCAAAAGGUUAGGAUCC 20 18842 CFTR-Intron2-2142 + CAUAAAGGAGUAAUACACAG 20 17242 CFTR-Intron2-3743 UCACACUUCUAAGAUCAAGG 20 18843 CFTR-Intron2-3744 + CUAGCCAUUUCACAUUCCAU 20 18844 CFTR-Intron2-3745 CUUCUAGGGGAUGCCAAGAU 20 18845 CFTR-Intron2-2486 + UUUUGAUUGGAAAGGAAACU 20 17586 CFTR-Intron2-3746 + CAUGGAUCUUGGCAUCCCCU 20 18846 CFTR-Intron2-3747 AGAAUUAAGCUAGUGGGAGU 20 18847 CFTR-Intron2-3748 + CACCUAGGUCUUCACAUAGU 20 18848 CFTR-Intron2-3749 + UUUGCACACUGCAGUUAUGU 20 18849 CFTR-Intron2-3750 CAGUGACAGAAACCCAAUUU 20 18850

Table 39C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 2 and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 39C 3rd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-3751 GUUAAUGAAUGAUGGAG 17 18851 CFTR-Intron2-3752 + GCCAUUUCACAUUCCAU 17 18852

Table 39D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 2. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 39D 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron2-3753 + CCAGAUAAUUCUGCAAA 17 18853 CFTR-Intron2-3754 UCCUUUGUGAAGAGAAA 17 18854 CFTR-Intron2-3755 + CUGUAAAAUAGAGAUAA 17 18855 CFTR-Intron2-3756 UUUCACUGUAUCCCCCA 17 18856 CFTR-Intron2-3757 + UAUCUCUCUGAGCCUCA 17 18857 CFTR-Intron2-3758 CAGAGACUCUUGAGUCA 17 18858 CFTR-Intron2-3759 + CCCAGCUACUCAGGAGA 17 18859 CFTR-Intron2-3760 UAGAAGGGCUCUCAUUA 17 18860 CFTR-Intron2-3761 CUUCGUCUCCUGGGUUC 17 18861 CFTR-Intron2-3762 + CUACUCAGGAGACUGAG 17 18862 CFTR-Intron2-3763 CUUGGCCUCCCAAAAUG 17 18863 CFTR-Intron2-3764 AGGUGUGAGCCACUAUG 17 18864 CFTR-Intron2-3765 CUUGGCCUCCCAAAGUG 17 18865 CFTR-Intron2-3766 + CUAUGACUCAAGAGUCU 17 18866 CFTR-Intron2-3767 UGACAGAAACCCAAUUU 17 18867 CFTR-Intron2-3768 AAGAAAACAGAAAGUUU 17 18868 CFTR-Intron2-3769 AUAUUAAACUUUAUUUU 17 18869 CFTR-Intron2-3770 + AAGCCAGAUAAUUCUGCAAA 20 18870 CFTR-Intron2-3771 UAUUCCUUUGUGAAGAGAAA 20 18871 CFTR-Intron2-3772 + UUUCUGUAAAAUAGAGAUAA 20 18872 CFTR-Intron2-3773 + UAUUAUCUCUCUGAGCCUCA 20 18873 CFTR-Intron2-1715 + AGUCCCAGCUACUCAGGAGA 20 16815 CFTR-Intron2-3774 UUAUAGAAGGGCUCUCAUUA 20 18874 CFTR-Intron2-3775 + UCCCAUCUAUUUCCCUCCCC 20 18875 CFTR-Intron2-3776 + UGUAUUUAUUAAGUUAUUGC 20 18876 CFTR-Intron2-3777 AAACUUCGUCUCCUGGGUUC 20 18877 CFTR-Intron2-3778 CCAGUUAAUGAAUGAUGGAG 20 18878 CFTR-Intron2-3779 + CAGCUACUCAGGAGACUGAG 20 18879 CFTR-Intron2-3291 CACCUUGGCCUCCCAAAAUG 20 18391 CFTR-Intron2-3780 UAUAGGUGUGAGCCACUAUG 20 18880 CFTR-Intron2-3352 CGCCUUGGCCUCCCAAAGUG 20 18452 CFTR-Intron2-3781 AGAUCCAUGCUUAGAGAUUG 20 18881 CFTR-Intron2-3782 AUUUUUCAAAGACCUUUAAU 20 18882 CFTR-Intron2-3783 + AAGGUUUUGAAAGCAAAUAU 20 18883 CFTR-Intron2-3784 UUAUGAAGUAAAUCGUGUAU 20 18884 CFTR-Intron2-3785 UAAAAGAAAACAGAAAGUUU 20 18885 CFTR-Intron2-3786 AAGAUAUUAAACUUUAUUUU 20 18886

Table 40A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 40A 1st Tier Target  DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-1 GCUUUCUAGUAUUAGAA 17 18887 CFTR-Intron10-2 GGCCUUUAAACAUUGAA 17 18888 CFTR-Intron10-3 GUAGUAUUAAACCAUAA 17 18889 CFTR-Intron10-4 GUUUACUAGAAAGAUAA 17 18890 CFTR-Intron10-5 GACCUAAGAUAUCCUAA 17 18891 CFTR-Intron10-6 GUAUUAGAAUGGGCUAA 17 18892 CFTR-Intron10-7 GCUGGAUAAGAUUCUAA 17 18893 CFTR-Intron10-8 + GAUCAAUAAUAGAGACA 17 18894 CFTR-Intron10-9 + GUGUUUAAAUAUUCCCA 17 18895 CFTR-Intron10-10 GUGCCACUAGUGAUGCA 17 18896 CFTR-Intron10-11 GUACAAGUCUAGUUUCA 17 18897 CFTR-Intron10-12 GGCUGGUAGUGUGAAGA 17 18898 CFTR-Intron10-13 + GUGAUGCAGACAACAGA 17 18899 CFTR-Intron10-14 + GACUAAAACUGAGUAGA 17 18900 CFTR-Intron10-15 + GGUACAAAUUUCAGGGA 17 18901 CFTR-Intron10-16 + GUCUCUCUAAGGUGUGA 17 18902 CFTR-Intron10-17 + GUUCUUAGGGUGGGAUA 17 18903 CFTR-Intron10-18 GUGUAGGGGUUAGCCUA 17 18904 CFTR-Intron10-19 + GCCUAUCACCUAGGCUA 17 18905 CFTR-Intron10-20 + GUGUGAGGGUCUCUCUA 17 18906 CFTR-Intron10-21 GACUGAAAGCUGGCUUA 17 18907 CFTR-Intron10-22 + GUAUGUAGGAAAACAAC 17 18908 CFTR-Intron10-23 + GUAUUAAGUAUAGCCAC 17 18909 CFTR-Intron10-24 GUGAGAUUAGAGGCCAC 17 18910 CFTR-Intron10-25 GAUGAGCAGAUAAUUAC 17 18911 CFTR-Intron10-26 + GUAUCUCCAAAUAUGCC 17 18912 CFTR-Intron10-27 GAAUGAAUGUGGUAUCC 17 18913 CFTR-Intron10-28 + GACAUCAGUUGGGUUCC 17 18914 CFTR-Intron10-29 + GUUGGAUGAGGGAAUGC 17 18915 CFTR-Intron10-30 + GCUAUUUAAACAGAAUC 17 18916 CFTR-Intron10-31 GACUGACUAUACCUGUC 17 18917 CFTR-Intron10-32 GUCUAUUGUGCCAGUUC 17 18918 CFTR-Intron10-33 + GAAUUGGUACAAAUUUC 17 18919 CFTR-Intron10-34 GAUGAUUCCAAGCUUUC 17 18920 CFTR-Intron10-35 + GAUAUCUUAGGUCAAAG 17 18921 CFTR-Intron10-36 GUCUAGUUUCAAGGAAG 17 18922 CFTR-Intron10-37 + GCUAAAGUAUUACCCAG 17 18923 CFTR-Intron10-38 GGCAUUCUAAGUAUUAG 17 18924 CFTR-Intron10-39 GUCAGAGAAGUAAUCGG 17 18925 CFTR-Intron10-40 GAAGUAAUCGGCGGUGG 17 18926 CFTR-Intron10-41 + GCUACCUUGGUUGGAUG 17 18927 CFTR-Intron10-42 GAUUGUCAUUUUAGCUG 17 18928 CFTR-Intron10-43 + GAAAUGGGGUAUAAGUG 17 18929 CFTR-Intron10-44 GAUGGUAUUGCAGGGUG 17 18930 CFTR-Intron10-45 GAGCCAAAAAUUGGGUG 17 18931 CFTR-Intron10-46 GGCAUCUCACCAGUGUG 17 18932 CFTR-Intron10-47 + GGUCUCUCUAAGGUGUG 17 18933 CFTR-Intron10-48 GGUAAGCUCAAGCAUUG 17 18934 CFTR-Intron10-49 GUAUUUACCAUAUAUUG 17 18935 CFTR-Intron10-50 GGUUUCCACUCAACAAU 17 18936 CFTR-Intron10-51 GCUGGUAGUGUGAAGAU 17 18937 CFTR-Intron10-52 GUGCAAAGCUUUCAGAU 17 18938 CFTR-Intron10-53 GAAGGGUGUUAUCAACU 17 18939 CFTR-Intron10-54 GAAUUGAAUAUGAGACU 17 18940 CFTR-Intron10-55 GGAAGGCAGUGGUCCCU 17 18941 CFTR-Intron10-56 GUGAAAAUAUCACUUCU 17 18942 CFTR-Intron10-57 GGAGCCAAAAAUUGGGU 17 18943 CFTR-Intron10-58 + GGAUUGGCUACCUUGGU 17 18944 CFTR-Intron10-59 GUCACUGUAUUGUCUGU 17 18945 CFTR-Intron10-60 GCAUCUCACCAGUGUGU 17 18946 CFTR-Intron10-61 + GAAGUAGAAGAACUAUU 17 18947 CFTR-Intron10-62 + GUUUGUCUUAGAUUAUU 17 18948 CFTR-Intron10-63 GAUUAGCUUAUAUACUU 17 18949 CFTR-Intron10-64 GAAGGCAGUGGUCCCUU 17 18950 CFTR-Intron10-65 + GAGUGCAUAAAGGUUGAAAA 20 18951 CFTR-Intron10-66 GCUAUUCUGUAGGGAGACAA 20 18952 CFTR-Intron10-67 GAUACUAAAUAAGUUAGCAA 20 18953 CFTR-Intron10-68 GAGGGUUGAUAAGAAGAGAA 20 18954 CFTR-Intron10-69 GCCGUUUACUAGAAAGAUAA 20 18955 CFTR-Intron10-70 GGGUGUAGGGGUUAGCCUAA 20 18956 CFTR-Intron10-71 GGGGCUGGAUAAGAUUCUAA 20 18957 CFTR-Intron10-72 + GGUAUAAGUGUGGAGUGUAA 20 18958 CFTR-Intron10-73 GGAAGAUCCAAUAGGAUUAA 20 18959 CFTR-Intron10-74 GGCUGGCAUAGAGUAAGACA 20 18960 CFTR-Intron10-75 GGCUAUUCUGUAGGGAGACA 20 18961 CFTR-Intron10-76 + GAAGUGUUUAAAUAUUCCCA 20 18962 CFTR-Intron10-77 + GUGCUAUUUAAACAGAAUCA 20 18963 CFTR-Intron10-78 + GGAUUGCUUGAUGUUAUUCA 20 18964 CFTR-Intron10-79 GAUGUACAAGUCUAGUUUCA 20 18965 CFTR-Intron10-80 GGGGGCUGGUAGUGUGAAGA 20 18966 CFTR-Intron10-81 + GCUGUGAUGCAGACAACAGA 20 18967 CFTR-Intron10-82 GCAAGUGCAAAGCUUUCAGA 20 18968 CFTR-Intron10-83 GGCAUAGAGUAAGACAGGGA 20 18969 CFTR-Intron10-84 + GUUGUUCUUAGGGUGGGAUA 20 18970 CFTR-Intron10-85 GGGGUGUAGGGGUUAGCCUA 20 18971 CFTR-Intron10-86 GUCUGGUUUGAAGAACAGUA 20 18972 CFTR-Intron10-87 + GCCAGGUUAAGUUGUUCUUA 20 18973 CFTR-Intron10-88 GAGUUUUAAACAGAAGUAAC 20 18974 CFTR-Intron10-89 + GACUGAAACUCCCCACACAC 20 18975 CFTR-Intron10-90 + GCUAAGAGACUCCUGAAUCC 20 18976 CFTR-Intron10-91 + GUUUUAGUAGAAACCUAAUC 20 18977 CFTR-Intron10-92 GGAUUAGGGAAUGCAGACUC 20 18978 CFTR-Intron10-93 GGAGUCUAUUGUGCCAGUUC 20 18979 CFTR-Intron10-94 + GCUUGACAUCAGUUGGGUUC 20 18980 CFTR-Intron10-95 GAUAAGAUUCUAAAGGAAAG 20 18981 CFTR-Intron10-96 + GGGUCAAUUGUAUUAGCAAG 20 18982 CFTR-Intron10-97 + GGCUUAACCCAUCUAUUAAG 20 18983 CFTR-Intron10-98 + GCAUAUUGGACCAGACACAG 20 18984 CFTR-Intron10-99 GCAUAUGAGAAAAGUCACAG 20 18985 CFTR-Intron10-100 + GCCUAGAUGAUUAUUAAUAG 20 18986 CFTR-Intron10-101 GUAAUCGGCGGUGGAGGUAG 20 18987 CFTR-Intron10-102 + GAUCAAUAAUAGAGACAAGG 20 18988 CFTR-Intron10-103 GUCUAGUUUCAAGGAAGAGG 20 18989 CFTR-Intron10-104 GUUUACUAACUCAAUCUAGG 20 18990 CFTR-Intron10-105 GUCAGAGAAGUAAUCGGCGG 20 18991 CFTR-Intron10-106 GGGCUGGUAGUGUGAAGAUG 20 18992 CFTR-Intron10-107 + GUUACAUAAAAAGAGAGGUG 20 18993 CFTR-Intron10-108 + GAGGGUCUCUCUAAGGUGUG 20 18994 CFTR-Intron10-109 GCUUUGAAGGAAGAUCCAAU 20 18995 CFTR-Intron10-110 GAGCUUUCUAGUAUUAGAAU 20 18996 CFTR-Intron10-111 GGGGCUGGUAGUGUGAAGAU 20 18997 CFTR-Intron10-112 GUCUUUUCCUCUUAAUAGAU 20 18998 CFTR-Intron10-113 GCAGAAGGGUGUUAUCAACU 20 18999 CFTR-Intron10-114 GAAGAAUUGAAUAUGAGACU 20 19000 CFTR-Intron10-115 + GUUACAACAGUCUUUAUACU 20 19001 CFTR-Intron10-116 + GUUACCUGGAUUGGCUACCU 20 19002 CFTR-Intron10-117 + GUUACUCAGUCCAGAAAGCU 20 19003 CFTR-Intron10-118 GGAGUUUACUAACUCAAUCU 20 19004 CFTR-Intron10-119 GAUUAGGGAAUGCAGACUCU 20 19005 CFTR-Intron10-120 + GGAAAGUUGUCCAAGAUAGU 20 19006 CFTR-Intron10-121 GUAUUAGAGGUUAAGGAGGU 20 19007 CFTR-Intron10-122 GGAAGCAGUGCUGCUGCUGU 20 19008 CFTR-Intron10-123 GAAGUCACUGUAUUGUCUGU 20 19009 CFTR-Intron10-124 GUUACCCAAUAAAAAAAAUU 20 19010 CFTR-Intron10-125 GCUUUCAGGAGCCAAAAAUU 20 19011 CFTR-Intron10-126 GGCUGCCUUUUAGUAGUAUU 20 19012 CFTR-Intron10-127 GAGGAAGGCAGUGGUCCCUU 20 19013 CFTR-Intron10-128 GUUUUGGAUGGAGCUUGGUU 20 19014 CFTR-Intron10-129 GGGUUUGAUUAGAUAAAUUU 20 19015 CFTR-Intron10-130 GUUGUUAUCUCUGAAAUUUU 20 19016 CFTR-Intron10-131 + GGGCUCCCCCACCCAAUUUU 20 19017

Table 40B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 40B 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-132 + AGCUAUGCCCUUAAAAA 17 19018 CFTR-Intron10-133 AUCAUCUAGGCUGCAAA 17 19019 CFTR-Intron10-134 ACCUUCAUGUUGAUAAA 17 19020 CFTR-Intron10-135 + UUCCUAAUACUACUAAA 17 19021 CFTR-Intron10-136 UAUUAGAAUGGGCUAAA 17 19022 CFTR-Intron10-137 + UCACGUGGUGUUUUAAA 17 19023 CFTR-Intron10-138 + UACCAUUAUCUACACAA 17 19024 CFTR-Intron10-139 AUUCUGUAGGGAGACAA 17 19025 CFTR-Intron10-140 ACUAAAUAAGUUAGCAA 17 19026 CFTR-Intron10-141 + AGCCAGCUUUCAGUCAA 17 19027 CFTR-Intron10-142 UGUUGAUAAAGGGUCAA 17 19028 CFTR-Intron10-143 ACUGAUGUCAAGCAGAA 17 19029 CFTR-Intron10-144 UUUAGUAGUAUUAGGAA 17 19030 CFTR-Intron10-145 UAAGAAAGACUCCUGAA 17 19031 CFTR-Intron10-146 + AAGCAAAGAGUGCAUAA 17 19032 CFTR-Intron10-147 ACCCAUUGUGUAGAUAA 17 19033 CFTR-Intron10-148 AACCUUCAUGUUGAUAA 17 19034 CFTR-Intron10-149 UUGGUGUAGUUCUAUAA 17 19035 CFTR-Intron10-150 UGUAGGGGUUAGCCUAA 17 19036 CFTR-Intron10-151 + AUAAGUGUGGAGUGUAA 17 19037 CFTR-Intron10-152 AGAUCCAAUAGGAUUAA 17 19038 CFTR-Intron10-153 + UCAACUUUAUCUGUUAA 17 19039 CFTR-Intron10-154 + UACCUUUCAAUGUUUAA 17 19040 CFTR-Intron10-155 UAGCAAUGGUCUAAACA 17 19041 CFTR-Intron10-156 + ACAAUCAAAUGGGAACA 17 19042 CFTR-Intron10-157 + ACCUAUAAGGAAUAACA 17 19043 CFTR-Intron10-158 UGGCAUAGAGUAAGACA 17 19044 CFTR-Intron10-159 UAUUCUGUAGGGAGACA 17 19045 CFTR-Intron10-160 + UUACAAUUCUUAUUACA 17 19046 CFTR-Intron10-161 AUUCCCUCAUCCAACCA 17 19047 CFTR-Intron10-162 + UAAAGACUUCACCCUCA 17 19048 CFTR-Intron10-163 + AAGCCAGCUUUCAGUCA 17 19049 CFTR-Intron10-164 + AUCUAAAAGCUAAUUCA 17 19050 CFTR-Intron10-165 + UUGCUUGAUGUUAUUCA 17 19051 CFTR-Intron10-166 UCUAGUUUCAAGGAAGA 17 19052 CFTR-Intron10-167 AACUGAUGUCAAGCAGA 17 19053 CFTR-Intron10-168 AGUGCAAAGCUUUCAGA 17 19054 CFTR-Intron10-169 + ACCCUUUAUCAACAUGA 17 19055 CFTR-Intron10-170 + CUACCUUGGUUGGAUGA 17 19056 CFTR-Intron10-171 AUGAAAAGCAGCUAUGA 17 19057 CFTR-Intron10-172 UUAAAGAAUGACUGUGA 17 19058 CFTR-Intron10-173 CGGUGUCUUCUGAAAUA 17 19059 CFTR-Intron10-174 + CUAGAUGAUUAUUAAUA 17 19060 CFTR-Intron10-175 ACUAAUUGUAGUACAUA 17 19061 CFTR-Intron10-176 + AAAUUACAGAACCUAUA 17 19062 CFTR-Intron10-177 UGAUCAUUGCCUCACUA 17 19063 CFTR-Intron10-178 AGUGCUCGUAAAGACUA 17 19064 CFTR-Intron10-179 UGACCUAAGAUAUCCUA 17 19065 CFTR-Intron10-180 AAUCGGCGGUGGAGGUA 17 19066 CFTR-Intron10-181 + ACUCUAUUUAGAGUGUA 17 19067 CFTR-Intron10-182 + AGGUUAAGUUGUUCUUA 17 19068 CFTR-Intron10-183 + UAUCAACAUGAAGGUUA 17 19069 CFTR-Intron10-184 CUAAGUAUUAGAGGUUA 17 19070 CFTR-Intron10-185 + CUAUUAUUCAACAUUUA 17 19071 CFTR-Intron10-186 + UCUUUACGAGCACUUUA 17 19072 CFTR-Intron10-187 + CAAGCCUGUAUUGUUUA 17 19073 CFTR-Intron10-188 + CUUACCGUAAUAGCAAC 17 19074 CFTR-Intron10-189 + UCAUCACUUGCCUGAAC 17 19075 CFTR-Intron10-190 + AACCUAUAAGGAAUAAC 17 19076 CFTR-Intron10-191 CUUAUUCUUGUAAUAAC 17 19077 CFTR-Intron10-192 UUUCUGGACUGAGUAAC 17 19078 CFTR-Intron10-193 + UGAAACUCCCCACACAC 17 19079 CFTR-Intron10-194 + CGUAUUUCAGAAGACAC 17 19080 CFTR-Intron10-195 CAUUUCAACUUAUACAC 17 19081 CFTR-Intron10-196 UUCUGUUUAAAUAGCAC 17 19082 CFTR-Intron10-197 AUAGAAUUUUGCAUCAC 17 19083 CFTR-Intron10-198 CUGGCAUAGAGUAAGAC 17 19084 CFTR-Intron10-199 + UGUUCUUCAAACCAGAC 17 19085 CFTR-Intron10-200 AGUGCCUAGCACUUGAC 17 19086 CFTR-Intron10-201 + UACAACAGUCUUUAUAC 17 19087 CFTR-Intron10-202 CAAAUUCCAAGACUUAC 17 19088 CFTR-Intron10-203 CUAAGAACAACUUAACC 17 19089 CFTR-Intron10-204 + CUACUUCCACUACUACC 17 19090 CFTR-Intron10-205 CUAACACCUACCCUACC 17 19091 CFTR-Intron10-206 + UUACUGUGAAUGGUGCC 17 19092 CFTR-Intron10-207 ACCAAGGUAGCCAAUCC 17 19093 CFTR-Intron10-208 + AAGAGACUCCUGAAUCC 17 19094 CFTR-Intron10-209 + UAUAGCUCUGAUAAUCC 17 19095 CFTR-Intron10-210 AAGACAGCUGGCUAUCC 17 19096 CFTR-Intron10-211 + AUUAGCAAGUGGACUCC 17 19097 CFTR-Intron10-212 UUCUUUUGAUAUACUCC 17 19098 CFTR-Intron10-213 UGCCCUUGACUGAAAGC 17 19099 CFTR-Intron10-214 UAAAUUUGGUGUCAGGC 17 19100 CFTR-Intron10-215 UAGUGUGAAGAUGGGGC 17 19101 CFTR-Intron10-216 + UCAUGUUAGACAUAUGC 17 19102 CFTR-Intron10-217 + CAAGACUUCACACCUGC 17 19103 CFTR-Intron10-218 AGCAGACCCAAAUCUGC 17 19104 CFTR-Intron10-219 + AUUUAUCUCGAAAUUGC 17 19105 CFTR-Intron10-220 + UUAGUAGAAACCUAAUC 17 19106 CFTR-Intron10-221 UUAGGGAAUGCAGACUC 17 19107 CFTR-Intron10-222 AGCUGUGCAUUUUCCUC 17 19108 CFTR-Intron10-223 ACUAAGGCUUAUUUCUC 17 19109 CFTR-Intron10-224 UAACUUUUCUUAUUGUC 17 19110 CFTR-Intron10-225 ACCAAAACUUUAUUGUC 17 19111 CFTR-Intron10-226 CUGGCUAUCCAGGAUUC 17 19112 CFTR-Intron10-227 + UGACAUCAGUUGGGUUC 17 19113 CFTR-Intron10-228 + UCAAUUGUAUUAGCAAG 17 19114 CFTR-Intron10-229 AGUAGGCUUCCUAUAAG 17 19115 CFTR-Intron10-230 + UUAACCCAUCUAUUAAG 17 19116 CFTR-Intron10-231 + UAUUGGACCAGACACAG 17 19117 CFTR-Intron10-232 CUAGUUUCAAGGAAGAG 17 19118 CFTR-Intron10-233 + UACCAAAUUGUAUUGAG 17 19119 CFTR-Intron10-234 + ACACCAAAUUUAUUGAG 17 19120 CFTR-Intron10-235 + AAAGUUGUCCAAGAUAG 17 19121 CFTR-Intron10-236 + UUUCCGUGCAUCACUAG 17 19122 CFTR-Intron10-237 CUUGAUCCAGGUAGUAG 17 19123 CFTR-Intron10-238 AUCGGCGGUGGAGGUAG 17 19124 CFTR-Intron10-239 AAGAGAAAGGGGUGUAG 17 19125 CFTR-Intron10-240 UCUCUGGGUGAGAUUAG 17 19126 CFTR-Intron10-241 + AUCAACAUGAAGGUUAG 17 19127 CFTR-Intron10-242 UGUGAGAAAAAGUUUAG 17 19128 CFTR-Intron10-243 AAAUCAGUGCUUUUUCG 17 19129 CFTR-Intron10-244 + CAAUAAUAGAGACAAGG 17 19130 CFTR-Intron10-245 AGUAUUAGAGGUUAAGG 17 19131 CFTR-Intron10-246 UUCAACUUAUACACAGG 17 19132 CFTR-Intron10-247 AUUAGAGGUUAAGGAGG 17 19133 CFTR-Intron10-248 UACUAACUCAAUCUAGG 17 19134 CFTR-Intron10-249 UCGGCGGUGGAGGUAGG 17 19135 CFTR-Intron10-250 AGAGAAGUAAUCGGCGG 17 19136 CFTR-Intron10-251 CAUAGAGUAAGACAGGG 17 19137 CFTR-Intron10-252 + UUAAGUUGUUCUUAGGG 17 19138 CFTR-Intron10-253 AGGAGCCAAAAAUUGGG 17 19139 CFTR-Intron10-254 AGCCAAAAAUUGGGUGG 17 19140 CFTR-Intron10-255 CUGGUAGUGUGAAGAUG 17 19141 CFTR-Intron10-256 UAUCAAUAUCUAAGAUG 17 19142 CFTR-Intron10-257 + AUCUGUUAGUAAUGCUG 17 19143 CFTR-Intron10-258 UUAAGGGCAUAGCUCUG 17 19144 CFTR-Intron10-259 + AACUCAGUACCAUAGUG 17 19145 CFTR-Intron10-260 + CUGUUAGUAAUGCUGUG 17 19146 CFTR-Intron10-261 CAUCUCACCAGUGUGUG 17 19147 CFTR-Intron10-262 CUCUCUUUUAACUAUUG 17 19148 CFTR-Intron10-263 + UGAGUGGAAAUUUUUUG 17 19149 CFTR-Intron10-264 UUUCAGGAGCCAAAAAU 17 19150 CFTR-Intron10-265 + ACCAUUAUCUACACAAU 17 19151 CFTR-Intron10-266 AUGGGCUAAAGGGCAAU 17 19152 CFTR-Intron10-267 CUUUCUAGUAUUAGAAU 17 19153 CFTR-Intron10-268 + AUGGCAUGAGUACGAAU 17 19154 CFTR-Intron10-269 + CCUAGAUGAUUAUUAAU 17 19155 CFTR-Intron10-270 UUUUCCUCUUAAUAGAU 17 19156 CFTR-Intron10-271 + AAAAAAGUUACCUGGAU 17 19157 CFTR-Intron10-272 + UUAUCCAUUAAUCCUAU 17 19158 CFTR-Intron10-273 + AAUGCUUGACCACUUAU 17 19159 CFTR-Intron10-274 UCCCUGUUAUUCCUUAU 17 19160 CFTR-Intron10-275 + ACAACAGUCUUUAUACU 17 19161 CFTR-Intron10-276 + UUGCUUCACCUGCUACU 17 19162 CFTR-Intron10-277 + AUCUUAUAGAGAUUACU 17 19163 CFTR-Intron10-278 + UUUUGAGCCUAUCACCU 17 19164 CFTR-Intron10-279 + ACCUGGAUUGGCUACCU 17 19165 CFTR-Intron10-280 + CACUUGUUGACAGUCCU 17 19166 CFTR-Intron10-281 + ACUCAGUCCAGAAAGCU 17 19167 CFTR-Intron10-282 + ACUCAUAAGGGACCGCU 17 19168 CFTR-Intron10-283 AAAUUUGGUGUCAGGCU 17 19169 CFTR-Intron10-284 + AGCCUAUCACCUAGGCU 17 19170 CFTR-Intron10-285 + UAUACCUGUCAAGUGCU 17 19171 CFTR-Intron10-286 CCUAUUAAUAAUCAUCU 17 19172 CFTR-Intron10-287 UAGGGAAUGCAGACUCU 17 19173 CFTR-Intron10-288 + UAGAGAGAAACAUCUCU 17 19174 CFTR-Intron10-289 CUAAGGCUUAUUUCUCU 17 19175 CFTR-Intron10-290 + UAAUUGCCAGUAAGUCU 17 19176 CFTR-Intron10-291 + AUUUUCUCGGUAUUUCU 17 19177 CFTR-Intron10-292 AUUUUUGACUAUACAGU 17 19178 CFTR-Intron10-293 + UUCUGCUUGACAUCAGU 17 19179 CFTR-Intron10-294 + ACCAAAUUGUAUUGAGU 17 19180 CFTR-Intron10-295 + AAGUUGUCCAAGAUAGU 17 19181 CFTR-Intron10-296 CAAAUAGAGAUGUUAGU 17 19182 CFTR-Intron10-297 + UGUGAAUGGUGCCAGGU 17 19183 CFTR-Intron10-298 UAAUCGGCGGUGGAGGU 17 19184 CFTR-Intron10-299 UGAUGGUAUUGCAGGGU 17 19185 CFTR-Intron10-300 + AUGGUGCCAGGUAGGGU 17 19186 CFTR-Intron10-301 + UAAGUUGUUCUUAGGGU 17 19187 CFTR-Intron10-302 UUGACUAUACAGUGGGU 17 19188 CFTR-Intron10-303 + AAAGCUGUUUCGUAUGU 17 19189 CFTR-Intron10-304 + UCUGUUAGUAAUGCUGU 17 19190 CFTR-Intron10-305 AGCAGUGCUGCUGCUGU 17 19191 CFTR-Intron10-306 UUUUUAGGCUAUUCUGU 17 19192 CFTR-Intron10-307 UUCAGGAGCCAAAAAUU 17 19193 CFTR-Intron10-308 ACCCACUCAAUACAAUU 17 19194 CFTR-Intron10-309 AUGCUAAUAAUACAAUU 17 19195 CFTR-Intron10-310 AAUAUCACCAACUCAUU 17 19196 CFTR-Intron10-311 + AUCUCUGCAAACAUAUU 17 19197 CFTR-Intron10-312 ACUUAACCUGGCAUAUU 17 19198 CFTR-Intron10-313 + CAACUAACAUCUCUAUU 17 19199 CFTR-Intron10-314 UGCCUUUUAGUAGUAUU 17 19200 CFTR-Intron10-315 + CAAUGGUUGUCUGUAUU 17 19201 CFTR-Intron10-316 + AUACUUAGAAUGCCCUU 17 19202 CFTR-Intron10-317 UUGCAGGGUGGGGCCUU 17 19203 CFTR-Intron10-318 AUGUGCAAAAAUAGCUU 17 19204 CFTR-Intron10-319 + CAGGUUAAGUUGUUCUU 17 19205 CFTR-Intron10-320 UUAGUUAGCAUAAAGUU 17 19206 CFTR-Intron10-321 + UCUGCUUGACAUCAGUU 17 19207 CFTR-Intron10-322 + UUAUCAACAUGAAGGUU 17 19208 CFTR-Intron10-323 AGUGCUUUUUCGAGGUU 17 19209 CFTR-Intron10-324 UUGGAUGGAGCUUGGUU 17 19210 CFTR-Intron10-325 + UUCAUGGAAAGCUUGUU 17 19211 CFTR-Intron10-326 UUGUGUACUUGUGAUUU 17 19212 CFTR-Intron10-327 UAUGCACUCUUUGCUUU 17 19213 CFTR-Intron10-328 + UCCUGACAAUAAAGUUU 17 19214 CFTR-Intron10-329 UGGAUGGAGCUUGGUUU 17 19215 CFTR-Intron10-330 AGAGCUAUAUUGUGUUU 17 19216 CFTR-Intron10-331 + CUCCCCCACCCAAUUUU 17 19217 CFTR-Intron10-332 + CAGAGCUAUGCCCUUAAAAA 20 19218 CFTR-Intron10-333 UGCUUCAGAAGUCUAUAAAA 20 19219 CFTR-Intron10-334 AUAAUCAUCUAGGCUGCAAA 20 19220 CFTR-Intron10-335 + CAGCUAAAAUGACAAUCAAA 20 19221 CFTR-Intron10-336 CGUGUUAUUCAGCCAAUAAA 20 19222 CFTR-Intron10-337 CUAACCUUCAUGUUGAUAAA 20 19223 CFTR-Intron10-338 + CCAUUCCUAAUACUACUAAA 20 19224 CFTR-Intron10-339 UAGUAUUAGAAUGGGCUAAA 20 19225 CFTR-Intron10-340 + CCCAUUAUCUUUCUAGUAAA 20 19226 CFTR-Intron10-341 UUAAUGGAUAAGUUGAACAA 20 19227 CFTR-Intron10-342 + UUUUACCAUUAUCUACACAA 20 19228 CFTR-Intron10-343 CUAGGUUUAAUUUUGUACAA 20 19229 CFTR-Intron10-344 + AAGUGUUUAAAUAUUCCCAA 20 19230 CFTR-Intron10-345 + UCAAAAGAAUAAGGCAUCAA 20 19231 CFTR-Intron10-346 + AUAAGCCAGCUUUCAGUCAA 20 19232 CFTR-Intron10-347 CCAACUGAUGUCAAGCAGAA 20 19233 CFTR-Intron10-348 AGAGCUUUCUAGUAUUAGAA 20 19234 CFTR-Intron10-349 + CUAAAACUGAGUAGAAGGAA 20 19235 CFTR-Intron10-350 CCUUUUAGUAGUAUUAGGAA 20 19236 CFTR-Intron10-351 AAUUAAGAAAGACUCCUGAA 20 19237 CFTR-Intron10-352 AGUGGCCUUUAAACAUUGAA 20 19238 CFTR-Intron10-353 AAUGUAGUAUUAAACCAUAA 20 19239 CFTR-Intron10-354 + CUAAAGCAAAGAGUGCAUAA 20 19240 CFTR-Intron10-355 AUAACCCAUUGUGUAGAUAA 20 19241 CFTR-Intron10-356 CCUAACCUUCAUGUUGAUAA 20 19242 CFTR-Intron10-357 AUUUUGGUGUAGUUCUAUAA 20 19243 CFTR-Intron10-358 UUUGACCUAAGAUAUCCUAA 20 19244 CFTR-Intron10-359 CUAGUAUUAGAAUGGGCUAA 20 19245 CFTR-Intron10-360 + UUGGGUAACAAUAAUAUUAA 20 19246 CFTR-Intron10-361 + AAUUCAACUUUAUCUGUUAA 20 19247 CFTR-Intron10-362 AGUUAGCAAUGGUCUAAACA 20 19248 CFTR-Intron10-363 + AUGACAAUCAAAUGGGAACA 20 19249 CFTR-Intron10-364 + AGAACCUAUAAGGAAUAACA 20 19250 CFTR-Intron10-365 AGUUUUAAACAGAAGUAACA 20 19251 CFTR-Intron10-366 UGCAUUCCCUCAUCCAACCA 20 19252 CFTR-Intron10-367 + UACUAAAGACUUCACCCUCA 20 19253 CFTR-Intron10-368 + CAUAAGCCAGCUUUCAGUCA 20 19254 CFTR-Intron10-369 + UAAAUCUAAAAGCUAAUUCA 20 19255 CFTR-Intron10-370 + ACGAAUUGGUACAAAUUUCA 20 19256 CFTR-Intron10-371 AUAAGAUUCUAAAGGAAAGA 20 19257 CFTR-Intron10-372 AAGUCUAGUUUCAAGGAAGA 20 19258 CFTR-Intron10-373 CCCAACUGAUGUCAAGCAGA 20 19259 CFTR-Intron10-374 + ACUGACUAAAACUGAGUAGA 20 19260 CFTR-Intron10-375 + UGGCUACCUUGGUUGGAUGA 20 19261 CFTR-Intron10-376 CCAGUUCAGGCAAGUGAUGA 20 19262 CFTR-Intron10-377 CUUAUGAAAAGCAGCUAUGA 20 19263 CFTR-Intron10-378 UUGUUAAAGAAUGACUGUGA 20 19264 CFTR-Intron10-379 + AGGGUCUCUCUAAGGUGUGA 20 19265 CFTR-Intron10-380 AACCGGUGUCUUCUGAAAUA 20 19266 CFTR-Intron10-381 + AGGAGUAUAUCAAAAGAAUA 20 19267 CFTR-Intron10-382 + AGUCCUCUGUGCUUUGAAUA 20 19268 CFTR-Intron10-383 CCCAUAAAUGUUGAAUAAUA 20 19269 CFTR-Intron10-384 + AGCCUAGAUGAUUAUUAAUA 20 19270 CFTR-Intron10-385 UAUUGAUCAUUGCCUCACUA 20 19271 CFTR-Intron10-386 UAAAGUGCUCGUAAAGACUA 20 19272 CFTR-Intron10-387 CUUUGACCUAAGAUAUCCUA 20 19273 CFTR-Intron10-388 + UGAGCCUAUCACCUAGGCUA 20 19274 CFTR-Intron10-389 AGUAAUCGGCGGUGGAGGUA 20 19275 CFTR-Intron10-390 UGUUUUUAGGCUAUUCUGUA 20 19276 CFTR-Intron10-391 + AGCACUCUAUUUAGAGUGUA 20 19277 CFTR-Intron10-392 UAAGAAGAGAAAGGGGUGUA 20 19278 CFTR-Intron10-393 + CAAUUAGUUUUAUGCCAUUA 20 19279 CFTR-Intron10-394 UUGCAGGAGGUGAGGGAUUA 20 19280 CFTR-Intron10-395 CUUGACUGAAAGCUGGCUUA 20 19281 CFTR-Intron10-396 + CUUUAUCAACAUGAAGGUUA 20 19282 CFTR-Intron10-397 AUUCUAAGUAUUAGAGGUUA 20 19283 CFTR-Intron10-398 + CCCCUAUUAUUCAACAUUUA 20 19284 CFTR-Intron10-399 + UAGUCUUUACGAGCACUUUA 20 19285 CFTR-Intron10-400 AGAAAGAUAAUGGGAGAAAC 20 19286 CFTR-Intron10-401 + UACGAUAUAAGAAAUGAAAC 20 19287 CFTR-Intron10-402 + UUCGUAUGUAGGAAAACAAC 20 19288 CFTR-Intron10-403 + CAGAACCUAUAAGGAAUAAC 20 19289 CFTR-Intron10-404 UAGCUUAUUCUUGUAAUAAC 20 19290 CFTR-Intron10-405 AUGAAACUGUUAUAAUUAAC 20 19291 CFTR-Intron10-406 + CUCCGUAUUUCAGAAGACAC 20 19292 CFTR-Intron10-407 UAUCAUUUCAACUUAUACAC 20 19293 CFTR-Intron10-408 + UUAGUAUUAAGUAUAGCCAC 20 19294 CFTR-Intron10-409 UGGGUGAGAUUAGAGGCCAC 20 19295 CFTR-Intron10-410 UGAUUCUGUUUAAAUAGCAC 20 19296 CFTR-Intron10-411 AGUAUAGAAUUUUGCAUCAC 20 19297 CFTR-Intron10-412 AGGCUGGCAUAGAGUAAGAC 20 19298 CFTR-Intron10-413 + UACUGUUCUUCAAACCAGAC 20 19299 CFTR-Intron10-414 + UGUUACAACAGUCUUUAUAC 20 19300 CFTR-Intron10-415 AUUGAUGAGCAGAUAAUUAC 20 19301 CFTR-Intron10-416 UUACAAAUUCCAAGACUUAC 20 19302 CFTR-Intron10-417 + UACAAAUAUUGACUAUUUAC 20 19303 CFTR-Intron10-418 ACCCUAAGAACAACUUAACC 20 19304 CFTR-Intron10-419 + AUACUACUUCCACUACUACC 20 19305 CFTR-Intron10-420 ACACUAACACCUACCCUACC 20 19306 CFTR-Intron10-421 + AGAUACUAAAAAAAGUUACC 20 19307 CFTR-Intron10-422 + UCUUUACUGUGAAUGGUGCC 20 19308 CFTR-Intron10-423 CCAACCAAGGUAGCCAAUCC 20 19309 CFTR-Intron10-424 + CAAUAUAGCUCUGAUAAUCC 20 19310 CFTR-Intron10-425 AGUGAAUGAAUGUGGUAUCC 20 19311 CFTR-Intron10-426 + UGUAUUAGCAAGUGGACUCC 20 19312 CFTR-Intron10-427 + CUUGACAUCAGUUGGGUUCC 20 19313 CFTR-Intron10-428 AGUAAGGAGGUCACUGAGGC 20 19314 CFTR-Intron10-429 AGUUUCAAGGAAGAGGGGGC 20 19315 CFTR-Intron10-430 UGGUAGUGUGAAGAUGGGGC 20 19316 CFTR-Intron10-431 + UUGGUUGGAUGAGGGAAUGC 20 19317 CFTR-Intron10-432 + UUUUCAUGUUAGACAUAUGC 20 19318 CFTR-Intron10-433 + AGUGCUAUUUAAACAGAAUC 20 19319 CFTR-Intron10-434 AAAAGCUGUGCAUUUUCCUC 20 19320 CFTR-Intron10-435 AAGACUAAGGCUUAUUUCUC 20 19321 CFTR-Intron10-436 UGGGACUGACUAUACCUGUC 20 19322 CFTR-Intron10-437 + AAUAGAGACAAGGUGGUGUC 20 19323 CFTR-Intron10-438 CACUCAAUAAAUUUGGUGUC 20 19324 CFTR-Intron10-439 UUCUAACUUUUCUUAUUGUC 20 19325 CFTR-Intron10-440 AGGACCAAAACUUUAUUGUC 20 19326 CFTR-Intron10-441 CAGCUGGCUAUCCAGGAUUC 20 19327 CFTR-Intron10-442 + UAUUAAGAGGAAAAGACUUC 20 19328 CFTR-Intron10-443 + UACGAAUUGGUACAAAUUUC 20 19329 CFTR-Intron10-444 CUUACUGGCAAUUAAAUUUC 20 19330 CFTR-Intron10-445 + UUGAUAAAUAAUUGCCUUUC 20 19331 CFTR-Intron10-446 + CCUAAAAACAUUAGCCAAAG 20 19332 CFTR-Intron10-447 + UAGGAUAUCUUAGGUCAAAG 20 19333 CFTR-Intron10-448 + UAGGGUGGGAUAUGGAGAAG 20 19334 CFTR-Intron10-449 CAAGUCUAGUUUCAAGGAAG 20 19335 CFTR-Intron10-450 UUUCCAUAUUCAAAGCACAG 20 19336 CFTR-Intron10-451 + ACAGCUAAAGUAUUACCCAG 20 19337 CFTR-Intron10-452 AGUCUAUAUUUGUUUUCCAG 20 19338 CFTR-Intron10-453 + UGCUAUUUAAACAGAAUCAG 20 19339 CFTR-Intron10-454 + AUAUUGUUACAUAAAAAGAG 20 19340 CFTR-Intron10-455 AGUCUAGUUUCAAGGAAGAG 20 19341 CFTR-Intron10-456 + AAUUACCAAAUUGUAUUGAG 20 19342 CFTR-Intron10-457 + CUGACACCAAAUUUAUUGAG 20 19343 CFTR-Intron10-458 CCAUAAAUGUUGAAUAAUAG 20 19344 CFTR-Intron10-459 + UGGAAAGUUGUCCAAGAUAG 20 19345 CFTR-Intron10-460 + ACUUUUCCGUGCAUCACUAG 20 19346 CFTR-Intron10-461 UGGCUUGAUCCAGGUAGUAG 20 19347 CFTR-Intron10-462 AUUUCUCUGGGUGAGAUUAG 20 19348 CFTR-Intron10-463 AAGGGCAUUCUAAGUAUUAG 20 19349 CFTR-Intron10-464 AGCUAUGAAGGCAGAGUUAG 20 19350 CFTR-Intron10-465 + UUUAUCAACAUGAAGGUUAG 20 19351 CFTR-Intron10-466 AUAAAAUCAGUGCUUUUUCG 20 19352 CFTR-Intron10-467 CUAAGUAUUAGAGGUUAAGG 20 19353 CFTR-Intron10-468 CAUUUCAACUUAUACACAGG 20 19354 CFTR-Intron10-469 + UUGUUACAUAAAAAGAGAGG 20 19355 CFTR-Intron10-470 AGUAUUAGAGGUUAAGGAGG 20 19356 CFTR-Intron10-471 UAAUCGGCGGUGGAGGUAGG 20 19357 CFTR-Intron10-472 ACUGUCAGAGAAGUAAUCGG 20 19358 CFTR-Intron10-473 AUUCUGUAGGGAGACAAGGG 20 19359 CFTR-Intron10-474 UGGCAUAGAGUAAGACAGGG 20 19360 CFTR-Intron10-475 + AGGUUAAGUUGUUCUUAGGG 20 19361 CFTR-Intron10-476 UUCAGGAGCCAAAAAUUGGG 20 19362 CFTR-Intron10-477 AGAGAAGUAAUCGGCGGUGG 20 19363 CFTR-Intron10-478 AGGAGCCAAAAAUUGGGUGG 20 19364 CFTR-Intron10-479 ACAAAGCUAGUGAAUGAAUG 20 19365 CFTR-Intron10-480 AUUUAUCAAUAUCUAAGAUG 20 19366 CFTR-Intron10-481 + UUGGCUACCUUGGUUGGAUG 20 19367 CFTR-Intron10-482 + CCUAUUAUUCAACAUUUAUG 20 19368 CFTR-Intron10-483 + CACGAAUAUAUUCUUUUAUG 20 19369 CFTR-Intron10-484 UUUGAUUGUCAUUUUAGCUG 20 19370 CFTR-Intron10-485 + AUCAUCUGUUAGUAAUGCUG 20 19371 CFTR-Intron10-486 UUUUUAAGGGCAUAGCUCUG 20 19372 CFTR-Intron10-487 + AAGGAAAUGGGGUAUAAGUG 20 19373 CFTR-Intron10-488 + UAAAACUCAGUACCAUAGUG 20 19374 CFTR-Intron10-489 CAGGAGCCAAAAAUUGGGUG 20 19375 CFTR-Intron10-490 + CAUCUGUUAGUAAUGCUGUG 20 19376 CFTR-Intron10-491 UAUGGCAUCUCACCAGUGUG 20 19377 CFTR-Intron10-492 UGGCAUCUCACCAGUGUGUG 20 19378 CFTR-Intron10-493 UACGGUAAGCUCAAGCAUUG 20 19379 CFTR-Intron10-494 UUGGUAUUUACCAUAUAUUG 20 19380 CFTR-Intron10-495 UUGCUCUCUUUUAACUAUUG 20 19381 CFTR-Intron10-496 + UAUUGAGUGGAAAUUUUUUG 20 19382 CFTR-Intron10-497 UGCUUUCAGGAGCCAAAAAU 20 19383 CFTR-Intron10-498 + AGCUAAAAUGACAAUCAAAU 20 19384 CFTR-Intron10-499 AGAAUGGGCUAAAGGGCAAU 20 19385 CFTR-Intron10-500 + UGUAUGGCAUGAGUACGAAU 20 19386 CFTR-Intron10-501 CCGUUUACUAGAAAGAUAAU 20 19387 CFTR-Intron10-502 AAUACUGUCAGAGAAGUAAU 20 19388 CFTR-Intron10-503 + CAGCCUAGAUGAUUAUUAAU 20 19389 CFTR-Intron10-504 CAAGUGCAAAGCUUUCAGAU 20 19390 CFTR-Intron10-505 + CUAAAAAAAGUUACCUGGAU 20 19391 CFTR-Intron10-506 + UCUUUGUGUUAACAAAAUAU 20 19392 CFTR-Intron10-507 + AACUUAUCCAUUAAUCCUAU 20 19393 CFTR-Intron10-508 + ACAAAUGCUUGACCACUUAU 20 19394 CFTR-Intron10-509 + CCCUAUUAUUCAACAUUUAU 20 19395 CFTR-Intron10-510 + UUCUUUAACAAACCUUUUAU 20 19396 CFTR-Intron10-511 AGCUUAUUCUUGUAAUAACU 20 19397 CFTR-Intron10-512 + CACUUGCUUCACCUGCUACU 20 19398 CFTR-Intron10-513 + AAAAUCUUAUAGAGAUUACU 20 19399 CFTR-Intron10-514 + UUUUUUUGAGCCUAUCACCU 20 19400 CFTR-Intron10-515 AGAGGAAGGCAGUGGUCCCU 20 19401 CFTR-Intron10-516 + AGGCACUUGUUGACAGUCCU 20 19402 CFTR-Intron10-517 AACAGGUUUUGGAUGGAGCU 20 19403 CFTR-Intron10-518 + AAAACUCAUAAGGGACCGCU 20 19404 CFTR-Intron10-519 AAUAAAUUUGGUGUCAGGCU 20 19405 CFTR-Intron10-520 + UUGAGCCUAUCACCUAGGCU 20 19406 CFTR-Intron10-521 UUCAAAUUAUUUCUACUGCU 20 19407 CFTR-Intron10-522 + UAAUAUACCUGUCAAGUGCU 20 19408 CFTR-Intron10-523 UCCCCUAUUAAUAAUCAUCU 20 19409 CFTR-Intron10-524 UCUUGCUUUUCCCACUAUCU 20 19410 CFTR-Intron10-525 AGACUAAGGCUUAUUUCUCU 20 19411 CFTR-Intron10-526 + AUUUAAUUGCCAGUAAGUCU 20 19412 CFTR-Intron10-527 + AAUAAUUUGAACAACAUUCU 20 19413 CFTR-Intron10-528 UAUGUGAAAAUAUCACUUCU 20 19414 CFTR-Intron10-529 + CCCUUCUGCUUGACAUCAGU 20 19415 CFTR-Intron10-530 + AGUCAGUUUUAUUUUUCAGU 20 19416 CFTR-Intron10-531 + UGUACAUUUUCCUAAUGAGU 20 19417 CFTR-Intron10-532 + AUUACCAAAUUGUAUUGAGU 20 19418 CFTR-Intron10-533 AGUAGUGGAAGUAGUAUAGU 20 19419 CFTR-Intron10-534 + UACUGUGAAUGGUGCCAGGU 20 19420 CFTR-Intron10-535 + UGUUACAUAAAAAGAGAGGU 20 19421 CFTR-Intron10-536 AAGUAAUCGGCGGUGGAGGU 20 19422 CFTR-Intron10-537 UCAGGAGCCAAAAAUUGGGU 20 19423 CFTR-Intron10-538 + CCUGGAUUGGCUACCUUGGU 20 19424 CFTR-Intron10-539 + UUAAAAGCUGUUUCGUAUGU 20 19425 CFTR-Intron10-540 + UCAUCUGUUAGUAAUGCUGU 20 19426 CFTR-Intron10-541 AUGUUUUUAGGCUAUUCUGU 20 19427 CFTR-Intron10-542 AUGGCAUCUCACCAGUGUGU 20 19428 CFTR-Intron10-543 CUUACCCACUCAAUACAAUU 20 19429 CFTR-Intron10-544 AAAAAUAUCACCAACUCAUU 20 19430 CFTR-Intron10-545 + AAGAUCUCUGCAAACAUAUU 20 19431 CFTR-Intron10-546 ACAACUUAACCUGGCAUAUU 20 19432 CFTR-Intron10-547 + AUCCAACUAACAUCUCUAUU 20 19433 CFTR-Intron10-548 + CAUCAAUGGUUGUCUGUAUU 20 19434 CFTR-Intron10-549 CAGAAGUAACAGGGCCACUU 20 19435 CFTR-Intron10-550 AUAGAUUAGCUUAUAUACUU 20 19436 CFTR-Intron10-551 + CUAAUACUUAGAAUGCCCUU 20 19437 CFTR-Intron10-552 UAGAUGUGCAAAAAUAGCUU 20 19438 CFTR-Intron10-553 + UGCCAGGUUAAGUUGUUCUU 20 19439 CFTR-Intron10-554 + CCUUCUGCUUGACAUCAGUU 20 19440 CFTR-Intron10-555 + CCUUUAUCAACAUGAAGGUU 20 19441 CFTR-Intron10-556 AUCAGUGCUUUUUCGAGGUU 20 19442 CFTR-Intron10-557 + UAAUUCAUGGAAAGCUUGUU 20 19443 CFTR-Intron10-558 CAUUUGUGUACUUGUGAUUU 20 19444 CFTR-Intron10-559 + AGAUCUCUGCAAACAUAUUU 20 19445 CFTR-Intron10-560 CUUUAUGCACUCUUUGCUUU 20 19446 CFTR-Intron10-561 + UUCUCCUGACAAUAAAGUUU 20 19447 CFTR-Intron10-562 AUAAUGGGAGAAACAGGUUU 20 19448 CFTR-Intron10-563 UUUUGGAUGGAGCUUGGUUU 20 19449 CFTR-Intron10-564 AUCAGAGCUAUAUUGUGUUU 20 19450 CFTR-Intron10-565 CCACUUUGGCUAAUGUUUUU 20 19451

Table 40C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 10 and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 40C 3rd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-566 + GACCAUCCCGGCUAAAA 17 19452 CFTR-Intron10-567 GUUGAUAAGAAGAGAAA 17 19453 CFTR-Intron10-568 GAUGUUUAUUUAUGAAA 17 19454 CFTR-Intron10-569 GUUAUUCAGCCAAUAAA 17 19455 CFTR-Intron10-570 GGUUUAAUUUUGUACAA 17 19456 CFTR-Intron10-571 + GACUAAUCACCUCCCAA 17 19457 CFTR-Intron10-572 + GUUCUCACAUGGCAGAA 17 19458 CFTR-Intron10-573 GGUUGAUAAGAAGAGAA 17 19459 CFTR-Intron10-574 + GAGGGAAUGCAGGAGAA 17 19460 CFTR-Intron10-575 + GGGAGGCUGAAGCGGAA 17 19461 CFTR-Intron10-576 + GGAUUUCAACAUAUGAA 17 19462 CFTR-Intron10-577 + GGUAACAAUAAUAUUAA 17 19463 CFTR-Intron10-578 GACCAGCGUGGGCAACA 17 19464 CFTR-Intron10-579 + GUACAGUGGUGCAAUCA 17 19465 CFTR-Intron10-580 GAAGGAAGGAAGUAAGA 17 19466 CFTR-Intron10-581 GAAAGCAAUAGUAGAGA 17 19467 CFTR-Intron10-582 GUAGGAGGAAGGAAGGA 17 19468 CFTR-Intron10-583 GGAAGUAGGAGGAAGGA 17 19469 CFTR-Intron10-584 GAAAAAGAAAGAGAGGA 17 19470 CFTR-Intron10-585 GAAAGGAAGUAGGAGGA 17 19471 CFTR-Intron10-586 + GUCCCAGCUACUUGGGA 17 19472 CFTR-Intron10-587 GUAUUCUAUCAUAUGGA 17 19473 CFTR-Intron10-588 GAGAAACAGGUUUUGGA 17 19474 CFTR-Intron10-589 GUUCAGGCAAGUGAUGA 17 19475 CFTR-Intron10-590 + GGGUGAGGGUCUCUCUA 17 19476 CFTR-Intron10-591 + GUGAAUGGUGCCAGGUA 17 19477 CFTR-Intron10-592 GAAGAGAAAGGGGUGUA 17 19478 CFTR-Intron10-593 + GAAAAAAAAUUCAAAAC 17 19479 CFTR-Intron10-594 + GAUAUAAGAAAUGAAAC 17 19480 CFTR-Intron10-595 GUAUUUUUAGUAGAGAC 17 19481 CFTR-Intron10-596 + GGAGAAUGGCGUGAACC 17 19482 CFTR-Intron10-597 + GAGAAUGGCGUGAACCC 17 19483 CFTR-Intron10-598 + GUCUCACUCUGUCACCC 17 19484 CFTR-Intron10-599 GUCUUACUCUGUCACCC 17 19485 CFTR-Intron10-600 + GAGAAUUGCUUGAGCCC 17 19486 CFTR-Intron10-601 GUCUCGCUCUGUCGCCC 17 19487 CFTR-Intron10-602 + GCCACUGCACUCCAGCC 17 19488 CFTR-Intron10-603 + GGAGAAUUGCUUGAGCC 17 19489 CFTR-Intron10-604 GCCACUGCACUCUAGCC 17 19490 CFTR-Intron10-605 + GUUUCACUGUGUUAGCC 17 19491 CFTR-Intron10-606 GUUUCACCGUUUUAGCC 17 19492 CFTR-Intron10-607 GCGCCCGCCACUACGCC 17 19493 CFTR-Intron10-608 GCGUGAGCCACCGCGCC 17 19494 CFTR-Intron10-609 GUUUCACCAUGUUGGCC 17 19495 CFTR-Intron10-610 GGAGAUCAAGACCAUCC 17 19496 CFTR-Intron10-611 + GGAGAUCGAGACCAUCC 17 19497 CFTR-Intron10-612 GUGAAUUGCUUGAGUCC 17 19498 CFTR-Intron10-613 GGUUUCACCGUUUUAGC 17 19499 CFTR-Intron10-614 GGCUGGAGUGCAGUGGC 17 19500 CFTR-Intron10-615 + GCACCCGCCAUCACGUC 17 19501 CFTR-Intron10-616 + GGGCGGAUCACGAGGUC 17 19502 CFTR-Intron10-617 GCAUGAGCCACUGUGUC 17 19503 CFTR-Intron10-618 + GGUGGGAUAUGGAGAAG 17 19504 CFTR-Intron10-619 + GUAAUAGCAACAGGAAG 17 19505 CFTR-Intron10-620 GAUUUUUGACUAUACAG 17 19506 CFTR-Intron10-621 GAGUUAGAGGAAGGCAG 17 19507 CFTR-Intron10-622 + GUUUGUGUUUUUUGUAG 17 19508 CFTR-Intron10-623 + GAGGCGGGCGGAUCACG 17 19509 CFTR-Intron10-624 GAGUCAAAAAUUAUACG 17 19510 CFTR-Intron10-625 GGAGUUUGAGACCAGCG 17 19511 CFTR-Intron10-626 GAACAAAGACUUGCAGG 17 19512 CFTR-Intron10-627 + GGCGUGAACCCGGGAGG 17 19513 CFTR-Intron10-628 GGAAGAAAGGAAGUAGG 17 19514 CFTR-Intron10-629 GUGAUGGUAUUGCAGGG 17 19515 CFTR-Intron10-630 GAAGAAAGAAGGAAAUG 17 19516 CFTR-Intron10-631 GAGGUGAUUAGUCCAUG 17 19517 CFTR-Intron10-632 + GAGGCAGGCAGAUCAUG 17 19518 CFTR-Intron10-633 + GAAUAUAUUCUUUUAUG 17 19519 CFTR-Intron10-634 + GUAGCAAAUGAUAAAAU 17 19520 CFTR-Intron10-635 GUUUACUAACUCAAUCU 17 19521 CFTR-Intron10-636 + GUGCAGUGGCGCGAUCU 17 19522 CFTR-Intron10-637 GCACAGUGGUGCGAUCU 17 19523 CFTR-Intron10-638 GUGCAGUGGCGGGAUCU 17 19524 CFTR-Intron10-639 GCUGUGCAUUUUCCUCU 17 19525 CFTR-Intron10-640 GAGUUUGAGACCAGCGU 17 19526 CFTR-Intron10-641 + GUGUUUUUUGUAGAGGU 17 19527 CFTR-Intron10-642 GUACUACUGUAAUAAUU 17 19528 CFTR-Intron10-643 GCAGGAGGUGAGGGAUU 17 19529 CFTR-Intron10-644 GUUAUCUCUGAAAUUUU 17 19530 CFTR-Intron10-645 + GAAUGCAGGAGAAUGGAAAA 20 19531 CFTR-Intron10-646 + GUGUUCUCACAUGGCAGAAA 20 19532 CFTR-Intron10-647 + GCAUCACGUGGUGUUUUAAA 20 19533 CFTR-Intron10-648 + GGGAGGCUGAGGCAGGAGAA 20 19534 CFTR-Intron10-649 + GAUGAGGGAAUGCAGGAGAA 20 19535 CFTR-Intron10-650 GGGAGACAAGGGAGGAAGCA 20 19536 CFTR-Intron10-651 + GGCUGGGAAGUCCAAGAUCA 20 19537 CFTR-Intron10-652 GAAGUAGGAGGAAGGAAGGA 20 19538 CFTR-Intron10-653 GAAGAAAGGAAGUAGGAGGA 20 19539 CFTR-Intron10-654 + GUAGUCCCAGCUACUUGGGA 20 19540 CFTR-Intron10-655 GGGAGGUGAUUAGUCCAUGA 20 19541 CFTR-Intron10-656 GACUGUUUAUGUUAUCUGUA 20 19542 CFTR-Intron10-657 GCCACUUCCUGUUGCUAUUA 20 19543 CFTR-Intron10-658 GUGUGUAUAUGUGUGUAUUA 20 19544 CFTR-Intron10-659 + GUUCAAGCCUGUAUUGUUUA 20 19545 CFTR-Intron10-660 + GAGCUUACCGUAAUAGCAAC 20 19546 CFTR-Intron10-661 + GCAGGAGAAUGGCGUGAACC 20 19547 CFTR-Intron10-662 GCAUAUAUAUAUUUUUAACC 20 19548 CFTR-Intron10-663 GACAGAGUCUUACUGUCACC 20 19549 CFTR-Intron10-664 GGAGUCUCGCUCUGUCGCCC 20 19550 CFTR-Intron10-665 + GCAGGAGAAUUGCUUGAGCC 20 19551 CFTR-Intron10-666 + GGAGUUUCACUGUGUUAGCC 20 19552 CFTR-Intron10-667 GGGGUUUCACCGUUUUAGCC 20 19553 CFTR-Intron10-668 GGGGUUUCACCAUGUUGGCC 20 19554 CFTR-Intron10-669 + GAUGUAUCUCCAAAUAUGCC 20 19555 CFTR-Intron10-670 GGAUGCCCUUGACUGAAAGC 20 19556 CFTR-Intron10-671 GAACACAGCAGGAAGACAGC 20 19557 CFTR-Intron10-672 GCCUCACCCUCCCAAGUAGC 20 19558 CFTR-Intron10-673 GCCUCAGCCUCCCAAGUAGC 20 19559 CFTR-Intron10-674 GGAAGAGUCUUCCAAGUAGC 20 19560 CFTR-Intron10-675 + GCCUCAGCCUCCCGAGUAGC 20 19561 CFTR-Intron10-676 + GUUUGCCAUGUUGCCCACGC 20 19562 CFTR-Intron10-677 GAGUCUUACUGUCACCAGGC 20 19563 CFTR-Intron10-678 GCACUUUUGGAGGCAGAGGC 20 19564 CFTR-Intron10-679 + GCACUUUGGGAGGCCGAGGC 20 19565 CFTR-Intron10-680 GCUACUCGGGAGGCUGAGGC 20 19566 CFTR-Intron10-681 + GCUACUUGGGAGGCUGAGGC 20 19567 CFTR-Intron10-682 + GCUACUUGGGAGGGUGAGGC 20 19568 CFTR-Intron10-683 + GAUUUCAACAUAUGAAUGGC 20 19569 CFTR-Intron10-684 + GUGCAAGACUUCACACCUGC 20 19570 CFTR-Intron10-685 GCUUCAGCCUCCCAAAGUGC 20 19571 CFTR-Intron10-686 GCCUCGGCCUCCCAAAGUGC 20 19572 CFTR-Intron10-687 GCCCGUAGUCCCAGCUACUC 20 19573 CFTR-Intron10-688 + GGCGGGCGGAUCACGAGGUC 20 19574 CFTR-Intron10-689 + GAAUUUAUUUCUCACAGUUC 20 19575 CFTR-Intron10-690 + GUGUGUGUGUGUCCUUGUUC 20 19576 CFTR-Intron10-691 GGGUUGAUAAGAAGAGAAAG 20 19577 CFTR-Intron10-692 GAUCACCUGAGCCUGAGAAG 20 19578 CFTR-Intron10-693 GAAAGAAGGAAGGAAGUAAG 20 19579 CFTR-Intron10-694 GUCACCAGGCUGGAGCACAG 20 19580 CFTR-Intron10-695 GUGGAUUUUUGACUAUACAG 20 19581 CFTR-Intron10-696 GCAGAGUUAGAGGAAGGCAG 20 19582 CFTR-Intron10-697 + GCCGAGGCGGGCGGAUCACG 20 19583 CFTR-Intron10-698 GUGGAGUCAAAAAUUAUACG 20 19584 CFTR-Intron10-699 + GAAAUGAAACAGGCCGGGCG 20 19585 CFTR-Intron10-700 GAGAAUGGCGUGAACCCAGG 20 19586 CFTR-Intron10-701 + GUUUGUGUUUUUUGUAGAGG 20 19587 CFTR-Intron10-702 + GAGAAUGGCGUGAACCCGGG 20 19588 CFTR-Intron10-703 + GAGAAUUGCUUGAGCCCGGG 20 19589 CFTR-Intron10-704 GUUCAGGCAAGUGAUGAUGG 20 19590 CFTR-Intron10-705 + GCCGAGGCAGGCAGAUCAUG 20 19591 CFTR-Intron10-706 GAACAGUAAGGAGGUCACUG 20 19592 CFTR-Intron10-707 GGUGAUGGUAUUGCAGGGUG 20 19593 CFTR-Intron10-708 GGCUCAAAAAAAAAAAAAAU 20 19594 CFTR-Intron10-709 GCACCACUGUACCCUAGCCU 20 19595 CFTR-Intron10-710 GCGCCACUGCACUCUAGCCU 20 19596 CFTR-Intron10-711 GGAGCACAGUGGUGCGAUCU 20 19597 CFTR-Intron10-712 GGAGUGCAGUGGCGGGAUCU 20 19598 CFTR-Intron10-713 GCUACUUGGGAGGCUGAGGU 20 19599 CFTR-Intron10-714 + GGUUAAGUUGUUCUUAGGGU 20 19600 CFTR-Intron10-715 GAGACGGGGUUUCACCAUGU 20 19601 CFTR-Intron10-716 GCCUCGGCCUCCCAAAGUGU 20 19602 CFTR-Intron10-717 GCAAUGCUAAUAAUACAAUU 20 19603 CFTR-Intron10-718 + GAUCAAGGUGCCAGCAGAUU 20 19604 CFTR-Intron10-719 + GUUUCCAAAUUUUUUUUAUU 20 19605 CFTR-Intron10-720 + GCCUGUAGUCCCAGCUACUU 20 19606 CFTR-Intron10-721 GUAUUGCAGGGUGGGGCCUU 20 19607 CFTR-Intron10-722 + GCCUGUAAUCCCAACACUUU 20 19608 CFTR-Intron10-723 + GCCUAUAAACCCAGCACUUU 20 19609 CFTR-Intron10-724 + GCCUGUAAUCCCAGCACUUU 20 19610 CFTR-Intron10-725 GAACACUUUAUAGUUUUUUU 20 19611

Table 40D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 10. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. pyogenes Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 40D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-726 + AACAAAGAAACAAAAAA 17 19612 CFTR-Intron10-727 + UAUGAUUUUAUGAAAAA 17 19613 CFTR-Intron10-728 + UGCAGGAGAAUGGAAAA 17 19614 CFTR-Intron10-729 + UGCAUAAAGGUUGAAAA 17 19615 CFTR-Intron10-730 UUCAGAAGUCUAUAAAA 17 19616 CFTR-Intron10-731 AAAGAAAAAACAGCAAA 17 19617 CFTR-Intron10-732 + AGUAAAAAAAAAUCAAA 17 19618 CFTR-Intron10-733 + CUAAAAUGACAAUCAAA 17 19619 CFTR-Intron10-734 + AAAAGCUGAAAGUCAAA 17 19620 CFTR-Intron10-735 + AUUCAAUGAAAAAGAAA 17 19621 CFTR-Intron10-736 + UUCUCACAUGGCAGAAA 17 19622 CFTR-Intron10-737 UAAACACUUCUGAGAAA 17 19623 CFTR-Intron10-738 + UAAACAAACAAAGGAAA 17 19624 CFTR-Intron10-739 + AUUAUCUUUCUAGUAAA 17 19625 CFTR-Intron10-740 + ACCAAAUAAACAAACAA 17 19626 CFTR-Intron10-741 AUGGAUAAGUUGAACAA 17 19627 CFTR-Intron10-742 AUUAGGAAAAUGUACAA 17 19628 CFTR-Intron10-743 + UGUUUAAAUAUUCCCAA 17 19629 CFTR-Intron10-744 + AAAGAAUAAGGCAUCAA 17 19630 CFTR-Intron10-745 + AAAUAUAUUCAAAAGAA 17 19631 CFTR-Intron10-746 + UGAGAGACAGUAAAGAA 17 19632 CFTR-Intron10-747 AAGGAAAUGAGGAAGAA 17 19633 CFTR-Intron10-748 + AGGCUGAGGCAGGAGAA 17 19634 CFTR-Intron10-749 + AAACUGAGUAGAAGGAA 17 19635 CFTR-Intron10-750 + UUUCUCUUUACUGUGAA 17 19636 CFTR-Intron10-751 + AAGAAAAGUAUCAAUAA 17 19637 CFTR-Intron10-752 + CAGUGACUUCAUAAUAA 17 19638 CFTR-Intron10-753 + AUAGAGAAAACUCAUAA 17 19639 CFTR-Intron10-754 + ACAAAAAUUAAAACUAA 17 19640 CFTR-Intron10-755 + UCUAGAAAACAAUGUAA 17 19641 CFTR-Intron10-756 AGAUAAAGUUGAAUUAA 17 19642 CFTR-Intron10-757 + AAGCCUGUAUUGUUUAA 17 19643 CFTR-Intron10-758 AUUUUGACCAUUUUUAA 17 19644 CFTR-Intron10-759 + UACCAUCCUGGCCAACA 17 19645 CFTR-Intron10-760 UUAUAGCAGCCUGAACA 17 19646 CFTR-Intron10-761 UUUAAACAGAAGUAACA 17 19647 CFTR-Intron10-762 + AGAGAGAACUGCUCACA 17 19648 CFTR-Intron10-763 + CCUGCUGUGUUCUCACA 17 19649 CFTR-Intron10-764 UGAAAUCCUAAUUCCCA 17 19650 CFTR-Intron10-765 UUUAUUUUUAUAUUCCA 17 19651 CFTR-Intron10-766 AGACAAGGGAGGAAGCA 17 19652 CFTR-Intron10-767 + UCAACAUAUGAAUGGCA 17 19653 CFTR-Intron10-768 UACAGGCUUGAACUGCA 17 19654 CFTR-Intron10-769 AAGGUGAUGGUAUUGCA 17 19655 CFTR-Intron10-770 + CUAUUUAAACAGAAUCA 17 19656 CFTR-Intron10-771 + UGGGAAGUCCAAGAUCA 17 19657 CFTR-Intron10-772 + UUCACUAAAAUAAUUCA 17 19658 CFTR-Intron10-773 + UAUAUUUUAUGCAUUCA 17 19659 CFTR-Intron10-774 AUAAGCCACACAGUUCA 17 19660 CFTR-Intron10-775 + UUGAGCCCAGGAGUUCA 17 19661 CFTR-Intron10-776 + AAUUGGUACAAAUUUCA 17 19662 CFTR-Intron10-777 AGAGGAAGGAAGAAAGA 17 19663 CFTR-Intron10-778 AGAUUCUAAAGGAAAGA 17 19664 CFTR-Intron10-779 AAGGAAGGAAGGAAAGA 17 19665 CFTR-Intron10-780 + UGUAUUUUUAGUAGAGA 17 19666 CFTR-Intron10-781 UUUUUUUUUUUUUGAGA 17 19667 CFTR-Intron10-782 CUUUUCCUCUUAAUAGA 17 19668 CFTR-Intron10-783 + AUAUUCAAAAGAAAGGA 17 19669 CFTR-Intron10-784 AAGGAAGGAAAGAAGGA 17 19670 CFTR-Intron10-785 + CACUGUGUUAGCCAGGA 17 19671 CFTR-Intron10-786 CACCAUGUUGGCCAGGA 17 19672 CFTR-Intron10-787 AAGGCAGAGUUAGAGGA 17 19673 CFTR-Intron10-788 AAAAUUAUACUAUAGGA 17 19674 CFTR-Intron10-789 AUAGAGUAAGACAGGGA 17 19675 CFTR-Intron10-790 CACCGUUUUAGCCGGGA 17 19676 CFTR-Intron10-791 UGGACUGAGUAACUGGA 17 19677 CFTR-Intron10-792 AUAUAUGUGUGUCUGGA 17 19678 CFTR-Intron10-793 AGGUGAUUAGUCCAUGA 17 19679 CFTR-Intron10-794 + UGGCAUAGCUGCACUGA 17 19680 CFTR-Intron10-795 AAAUUAGCCAGACGUGA 17 19681 CFTR-Intron10-796 CCUAAUUCCCAAGGUGA 17 19682 CFTR-Intron10-797 AGACUUGCAGGAGGUGA 17 19683 CFTR-Intron10-798 + AUGGCAGAAAGGGGUGA 17 19684 CFTR-Intron10-799 UUCAGGACAUGCUUUGA 17 19685 CFTR-Intron10-800 + UUCAAUUCUUCAAAAUA 17 19686 CFTR-Intron10-801 + AGUAUAUCAAAAGAAUA 17 19687 CFTR-Intron10-802 + CCUCUGUGCUUUGAAUA 17 19688 CFTR-Intron10-803 AUAAAUGUUGAAUAAUA 17 19689 CFTR-Intron10-804 CAUAGUAUUCUAUCAUA 17 19690 CFTR-Intron10-805 + CAUAGAGAAAACUCAUA 17 19691 CFTR-Intron10-806 + CUGCAGACCUCAAUAUA 17 19692 CFTR-Intron10-807 AAGUUUCUCAUCUUAUA 17 19693 CFTR-Intron10-808 + CCGAGUAGCUGGGACUA 17 19694 CFTR-Intron10-809 UGGUUUGAAGAACAGUA 17 19695 CFTR-Intron10-810 UGUUUAUGUUAUCUGUA 17 19696 CFTR-Intron10-811 UUUUAGGCUAUUCUGUA 17 19697 CFTR-Intron10-812 + ACUAGUGGCACUUUGUA 17 19698 CFTR-Intron10-813 + UUAGUUUUAUGCCAUUA 17 19699 CFTR-Intron10-814 CAGGAGGUGAGGGAUUA 17 19700 CFTR-Intron10-815 ACUUCCUGUUGCUAUUA 17 19701 CFTR-Intron10-816 UGUAUAUGUGUGUAUUA 17 19702 CFTR-Intron10-817 + AUGUUAUUCAAGGUUUA 17 19703 CFTR-Intron10-818 CAUUUUGACCAUUUUUA 17 19704 CFTR-Intron10-819 AAGAUAAUGGGAGAAAC 17 19705 CFTR-Intron10-820 + UGUGGCUUAUAAACAAC 17 19706 CFTR-Intron10-821 UUUUAAACAGAAGUAAC 17 19707 CFTR-Intron10-822 AAACUGUUAUAAUUAAC 17 19708 CFTR-Intron10-823 UGACCCUUAAACAAUAC 17 19709 CFTR-Intron10-824 + CAAGUAGCUGGGACUAC 17 19710 CFTR-Intron10-825 + CGAGUAGCUGGGACUAC 17 19711 CFTR-Intron10-826 CAAAGUGCUGGGAUUAC 17 19712 CFTR-Intron10-827 CAAAGUGUUGGGAUUAC 17 19713 CFTR-Intron10-828 + UGCAAUAUGCAAUUUAC 17 19714 CFTR-Intron10-829 + AAAUAUUGACUAUUUAC 17 19715 CFTR-Intron10-830 UAUAUAUAUUUUUAACC 17 19716 CFTR-Intron10-831 AGAGUCUUACUGUCACC 17 19717 CFTR-Intron10-832 + UACUAAAAAAAGUUACC 17 19718 CFTR-Intron10-833 + AAAGGUCAAUUGAGCCC 17 19719 CFTR-Intron10-834 UGCAAGCUCCGCCUCCC 17 19720 CFTR-Intron10-835 UGCAACCUCUGCCUCCC 17 19721 CFTR-Intron10-836 + ACCACUGUGCUCCAGCC 17 19722 CFTR-Intron10-837 + ACCACUGAAGUUCAGCC 17 19723 CFTR-Intron10-838 + AAUACAAAAAAUUAGCC 17 19724 CFTR-Intron10-839 + AAGAAAUGAAACAGGCC 17 19725 CFTR-Intron10-840 + AGAGAUCAAUACCAUCC 17 19726 CFTR-Intron10-841 UGAUGGUGGCUUGAUCC 17 19727 CFTR-Intron10-842 + CGCUGGUCUCAAACUCC 17 19728 CFTR-Intron10-843 CUGUAACCUUGAACUCC 17 19729 CFTR-Intron10-844 CUGCAAGCUCCGCCUCC 17 19730 CFTR-Intron10-845 CUGCAACCUCUGCCUCC 17 19731 CFTR-Intron10-846 + CUGCAAGUUCUGCCUCC 17 19732 CFTR-Intron10-847 CCAUGUGAGAACACAGC 17 19733 CFTR-Intron10-848 CACAGCAGGAAGACAGC 17 19734 CFTR-Intron10-849 AGUGCAGCUAUGCCAGC 17 19735 CFTR-Intron10-850 UUUUAAAACAAAAUAGC 17 19736 CFTR-Intron10-851 AAACAAAAGAAAAUAGC 17 19737 CFTR-Intron10-852 UCACCCUCCCAAGUAGC 17 19738 CFTR-Intron10-853 + UCAGCCUCCCAAGUAGC 17 19739 CFTR-Intron10-854 AGAGUCUUCCAAGUAGC 17 19740 CFTR-Intron10-855 + UCAGCCUCCCGAGUAGC 17 19741 CFTR-Intron10-856 + AAAUACAAAAAAUUAGC 17 19742 CFTR-Intron10-857 + UGCCAUGUUGCCCACGC 17 19743 CFTR-Intron10-858 + UAAGAAAUGAAACAGGC 17 19744 CFTR-Intron10-859 UCUUACUGUCACCAGGC 17 19745 CFTR-Intron10-860 CGCUCUGUCGCCCAGGC 17 19746 CFTR-Intron10-861 CUUUUGGAGGCAGAGGC 17 19747 CFTR-Intron10-862 + CUUUGGGAGGCCGAGGC 17 19748 CFTR-Intron10-863 + CUCACAGUUCUGGAGGC 17 19749 CFTR-Intron10-864 AAGGAGGUCACUGAGGC 17 19750 CFTR-Intron10-865 ACUCGGGAGGCUGAGGC 17 19751 CFTR-Intron10-866 + ACUUGGGAGGCUGAGGC 17 19752 CFTR-Intron10-867 + ACUUGGGAGGGUGAGGC 17 19753 CFTR-Intron10-868 UUCAAGGAAGAGGGGGC 17 19754 CFTR-Intron10-869 + UUCAACAUAUGAAUGGC 17 19755 CFTR-Intron10-870 UAGCCAGACGUGAUGGC 17 19756 CFTR-Intron10-871 + UAGCCGGGCGUAGUGGC 17 19757 CFTR-Intron10-872 UCAGCCUCCCAAAGUGC 17 19758 CFTR-Intron10-873 UCGGCCUCCCAAAGUGC 17 19759 CFTR-Intron10-874 CAAGGUGAUGGUAUUGC 17 19760 CFTR-Intron10-875 UUUGAACAAAGACUUGC 17 19761 CFTR-Intron10-876 CGUAGUCCCAGCUACUC 17 19762 CFTR-Intron10-877 + CUCCACUUCUCAGGCUC 17 19763 CFTR-Intron10-878 + AUAGAGAGAAACAUCUC 17 19764 CFTR-Intron10-879 + UGCAGCCUCCACUUCUC 17 19765 CFTR-Intron10-880 + AGAGACAAGGUGGUGUC 17 19766 CFTR-Intron10-881 UCAAUAAAUUUGGUGUC 17 19767 CFTR-Intron10-882 AUGUAUAUAUGUGUGUC 17 19768 CFTR-Intron10-883 + UCUUUCUAAUUUCAUUC 17 19769 CFTR-Intron10-884 AGGAAGUGAUCAGAUUC 17 19770 CFTR-Intron10-885 + UAAGAGGAAAAGACUUC 17 19771 CFTR-Intron10-886 + UUUAUUUCUCACAGUUC 17 19772 CFTR-Intron10-887 + UGUGUGUGUCCUUGUUC 17 19773 CFTR-Intron10-888 ACUGGCAAUUAAAUUUC 17 19774 CFTR-Intron10-889 UCUUUUGAAUAUAUUUC 17 19775 CFTR-Intron10-890 + AUAAAUAAUUGCCUUUC 17 19776 CFTR-Intron10-891 AUUAUAACACUGCUUUC 17 19777 CFTR-Intron10-892 + AAAAUUUGUUUUCUUUC 17 19778 CFTR-Intron10-893 + AAAAACAUUAGCCAAAG 17 19779 CFTR-Intron10-894 + UCUCACAUGGCAGAAAG 17 19780 CFTR-Intron10-895 UUGAUAAGAAGAGAAAG 17 19781 CFTR-Intron10-896 AAGAUUCUAAAGGAAAG 17 19782 CFTR-Intron10-897 UGAAUUUUUUUUCCAAG 17 19783 CFTR-Intron10-898 CACCUGAGCCUGAGAAG 17 19784 CFTR-Intron10-899 + ACUUUGGGAGGCUGAAG 17 19785 CFTR-Intron10-900 + AAAAAUUCACAAAUAAG 17 19786 CFTR-Intron10-901 AAAUUAGAAAGAAUAAG 17 19787 CFTR-Intron10-902 AAAAAUAAAAAUAUAAG 17 19788 CFTR-Intron10-903 AGAAGGAAGGAAGUAAG 17 19789 CFTR-Intron10-904 CCAUAUUCAAAGCACAG 17 19790 CFTR-Intron10-905 ACCAGGCUGGAGCACAG 17 19791 CFTR-Intron10-906 + UUAAUGGCUGUGCACAG 17 19792 CFTR-Intron10-907 UAUGAGAAAAGUCACAG 17 19793 CFTR-Intron10-908 + CCUAGGCUAGGGUACAG 17 19794 CFTR-Intron10-909 + UGUUUAAAACUCUCCAG 17 19795 CFTR-Intron10-910 CUAUAUUUGUUUUCCAG 17 19796 CFTR-Intron10-911 + AGGAAAGGAGGUAGCAG 17 19797 CFTR-Intron10-912 + UUGAGCCCGGGAGGCAG 17 19798 CFTR-Intron10-913 AGCACUUUUGGAGGCAG 17 19799 CFTR-Intron10-914 + CAACAUAUGAAUGGCAG 17 19800 CFTR-Intron10-915 + CCCAGGCUAGAGUGCAG 17 19801 CFTR-Intron10-916 CCCAGGCUGGAGUGCAG 17 19802 CFTR-Intron10-917 UGUCAGGCUGGGUGCAG 17 19803 CFTR-Intron10-918 + UAUUUAAACAGAAUCAG 17 19804 CFTR-Intron10-919 AAUGUUAAUUUAUUCAG 17 19805 CFTR-Intron10-920 CCCAGGCUGAACUUCAG 17 19806 CFTR-Intron10-921 + UUGUUACAUAAAAAGAG 17 19807 CFTR-Intron10-922 AACAGAAAAAGAAAGAG 17 19808 CFTR-Intron10-923 AAAUUAUACUAUAGGAG 17 19809 CFTR-Intron10-924 + AAUAGCCUAUUGUUGAG 17 19810 CFTR-Intron10-925 UAAAUGUUGAAUAAUAG 17 19811 CFTR-Intron10-926 + UAGAUGAUUAUUAAUAG 17 19812 CFTR-Intron10-927 UAAAAAGUGAUCUCUAG 17 19813 CFTR-Intron10-928 + AAAUUAGCCGGGCGUAG 17 19814 CFTR-Intron10-929 UAUGAAGGCAGAGUUAG 17 19815 CFTR-Intron10-930 + AGAUGAUUAGCAUCACG 17 19816 CFTR-Intron10-931 UAUUUUUAGUAGAGACG 17 19817 CFTR-Intron10-932 + AACACUUUGGGAGGCCG 17 19818 CFTR-Intron10-933 + AGCACUUUGGGAGGCCG 17 19819 CFTR-Intron10-934 + AUGAAACAGGCCGGGCG 17 19820 CFTR-Intron10-935 + AAAAAAAAAUCAAAAGG 17 19821 CFTR-Intron10-936 + CUGAGUAGAAGGAAAGG 17 19822 CFTR-Intron10-937 UUUGAAGAACAGUAAGG 17 19823 CFTR-Intron10-938 AAUGGCGUGAACCCAGG 17 19824 CFTR-Intron10-939 UAGUUUCAAGGAAGAGG 17 19825 CFTR-Intron10-940 + UUACAUAAAAAGAGAGG 17 19826 CFTR-Intron10-941 + UGUGUUUUUUGUAGAGG 17 19827 CFTR-Intron10-942 + ACUUUGGGAGGCCGAGG 17 19828 CFTR-Intron10-943 UACUUGGGAGGCUGAGG 17 19829 CFTR-Intron10-944 AAAAAUUAUACUAUAGG 17 19830 CFTR-Intron10-945 + AAACAGGCCGGGCGCGG 17 19831 CFTR-Intron10-946 CUGUAGGGAGACAAGGG 17 19832 CFTR-Intron10-947 + AAUGGCGUGAACCCGGG 17 19833 CFTR-Intron10-948 + AAUUGCUUGAGCCCGGG 17 19834 CFTR-Intron10-949 + UGGGAGGCCGAGGCGGG 17 19835 CFTR-Intron10-950 AGUCCCAGCUACUCGGG 17 19836 CFTR-Intron10-951 UGGGAGGCUGAGGUGGG 17 19837 CFTR-Intron10-952 + AGUCCCAGCUACUUGGG 17 19838 CFTR-Intron10-953 + AAUCCCAACACUUUGGG 17 15660 CFTR-Intron10-954 + AAACCCAGCACUUUGGG 17 19839 CFTR-Intron10-955 + AAUCCCAGCACUUUGGG 17 19840 CFTR-Intron10-956 AGGGUGGGGCCUUUGGG 17 19841 CFTR-Intron10-957 CAGGCAAGUGAUGAUGG 17 19842 CFTR-Intron10-958 UUAGCCAGACGUGAUGG 17 19843 CFTR-Intron10-959 + AUUUCUCACAGUUCUGG 17 19844 CFTR-Intron10-960 CUGAGCCUGAGAAGUGG 17 19845 CFTR-Intron10-961 AGGCUGGAGUGCAGUGG 17 19846 CFTR-Intron10-962 + UUAGCCGGGCGUAGUGG 17 19847 CFTR-Intron10-963 AAAAUAGCUGGGUGUGG 17 19848 CFTR-Intron10-964 + UCAAAAAAUAUUUGUGG 17 19849 CFTR-Intron10-965 AAUCCUAGCACUUUUGG 17 19850 CFTR-Intron10-966 AAUUUUAUAUAGAAAUG 17 19851 CFTR-Intron10-967 + AACAAACAAAGGAAAUG 17 19852 CFTR-Intron10-968 AAGCUAGUGAAUGAAUG 17 19853 CFTR-Intron10-969 + AUUAUUCAACAUUUAUG 17 19854 CFTR-Intron10-970 CAGUAAGGAGGUCACUG 17 19855 CFTR-Intron10-971 AGCUACUCGGGAGGCUG 17 19856 CFTR-Intron10-972 + AGCUACUUGGGAGGCUG 17 19857 CFTR-Intron10-973 + CAAAAAUUAGCUGAGUG 17 19858 CFTR-Intron10-974 + ACAUAAAAAGAGAGGUG 17 19859 CFTR-Intron10-975 + UGUUUUUUGUAGAGGUG 17 19860 CFTR-Intron10-976 AAGACUUGCAGGAGGUG 17 19861 CFTR-Intron10-977 + AGCUACUUGGGAGGGUG 17 19862 CFTR-Intron10-978 + CAUGGCAGAAAGGGGUG 17 19863 CFTR-Intron10-979 AAGAAAAUAGCUGGGUG 17 19864 CFTR-Intron10-980 + AAAUACCAUGAACUGUG 17 19865 CFTR-Intron10-981 UUUAUAAAAAAUAAUUG 17 19866 CFTR-Intron10-982 + UAUUCAAAAAAUAUUUG 17 19867 CFTR-Intron10-983 ACAUUGGAAAAUUUUUG 17 19868 CFTR-Intron10-984 UAGUAGUUAAGUUUUUG 17 19869 CFTR-Intron10-985 UCAAAAAAAAAAAAAAU 17 19870 CFTR-Intron10-986 + UAAAAUGACAAUCAAAU 17 19871 CFTR-Intron10-987 + CUAUUUGGAUGUCAAAU 17 19872 CFTR-Intron10-988 + AAACAAACAAAGGAAAU 17 19873 CFTR-Intron10-989 UUGAAGGAAGAUCCAAU 17 19874 CFTR-Intron10-990 CAUAAAUGUUGAAUAAU 17 19875 CFTR-Intron10-991 UUUACUAGAAAGAUAAU 17 19876 CFTR-Intron10-992 ACUGUCAGAGAAGUAAU 17 19877 CFTR-Intron10-993 UUUUUCAGUUAAUACAU 17 19878 CFTR-Intron10-994 + UACAAUUCUUAUUACAU 17 19879 CFTR-Intron10-995 ACAGGCUUGAACUGCAU 17 19880 CFTR-Intron10-996 ACCCUAGCCUAGGUGAU 17 19881 CFTR-Intron10-997 + UUGUGUUAACAAAAUAU 17 19882 CFTR-Intron10-998 + AAUAUAUAUAUGCAUAU 17 19883 CFTR-Intron10-999 UUAAAAAAUUAUACUAU 17 19884 CFTR-Intron10-1000 AAAGUUUCUCAUCUUAU 17 19885 CFTR-Intron10-1001 + UAUUAUUCAACAUUUAU 17 19886 CFTR-Intron10-1002 CAAAGUGCUGGGUUUAU 17 19887 CFTR-Intron10-1003 + UCAGACUUUUAUUUUAU 17 19888 CFTR-Intron10-1004 + UUUAACAAACCUUUUAU 17 19889 CFTR-Intron10-1005 + UUCCAAAUUUUUUUUAU 17 19890 CFTR-Intron10-1006 UUAUUCUUGUAAUAACU 17 19891 CFTR-Intron10-1007 CCGUAGUCCCAGCUACU 17 19892 CFTR-Intron10-1008 + CUGUAGUCCCAGCUACU 17 19893 CFTR-Intron10-1009 + CUGCAAUACCAUCACCU 17 19894 CFTR-Intron10-1010 + CCACUGCACUCCAGCCU 17 19895 CFTR-Intron10-1011 + CCACUGAAGUUCAGCCU 17 19896 CFTR-Intron10-1012 CCACUGUACCCUAGCCU 17 19897 CFTR-Intron10-1013 CCACUGCACUCUAGCCU 17 19898 CFTR-Intron10-1014 UCGUGAUCCGCCCGCCU 17 19899 CFTR-Intron10-1015 UCAUGAUCUGCCUGCCU 17 19900 CFTR-Intron10-1016 UGUAACCUUGAACUCCU 17 19901 CFTR-Intron10-1017 + UGCAAGUUCUGCCUCCU 17 19902 CFTR-Intron10-1018 AGGUUUUGGAUGGAGCU 17 19903 CFTR-Intron10-1019 AACAAAAGAAAAUAGCU 17 19904 CFTR-Intron10-1020 CACCCUCCCAAGUAGCU 17 19905 CFTR-Intron10-1021 + CAGCCUCCCAAGUAGCU 17 19906 CFTR-Intron10-1022 + CAGCCUCCCGAGUAGCU 17 19907 CFTR-Intron10-1023 + UCACAGUUCUGGAGGCU 17 19908 CFTR-Intron10-1024 AAAUUAUUUCUACUGCU 17 19909 CFTR-Intron10-1025 + CUGCCUCCAAAAGUGCU 17 19910 CFTR-Intron10-1026 CAGCCUCCCAAAGUGCU 17 19911 CFTR-Intron10-1027 CGGCCUCCCAAAGUGCU 17 19912 CFTR-Intron10-1028 AAAAAAGUUGAGUUGCU 17 19913 CFTR-Intron10-1029 UGCUGGCACCUUGAUCU 17 19914 CFTR-Intron10-1030 UGCUUUUCCCACUAUCU 17 19915 CFTR-Intron10-1031 + AAUUUGAACAACAUUCU 17 19916 CFTR-Intron10-1032 + UUUUUCAUUAUGAUUCU 17 19917 CFTR-Intron10-1033 + CUUUUUCUUAAUUUUCU 17 19918 CFTR-Intron10-1034 UGAGGAAGAAAGGAAGU 17 19919 CFTR-Intron10-1035 UCUGCAAUUGUAUCAGU 17 19920 CFTR-Intron10-1036 + CAGUUUUAUUUUUCAGU 17 19921 CFTR-Intron10-1037 + ACAUUUUCCUAAUGAGU 17 19922 CFTR-Intron10-1038 AGUGGAAGUAGUAUAGU 17 19923 CFTR-Intron10-1039 + UACAUAAAAAGAGAGGU 17 19924 CFTR-Intron10-1040 UUAGAGGUUAAGGAGGU 17 19925 CFTR-Intron10-1041 ACUUGGGAGGCUGAGGU 17 19926 CFTR-Intron10-1042 ACGGGGUUUCACCAUGU 17 19927 CFTR-Intron10-1043 UCGGCCUCCCAAAGUGU 17 19928 CFTR-Intron10-1044 AGAAGAGAAAGGGGUGU 17 19929 CFTR-Intron10-1045 ACCCAAUAAAAAAAAUU 17 19930 CFTR-Intron10-1046 UUUCCACUCAAUAAAUU 17 19931 CFTR-Intron10-1047 + CCAUCACCUUGGGAAUU 17 19932 CFTR-Intron10-1048 CACUAUUGAUUGACAUU 17 19933 CFTR-Intron10-1049 + CAAGGUGCCAGCAGAUU 17 19934 CFTR-Intron10-1050 UAUUCUUUUUAGAGAUU 17 19935 CFTR-Intron10-1051 UACUUUUCUUCCUGAUU 17 19936 CFTR-Intron10-1052 UUUUCAUUGAAUGUAUU 17 19937 CFTR-Intron10-1053 UCCUUUGUUUGUUUAUU 17 19938 CFTR-Intron10-1054 + CAGACUUUUAUUUUAUU 17 19939 CFTR-Intron10-1055 + UCCAAAUUUUUUUUAUU 17 19940 CFTR-Intron10-1056 + CUGUAAUCCCAACACUU 17 19941 CFTR-Intron10-1057 AAGUAACAGGGCCACUU 17 19942 CFTR-Intron10-1058 + CUAUAAACCCAGCACUU 17 19943 CFTR-Intron10-1059 + CUGUAAUCCCAGCACUU 17 19944 CFTR-Intron10-1060 AAUUGAAUAUGAGACUU 17 19945 CFTR-Intron10-1061 + UGUAGUCCCAGCUACUU 17 19946 CFTR-Intron10-1062 + UGCAAUACCAUCACCUU 17 19947 CFTR-Intron10-1063 + AUGUUAAAUUUUCCCUU 17 19948 CFTR-Intron10-1064 + UUCCCUUAGGAUAUCUU 17 19949 CFTR-Intron10-1065 AAGCAAGGAGAUGAGUU 17 19950 CFTR-Intron10-1066 CGGCCUCCCAAAGUGUU 17 19951 CFTR-Intron10-1067 UGUUAUCUCUGAAAUUU 17 19952 CFTR-Intron10-1068 UUUGAUUAGAUAAAUUU 17 19953 CFTR-Intron10-1069 UCAAUAUUUUGGAAUUU 17 19954 CFTR-Intron10-1070 ACUAUUGAUUGACAUUU 17 19955 CFTR-Intron10-1071 + AAGGUGCCAGCAGAUUU 17 19956 CFTR-Intron10-1072 UAGUUUUAUCAAUAUUU 17 19957 CFTR-Intron10-1073 + UCUCUGCAAACAUAUUU 17 19958 CFTR-Intron10-1074 CAUUAUUCAUGAUAUUU 17 19959 CFTR-Intron10-1075 UUUCAUUGAAUGUAUUU 17 19960 CFTR-Intron10-1076 + UGUAAUCCCAACACUUU 17 19961 CFTR-Intron10-1077 + UAUAAACCCAGCACUUU 17 19962 CFTR-Intron10-1078 + UGUAAUCCCAGCACUUU 17 19963 CFTR-Intron10-1079 UGUAAUCCUAGCACUUU 17 19964 CFTR-Intron10-1080 UGCAGGGUGGGGCCUUU 17 19965 CFTR-Intron10-1081 UUUAACUGAAUAUCUUU 17 19966 CFTR-Intron10-1082 AUGGGAGAAACAGGUUU 17 19967 CFTR-Intron10-1083 AUACAUUGGAAAAUUUU 17 19968 CFTR-Intron10-1084 CAAUAUUUUGGAAUUUU 17 19969 CFTR-Intron10-1085 UACAUUGGAAAAUUUUU 17 19970 CFTR-Intron10-1086 CUUUGGCUAAUGUUUUU 17 19971 CFTR-Intron10-1087 CACUUUAUAGUUUUUUU 17 19972 CFTR-Intron10-1088 + ACAAACAAAGAAACAAAAAA 20 19973 CFTR-Intron10-1089 + ACAUAUGAUUUUAUGAAAAA 20 19974 CFTR-Intron10-1090 + CGAGACCAUCCCGGCUAAAA 20 19975 CFTR-Intron10-1091 UAGAAAGAAAAAACAGCAAA 20 19976 CFTR-Intron10-1092 + AUUAGUAAAAAAAAAUCAAA 20 19977 CFTR-Intron10-1093 + AAGAAAAGCUGAAAGUCAAA 20 19978 CFTR-Intron10-1094 + UACAUUCAAUGAAAAAGAAA 20 19979 CFTR-Intron10-1095 AGGGUUGAUAAGAAGAGAAA 20 19980 CFTR-Intron10-1096 AUUUAAACACUUCUGAGAAA 20 19981 CFTR-Intron10-1097 + AAAUAAACAAACAAAGGAAA 20 19982 CFTR-Intron10-1098 AAGGAUGUUUAUUUAUGAAA 20 19983 CFTR-Intron10-1099 + AAAACCAAAUAAACAAACAA 20 19984 CFTR-Intron10-1100 CUCAUUAGGAAAAUGUACAA 20 19985 CFTR-Intron10-1101 + AUGGACUAAUCACCUCCCAA 20 19986 CFTR-Intron10-1102 UCAUGUUGAUAAAGGGUCAA 20 19987 CFTR-Intron10-1103 + CUGAAAUAUAUUCAAAAGAA 20 19988 CFTR-Intron10-1104 + AGAUGAGAGACAGUAAAGAA 20 19989 CFTR-Intron10-1105 AAGAAGGAAAUGAGGAAGAA 20 19990 CFTR-Intron10-1106 + UGUGUUCUCACAUGGCAGAA 20 19991 CFTR-Intron10-1107 + UUUGGGAGGCUGAAGCGGAA 20 19992 CFTR-Intron10-1108 + UUAGGAUUUCAACAUAUGAA 20 19993 CFTR-Intron10-1109 + ACAUUUCUCUUUACUGUGAA 20 19994 CFTR-Intron10-1110 + AGGAAGAAAAGUAUCAAUAA 20 19995 CFTR-Intron10-1111 + AUACAGUGACUUCAUAAUAA 20 19996 CFTR-Intron10-1112 + AACAUAGAGAAAACUCAUAA 20 19997 CFTR-Intron10-1113 + UGAACAAAAAUUAAAACUAA 20 19998 CFTR-Intron10-1114 + UUUUCUAGAAAACAAUGUAA 20 19999 CFTR-Intron10-1115 AACAGAUAAAGUUGAAUUAA 20 20000 CFTR-Intron10-1116 + UGUUACCUUUCAAUGUUUAA 20 20001 CFTR-Intron10-1117 + UUCAAGCCUGUAUUGUUUAA 20 20002 CFTR-Intron10-1118 AUCAUUUUGACCAUUUUUAA 20 20003 CFTR-Intron10-1119 + CAAUACCAUCCUGGCCAACA 20 20004 CFTR-Intron10-1120 UGAGACCAGCGUGGGCAACA 20 20005 CFTR-Intron10-1121 UUGUUAUAGCAGCCUGAACA 20 20006 CFTR-Intron10-1122 + UGGAGAGAGAACUGCUCACA 20 20007 CFTR-Intron10-1123 + CUUCCUGCUGUGUUCUCACA 20 20008 CFTR-Intron10-1124 + AAUGAUCAAUAAUAGAGACA 20 20009 CFTR-Intron10-1125 + AUUUUACAAUUCUUAUUACA 20 20010 CFTR-Intron10-1126 UGUUGAAAUCCUAAUUCCCA 20 20011 CFTR-Intron10-1127 UUCUUUAUUUUUAUAUUCCA 20 20012 CFTR-Intron10-1128 + AUUUCAACAUAUGAAUGGCA 20 20013 CFTR-Intron10-1129 AAAGUGCCACUAGUGAUGCA 20 20014 CFTR-Intron10-1130 CAAUACAGGCUUGAACUGCA 20 20015 CFTR-Intron10-1131 CCCAAGGUGAUGGUAUUGCA 20 20016 CFTR-Intron10-1132 + AGGGUACAGUGGUGCAAUCA 20 20017 CFTR-Intron10-1133 + UGCUUCACUAAAAUAAUUCA 20 20018 CFTR-Intron10-1134 + ACAUAUAUUUUAUGCAUUCA 20 20019 CFTR-Intron10-1135 UUUAUAAGCCACACAGUUCA 20 20020 CFTR-Intron10-1136 + CAAUUGAGCCCAGGAGUUCA 20 20021 CFTR-Intron10-1137 AAGAGAGGAAGGAAGAAAGA 20 20022 CFTR-Intron10-1138 AGGAAGGAAGGAAGGAAAGA 20 20023 CFTR-Intron10-1139 AAAGAAGGAAGGAAGUAAGA 20 20024 CFTR-Intron10-1140 AAUGAAAGCAAUAGUAGAGA 20 20025 CFTR-Intron10-1141 + UUUUGUAUUUUUAGUAGAGA 20 20026 CFTR-Intron10-1142 UUUUUUUUUUUUUUUUGAGA 20 20027 CFTR-Intron10-1143 AGUCUUUUCCUCUUAAUAGA 20 20028 CFTR-Intron10-1144 + AAUAUAUUCAAAAGAAAGGA 20 20029 CFTR-Intron10-1145 AGGAAGGAAGGAAAGAAGGA 20 20030 CFTR-Intron10-1146 AAAGGAAGUAGGAGGAAGGA 20 20031 CFTR-Intron10-1147 + UUUCACUGUGUUAGCCAGGA 20 20032 CFTR-Intron10-1148 UUUCACCAUGUUGGCCAGGA 20 20033 CFTR-Intron10-1149 ACAGAAAAAGAAAGAGAGGA 20 20034 CFTR-Intron10-1150 AUGAAGGCAGAGUUAGAGGA 20 20035 CFTR-Intron10-1151 UAAAAAAUUAUACUAUAGGA 20 20036 CFTR-Intron10-1152 + AUUGGUACAAAUUUCAGGGA 20 20037 CFTR-Intron10-1153 UUUCACCGUUUUAGCCGGGA 20 20038 CFTR-Intron10-1154 AUAGUAUUCUAUCAUAUGGA 20 20039 CFTR-Intron10-1155 UUCUGGACUGAGUAACUGGA 20 20040 CFTR-Intron10-1156 UGUAUAUAUGUGUGUCUGGA 20 20041 CFTR-Intron10-1157 UGGGAGAAACAGGUUUUGGA 20 20042 CFTR-Intron10-1158 + UUGACCCUUUAUCAACAUGA 20 20043 CFTR-Intron10-1159 + UGCUGGCAUAGCUGCACUGA 20 20044 CFTR-Intron10-1160 AAAAAAUUAGCCAGACGUGA 20 20045 CFTR-Intron10-1161 AAUCCUAAUUCCCAAGGUGA 20 20046 CFTR-Intron10-1162 CAAAGACUUGCAGGAGGUGA 20 20047 CFTR-Intron10-1163 + CACAUGGCAGAAAGGGGUGA 20 20048 CFTR-Intron10-1164 AGAUUCAGGACAUGCUUUGA 20 20049 CFTR-Intron10-1165 + AUAUUCAAUUCUUCAAAAUA 20 20050 CFTR-Intron10-1166 AAAACUAAUUGUAGUACAUA 20 20051 CFTR-Intron10-1167 AUGCAUAGUAUUCUAUCAUA 20 20052 CFTR-Intron10-1168 + AAACAUAGAGAAAACUCAUA 20 20053 CFTR-Intron10-1169 + UAGCUGCAGACCUCAAUAUA 20 20054 CFTR-Intron10-1170 + CAAAAAUUACAGAACCUAUA 20 20055 CFTR-Intron10-1171 AAAAAGUUUCUCAUCUUAUA 20 20056 CFTR-Intron10-1172 + CUCCCGAGUAGCUGGGACUA 20 20057 CFTR-Intron10-1173 + AAGGGGUGAGGGUCUCUCUA 20 20058 CFTR-Intron10-1174 + AAGGUGUGAGGGUCUCUCUA 20 20059 CFTR-Intron10-1175 + ACUGUGAAUGGUGCCAGGUA 20 20060 CFTR-Intron10-1176 + AUCACUAGUGGCACUUUGUA 20 20061 CFTR-Intron10-1177 + UUGAUGUUAUUCAAGGUUUA 20 20062 CFTR-Intron10-1178 UAUCAUUUUGACCAUUUUUA 20 20063 CFTR-Intron10-1179 + UUGGAAAAAAAAUUCAAAAC 20 20064 CFTR-Intron10-1180 + CUGUGUGGCUUAUAAACAAC 20 20065 CFTR-Intron10-1181 + CCAUCAUCACUUGCCUGAAC 20 20066 CFTR-Intron10-1182 AGCUUUCUGGACUGAGUAAC 20 20067 CFTR-Intron10-1183 UUUGUAUUUUUAGUAGAGAC 20 20068 CFTR-Intron10-1184 ACAAGUGCCUAGCACUUGAC 20 20069 CFTR-Intron10-1185 AAUUGACCCUUAAACAAUAC 20 20070 CFTR-Intron10-1186 + UCCCAAGUAGCUGGGACUAC 20 20071 CFTR-Intron10-1187 + UCCCGAGUAGCUGGGACUAC 20 20072 CFTR-Intron10-1188 UCCCAAAGUGCUGGGAUUAC 20 20073 CFTR-Intron10-1189 UCCCAAAGUGUUGGGAUUAC 20 20074 CFTR-Intron10-1190 + UACUGCAAUAUGCAAUUUAC 20 20075 CFTR-Intron10-1191 + CAGGAGAAUGGCGUGAACCC 20 20076 CFTR-Intron10-1192 + AGAGUCUCACUCUGUCACCC 20 20077 CFTR-Intron10-1193 UAGGUCUUACUCUGUCACCC 20 20078 CFTR-Intron10-1194 + CGGAAAGGUCAAUUGAGCCC 20 20079 CFTR-Intron10-1195 + CAGGAGAAUUGCUUGAGCCC 20 20080 CFTR-Intron10-1196 CACUGCAAGCUCCGCCUCCC 20 20081 CFTR-Intron10-1197 CACUGCAACCUCUGCCUCCC 20 20082 CFTR-Intron10-1198 + CCCGCCACUGCACUCCAGCC 20 20083 CFTR-Intron10-1199 + CGCACCACUGUGCUCCAGCC 20 20084 CFTR-Intron10-1200 + CACACCACUGAAGUUCAGCC 20 20085 CFTR-Intron10-1201 CGCGCCACUGCACUCUAGCC 20 20086 CFTR-Intron10-1202 + AAAAAUACAAAAAAUUAGCC 20 20087 CFTR-Intron10-1203 CAGGCGCCCGCCACUACGCC 20 20088 CFTR-Intron10-1204 CAGGCGUGAGCCACCGCGCC 20 20089 CFTR-Intron10-1205 + UAUAAGAAAUGAAACAGGCC 20 20090 CFTR-Intron10-1206 UUAGGAGAUCAAGACCAUCC 20 20091 CFTR-Intron10-1207 + UCAGGAGAUCGAGACCAUCC 20 20092 CFTR-Intron10-1208 + UCAAGAGAUCAAUACCAUCC 20 20093 CFTR-Intron10-1209 UGAUGAUGGUGGCUUGAUCC 20 20094 CFTR-Intron10-1210 AGGAAGACAGCUGGCUAUCC 20 20095 CFTR-Intron10-1211 + CCACGCUGGUCUCAAACUCC 20 20096 CFTR-Intron10-1212 UCACUGUAACCUUGAACUCC 20 20097 CFTR-Intron10-1213 UUAUUCUUUUGAUAUACUCC 20 20098 CFTR-Intron10-1214 UCACUGCAAGCUCCGCCUCC 20 20099 CFTR-Intron10-1215 UCACUGCAACCUCUGCCUCC 20 20100 CFTR-Intron10-1216 + UCACUGCAAGUUCUGCCUCC 20 20101 CFTR-Intron10-1217 CAGGUGAAUUGCUUGAGUCC 20 20102 CFTR-Intron10-1218 CUGCCAUGUGAGAACACAGC 20 20103 CFTR-Intron10-1219 AUCAGUGCAGCUAUGCCAGC 20 20104 CFTR-Intron10-1220 AGCUUUUAAAACAAAAUAGC 20 20105 CFTR-Intron10-1221 CACAAACAAAAGAAAAUAGC 20 20106 CFTR-Intron10-1222 + ACCUCAGCCUCCCAAGUAGC 20 20107 CFTR-Intron10-1223 + UAAAAAUACAAAAAAUUAGC 20 20108 CFTR-Intron10-1224 CGGGGUUUCACCGUUUUAGC 20 20109 CFTR-Intron10-1225 + AUAUAAGAAAUGAAACAGGC 20 20110 CFTR-Intron10-1226 UCUCGCUCUGUCGCCCAGGC 20 20111 CFTR-Intron10-1227 CAAUAAAUUUGGUGUCAGGC 20 20112 CFTR-Intron10-1228 + ACACUUUGGGAGGCCGAGGC 20 20113 CFTR-Intron10-1229 + UUUCUCACAGUUCUGGAGGC 20 20114 CFTR-Intron10-1230 AAUUAGCCAGACGUGAUGGC 20 20115 CFTR-Intron10-1231 CCAGGCUGGAGUGCAGUGGC 20 20116 CFTR-Intron10-1232 + AAUUAGCCGGGCGUAGUGGC 20 20117 CFTR-Intron10-1233 CUUAGCAGACCCAAAUCUGC 20 20118 CFTR-Intron10-1234 + UUCAUUUAUCUCGAAAUUGC 20 20119 CFTR-Intron10-1235 UCCCAAGGUGAUGGUAUUGC 20 20120 CFTR-Intron10-1236 ACAUUUGAACAAAGACUUGC 20 20121 CFTR-Intron10-1237 + AGCCUCCACUUCUCAGGCUC 20 20122 CFTR-Intron10-1238 + UAUAUAGAGAGAAACAUCUC 20 20123 CFTR-Intron10-1239 + CACUGCAGCCUCCACUUCUC 20 20124 CFTR-Intron10-1240 + CGGGCACCCGCCAUCACGUC 20 20125 CFTR-Intron10-1241 UAGGCAUGAGCCACUGUGUC 20 20126 CFTR-Intron10-1242 UGUAUGUAUAUAUGUGUGUC 20 20127 CFTR-Intron10-1243 + UAUUCUUUCUAAUUUCAUUC 20 20128 CFTR-Intron10-1244 AGUAGGAAGUGAUCAGAUUC 20 20129 CFTR-Intron10-1245 CUUUCUUUUGAAUAUAUUUC 20 20130 CFTR-Intron10-1246 AAAGAUGAUUCCAAGCUUUC 20 20131 CFTR-Intron10-1247 UUCAUUAUAACACUGCUUUC 20 20132 CFTR-Intron10-1248 + AAGAAAAUUUGUUUUCUUUC 20 20133 CFTR-Intron10-1249 + UGUUCUCACAUGGCAGAAAG 20 20134 CFTR-Intron10-1250 UUUUGAAUUUUUUUUCCAAG 20 20135 CFTR-Intron10-1251 + ACCGUAAUAGCAACAGGAAG 20 20136 CFTR-Intron10-1252 + AGCACUUUGGGAGGCUGAAG 20 20137 CFTR-Intron10-1253 + AAAAAAAAUUCACAAAUAAG 20 20138 CFTR-Intron10-1254 AUGAAAUUAGAAAGAAUAAG 20 20139 CFTR-Intron10-1255 AUCAAAAAUAAAAAUAUAAG 20 20140 CFTR-Intron10-1256 AUCAGUAGGCUUCCUAUAAG 20 20141 CFTR-Intron10-1257 + AUAUUAAUGGCUGUGCACAG 20 20142 CFTR-Intron10-1258 + UCACCUAGGCUAGGGUACAG 20 20143 CFTR-Intron10-1259 + UUCUGUUUAAAACUCUCCAG 20 20144 CFTR-Intron10-1260 + AGAAGGAAAGGAGGUAGCAG 20 20145 CFTR-Intron10-1261 + UGCUUGAGCCCGGGAGGCAG 20 20146 CFTR-Intron10-1262 CCUAGCACUUUUGGAGGCAG 20 20147 CFTR-Intron10-1263 + UUUCAACAUAUGAAUGGCAG 20 20148 CFTR-Intron10-1264 + UCACCCAGGCUAGAGUGCAG 20 20149 CFTR-Intron10-1265 UCGCCCAGGCUGGAGUGCAG 20 20150 CFTR-Intron10-1266 UGGUGUCAGGCUGGGUGCAG 20 20151 CFTR-Intron10-1267 AGGAAUGUUAAUUUAUUCAG 20 20152 CFTR-Intron10-1268 UCACCCAGGCUGAACUUCAG 20 20153 CFTR-Intron10-1269 ACAAACAGAAAAAGAAAGAG 20 20154 CFTR-Intron10-1270 AAAAAAUUAUACUAUAGGAG 20 20155 CFTR-Intron10-1271 + ACUAAUAGCCUAUUGUUGAG 20 20156 CFTR-Intron10-1272 CAGUAAAAAGUGAUCUCUAG 20 20157 CFTR-Intron10-1273 + AAAAAAUUAGCCGGGCGUAG 20 20158 CFTR-Intron10-1274 AAGAAGAGAAAGGGGUGUAG 20 20159 CFTR-Intron10-1275 + UUUGUUUGUGUUUUUUGUAG 20 20160 CFTR-Intron10-1276 AAAUGUGAGAAAAAGUUUAG 20 20161 CFTR-Intron10-1277 + CGGAGAUGAUUAGCAUCACG 20 20162 CFTR-Intron10-1278 UUGUAUUUUUAGUAGAGACG 20 20163 CFTR-Intron10-1279 + CCCAACACUUUGGGAGGCCG 20 20164 CFTR-Intron10-1280 + CCCAGCACUUUGGGAGGCCG 20 20165 CFTR-Intron10-1281 CCAGGAGUUUGAGACCAGCG 20 20166 CFTR-Intron10-1282 + AGUAAAAAAAAAUCAAAAGG 20 20167 CFTR-Intron10-1283 + AAACUGAGUAGAAGGAAAGG 20 20168 CFTR-Intron10-1284 UGGUUUGAAGAACAGUAAGG 20 20169 CFTR-Intron10-1285 UUUGAACAAAGACUUGCAGG 20 20170 CFTR-Intron10-1286 + AGCACUUUGGGAGGCCGAGG 20 20171 CFTR-Intron10-1287 + AAUGGCGUGAACCCGGGAGG 20 20172 CFTR-Intron10-1288 AGCUACUUGGGAGGCUGAGG 20 20173 CFTR-Intron10-1289 UUAAAAAAUUAUACUAUAGG 20 20174 CFTR-Intron10-1290 UGAGGAAGAAAGGAAGUAGG 20 20175 CFTR-Intron10-1291 + AUGAAACAGGCCGGGCGCGG 20 20176 CFTR-Intron10-1292 AAGGUGAUGGUAUUGCAGGG 20 20177 CFTR-Intron10-1293 + CUUUGGGAGGCCGAGGCGGG 20 20178 CFTR-Intron10-1294 CGUAGUCCCAGCUACUCGGG 20 20179 CFTR-Intron10-1295 ACUUGGGAGGCUGAGGUGGG 20 20180 CFTR-Intron10-1296 + UGUAGUCCCAGCUACUUGGG 20 20181 CFTR-Intron10-1297 + UGUAAUCCCAACACUUUGGG 20 20182 CFTR-Intron10-1298 + UAUAAACCCAGCACUUUGGG 20 20183 CFTR-Intron10-1299 + UGUAAUCCCAGCACUUUGGG 20 20184 CFTR-Intron10-1300 UGCAGGGUGGGGCCUUUGGG 20 20185 CFTR-Intron10-1301 AAAUUAGCCAGACGUGAUGG 20 20186 CFTR-Intron10-1302 + UUUAUUUCUCACAGUUCUGG 20 20187 CFTR-Intron10-1303 CACCUGAGCCUGAGAAGUGG 20 20188 CFTR-Intron10-1304 CCCAGGCUGGAGUGCAGUGG 20 20189 CFTR-Intron10-1305 + AAAUUAGCCGGGCGUAGUGG 20 20190 CFTR-Intron10-1306 AAGAAAAUAGCUGGGUGUGG 20 20191 CFTR-Intron10-1307 + UAUUCAAAAAAUAUUUGUGG 20 20192 CFTR-Intron10-1308 UGUAAUCCUAGCACUUUUGG 20 20193 CFTR-Intron10-1309 AGGAAUUUUAUAUAGAAAUG 20 20194 CFTR-Intron10-1310 + AUAAACAAACAAAGGAAAUG 20 20195 CFTR-Intron10-1311 AAGGAAGAAAGAAGGAAAUG 20 20196 CFTR-Intron10-1312 UGGGAGGUGAUUAGUCCAUG 20 20197 CFTR-Intron10-1313 CCCAGCUACUCGGGAGGCUG 20 20198 CFTR-Intron10-1314 + CCCAGCUACUUGGGAGGCUG 20 20199 CFTR-Intron10-1315 + AUACAAAAAUUAGCUGAGUG 20 20200 CFTR-Intron10-1316 + UUGUGUUUUUUGUAGAGGUG 20 20201 CFTR-Intron10-1317 ACAAAGACUUGCAGGAGGUG 20 20202 CFTR-Intron10-1318 + CCCAGCUACUUGGGAGGGUG 20 20203 CFTR-Intron10-1319 + UCACAUGGCAGAAAGGGGUG 20 20204 CFTR-Intron10-1320 CAAAAGAAAAUAGCUGGGUG 20 20205 CFTR-Intron10-1321 + ACAAAAUACCAUGAACUGUG 20 20206 CFTR-Intron10-1322 AUUUUUAUAAAAAAUAAUUG 20 20207 CFTR-Intron10-1323 + AUCUAUUCAAAAAAUAUUUG 20 20208 CFTR-Intron10-1324 AAUACAUUGGAAAAUUUUUG 20 20209 CFTR-Intron10-1325 UAUUAGUAGUUAAGUUUUUG 20 20210 CFTR-Intron10-1326 + AUAGUAGCAAAUGAUAAAAU 20 20211 CFTR-Intron10-1327 + UCUCUAUUUGGAUGUCAAAU 20 20212 CFTR-Intron10-1328 + AAUAAACAAACAAAGGAAAU 20 20213 CFTR-Intron10-1329 UAAGGUUUCCACUCAACAAU 20 20214 CFTR-Intron10-1330 + UUUACCAUUAUCUACACAAU 20 20215 CFTR-Intron10-1331 CCCCAUAAAUGUUGAAUAAU 20 20216 CFTR-Intron10-1332 UUUUUUUUCAGUUAAUACAU 20 20217 CFTR-Intron10-1333 + UUUUACAAUUCUUAUUACAU 20 20218 CFTR-Intron10-1334 AAUACAGGCUUGAACUGCAU 20 20219 CFTR-Intron10-1335 UGUACCCUAGCCUAGGUGAU 20 20220 CFTR-Intron10-1336 + AAAAAUAUAUAUAUGCAUAU 20 20221 CFTR-Intron10-1337 CUAUUAAAAAAUUAUACUAU 20 20222 CFTR-Intron10-1338 UUCUCCCUGUUAUUCCUUAU 20 20223 CFTR-Intron10-1339 UAAAAAGUUUCUCAUCUUAU 20 20224 CFTR-Intron10-1340 UCCCAAAGUGCUGGGUUUAU 20 20225 CFTR-Intron10-1341 + UUCUCAGACUUUUAUUUUAU 20 20226 CFTR-Intron10-1342 + AGUUUCCAAAUUUUUUUUAU 20 20227 CFTR-Intron10-1343 UGCCCGUAGUCCCAGCUACU 20 20228 CFTR-Intron10-1344 + CGCCUGUAGUCCCAGCUACU 20 20229 CFTR-Intron10-1345 + UGCCUGUAGUCCCAGCUACU 20 17606 CFTR-Intron10-1346 + ACCCUGCAAUACCAUCACCU 20 20230 CFTR-Intron10-1347 + CCGCCACUGCACUCCAGCCU 20 20231 CFTR-Intron10-1348 + ACACCACUGAAGUUCAGCCU 20 20232 CFTR-Intron10-1349 ACCUCGUGAUCCGCCCGCCU 20 20233 CFTR-Intron10-1350 ACCUCAUGAUCUGCCUGCCU 20 20234 CFTR-Intron10-1351 CACUGUAACCUUGAACUCCU 20 20235 CFTR-Intron10-1352 + CACUGCAAGUUCUGCCUCCU 20 20236 CFTR-Intron10-1353 ACAAACAAAAGAAAAUAGCU 20 20237 CFTR-Intron10-1354 CCUCACCCUCCCAAGUAGCU 20 20238 CFTR-Intron10-1355 + CCUCAGCCUCCCAAGUAGCU 20 20239 CFTR-Intron10-1356 + CCUCAGCCUCCCGAGUAGCU 20 20240 CFTR-Intron10-1357 + UUCUCACAGUUCUGGAGGCU 20 20241 CFTR-Intron10-1358 + CCUCUGCCUCCAAAAGUGCU 20 20242 CFTR-Intron10-1359 CUUCAGCCUCCCAAAGUGCU 20 20243 CFTR-Intron10-1360 CCUCGGCCUCCCAAAGUGCU 20 20244 CFTR-Intron10-1361 AAGAAAAAAGUUGAGUUGCU 20 20245 CFTR-Intron10-1362 + AGAGUGCAGUGGCGCGAUCU 20 20246 CFTR-Intron10-1363 AUCUGCUGGCACCUUGAUCU 20 20247 CFTR-Intron10-1364 AAAGCUGUGCAUUUUCCUCU 20 20248 CFTR-Intron10-1365 + AUAUAGAGAGAAACAUCUCU 20 20249 CFTR-Intron10-1366 + AUAUUUUUCAUUAUGAUUCU 20 20250 CFTR-Intron10-1367 + UUAAUUUUCUCGGUAUUUCU 20 20251 CFTR-Intron10-1368 + UUACUUUUUCUUAAUUUUCU 20 20252 CFTR-Intron10-1369 AAAUGAGGAAGAAAGGAAGU 20 20253 CFTR-Intron10-1370 UGGAUUUUUGACUAUACAGU 20 20254 CFTR-Intron10-1371 ACAUCUGCAAUUGUAUCAGU 20 20255 CFTR-Intron10-1372 AUCCAAAUAGAGAUGUUAGU 20 20256 CFTR-Intron10-1373 CAGGAGUUUGAGACCAGCGU 20 20257 CFTR-Intron10-1374 + UUUGUGUUUUUUGUAGAGGU 20 20258 CFTR-Intron10-1375 AGGUGAUGGUAUUGCAGGGU 20 20259 CFTR-Intron10-1376 + UGAAUGGUGCCAGGUAGGGU 20 20260 CFTR-Intron10-1377 UUUUUGACUAUACAGUGGGU 20 20261 CFTR-Intron10-1378 AUAAGAAGAGAAAGGGGUGU 20 20262 CFTR-Intron10-1379 AAAUUUCCACUCAAUAAAUU 20 20263 CFTR-Intron10-1380 + AUACCAUCACCUUGGGAAUU 20 20264 CFTR-Intron10-1381 AUGGUACUACUGUAAUAAUU 20 20265 CFTR-Intron10-1382 AAUCACUAUUGAUUGACAUU 20 20266 CFTR-Intron10-1383 UUUUAUUCUUUUUAGAGAUU 20 20267 CFTR-Intron10-1384 CUUGCAGGAGGUGAGGGAUU 20 20268 CFTR-Intron10-1385 UGAUACUUUUCUUCCUGAUU 20 20269 CFTR-Intron10-1386 + AUAGAAGUAGAAGAACUAUU 20 20270 CFTR-Intron10-1387 UCUUUUUCAUUGAAUGUAUU 20 20271 CFTR-Intron10-1388 + UCUGUUUGUCUUAGAUUAUU 20 20272 CFTR-Intron10-1389 AUUUCCUUUGUUUGUUUAUU 20 20273 CFTR-Intron10-1390 + UCUCAGACUUUUAUUUUAUU 20 20274 CFTR-Intron10-1391 + UGCCUGUAAUCCCAACACUU 20 20275 CFTR-Intron10-1392 + UGCCUAUAAACCCAGCACUU 20 20276 CFTR-Intron10-1393 + CGCCUGUAAUCCCAGCACUU 20 20277 CFTR-Intron10-1394 AAGAAUUGAAUAUGAGACUU 20 20278 CFTR-Intron10-1395 + CCCUGCAAUACCAUCACCUU 20 20279 CFTR-Intron10-1396 + AAAAUGUUAAAUUUUCCCUU 20 20280 CFTR-Intron10-1397 + AUUUUCCCUUAGGAUAUCUU 20 20281 CFTR-Intron10-1398 CUUUUAGUUAGCAUAAAGUU 20 20282 CFTR-Intron10-1399 AGGAAGCAAGGAGAUGAGUU 20 20283 CFTR-Intron10-1400 CCUCGGCCUCCCAAAGUGUU 20 20284 CFTR-Intron10-1401 AGUUGUUAUCUCUGAAAUUU 20 20285 CFTR-Intron10-1402 UUAUCAAUAUUUUGGAAUUU 20 20286 CFTR-Intron10-1403 AUCACUAUUGAUUGACAUUU 20 20287 CFTR-Intron10-1404 + AUCAAGGUGCCAGCAGAUUU 20 20288 CFTR-Intron10-1405 AAAUAGUUUUAUCAAUAUUU 20 20289 CFTR-Intron10-1406 CAUCAUUAUUCAUGAUAUUU 20 20290 CFTR-Intron10-1407 CUUUUUCAUUGAAUGUAUUU 20 20291 CFTR-Intron10-1408 ACUUGUAAUCCUAGCACUUU 20 20292 CFTR-Intron10-1409 UAUUGCAGGGUGGGGCCUUU 20 20293 CFTR-Intron10-1410 AAAUUUAACUGAAUAUCUUU 20 20294 CFTR-Intron10-1411 UUAAUACAUUGGAAAAUUUU 20 20295 CFTR-Intron10-1412 UAUCAAUAUUUUGGAAUUUU 20 20296 CFTR-Intron10-1413 UAAUACAUUGGAAAAUUUUU 20 20297

Table 41A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 41A 1st Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-1414 + GAUAAUACUACUGACUAAAA 20 20298 CFTR-Intron10-1415 + GUAACUCCAGUGCUAUUUAAA 21 20299 CFTR-Intron10-1416 + GGUAACUCCAGUGCUAUUUAAA 22 20300 CFTR-Intron10-1417 + GACUCCAGGAGUAUAUCAA 19 20301 CFTR-Intron10-1418 + GGACUCCAGGAGUAUAUCAA 20 20302 CFTR-Intron10-1419 + GUGGACUCCAGGAGUAUAUCAA 22 20303 CFTR-Intron10-1420 + GAUGAGAGACAGUAAAGAA 19 20304 CFTR-Intron10-1421 + GCUAUUUUUGCACAUCUAUCA 21 20305 CFTR-Intron10-1422 + GCUACCUUGGUUGGAUGA 18 20306 CFTR-Intron10-1423 + GGCUACCUUGGUUGGAUGA 19 20307 CFTR-Intron10-1424 + GAUUGGCUACCUUGGUUGGAUGA 23 20308 CFTR-Intron10-1425 + GGAUUGGCUACCUUGGUUGGAUGA 24 20309 CFTR-Intron10-1426 + GAAUAUCCAUCCAUAUGA 18 20310 CFTR-Intron10-1427 + GUUACAACAGUCUUUAUA 18 20311 CFTR-Intron10-1428 + GUUCAACUUAUCCAUUAAUCCUA 23 20312 CFTR-Intron10-1429 + GAUACAAAUUACCAAAUUGUA 21 20313 CFTR-Intron10-1430 + GCACCCAGCCUGACACCAAAUUUA 24 20314 CFTR-Intron10-1431 + GUACAAAUAUUGACUAUUUA 20 20315 CFTR-Intron10-1432 + GCAAGUACAAAUAUUGACUAUUUA 24 20316 CFTR-Intron10-1433 + GAGCUCAUAUUAGUGAAC 18 20317 CFTR-Intron10-1434 + GAUACUAAAAAAAGUUAC 18 20318 CFTR-Intron10-1435 + GUAUUAGCAAGUGGACUCC 19 20319 CFTR-Intron10-1436 + GCACUCUAUUUAGAGUGUAUGGC 23 20320 CFTR-Intron10-1437 + GAAAAGGCUCUUUAUAAUGC 20 20321 CFTR-Intron10-1438 + GCUAAGAGACUCCUGAAUC 19 20322 CFTR-Intron10-1439 + GUCUGCUAAGAGACUCCUGAAUC 23 20323 CFTR-Intron10-1440 + GGUCUGCUAAGAGACUCCUGAAUC 24 20324 CFTR-Intron10-1441 + GUAGAAGACCUAAAUAUC 18 20325 CFTR-Intron10-1442 + GAUGUAGAAGACCUAAAUAUC 21 20326 CFTR-Intron10-1443 + GAAGAUGUAGAAGACCUAAAUAUC 24 20327 CFTR-Intron10-1444 + GGGUCUGCUAAGAGACUC 18 20328 CFTR-Intron10-1445 + GAUUUGGGUCUGCUAAGAGACUC 23 20329 CFTR-Intron10-1446 + GAUAUUUUUCAUUAUGAUUC 20 20330 CFTR-Intron10-94 + GCUUGACAUCAGUUGGGUUC 20 18980 CFTR-Intron10-1447 + GAUAAAUAAUUGCCUUUC 18 20331 CFTR-Intron10-1448 + GAUAUUGAUAAAUAAUUGCCUUUC 24 20332 CFTR-Intron10-1449 + GUUGGAUGAGGGAAUGCAG 19 20333 CFTR-Intron10-1450 + GGUUGGAUGAGGGAAUGCAG 20 20334 CFTR-Intron10-1451 + GAAUUGAUCUUGAAGACAUACG 22 20335 CFTR-Intron10-1452 + GCCUAGAUGAUUAUUAAUAGGG 22 20336 CFTR-Intron10-1453 + GUUAAGUUGUUCUUAGGG 18 20337 CFTR-Intron10-1454 + GGUUAAGUUGUUCUUAGGG 19 20338 CFTR-Intron10-1455 + GCCAGGUUAAGUUGUUCUUAGGG 23 20339 CFTR-Intron10-1456 + GUUACCUGGAUUGGCUACCUUGG 23 20340 CFTR-Intron10-1457 + GGAAAUGGGGUAUAAGUG 18 20341 CFTR-Intron10-107 + GUUACAUAAAAAGAGAGGUG 20 18993 CFTR-Intron10-1458 + GCUAAUAGCUUAUUCUAUACAU 22 20342 CFTR-Intron10-1459 + GAGCUAAUAGCUUAUUCUAUACAU 24 20343 CFTR-Intron10-1460 + GAAUAAUGAUGUACAUUUAAUAU 23 20344 CFTR-Intron10-1461 + GUAAUGGAAACACUAUAUAU 20 20345 CFTR-Intron10-1462 + GUACAUCCAACUAACAUCUCUAU 23 20346 CFTR-Intron10-1463 + GGAAAAUGUUAAAUUUUCCCU 21 20347 CFTR-Intron10-1464 + GCACUUGUUGACAGUCCU 18 20348 CFTR-Intron10-1465 + GGCACUUGUUGACAGUCCU 19 20349 CFTR-Intron10-1466 + GCUAGGCACUUGUUGACAGUCCU 23 20350 CFTR-Intron10-117 + GUUACUCAGUCCAGAAAGCU 20 19003 CFTR-Intron10-1467 + GUGCAAGUCCUCUGUGCU 18 20351 CFTR-Intron10-1468 + GCCAGGUUAAGUUGUUCU 18 20352 CFTR-Intron10-1469 + GAGGGUCUCUCUAAGGUGU 19 20353 CFTR-Intron10-1470 + GUGAGGGUCUCUCUAAGGUGU 21 20354 CFTR-Intron10-1471 + GGUGAGGGUCUCUCUAAGGUGU 22 20355 CFTR-Intron10-1472 + GGGUGAGGGUCUCUCUAAGGUGU 23 20356 CFTR-Intron10-1473 + GGGGUGAGGGUCUCUCUAAGGUGU 24 20357 CFTR-Intron10-1474 + GGAAAUCAGCACUCUAUU 18 20358 CFTR-Intron10-1475 + GGGAAAUCAGCACUCUAUU 19 20359 CFTR-Intron10-1476 + GGGGAAAUCAGCACUCUAUU 20 20360 CFTR-Intron10-1477 + GUGGGGAAAUCAGCACUCUAUU 22 20361 CFTR-Intron10-1478 + GUAACUCUUUAUUCACUU 18 20362 CFTR-Intron10-1479 GCUUUCAGGAGCCAAAAA 18 20363 CFTR-Intron10-1480 GAUAAGAUUCUAAAGGAAA 19 20364 CFTR-Intron10-1481 GGAUAAGAUUCUAAAGGAAA 20 20365 CFTR-Intron10-1482 GCUGGAUAAGAUUCUAAAGGAAA 23 20366 CFTR-Intron10-1483 GGCUGGAUAAGAUUCUAAAGGAAA 24 20367 CFTR-Intron10-1484 GUACUCAUGCCAUACACUCUAAA 23 20368 CFTR-Intron10-1485 GCUUUGAAGGAAGAUCCAA 19 20369 CFTR-Intron10-1486 GGAGAACCAUAUUUUGAAGAA 21 20370 CFTR-Intron10-1487 GAGGAGAACCAUAUUUUGAAGAA 23 20371 CFTR-Intron10-1488 GGGUUGAUAAGAAGAGAA 18 20372 CFTR-Intron10-68 GAGGGUUGAUAAGAAGAGAA 20 18954 CFTR-Intron10-1489 GAAAGAGGGUUGAUAAGAAGAGAA 24 20373 CFTR-Intron10-1490 GUACUUGCUCUCUGACCACAUAA 23 20374 CFTR-Intron10-1491 GUAUAUGAUAUACUCUUAA 19 20375 CFTR-Intron10-1492 GAUGUAUAUGAUAUACUCUUAA 22 20376 CFTR-Intron10-1493 GGAUGUAUAUGAUAUACUCUUAA 23 20377 CFTR-Intron10-1494 GUAUAGAAUUUUGCAUCA 18 20378 CFTR-Intron10-1495 GGUAGUAAUUGUGUUUCA 18 20379 CFTR-Intron10-1496 GAAAAGGUAGUAAUUGUGUUUCA 23 20380 CFTR-Intron10-1497 GAUCUAGCUAAAAUAUAAGA 20 20381 CFTR-Intron10-1498 GAUUCCAAGCUUUCUGGA 18 20382 CFTR-Intron10-1499 GAUAUACUCUUAAGUGAAUA 20 20383 CFTR-Intron10-1500 GAUGGAUAUUCUAUGAUAUA 20 20384 CFTR-Intron10-1501 GGAUGGAUAUUCUAUGAUAUA 21 20385 CFTR-Intron10-1502 GUUUUUGCUUGCUUUUUAUA 20 20386 CFTR-Intron10-1503 GUCUGAGAAGACAAAGCUA 19 20387 CFTR-Intron10-1504 GUAAUCGGCGGUGGAGGUA 19 20388 CFTR-Intron10-1505 GAAGUAAUCGGCGGUGGAGGUA 22 20389 CFTR-Intron10-1506 GAGAAGUAAUCGGCGGUGGAGGUA 24 20390 CFTR-Intron10-1507 GAUCAUUGCCUCACUAUGGUA 21 20391 CFTR-Intron10-1508 GUAAUAACUGGGACUCAUAUGUA 23 20392 CFTR-Intron10-1509 GAAGAUCCAAUAGGAUUA 18 20393 CFTR-Intron10-1510 GGAAGAUCCAAUAGGAUUA 19 20394 CFTR-Intron10-1511 GAAGGAAGAUCCAAUAGGAUUA 22 20395 CFTR-Intron10-1512 GCAGGAGGUGAGGGAUUA 18 20396 CFTR-Intron10-1513 GUUAGCAAUGGUCUAAAC 18 20397 CFTR-Intron10-1514 GAUUCUGUUUAAAUAGCAC 19 20398 CFTR-Intron10-1515 GAGAAGGUCAAACUUGAC 18 20399 CFTR-Intron10-1516 GUAGAGAAGGUCAAACUUGAC 21 20400 CFTR-Intron10-1517 GCCUUAUUCUUUUGAUAUACUCC 23 20401 CFTR-Intron10-1518 GUCUUGCGCUUAUGAAACUUCC 22 20402 CFTR-Intron10-1519 GCUUUUAAAACAAAAUAGC 19 20403 CFTR-Intron10-1520 GGAAGACAGCUGGCUAUC 18 20404 CFTR-Intron10-1521 GCAGGAAGACAGCUGGCUAUC 21 20405 CFTR-Intron10-1522 GCUGGCUAUCCAGGAUUC 18 20406 CFTR-Intron10-1523 GACAGCUGGCUAUCCAGGAUUC 22 20407 CFTR-Intron10-1524 GUUCUGUAAUUUUUGCUUC 19 20408 CFTR-Intron10-1525 GGUUCUGUAAUUUUUGCUUC 20 20409 CFTR-Intron10-1526 GACUUUGUAGUGAUCUUC 18 20410 CFTR-Intron10-1527 GAAGACUUUGUAGUGAUCUUC 21 20411 CFTR-Intron10-1528 GAGAAGACUUUGUAGUGAUCUUC 23 20412 CFTR-Intron10-1529 GGAGAAGACUUUGUAGUGAUCUUC 24 20413 CFTR-Intron10-1530 GCUUUUCAAAAUACUUUC 18 20414 CFTR-Intron10-1531 GAAGCUUUUCAAAAUACUUUC 21 20415 CFTR-Intron10-1532 GUAACAGUACAAGAAAAAAG 20 20416 CFTR-Intron10-99 GCAUAUGAGAAAAGUCACAG 20 18985 CFTR-Intron10-1533 GGCAUAUGAGAAAAGUCACAG 21 20417 CFTR-Intron10-1534 GAACCCAACUGAUGUCAAGCAG 22 20418 CFTR-Intron10-1535 GGAACCCAACUGAUGUCAAGCAG 23 20419 CFTR-Intron10-1536 GUAUUAGAGGUUAAGGAG 18 20420 CFTR-Intron10-1537 GUCUUUUCCUCUUAAUAG 18 20421 CFTR-Intron10-1538 GAAGUCUUUUCCUCUUAAUAG 21 20422 CFTR-Intron10-1539 GAAAAGCAGCUAUGAAGG 18 20423 CFTR-Intron10-1540 GCUUAUGAAAAGCAGCUAUGAAGG 24 20424 CFTR-Intron10-1541 GGCAUAGAGUAAGACAGG 18 20425 CFTR-Intron10-1542 GCUGGCAUAGAGUAAGACAGG 21 20426 CFTR-Intron10-1543 GGCUGGCAUAGAGUAAGACAGG 22 20427 CFTR-Intron10-1544 GAGGCUGGCAUAGAGUAAGACAGG 24 20428 CFTR-Intron10-1545 GGUAGUGUGAAGAUGGGG 18 20429 CFTR-Intron10-1546 GCUGGUAGUGUGAAGAUGGGG 21 20430 CFTR-Intron10-1547 GGCUGGUAGUGUGAAGAUGGGG 22 20431 CFTR-Intron10-1548 GGGCUGGUAGUGUGAAGAUGGGG 23 20432 CFTR-Intron10-1549 GGGGCUGGUAGUGUGAAGAUGGGG 24 20433 CFTR-Intron10-1550 GGGAAUGCAGACUCUGGG 18 20434 CFTR-Intron10-1551 GAUUAGGGAAUGCAGACUCUGGG 23 20435 CFTR-Intron10-1552 GGAUUAGGGAAUGCAGACUCUGGG 24 20436 CFTR-Intron10-1553 GGGGGAGCCCCAUAAAUG 18 20437 CFTR-Intron10-1554 GUGGGGGAGCCCCAUAAAUG 20 20438 CFTR-Intron10-1555 GUGAGAUUAGAGGCCACUG 19 20439 CFTR-Intron10-1556 GGUGAGAUUAGAGGCCACUG 20 20440 CFTR-Intron10-1557 GCACAUAUGUUCAGACUG 18 20441 CFTR-Intron10-1558 GACUUGCACAUAUGUUCAGACUG 23 20442 CFTR-Intron10-1559 GGACUUGCACAUAUGUUCAGACUG 24 20443 CFTR-Intron10-1560 GCAUCUCACCAGUGUGUG 18 20444 CFTR-Intron10-1561 GGCAUCUCACCAGUGUGUG 19 20445 CFTR-Intron10-1562 GAGGAGAACCAUAUUUUG 18 20446 CFTR-Intron10-1563 GAUGAGGAGAACCAUAUUUUG 21 20447 CFTR-Intron10-1564 GCCCCAUAAAUGUUGAAUAAU 21 20448 CFTR-Intron10-1565 GAGCCCCAUAAAUGUUGAAUAAU 23 20449 CFTR-Intron10-1566 GGAGCCCCAUAAAUGUUGAAUAAU 24 20450 CFTR-Intron10-1567 GAUUUUUUCCCAUGUAAU 18 20451 CFTR-Intron10-1568 GAAUCACUAUUGAUUGACAU 20 20452 CFTR-Intron10-1569 GUAGUUUCUAUUAAUAGAU 19 20453 CFTR-Intron10-1570 GUGUAGUUUCUAUUAAUAGAU 21 20454 CFTR-Intron10-1571 GAAAGAGCUUUCUAGUAU 18 20455 CFTR-Intron10-1572 GAGAAAGAGCUUUCUAGUAU 20 20456 CFTR-Intron10-1573 GUUCAAAUUAUUUCUACUGCU 21 20457 CFTR-Intron10-1574 GUUGUUCAAAUUAUUUCUACUGCU 24 20458 CFTR-Intron10-1575 GUAAAGACUAAGGCUUAUUUCU 22 20459 CFTR-Intron10-1576 GAUAAGAAGAGAAAGGGGUGU 21 20460 CFTR-Intron10-1577 GUUGAUAAGAAGAGAAAGGGGUGU 24 20461 CFTR-Intron10-1578 GUUGUUAUCUCUGAAAUU 18 20462 CFTR-Intron10-1579 GCUAUUACGGUAAGCUCAAGCAUU 24 20463 CFTR-Intron10-1580 GCUGCCUUUUAGUAGUAUU 19 20464 CFTR-Intron10-126 GGCUGCCUUUUAGUAGUAUU 20 19012 CFTR-Intron10-1581 GAGGCUGCCUUUUAGUAGUAUU 22 20465 CFTR-Intron10-1582 GGAGGCUGCCUUUUAGUAGUAUU 23 20466 CFTR-Intron10-1583 GAAUAGAUUAGCUUAUAUACUU 22 20467 CFTR-Intron10-1584 GUUAGAGGAAGGCAGUGGUCCCUU 24 20468 CFTR-Intron10-1585 GAUGUGCAAAAAUAGCUU 18 20469 CFTR-Intron10-1586 GAUAGAUGUGCAAAAAUAGCUU 22 20470 CFTR-Intron10-1587 GUUACAUGACCUUCCUUUCUU 21 20471 CFTR-Intron10-1588 GAUAAUGGGAGAAACAGGUU 20 20472 CFTR-Intron10-1589 GCACUGGAGUUACCUGUU 18 20473 CFTR-Intron10-1590 GCAAAUAGUUUUAUCAAUAUUU 22 20474 CFTR-Intron10-1591 GUUUUGGAUGGAGCUUGGUUU 21 20475 CFTR-Intron10-1592 GGUUUUGGAUGGAGCUUGGUUU 22 20476 CFTR-Intron10-1593 GUCCUCCACAAAUAUUUU 18 20477

Table 41B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 41B 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-1594 + CAUAUGAUUUUAUGAAAA 18 20478 CFTR-Intron10-1595 + ACAUAUGAUUUUAUGAAAA 19 20479 CFTR-Intron10-1596 + UACAUAUGAUUUUAUGAAAA 20 20480 CFTR-Intron10-1597 + UAAUACUACUGACUAAAA 18 20481 CFTR-Intron10-1598 + AUAAUACUACUGACUAAAA 19 20482 CFTR-Intron10-1599 + ACUCCAGUGCUAUUUAAA 18 20483 CFTR-Intron10-1600 + AACUCCAGUGCUAUUUAAA 19 20484 CFTR-Intron10-1601 + UAACUCCAGUGCUAUUUAAA 20 20485 CFTR-Intron10-1602 + AGGUAACUCCAGUGCUAUUUAAA 23 20486 CFTR-Intron10-1603 + CAGGUAACUCCAGUGCUAUUUAAA 24 20487 CFTR-Intron10-1604 + ACUCCAGGAGUAUAUCAA 18 20488 CFTR-Intron10-1605 + UGGACUCCAGGAGUAUAUCAA 21 20489 CFTR-Intron10-1606 + AGUGGACUCCAGGAGUAUAUCAA 23 20490 CFTR-Intron10-1607 + AAGUGGACUCCAGGAGUAUAUCAA 24 20491 CFTR-Intron10-1608 + AUGAGAGACAGUAAAGAA 18 20492 CFTR-Intron10-1104 + AGAUGAGAGACAGUAAAGAA 20 19989 CFTR-Intron10-1609 + AGGGUGGGAUAUGGAGAA 18 20493 CFTR-Intron10-1610 + UAGGGUGGGAUAUGGAGAA 19 20494 CFTR-Intron10-1611 + UUAGGGUGGGAUAUGGAGAA 20 20495 CFTR-Intron10-1612 + UUUACCAUUAUCUACACA 18 20496 CFTR-Intron10-1613 + UUUUACCAUUAUCUACACA 19 20497 CFTR-Intron10-1614 + UUUUUACCAUUAUCUACACA 20 20498 CFTR-Intron10-1615 + UAGUGAACUAGAGUCACA 18 20499 CFTR-Intron10-1616 + UUAGUGAACUAGAGUCACA 19 20500 CFTR-Intron10-1617 + AUUAGUGAACUAGAGUCACA 20 20501 CFTR-Intron10-1618 + UAUUAGUGAACUAGAGUCACA 21 20502 CFTR-Intron10-1619 + AUAUUAGUGAACUAGAGUCACA 22 20503 CFTR-Intron10-1620 + CAUAUUAGUGAACUAGAGUCACA 23 20504 CFTR-Intron10-1621 + UCAUAUUAGUGAACUAGAGUCACA 24 20505 CFTR-Intron10-1622 + UGGAGAAGAGGAUGACCA 18 20506 CFTR-Intron10-1623 + AUGGAGAAGAGGAUGACCA 19 20507 CFTR-Intron10-1624 + UAUGGAGAAGAGGAUGACCA 20 20508 CFTR-Intron10-1625 + AGAGACACACCUAAAGCA 18 20509 CFTR-Intron10-1626 + AAGAGACACACCUAAAGCA 19 20510 CFTR-Intron10-1627 + AAAGAGACACACCUAAAGCA 20 20511 CFTR-Intron10-1628 + UAGUGAUUCAUUAUAUCA 18 20512 CFTR-Intron10-1629 + AUAGUGAUUCAUUAUAUCA 19 20513 CFTR-Intron10-1630 + AAUAGUGAUUCAUUAUAUCA 20 20514 CFTR-Intron10-1631 + AUUUUUGCACAUCUAUCA 18 20515 CFTR-Intron10-1632 + UAUUUUUGCACAUCUAUCA 19 20516 CFTR-Intron10-1633 + CUAUUUUUGCACAUCUAUCA 20 20517 CFTR-Intron10-1634 + AGCUAUUUUUGCACAUCUAUCA 22 20518 CFTR-Intron10-1635 + AAGCUAUUUUUGCACAUCUAUCA 23 20519 CFTR-Intron10-1636 + AAAGCUAUUUUUGCACAUCUAUCA 24 20520 CFTR-Intron10-1637 + AAAAGGCAGCCUCCUAGA 18 20521 CFTR-Intron10-1638 + UAAAAGGCAGCCUCCUAGA 19 20522 CFTR-Intron10-1639 + CUAAAAGGCAGCCUCCUAGA 20 20523 CFTR-Intron10-375 + UGGCUACCUUGGUUGGAUGA 20 19261 CFTR-Intron10-1640 + UUGGCUACCUUGGUUGGAUGA 21 20524 CFTR-Intron10-1641 + AUUGGCUACCUUGGUUGGAUGA 22 20525 CFTR-Intron10-1642 + AGAAUAUCCAUCCAUAUGA 19 20526 CFTR-Intron10-1643 + UAGAAUAUCCAUCCAUAUGA 20 20527 CFTR-Intron10-1644 + AUAGAAUAUCCAUCCAUAUGA 21 20528 CFTR-Intron10-1645 + CAUAGAAUAUCCAUCCAUAUGA 22 20529 CFTR-Intron10-1646 + UCAUAGAAUAUCCAUCCAUAUGA 23 20530 CFTR-Intron10-1647 + AUCAUAGAAUAUCCAUCCAUAUGA 24 20531 CFTR-Intron10-1648 + AUUACCAAAUUGUAUUGA 18 20532 CFTR-Intron10-1649 + AAUUACCAAAUUGUAUUGA 19 20533 CFTR-Intron10-1650 + AAAUUACCAAAUUGUAUUGA 20 20534 CFTR-Intron10-1651 + AAAAUUACAGAACCUAUA 18 20535 CFTR-Intron10-1652 + AAAAAUUACAGAACCUAUA 19 20536 CFTR-Intron10-1170 + CAAAAAUUACAGAACCUAUA 20 20055 CFTR-Intron10-1653 + UGUUACAACAGUCUUUAUA 19 20537 CFTR-Intron10-1654 + UUGUUACAACAGUCUUUAUA 20 20538 CFTR-Intron10-1655 + UCCUCCCUUGUCUCCCUA 18 20539 CFTR-Intron10-1656 + UUCCUCCCUUGUCUCCCUA 19 20540 CFTR-Intron10-1657 + CUUCCUCCCUUGUCUCCCUA 20 20541 CFTR-Intron10-1658 + ACUUAUCCAUUAAUCCUA 18 20542 CFTR-Intron10-1659 + AACUUAUCCAUUAAUCCUA 19 20543 CFTR-Intron10-1660 + CAACUUAUCCAUUAAUCCUA 20 20544 CFTR-Intron10-1661 + UCAACUUAUCCAUUAAUCCUA 21 20545 CFTR-Intron10-1662 + UUCAACUUAUCCAUUAAUCCUA 22 20546 CFTR-Intron10-1663 + UGUUCAACUUAUCCAUUAAUCCUA 24 20547 CFTR-Intron10-1664 + ACAAAUUACCAAAUUGUA 18 20548 CFTR-Intron10-1665 + UACAAAUUACCAAAUUGUA 19 20549 CFTR-Intron10-1666 + AUACAAAUUACCAAAUUGUA 20 20550 CFTR-Intron10-1667 + UGAUACAAAUUACCAAAUUGUA 22 20551 CFTR-Intron10-1668 + CUGAUACAAAUUACCAAAUUGUA 23 20552 CFTR-Intron10-1669 + UCUGAUACAAAUUACCAAAUUGUA 24 20553 CFTR-Intron10-1670 + AGCCUGACACCAAAUUUA 18 20554 CFTR-Intron10-1671 + CAGCCUGACACCAAAUUUA 19 20555 CFTR-Intron10-1672 + CCAGCCUGACACCAAAUUUA 20 20556 CFTR-Intron10-1673 + CCCAGCCUGACACCAAAUUUA 21 20557 CFTR-Intron10-1674 + ACCCAGCCUGACACCAAAUUUA 22 20558 CFTR-Intron10-1675 + CACCCAGCCUGACACCAAAUUUA 23 20559 CFTR-Intron10-1676 + ACAAAUAUUGACUAUUUA 18 20560 CFTR-Intron10-1677 + UACAAAUAUUGACUAUUUA 19 20561 CFTR-Intron10-1678 + AGUACAAAUAUUGACUAUUUA 21 20562 CFTR-Intron10-1679 + AAGUACAAAUAUUGACUAUUUA 22 20563 CFTR-Intron10-1680 + CAAGUACAAAUAUUGACUAUUUA 23 20564 CFTR-Intron10-1681 + AGAGCUCAUAUUAGUGAAC 19 20565 CFTR-Intron10-1682 + CAGAGCUCAUAUUAGUGAAC 20 20566 CFTR-Intron10-1683 + UCAGAGCUCAUAUUAGUGAAC 21 20567 CFTR-Intron10-1684 + AUCAGAGCUCAUAUUAGUGAAC 22 20568 CFTR-Intron10-1685 + UAUCAGAGCUCAUAUUAGUGAAC 23 20569 CFTR-Intron10-1686 + UUAUCAGAGCUCAUAUUAGUGAAC 24 20570 CFTR-Intron10-1687 + UCUAUUAAUAGAAACUAC 18 20571 CFTR-Intron10-1688 + AUCUAUUAAUAGAAACUAC 19 20572 CFTR-Intron10-1689 + AAUCUAUUAAUAGAAACUAC 20 20573 CFTR-Intron10-1690 + UAAUCUAUUAAUAGAAACUAC 21 20574 CFTR-Intron10-1691 + CUAAUCUAUUAAUAGAAACUAC 22 20575 CFTR-Intron10-1692 + UCUAAUCUAUUAAUAGAAACUAC 23 20576 CFTR-Intron10-1693 + CUCUAAUCUAUUAAUAGAAACUAC 24 20577 CFTR-Intron10-1694 + UACUACUUCCACUACUAC 18 20578 CFTR-Intron10-1695 + AUACUACUUCCACUACUAC 19 20579 CFTR-Intron10-1696 + UAUACUACUUCCACUACUAC 20 20580 CFTR-Intron10-1697 + CUAUACUACUUCCACUACUAC 21 20581 CFTR-Intron10-1698 + ACUAUACUACUUCCACUACUAC 22 20582 CFTR-Intron10-1699 + UACUAUACUACUUCCACUACUAC 23 20583 CFTR-Intron10-1700 + CUACUAUACUACUUCCACUACUAC 24 20584 CFTR-Intron10-1701 + AUGAGUCCCAGUUAUUAC 18 20585 CFTR-Intron10-1702 + UAUGAGUCCCAGUUAUUAC 19 20586 CFTR-Intron10-1703 + AUAUGAGUCCCAGUUAUUAC 20 20587 CFTR-Intron10-1704 + CAUAUGAGUCCCAGUUAUUAC 21 20588 CFTR-Intron10-1705 + ACAUAUGAGUCCCAGUUAUUAC 22 20589 CFTR-Intron10-1706 + UACAUAUGAGUCCCAGUUAUUAC 23 20590 CFTR-Intron10-1707 + AUACAUAUGAGUCCCAGUUAUUAC 24 20591 CFTR-Intron10-1708 + AGAUACUAAAAAAAGUUAC 19 20592 CFTR-Intron10-1709 + AAGAUACUAAAAAAAGUUAC 20 20593 CFTR-Intron10-1710 + UAUUAGCAAGUGGACUCC 18 20594 CFTR-Intron10-426 + UGUAUUAGCAAGUGGACUCC 20 19312 CFTR-Intron10-1711 + UUGUAUUAGCAAGUGGACUCC 21 20595 CFTR-Intron10-1712 + AUUGUAUUAGCAAGUGGACUCC 22 20596 CFTR-Intron10-1713 + AAUUGUAUUAGCAAGUGGACUCC 23 20597 CFTR-Intron10-1714 + CAAUUGUAUUAGCAAGUGGACUCC 24 20598 CFTR-Intron10-1715 + UGAGCCUAUCACCUAGGC 18 20599 CFTR-Intron10-1716 + UUGAGCCUAUCACCUAGGC 19 20600 CFTR-Intron10-1717 + UUUGAGCCUAUCACCUAGGC 20 20601 CFTR-Intron10-1718 + CUAUUUAGAGUGUAUGGC 18 20602 CFTR-Intron10-1719 + UCUAUUUAGAGUGUAUGGC 19 20603 CFTR-Intron10-1720 + CUCUAUUUAGAGUGUAUGGC 20 20604 CFTR-Intron10-1721 + ACUCUAUUUAGAGUGUAUGGC 21 20605 CFTR-Intron10-1722 + CACUCUAUUUAGAGUGUAUGGC 22 20606 CFTR-Intron10-1723 + AGCACUCUAUUUAGAGUGUAUGGC 24 20607 CFTR-Intron10-1724 + AAAGGCUCUUUAUAAUGC 18 20608 CFTR-Intron10-1725 + AAAAGGCUCUUUAUAAUGC 19 20609 CFTR-Intron10-1726 + AGAAAAGGCUCUUUAUAAUGC 21 20610 CFTR-Intron10-1727 + AAGAAAAGGCUCUUUAUAAUGC 22 20611 CFTR-Intron10-1728 + AAAGAAAAGGCUCUUUAUAAUGC 23 20612 CFTR-Intron10-1729 + AAAAGAAAAGGCUCUUUAUAAUGC 24 20613 CFTR-Intron10-1730 + CUAAGAGACUCCUGAAUC 18 20614 CFTR-Intron10-1731 + UGCUAAGAGACUCCUGAAUC 20 20615 CFTR-Intron10-1732 + CUGCUAAGAGACUCCUGAAUC 21 20616 CFTR-Intron10-1733 + UCUGCUAAGAGACUCCUGAAUC 22 20617 CFTR-Intron10-1734 + UGUAGAAGACCUAAAUAUC 19 20618 CFTR-Intron10-1735 + AUGUAGAAGACCUAAAUAUC 20 20619 CFTR-Intron10-1736 + AGAUGUAGAAGACCUAAAUAUC 22 20620 CFTR-Intron10-1737 + AAGAUGUAGAAGACCUAAAUAUC 23 20621 CFTR-Intron10-1738 + UGGGUCUGCUAAGAGACUC 19 20622 CFTR-Intron10-1739 + UUGGGUCUGCUAAGAGACUC 20 20623 CFTR-Intron10-1740 + UUUGGGUCUGCUAAGAGACUC 21 20624 CFTR-Intron10-1741 + AUUUGGGUCUGCUAAGAGACUC 22 20625 CFTR-Intron10-1742 + AGAUUUGGGUCUGCUAAGAGACUC 24 20626 CFTR-Intron10-1743 + UACUAUUGCUUUCAUUAAGUC 21 20627 CFTR-Intron10-1744 + CUACUAUUGCUUUCAUUAAGUC 22 20628 CFTR-Intron10-1745 + UCUACUAUUGCUUUCAUUAAGUC 23 20629 CFTR-Intron10-1746 + CUCUACUAUUGCUUUCAUUAAGUC 24 20630 CFTR-Intron10-1747 + UAGAGACAAGGUGGUGUC 18 20631 CFTR-Intron10-1748 + AUAGAGACAAGGUGGUGUC 19 20632 CFTR-Intron10-437 + AAUAGAGACAAGGUGGUGUC 20 19323 CFTR-Intron10-1749 + UAAUAGAGACAAGGUGGUGUC 21 20633 CFTR-Intron10-1750 + AUAAUAGAGACAAGGUGGUGUC 22 20634 CFTR-Intron10-1751 + AAUAAUAGAGACAAGGUGGUGUC 23 20635 CFTR-Intron10-1752 + CAAUAAUAGAGACAAGGUGGUGUC 24 20636 CFTR-Intron10-1753 + UAUUUUUCAUUAUGAUUC 18 20637 CFTR-Intron10-1754 + AUAUUUUUCAUUAUGAUUC 19 20638 CFTR-Intron10-1755 + UUGACAUCAGUUGGGUUC 18 20639 CFTR-Intron10-1756 + CUUGACAUCAGUUGGGUUC 19 20640 CFTR-Intron10-1757 + UGCUUGACAUCAGUUGGGUUC 21 20641 CFTR-Intron10-1758 + CUGCUUGACAUCAGUUGGGUUC 22 20642 CFTR-Intron10-1759 + UCUGCUUGACAUCAGUUGGGUUC 23 20643 CFTR-Intron10-1760 + UUCUGCUUGACAUCAGUUGGGUUC 24 20644 CFTR-Intron10-1761 + UGAUAAAUAAUUGCCUUUC 19 20645 CFTR-Intron10-445 + UUGAUAAAUAAUUGCCUUUC 20 19331 CFTR-Intron10-1762 + AUUGAUAAAUAAUUGCCUUUC 21 20646 CFTR-Intron10-1763 + UAUUGAUAAAUAAUUGCCUUUC 22 20647 CFTR-Intron10-1764 + AUAUUGAUAAAUAAUUGCCUUUC 23 20648 CFTR-Intron10-1765 + UUGGAUGAGGGAAUGCAG 18 20649 CFTR-Intron10-1766 + UGGUUGGAUGAGGGAAUGCAG 21 20650 CFTR-Intron10-1767 + UUGGUUGGAUGAGGGAAUGCAG 22 20651 CFTR-Intron10-1768 + CUUGGUUGGAUGAGGGAAUGCAG 23 20652 CFTR-Intron10-1769 + CCUUGGUUGGAUGAGGGAAUGCAG 24 20653 CFTR-Intron10-1770 + CCUUCUGCUUGACAUCAG 18 20654 CFTR-Intron10-1771 + CCCUUCUGCUUGACAUCAG 19 20655 CFTR-Intron10-1772 + ACCCUUCUGCUUGACAUCAG 20 20656 CFTR-Intron10-1773 + CACCCUUCUGCUUGACAUCAG 21 20657 CFTR-Intron10-1774 + ACACCCUUCUGCUUGACAUCAG 22 20658 CFTR-Intron10-1775 + AACACCCUUCUGCUUGACAUCAG 23 20659 CFTR-Intron10-1776 + UAACACCCUUCUGCUUGACAUCAG 24 20660 CFTR-Intron10-1777 + AAUUGAUCUUGAAGACAUACG 21 20661 CFTR-Intron10-1778 + AGAAUUGAUCUUGAAGACAUACG 23 20662 CFTR-Intron10-1779 + UAGAAUUGAUCUUGAAGACAUACG 24 20663 CFTR-Intron10-1780 + ACUGUGAAUGGUGCCAGG 18 20664 CFTR-Intron10-1781 + UACUGUGAAUGGUGCCAGG 19 20665 CFTR-Intron10-1782 + UUACUGUGAAUGGUGCCAGG 20 20666 CFTR-Intron10-1783 + UUUACUGUGAAUGGUGCCAGG 21 20667 CFTR-Intron10-1784 + CUUUACUGUGAAUGGUGCCAGG 22 20668 CFTR-Intron10-1785 + UCUUUACUGUGAAUGGUGCCAGG 23 20669 CFTR-Intron10-1786 + CUCUUUACUGUGAAUGGUGCCAGG 24 20670 CFTR-Intron10-1787 + AGAUGAUUAUUAAUAGGG 18 20671 CFTR-Intron10-1788 + UAGAUGAUUAUUAAUAGGG 19 20672 CFTR-Intron10-1789 + CUAGAUGAUUAUUAAUAGGG 20 20673 CFTR-Intron10-1790 + CCUAGAUGAUUAUUAAUAGGG 21 20674 CFTR-Intron10-1791 + AGCCUAGAUGAUUAUUAAUAGGG 23 20675 CFTR-Intron10-1792 + CAGCCUAGAUGAUUAUUAAUAGGG 24 20676 CFTR-Intron10-475 + AGGUUAAGUUGUUCUUAGGG 20 19361 CFTR-Intron10-1793 + CAGGUUAAGUUGUUCUUAGGG 21 20677 CFTR-Intron10-1794 + CCAGGUUAAGUUGUUCUUAGGG 22 20678 CFTR-Intron10-1795 + UGCCAGGUUAAGUUGUUCUUAGGG 24 20679 CFTR-Intron10-1796 + UAACAAACCUUUUAUUGG 18 20680 CFTR-Intron10-1797 + UUAACAAACCUUUUAUUGG 19 20681 CFTR-Intron10-1798 + UUUAACAAACCUUUUAUUGG 20 20682 CFTR-Intron10-1799 + CUGGAUUGGCUACCUUGG 18 20683 CFTR-Intron10-1800 + CCUGGAUUGGCUACCUUGG 19 20684 CFTR-Intron10-1801 + ACCUGGAUUGGCUACCUUGG 20 20685 CFTR-Intron10-1802 + UACCUGGAUUGGCUACCUUGG 21 20686 CFTR-Intron10-1803 + UUACCUGGAUUGGCUACCUUGG 22 20687 CFTR-Intron10-1804 + AGUUACCUGGAUUGGCUACCUUGG 24 20688 CFTR-Intron10-1805 + AGGAAAUGGGGUAUAAGUG 19 20689 CFTR-Intron10-487 + AAGGAAAUGGGGUAUAAGUG 20 19373 CFTR-Intron10-1806 + UACAUAAAAAGAGAGGUG 18 20690 CFTR-Intron10-1807 + UUACAUAAAAAGAGAGGUG 19 20691 CFTR-Intron10-1808 + UGUUACAUAAAAAGAGAGGUG 21 20692 CFTR-Intron10-1809 + UUGUUACAUAAAAAGAGAGGUG 22 20693 CFTR-Intron10-1810 + AUUGUUACAUAAAAAGAGAGGUG 23 20694 CFTR-Intron10-1811 + UAUUGUUACAUAAAAAGAGAGGUG 24 20695 CFTR-Intron10-1812 + ACAGUUUCAUCUUACUUG 18 20696 CFTR-Intron10-1813 + AACAGUUUCAUCUUACUUG 19 20697 CFTR-Intron10-1814 + UAACAGUUUCAUCUUACUUG 20 20698 CFTR-Intron10-1815 + AUAACAGUUUCAUCUUACUUG 21 20699 CFTR-Intron10-1816 + UAUAACAGUUUCAUCUUACUUG 22 20700 CFTR-Intron10-1817 + UUAUAACAGUUUCAUCUUACUUG 23 20701 CFTR-Intron10-1818 + AUUAUAACAGUUUCAUCUUACUUG 24 20702 CFTR-Intron10-1819 + UAUUACAUGGGAAAAAAU 18 20703 CFTR-Intron10-1820 + UUAUUACAUGGGAAAAAAU 19 20704 CFTR-Intron10-1821 + CUUAUUACAUGGGAAAAAAU 20 20705 CFTR-Intron10-1822 + UCUUAUUACAUGGGAAAAAAU 21 20706 CFTR-Intron10-1823 + UUCUUAUUACAUGGGAAAAAAU 22 20707 CFTR-Intron10-1824 + AUUCUUAUUACAUGGGAAAAAAU 23 20708 CFTR-Intron10-1825 + AAUUCUUAUUACAUGGGAAAAAAU 24 20709 CFTR-Intron10-1826 + AUAGCUUAUUCUAUACAU 18 20710 CFTR-Intron10-1827 + AAUAGCUUAUUCUAUACAU 19 20711 CFTR-Intron10-1828 + UAAUAGCUUAUUCUAUACAU 20 20712 CFTR-Intron10-1829 + CUAAUAGCUUAUUCUAUACAU 21 20713 CFTR-Intron10-1830 + AGCUAAUAGCUUAUUCUAUACAU 23 20714 CFTR-Intron10-1831 + AUGAUGUACAUUUAAUAU 18 20715 CFTR-Intron10-1832 + AAUGAUGUACAUUUAAUAU 19 20716 CFTR-Intron10-1833 + UAAUGAUGUACAUUUAAUAU 20 20717 CFTR-Intron10-1834 + AUAAUGAUGUACAUUUAAUAU 21 20718 CFTR-Intron10-1835 + AAUAAUGAUGUACAUUUAAUAU 22 20719 CFTR-Intron10-1836 + UGAAUAAUGAUGUACAUUUAAUAU 24 20720 CFTR-Intron10-1837 + AGAUCUCUGCAAACAUAU 18 20721 CFTR-Intron10-1838 + AAGAUCUCUGCAAACAUAU 19 20722 CFTR-Intron10-1839 + UAAGAUCUCUGCAAACAUAU 20 20723 CFTR-Intron10-1840 + AUAAGAUCUCUGCAAACAUAU 21 20724 CFTR-Intron10-1841 + CAUAAGAUCUCUGCAAACAUAU 22 20725 CFTR-Intron10-1842 + ACAUAAGAUCUCUGCAAACAUAU 23 20726 CFTR-Intron10-1843 + UACAUAAGAUCUCUGCAAACAUAU 24 20727 CFTR-Intron10-1844 + AAUGGAAACACUAUAUAU 18 20728 CFTR-Intron10-1845 + UAAUGGAAACACUAUAUAU 19 20729 CFTR-Intron10-1846 + UGUAAUGGAAACACUAUAUAU 21 20730 CFTR-Intron10-1847 + AUGUAAUGGAAACACUAUAUAU 22 20731 CFTR-Intron10-1848 + AAUGUAAUGGAAACACUAUAUAU 23 20732 CFTR-Intron10-1849 + CAAUGUAAUGGAAACACUAUAUAU 24 20733 CFTR-Intron10-1850 + UCCAACUAACAUCUCUAU 18 20734 CFTR-Intron10-1851 + AUCCAACUAACAUCUCUAU 19 20735 CFTR-Intron10-1852 + CAUCCAACUAACAUCUCUAU 20 20736 CFTR-Intron10-1853 + ACAUCCAACUAACAUCUCUAU 21 20737 CFTR-Intron10-1854 + UACAUCCAACUAACAUCUCUAU 22 20738 CFTR-Intron10-1855 + UGUACAUCCAACUAACAUCUCUAU 24 20739 CFTR-Intron10-1856 + UCCUUAACCUCUAAUACU 18 20740 CFTR-Intron10-1857 + CUCCUUAACCUCUAAUACU 19 20741 CFTR-Intron10-1858 + CCUCCUUAACCUCUAAUACU 20 20742 CFTR-Intron10-1859 + ACCUCCUUAACCUCUAAUACU 21 20743 CFTR-Intron10-1860 + CACCUCCUUAACCUCUAAUACU 22 20744 CFTR-Intron10-1861 + CCACCUCCUUAACCUCUAAUACU 23 20745 CFTR-Intron10-1862 + CCCACCUCCUUAACCUCUAAUACU 24 20746 CFTR-Intron10-1863 + UGGAAAAUGUUAAAUUUUCCCU 22 20747 CFTR-Intron10-1864 + CUGGAAAAUGUUAAAUUUUCCCU 23 20748 CFTR-Intron10-1865 + UCUGGAAAAUGUUAAAUUUUCCCU 24 20749 CFTR-Intron10-516 + AGGCACUUGUUGACAGUCCU 20 19402 CFTR-Intron10-1866 + UAGGCACUUGUUGACAGUCCU 21 20750 CFTR-Intron10-1867 + CUAGGCACUUGUUGACAGUCCU 22 20751 CFTR-Intron10-1868 + UGCUAGGCACUUGUUGACAGUCCU 24 20752 CFTR-Intron10-1869 + UACUCAGUCCAGAAAGCU 18 20753 CFTR-Intron10-1870 + UUACUCAGUCCAGAAAGCU 19 20754 CFTR-Intron10-1871 + UGUGCAAGUCCUCUGUGCU 19 20755 CFTR-Intron10-1872 + AUGUGCAAGUCCUCUGUGCU 20 20756 CFTR-Intron10-1873 + UAUGUGCAAGUCCUCUGUGCU 21 20757 CFTR-Intron10-1874 + AUAUGUGCAAGUCCUCUGUGCU 22 20758 CFTR-Intron10-1875 + CAUAUGUGCAAGUCCUCUGUGCU 23 20759 CFTR-Intron10-1876 + ACAUAUGUGCAAGUCCUCUGUGCU 24 20760 CFTR-Intron10-1877 + UUAAUUGCCAGUAAGUCU 18 20761 CFTR-Intron10-1878 + UUUAAUUGCCAGUAAGUCU 19 20762 CFTR-Intron10-526 + AUUUAAUUGCCAGUAAGUCU 20 19412 CFTR-Intron10-1879 + UGCCAGGUUAAGUUGUUCU 19 20763 CFTR-Intron10-1880 + AUGCCAGGUUAAGUUGUUCU 20 20764 CFTR-Intron10-1881 + AGAGUGUAUGGCAUGAGU 18 20765 CFTR-Intron10-1882 + UAGAGUGUAUGGCAUGAGU 19 20766 CFTR-Intron10-1883 + UUAGAGUGUAUGGCAUGAGU 20 20767 CFTR-Intron10-1884 + UUUAGAGUGUAUGGCAUGAGU 21 20768 CFTR-Intron10-1885 + AUUUAGAGUGUAUGGCAUGAGU 22 20769 CFTR-Intron10-1886 + UAUUUAGAGUGUAUGGCAUGAGU 23 20770 CFTR-Intron10-1887 + CUAUUUAGAGUGUAUGGCAUGAGU 24 20771 CFTR-Intron10-1888 + AGGGUCUCUCUAAGGUGU 18 20772 CFTR-Intron10-1889 + UGAGGGUCUCUCUAAGGUGU 20 20773 CFTR-Intron10-1890 + UGGGGAAAUCAGCACUCUAUU 21 20774 CFTR-Intron10-1891 + UGUGGGGAAAUCAGCACUCUAUU 23 20775 CFTR-Intron10-1892 + CUGUGGGGAAAUCAGCACUCUAUU 24 20776 CFTR-Intron10-1893 + UGUAACUCUUUAUUCACUU 19 20777 CFTR-Intron10-1894 + UUGUAACUCUUUAUUCACUU 20 20778 CFTR-Intron10-1895 + UUUGUAACUCUUUAUUCACUU 21 20779 CFTR-Intron10-1896 + UUUUGUAACUCUUUAUUCACUU 22 20780 CFTR-Intron10-1897 + AUUUUGUAACUCUUUAUUCACUU 23 20781 CFTR-Intron10-1898 + CAUUUUGUAACUCUUUAUUCACUU 24 20782 CFTR-Intron10-1899 + UAUCAACCCUCUUUCCUU 18 20783 CFTR-Intron10-1900 + UUAUCAACCCUCUUUCCUU 19 20784 CFTR-Intron10-1901 + CUUAUCAACCCUCUUUCCUU 20 20785 CFTR-Intron10-1902 + UCUUAUCAACCCUCUUUCCUU 21 20786 CFTR-Intron10-1903 + UUCUUAUCAACCCUCUUUCCUU 22 20787 CFTR-Intron10-1904 + CUUCUUAUCAACCCUCUUUCCUU 23 20788 CFTR-Intron10-1905 + UCUUCUUAUCAACCCUCUUUCCUU 24 20789 CFTR-Intron10-1906 + UUUAUCAACAUGAAGGUU 18 20790 CFTR-Intron10-1907 + CUUUAUCAACAUGAAGGUU 19 20791 CFTR-Intron10-555 + CCUUUAUCAACAUGAAGGUU 20 19441 CFTR-Intron10-1908 UGCUUUCAGGAGCCAAAAA 19 20792 CFTR-Intron10-1909 CUGCUUUCAGGAGCCAAAAA 20 20793 CFTR-Intron10-1910 ACUGCUUUCAGGAGCCAAAAA 21 20794 CFTR-Intron10-1911 CACUGCUUUCAGGAGCCAAAAA 22 20795 CFTR-Intron10-1912 ACACUGCUUUCAGGAGCCAAAAA 23 20796 CFTR-Intron10-1913 AACACUGCUUUCAGGAGCCAAAAA 24 20797 CFTR-Intron10-1914 UUAAACACUUCUGAGAAA 18 20798 CFTR-Intron10-1915 UUUAAACACUUCUGAGAAA 19 20799 CFTR-Intron10-1096 AUUUAAACACUUCUGAGAAA 20 19981 CFTR-Intron10-1916 AUAAGAUUCUAAAGGAAA 18 20800 CFTR-Intron10-1917 UGGAUAAGAUUCUAAAGGAAA 21 20801 CFTR-Intron10-1918 CUGGAUAAGAUUCUAAAGGAAA 22 20802 CFTR-Intron10-1919 CAUGCCAUACACUCUAAA 18 20803 CFTR-Intron10-1920 UCAUGCCAUACACUCUAAA 19 20804 CFTR-Intron10-1921 CUCAUGCCAUACACUCUAAA 20 20805 CFTR-Intron10-1922 ACUCAUGCCAUACACUCUAAA 21 20806 CFTR-Intron10-1923 UACUCAUGCCAUACACUCUAAA 22 20807 CFTR-Intron10-1924 CGUACUCAUGCCAUACACUCUAAA 24 20808 CFTR-Intron10-1925 AGGUUUAAUUUUGUACAA 18 20809 CFTR-Intron10-1926 UAGGUUUAAUUUUGUACAA 19 20810 CFTR-Intron10-343 CUAGGUUUAAUUUUGUACAA 20 19229 CFTR-Intron10-1927 UCUAGGUUUAAUUUUGUACAA 21 20811 CFTR-Intron10-1928 UUCUAGGUUUAAUUUUGUACAA 22 20812 CFTR-Intron10-1929 CUUCUAGGUUUAAUUUUGUACAA 23 20813 CFTR-Intron10-1930 ACUUCUAGGUUUAAUUUUGUACAA 24 20814 CFTR-Intron10-1931 CUUUGAAGGAAGAUCCAA 18 20815 CFTR-Intron10-1932 UGCUUUGAAGGAAGAUCCAA 20 20816 CFTR-Intron10-1933 UAAUCAUCUAGGCUGCAA 18 20817 CFTR-Intron10-1934 AUAAUCAUCUAGGCUGCAA 19 20818 CFTR-Intron10-1935 AAUAAUCAUCUAGGCUGCAA 20 20819 CFTR-Intron10-1936 UAAUAAUCAUCUAGGCUGCAA 21 20820 CFTR-Intron10-1937 UUAAUAAUCAUCUAGGCUGCAA 22 20821 CFTR-Intron10-1938 AUUAAUAAUCAUCUAGGCUGCAA 23 20822 CFTR-Intron10-1939 UAUUAAUAAUCAUCUAGGCUGCAA 24 20823 CFTR-Intron10-1940 AGGAGAACCAUAUUUUGAAGAA 22 20824 CFTR-Intron10-1941 UGAGGAGAACCAUAUUUUGAAGAA 24 20825 CFTR-Intron10-1942 AGGGUUGAUAAGAAGAGAA 19 20826 CFTR-Intron10-1943 AGAGGGUUGAUAAGAAGAGAA 21 20827 CFTR-Intron10-1944 AAGAGGGUUGAUAAGAAGAGAA 22 20828 CFTR-Intron10-1945 AAAGAGGGUUGAUAAGAAGAGAA 23 20829 CFTR-Intron10-1946 UGCUCUCUGACCACAUAA 18 20830 CFTR-Intron10-1947 UUGCUCUCUGACCACAUAA 19 20831 CFTR-Intron10-1948 CUUGCUCUCUGACCACAUAA 20 20832 CFTR-Intron10-1949 ACUUGCUCUCUGACCACAUAA 21 20833 CFTR-Intron10-1950 UACUUGCUCUCUGACCACAUAA 22 20834 CFTR-Intron10-1951 UGUACUUGCUCUCUGACCACAUAA 24 20835 CFTR-Intron10-1952 UAUAUGAUAUACUCUUAA 18 20836 CFTR-Intron10-1953 UGUAUAUGAUAUACUCUUAA 20 20837 CFTR-Intron10-1954 AUGUAUAUGAUAUACUCUUAA 21 20838 CFTR-Intron10-1955 CGGAUGUAUAUGAUAUACUCUUAA 24 20839 CFTR-Intron10-1956 AACUCAUUAGGAAAAUGUACA 21 20840 CFTR-Intron10-1957 CAACUCAUUAGGAAAAUGUACA 22 20841 CFTR-Intron10-1958 CCAACUCAUUAGGAAAAUGUACA 23 20842 CFTR-Intron10-1959 ACCAACUCAUUAGGAAAAUGUACA 24 20843 CFTR-Intron10-1960 AUGAAGUUAAAAACAUCA 18 20844 CFTR-Intron10-1961 UAUGAAGUUAAAAACAUCA 19 20845 CFTR-Intron10-1962 AUAUGAAGUUAAAAACAUCA 20 20846 CFTR-Intron10-1963 AGUAUAGAAUUUUGCAUCA 19 20847 CFTR-Intron10-1964 UAGUAUAGAAUUUUGCAUCA 20 20848 CFTR-Intron10-1965 AGGUAGUAAUUGUGUUUCA 19 20849 CFTR-Intron10-1966 AAGGUAGUAAUUGUGUUUCA 20 20850 CFTR-Intron10-1967 AAAGGUAGUAAUUGUGUUUCA 21 20851 CFTR-Intron10-1968 AAAAGGUAGUAAUUGUGUUUCA 22 20852 CFTR-Intron10-1969 UGAAAAGGUAGUAAUUGUGUUUCA 24 20853 CFTR-Intron10-1970 AGAGCCUUUUCUUUUUCA 18 20854 CFTR-Intron10-1971 AAGAGCCUUUUCUUUUUCA 19 20855 CFTR-Intron10-1972 AAAGAGCCUUUUCUUUUUCA 20 20856 CFTR-Intron10-1973 UCUAGCUAAAAUAUAAGA 18 20857 CFTR-Intron10-1974 AUCUAGCUAAAAUAUAAGA 19 20858 CFTR-Intron10-1975 CUUGACCAGAAUGAAAUUAGA 21 20859 CFTR-Intron10-1976 ACUUGACCAGAAUGAAAUUAGA 22 20860 CFTR-Intron10-1977 AACUUGACCAGAAUGAAAUUAGA 23 20861 CFTR-Intron10-1978 AAACUUGACCAGAAUGAAAUUAGA 24 20862 CFTR-Intron10-1979 AGGAAAAUGUACAAAGGA 18 20863 CFTR-Intron10-1980 UAGGAAAAUGUACAAAGGA 19 20864 CFTR-Intron10-1981 UUAGGAAAAUGUACAAAGGA 20 20865 CFTR-Intron10-1982 UGAUUCCAAGCUUUCUGGA 19 20866 CFTR-Intron10-1983 AUGAUUCCAAGCUUUCUGGA 20 20867 CFTR-Intron10-1984 UAUACUCUUAAGUGAAUA 18 20868 CFTR-Intron10-1985 AUAUACUCUUAAGUGAAUA 19 20869 CFTR-Intron10-1986 UGAUAUACUCUUAAGUGAAUA 21 20870 CFTR-Intron10-1987 AUGAUAUACUCUUAAGUGAAUA 22 20871 CFTR-Intron10-1988 UAUGAUAUACUCUUAAGUGAAUA 23 20872 CFTR-Intron10-1989 AUAUGAUAUACUCUUAAGUGAAUA 24 20873 CFTR-Intron10-1990 CUAACCUUCAUGUUGAUA 18 20874 CFTR-Intron10-1991 CCUAACCUUCAUGUUGAUA 19 20875 CFTR-Intron10-1992 CCCUAACCUUCAUGUUGAUA 20 20876 CFTR-Intron10-1993 UGGAUAUUCUAUGAUAUA 18 20877 CFTR-Intron10-1994 AUGGAUAUUCUAUGAUAUA 19 20878 CFTR-Intron10-1995 UGGAUGGAUAUUCUAUGAUAUA 22 20879 CFTR-Intron10-1996 AUGGAUGGAUAUUCUAUGAUAUA 23 20880 CFTR-Intron10-1997 UAUGGAUGGAUAUUCUAUGAUAUA 24 20881 CFTR-Intron10-1998 AUACUUUCUAGAAUUAUA 18 20882 CFTR-Intron10-1999 AAUACUUUCUAGAAUUAUA 19 20883 CFTR-Intron10-2000 AAAUACUUUCUAGAAUUAUA 20 20884 CFTR-Intron10-2001 UUUUGCUUGCUUUUUAUA 18 20885 CFTR-Intron10-2002 UUUUUGCUUGCUUUUUAUA 19 20886 CFTR-Intron10-2003 UCUGAGAAGACAAAGCUA 18 20887 CFTR-Intron10-2004 AGUCUGAGAAGACAAAGCUA 20 20888 CFTR-Intron10-2005 AAGUCUGAGAAGACAAAGCUA 21 20889 CFTR-Intron10-2006 AAAGUCUGAGAAGACAAAGCUA 22 20890 CFTR-Intron10-2007 AAAAGUCUGAGAAGACAAAGCUA 23 20891 CFTR-Intron10-2008 UAAAAGUCUGAGAAGACAAAGCUA 24 20892 CFTR-Intron10-2009 AGUGAAGCAAUAUUAGUA 18 20893 CFTR-Intron10-2010 UAGUGAAGCAAUAUUAGUA 19 20894 CFTR-Intron10-2011 UUAGUGAAGCAAUAUUAGUA 20 20895 CFTR-Intron10-2012 UUUAGUGAAGCAAUAUUAGUA 21 20896 CFTR-Intron10-2013 UUUUAGUGAAGCAAUAUUAGUA 22 20897 CFTR-Intron10-2014 AUUUUAGUGAAGCAAUAUUAGUA 23 20898 CFTR-Intron10-2015 UAUUUUAGUGAAGCAAUAUUAGUA 24 20899 CFTR-Intron10-2016 UAAUCGGCGGUGGAGGUA 18 20900 CFTR-Intron10-389 AGUAAUCGGCGGUGGAGGUA 20 19275 CFTR-Intron10-2017 AAGUAAUCGGCGGUGGAGGUA 21 20901 CFTR-Intron10-2018 AGAAGUAAUCGGCGGUGGAGGUA 23 20902 CFTR-Intron10-2019 CAUUGCCUCACUAUGGUA 18 20903 CFTR-Intron10-2020 UCAUUGCCUCACUAUGGUA 19 20904 CFTR-Intron10-2021 AUCAUUGCCUCACUAUGGUA 20 20905 CFTR-Intron10-2022 UGAUCAUUGCCUCACUAUGGUA 22 20906 CFTR-Intron10-2023 UUGAUCAUUGCCUCACUAUGGUA 23 20907 CFTR-Intron10-2024 AUUGAUCAUUGCCUCACUAUGGUA 24 20908 CFTR-Intron10-2025 AACUGGGACUCAUAUGUA 18 20909 CFTR-Intron10-2026 UAACUGGGACUCAUAUGUA 19 20910 CFTR-Intron10-2027 AUAACUGGGACUCAUAUGUA 20 20911 CFTR-Intron10-2028 AAUAACUGGGACUCAUAUGUA 21 20912 CFTR-Intron10-2029 UAAUAACUGGGACUCAUAUGUA 22 20913 CFTR-Intron10-2030 UGUAAUAACUGGGACUCAUAUGUA 24 20914 CFTR-Intron10-2031 AGGAAGAUCCAAUAGGAUUA 20 20915 CFTR-Intron10-2032 AAGGAAGAUCCAAUAGGAUUA 21 20916 CFTR-Intron10-2033 UGAAGGAAGAUCCAAUAGGAUUA 23 20917 CFTR-Intron10-2034 UUGAAGGAAGAUCCAAUAGGAUUA 24 20918 CFTR-Intron10-2035 UGCAGGAGGUGAGGGAUUA 19 20919 CFTR-Intron10-394 UUGCAGGAGGUGAGGGAUUA 20 19280 CFTR-Intron10-2036 CAGCCAAUAAAAGGUUUGUUA 21 20920 CFTR-Intron10-2037 UCAGCCAAUAAAAGGUUUGUUA 22 20921 CFTR-Intron10-2038 UUCAGCCAAUAAAAGGUUUGUUA 23 20922 CFTR-Intron10-2039 AUUCAGCCAAUAAAAGGUUUGUUA 24 20923 CFTR-Intron10-2040 AGUUAGCAAUGGUCUAAAC 19 20924 CFTR-Intron10-2041 AAGUUAGCAAUGGUCUAAAC 20 20925 CFTR-Intron10-2042 AUUCUGUUUAAAUAGCAC 18 20926 CFTR-Intron10-410 UGAUUCUGUUUAAAUAGCAC 20 19296 CFTR-Intron10-2043 CUGAUUCUGUUUAAAUAGCAC 21 20927 CFTR-Intron10-2044 CCUGAUUCUGUUUAAAUAGCAC 22 20928 CFTR-Intron10-2045 CCCUGAUUCUGUUUAAAUAGCAC 23 20929 CFTR-Intron10-2046 CCCCUGAUUCUGUUUAAAUAGCAC 24 20930 CFTR-Intron10-2047 AGAGAAGGUCAAACUUGAC 19 20931 CFTR-Intron10-2048 UAGAGAAGGUCAAACUUGAC 20 20932 CFTR-Intron10-2049 AGUAGAGAAGGUCAAACUUGAC 22 20933 CFTR-Intron10-2050 UAGUAGAGAAGGUCAAACUUGAC 23 20934 CFTR-Intron10-2051 AUAGUAGAGAAGGUCAAACUUGAC 24 20935 CFTR-Intron10-2052 CUCUAUAUAAAGUGAUCC 18 20936 CFTR-Intron10-2053 UCUCUAUAUAAAGUGAUCC 19 20937 CFTR-Intron10-2054 CUCUCUAUAUAAAGUGAUCC 20 20938 CFTR-Intron10-2055 UCUCUCUAUAUAAAGUGAUCC 21 20939 CFTR-Intron10-2056 UUCUCUCUAUAUAAAGUGAUCC 22 20940 CFTR-Intron10-2057 UUUCUCUCUAUAUAAAGUGAUCC 23 20941 CFTR-Intron10-2058 AUUUCUCUCUAUAUAAAGUGAUCC 24 20942 CFTR-Intron10-2059 AUUCUUUUGAUAUACUCC 18 20943 CFTR-Intron10-2060 UAUUCUUUUGAUAUACUCC 19 20944 CFTR-Intron10-1213 UUAUUCUUUUGAUAUACUCC 20 20098 CFTR-Intron10-2061 CUUAUUCUUUUGAUAUACUCC 21 20945 CFTR-Intron10-2062 CCUUAUUCUUUUGAUAUACUCC 22 20946 CFTR-Intron10-2063 UGCCUUAUUCUUUUGAUAUACUCC 24 20947 CFTR-Intron10-2064 UGCGCUUAUGAAACUUCC 18 20948 CFTR-Intron10-2065 UUGCGCUUAUGAAACUUCC 19 20949 CFTR-Intron10-2066 CUUGCGCUUAUGAAACUUCC 20 20950 CFTR-Intron10-2067 UCUUGCGCUUAUGAAACUUCC 21 20951 CFTR-Intron10-2068 UGUCUUGCGCUUAUGAAACUUCC 23 20952 CFTR-Intron10-2069 AUGUCUUGCGCUUAUGAAACUUCC 24 20953 CFTR-Intron10-2070 AAACCAAACAAGCUUUCC 18 20954 CFTR-Intron10-2071 AAAACCAAACAAGCUUUCC 19 20955 CFTR-Intron10-2072 UAAAACCAAACAAGCUUUCC 20 20956 CFTR-Intron10-2073 CUUUUAAAACAAAAUAGC 18 20957 CFTR-Intron10-1220 AGCUUUUAAAACAAAAUAGC 20 20105 CFTR-Intron10-2074 AGGAAGACAGCUGGCUAUC 19 20958 CFTR-Intron10-2075 CAGGAAGACAGCUGGCUAUC 20 20959 CFTR-Intron10-2076 AGCAGGAAGACAGCUGGCUAUC 22 20960 CFTR-Intron10-2077 CAGCAGGAAGACAGCUGGCUAUC 23 20961 CFTR-Intron10-2078 ACAGCAGGAAGACAGCUGGCUAUC 24 20962 CFTR-Intron10-2079 AGCUGGCUAUCCAGGAUUC 19 20963 CFTR-Intron10-441 CAGCUGGCUAUCCAGGAUUC 20 19327 CFTR-Intron10-2080 ACAGCUGGCUAUCCAGGAUUC 21 20964 CFTR-Intron10-2081 AGACAGCUGGCUAUCCAGGAUUC 23 20965 CFTR-Intron10-2082 AAGACAGCUGGCUAUCCAGGAUUC 24 20966 CFTR-Intron10-2083 UUCUGUAAUUUUUGCUUC 18 20967 CFTR-Intron10-2084 AGACUUUGUAGUGAUCUUC 19 20968 CFTR-Intron10-2085 AAGACUUUGUAGUGAUCUUC 20 20969 CFTR-Intron10-2086 AGAAGACUUUGUAGUGAUCUUC 22 20970 CFTR-Intron10-2087 AGCUUUUCAAAAUACUUUC 19 20971 CFTR-Intron10-2088 AAGCUUUUCAAAAUACUUUC 20 20972 CFTR-Intron10-2089 UGAAGCUUUUCAAAAUACUUUC 22 20973 CFTR-Intron10-2090 UUGAAGCUUUUCAAAAUACUUUC 23 20974 CFTR-Intron10-2091 CUUGAAGCUUUUCAAAAUACUUUC 24 20975 CFTR-Intron10-2092 AACAGUACAAGAAAAAAG 18 20976 CFTR-Intron10-2093 UAACAGUACAAGAAAAAAG 19 20977 CFTR-Intron10-2094 UGCCAUUAACAGAUAAAG 18 20978 CFTR-Intron10-2095 UUGCCAUUAACAGAUAAAG 19 20979 CFTR-Intron10-2096 UUUGCCAUUAACAGAUAAAG 20 20980 CFTR-Intron10-2097 AUAUGAGAAAAGUCACAG 18 20981 CFTR-Intron10-2098 CAUAUGAGAAAAGUCACAG 19 20982 CFTR-Intron10-2099 UGGCAUAUGAGAAAAGUCACAG 22 20983 CFTR-Intron10-2100 AUGGCAUAUGAGAAAAGUCACAG 23 20984 CFTR-Intron10-2101 AAUGGCAUAUGAGAAAAGUCACAG 24 20985 CFTR-Intron10-2102 CCAACUGAUGUCAAGCAG 18 20986 CFTR-Intron10-2103 CCCAACUGAUGUCAAGCAG 19 20987 CFTR-Intron10-2104 ACCCAACUGAUGUCAAGCAG 20 20988 CFTR-Intron10-2105 AACCCAACUGAUGUCAAGCAG 21 20989 CFTR-Intron10-2106 CGGAACCCAACUGAUGUCAAGCAG 24 20990 CFTR-Intron10-2107 AGUAUUAGAGGUUAAGGAG 19 20991 CFTR-Intron10-2108 AAGUAUUAGAGGUUAAGGAG 20 20992 CFTR-Intron10-2109 UAAGUAUUAGAGGUUAAGGAG 21 20993 CFTR-Intron10-2110 CUAAGUAUUAGAGGUUAAGGAG 22 20994 CFTR-Intron10-2111 UCUAAGUAUUAGAGGUUAAGGAG 23 20995 CFTR-Intron10-2112 UUCUAAGUAUUAGAGGUUAAGGAG 24 20996 CFTR-Intron10-2113 AGUCUUUUCCUCUUAAUAG 19 20997 CFTR-Intron10-2114 AAGUCUUUUCCUCUUAAUAG 20 20998 CFTR-Intron10-2115 UGAAGUCUUUUCCUCUUAAUAG 22 20999 CFTR-Intron10-2116 CUGAAGUCUUUUCCUCUUAAUAG 23 21000 CFTR-Intron10-2117 CCUGAAGUCUUUUCCUCUUAAUAG 24 21001 CFTR-Intron10-2118 UGAAAAGCAGCUAUGAAGG 19 21002 CFTR-Intron10-2119 AUGAAAAGCAGCUAUGAAGG 20 21003 CFTR-Intron10-2120 UAUGAAAAGCAGCUAUGAAGG 21 21004 CFTR-Intron10-2121 UUAUGAAAAGCAGCUAUGAAGG 22 21005 CFTR-Intron10-2122 CUUAUGAAAAGCAGCUAUGAAGG 23 21006 CFTR-Intron10-2123 UUUCAACUUAUACACAGG 18 21007 CFTR-Intron10-2124 AUUUCAACUUAUACACAGG 19 21008 CFTR-Intron10-468 CAUUUCAACUUAUACACAGG 20 19354 CFTR-Intron10-2125 UCAUUUCAACUUAUACACAGG 21 21009 CFTR-Intron10-2126 AUCAUUUCAACUUAUACACAGG 22 21010 CFTR-Intron10-2127 UAUCAUUUCAACUUAUACACAGG 23 21011 CFTR-Intron10-2128 AUAUCAUUUCAACUUAUACACAGG 24 21012 CFTR-Intron10-2129 UGGCAUAGAGUAAGACAGG 19 21013 CFTR-Intron10-2130 CUGGCAUAGAGUAAGACAGG 20 21014 CFTR-Intron10-2131 AGGCUGGCAUAGAGUAAGACAGG 23 21015 CFTR-Intron10-2132 AAUAAAUUUGGUGUCAGG 18 21016 CFTR-Intron10-2133 CAAUAAAUUUGGUGUCAGG 19 21017 CFTR-Intron10-2134 UCAAUAAAUUUGGUGUCAGG 20 21018 CFTR-Intron10-2135 CUCAAUAAAUUUGGUGUCAGG 21 21019 CFTR-Intron10-2136 ACUCAAUAAAUUUGGUGUCAGG 22 21020 CFTR-Intron10-2137 CACUCAAUAAAUUUGGUGUCAGG 23 21021 CFTR-Intron10-2138 CCACUCAAUAAAUUUGGUGUCAGG 24 21022 CFTR-Intron10-2139 UGGUAGUGUGAAGAUGGGG 19 21023 CFTR-Intron10-2140 CUGGUAGUGUGAAGAUGGGG 20 21024 CFTR-Intron10-2141 AGGGAAUGCAGACUCUGGG 19 21025 CFTR-Intron10-2142 UAGGGAAUGCAGACUCUGGG 20 21026 CFTR-Intron10-2143 UUAGGGAAUGCAGACUCUGGG 21 21027 CFTR-Intron10-2144 AUUAGGGAAUGCAGACUCUGGG 22 21028 CFTR-Intron10-2145 UGGGGGAGCCCCAUAAAUG 19 21029 CFTR-Intron10-2146 UUUUUAUGUAACAAUAUG 18 21030 CFTR-Intron10-2147 CUUUUUAUGUAACAAUAUG 19 21031 CFTR-Intron10-2148 UCUUUUUAUGUAACAAUAUG 20 21032 CFTR-Intron10-2149 CUCUUUUUAUGUAACAAUAUG 21 21033 CFTR-Intron10-2150 UCUCUUUUUAUGUAACAAUAUG 22 21034 CFTR-Intron10-2151 CUCUCUUUUUAUGUAACAAUAUG 23 21035 CFTR-Intron10-2152 CCUCUCUUUUUAUGUAACAAUAUG 24 21036 CFTR-Intron10-2153 UGAGAUUAGAGGCCACUG 18 21037 CFTR-Intron10-2154 UGCACAUAUGUUCAGACUG 19 21038 CFTR-Intron10-2155 UUGCACAUAUGUUCAGACUG 20 21039 CFTR-Intron10-2156 CUUGCACAUAUGUUCAGACUG 21 21040 CFTR-Intron10-2157 ACUUGCACAUAUGUUCAGACUG 22 21041 CFTR-Intron10-2158 UGUUAAAGAAUGACUGUG 18 21042 CFTR-Intron10-2159 UUGUUAAAGAAUGACUGUG 19 21043 CFTR-Intron10-2160 UUUGUUAAAGAAUGACUGUG 20 21044 CFTR-Intron10-492 UGGCAUCUCACCAGUGUGUG 20 19378 CFTR-Intron10-2161 AUGGCAUCUCACCAGUGUGUG 21 21045 CFTR-Intron10-2162 UAUGGCAUCUCACCAGUGUGUG 22 21046 CFTR-Intron10-2163 UUAUGGCAUCUCACCAGUGUGUG 23 21047 CFTR-Intron10-2164 CUUAUGGCAUCUCACCAGUGUGUG 24 21048 CFTR-Intron10-2165 UGAGGAGAACCAUAUUUUG 19 21049 CFTR-Intron10-2166 AUGAGGAGAACCAUAUUUUG 20 21050 CFTR-Intron10-2167 AGAUGAGGAGAACCAUAUUUUG 22 21051 CFTR-Intron10-2168 AAGAUGAGGAGAACCAUAUUUUG 23 21052 CFTR-Intron10-2169 UAAGAUGAGGAGAACCAUAUUUUG 24 21053 CFTR-Intron10-2170 CCAUAAAUGUUGAAUAAU 18 21054 CFTR-Intron10-2171 CCCAUAAAUGUUGAAUAAU 19 21055 CFTR-Intron10-1331 CCCCAUAAAUGUUGAAUAAU 20 20216 CFTR-Intron10-2172 AGCCCCAUAAAUGUUGAAUAAU 22 21056 CFTR-Intron10-2173 AGAUUUUUUCCCAUGUAAU 19 21057 CFTR-Intron10-2174 CAGAUUUUUUCCCAUGUAAU 20 21058 CFTR-Intron10-2175 AUCACUAUUGAUUGACAU 18 21059 CFTR-Intron10-2176 AAUCACUAUUGAUUGACAU 19 21060 CFTR-Intron10-2177 UGAAUCACUAUUGAUUGACAU 21 21061 CFTR-Intron10-2178 AUGAAUCACUAUUGAUUGACAU 22 21062 CFTR-Intron10-2179 AAUGAAUCACUAUUGAUUGACAU 23 21063 CFTR-Intron10-2180 UAAUGAAUCACUAUUGAUUGACAU 24 21064 CFTR-Intron10-2181 UAGUUUCUAUUAAUAGAU 18 21065 CFTR-Intron10-2182 UGUAGUUUCUAUUAAUAGAU 20 21066 CFTR-Intron10-2183 CGUGUAGUUUCUAUUAAUAGAU 22 21067 CFTR-Intron10-2184 UCGUGUAGUUUCUAUUAAUAGAU 23 21068 CFTR-Intron10-2185 UUCGUGUAGUUUCUAUUAAUAGAU 24 21069 CFTR-Intron10-2186 AGAAAGAGCUUUCUAGUAU 19 21070 CFTR-Intron10-2187 AAAGCUGUGCAUUUUCCU 18 21071 CFTR-Intron10-2188 AAAAGCUGUGCAUUUUCCU 19 21072 CFTR-Intron10-2189 AAAAAGCUGUGCAUUUUCCU 20 21073 CFTR-Intron10-2190 UGUUCAAAUUAUUUCUACUGCU 22 21074 CFTR-Intron10-2191 UUGUUCAAAUUAUUUCUACUGCU 23 21075 CFTR-Intron10-2192 UGUAGGCUAUAUGUAUCU 18 21076 CFTR-Intron10-2193 CUGUAGGCUAUAUGUAUCU 19 21077 CFTR-Intron10-2194 UCUGUAGGCUAUAUGUAUCU 20 21078 CFTR-Intron10-2195 AGACUAAGGCUUAUUUCU 18 21079 CFTR-Intron10-2196 AAGACUAAGGCUUAUUUCU 19 21080 CFTR-Intron10-2197 AAAGACUAAGGCUUAUUUCU 20 21081 CFTR-Intron10-2198 UAAAGACUAAGGCUUAUUUCU 21 21082 CFTR-Intron10-2199 CGUAAAGACUAAGGCUUAUUUCU 23 21083 CFTR-Intron10-2200 UCGUAAAGACUAAGGCUUAUUUCU 24 21084 CFTR-Intron10-2201 AAGAAGAGAAAGGGGUGU 18 21085 CFTR-Intron10-2202 UAAGAAGAGAAAGGGGUGU 19 21086 CFTR-Intron10-1378 AUAAGAAGAGAAAGGGGUGU 20 20262 CFTR-Intron10-2203 UGAUAAGAAGAGAAAGGGGUGU 22 21087 CFTR-Intron10-2204 UUGAUAAGAAGAGAAAGGGGUGU 23 21088 CFTR-Intron10-2205 AGUUGUUAUCUCUGAAAUU 19 21089 CFTR-Intron10-2206 AAGUUGUUAUCUCUGAAAUU 20 21090 CFTR-Intron10-2207 CAAGUUGUUAUCUCUGAAAUU 21 21091 CFTR-Intron10-2208 UCAAGUUGUUAUCUCUGAAAUU 22 21092 CFTR-Intron10-2209 AUCAAGUUGUUAUCUCUGAAAUU 23 21093 CFTR-Intron10-2210 UAUCAAGUUGUUAUCUCUGAAAUU 24 21094 CFTR-Intron10-2211 ACGGUAAGCUCAAGCAUU 18 21095 CFTR-Intron10-2212 UACGGUAAGCUCAAGCAUU 19 21096 CFTR-Intron10-2213 UUACGGUAAGCUCAAGCAUU 20 21097 CFTR-Intron10-2214 AUUACGGUAAGCUCAAGCAUU 21 21098 CFTR-Intron10-2215 UAUUACGGUAAGCUCAAGCAUU 22 21099 CFTR-Intron10-2216 CUAUUACGGUAAGCUCAAGCAUU 23 21100 CFTR-Intron10-2217 CUGCCUUUUAGUAGUAUU 18 21101 CFTR-Intron10-2218 AGGCUGCCUUUUAGUAGUAUU 21 21102 CFTR-Intron10-2219 AGGAGGCUGCCUUUUAGUAGUAUU 24 21103 CFTR-Intron10-2220 AGAUUAGCUUAUAUACUU 18 21104 CFTR-Intron10-2221 UAGAUUAGCUUAUAUACUU 19 21105 CFTR-Intron10-550 AUAGAUUAGCUUAUAUACUU 20 19436 CFTR-Intron10-2222 AAUAGAUUAGCUUAUAUACUU 21 21106 CFTR-Intron10-2223 UGAAUAGAUUAGCUUAUAUACUU 23 21107 CFTR-Intron10-2224 UUGAAUAGAUUAGCUUAUAUACUU 24 21108 CFTR-Intron10-2225 UUUUCCAAGCGGUCCCUU 18 21109 CFTR-Intron10-2226 UUUUUCCAAGCGGUCCCUU 19 21110 CFTR-Intron10-2227 UUUUUUCCAAGCGGUCCCUU 20 21111 CFTR-Intron10-2228 UUUUUUUCCAAGCGGUCCCUU 21 21112 CFTR-Intron10-2229 UUUUUUUUCCAAGCGGUCCCUU 22 21113 CFTR-Intron10-2230 AUUUUUUUUCCAAGCGGUCCCUU 23 21114 CFTR-Intron10-2231 AAUUUUUUUUCCAAGCGGUCCCUU 24 21115 CFTR-Intron10-2232 AGAGGAAGGCAGUGGUCCCUU 21 21116 CFTR-Intron10-2233 UAGAGGAAGGCAGUGGUCCCUU 22 21117 CFTR-Intron10-2234 UUAGAGGAAGGCAGUGGUCCCUU 23 21118 CFTR-Intron10-2235 AGAUGUGCAAAAAUAGCUU 19 21119 CFTR-Intron10-552 UAGAUGUGCAAAAAUAGCUU 20 19438 CFTR-Intron10-2236 AUAGAUGUGCAAAAAUAGCUU 21 21120 CFTR-Intron10-2237 UGAUAGAUGUGCAAAAAUAGCUU 23 21121 CFTR-Intron10-2238 AUGAUAGAUGUGCAAAAAUAGCUU 24 21122 CFTR-Intron10-2239 ACAUGACCUUCCUUUCUU 18 21123 CFTR-Intron10-2240 UACAUGACCUUCCUUUCUU 19 21124 CFTR-Intron10-2241 UUACAUGACCUUCCUUUCUU 20 21125 CFTR-Intron10-2242 UGUUACAUGACCUUCCUUUCUU 22 21126 CFTR-Intron10-2243 CUGUUACAUGACCUUCCUUUCUU 23 21127 CFTR-Intron10-2244 UCUGUUACAUGACCUUCCUUUCUU 24 21128 CFTR-Intron10-2245 UAAUGGGAGAAACAGGUU 18 21129 CFTR-Intron10-2246 AUAAUGGGAGAAACAGGUU 19 21130 CFTR-Intron10-2247 AGCACUGGAGUUACCUGUU 19 21131 CFTR-Intron10-2248 UAGCACUGGAGUUACCUGUU 20 21132 CFTR-Intron10-2249 AUAGCACUGGAGUUACCUGUU 21 21133 CFTR-Intron10-2250 AAUAGCACUGGAGUUACCUGUU 22 21134 CFTR-Intron10-2251 AAAUAGCACUGGAGUUACCUGUU 23 21135 CFTR-Intron10-2252 UAAAUAGCACUGGAGUUACCUGUU 24 21136 CFTR-Intron10-2253 CAAAUAGUUUUAUCAAUAUUU 21 21137 CFTR-Intron10-2254 UGCAAAUAGUUUUAUCAAUAUUU 23 21138 CFTR-Intron10-2255 CUGCAAAUAGUUUUAUCAAUAUUU 24 21139 CFTR-Intron10-2256 UUGGAUGGAGCUUGGUUU 18 21140 CFTR-Intron10-2257 UUUGGAUGGAGCUUGGUUU 19 21141 CFTR-Intron10-563 UUUUGGAUGGAGCUUGGUUU 20 19449 CFTR-Intron10-2258 AGGUUUUGGAUGGAGCUUGGUUU 23 21142 CFTR-Intron10-2259 CAGGUUUUGGAUGGAGCUUGGUUU 24 21143 CFTR-Intron10-2260 UGUCCUCCACAAAUAUUUU 19 21144 CFTR-Intron10-2261 AUGUCCUCCACAAAUAUUUU 20 21145

Table 41C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10, start with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 41C 3rd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-2262 + GUAAGACCUAAUCUCUAAA 19 21146 CFTR-Intron10-2263 + GAGUAAGACCUAAUCUCUAAA 21 21147 CFTR-Intron10-2264 + GACAGAUGAGAGACAGUAAAGAA 23 21148 CFTR-Intron10-2265 + GGACAGAUGAGAGACAGUAAAGAA 24 21149 CFTR-Intron10-2266 + GUGUUCUCACAUGGCAGAA 19 21150 CFTR-Intron10-2267 + GCUGUGUUCUCACAUGGCAGAA 22 21151 CFTR-Intron10-2268 + GUUCUUAGGGUGGGAUAUGGAGAA 24 21152 CFTR-Intron10-2269 + GAAGAAAAGUAUCAAUAA 18 21153 CFTR-Intron10-2270 + GGAAGAAAAGUAUCAAUAA 19 21154 CFTR-Intron10-2271 + GUUUUUACCAUUAUCUACACA 21 21155 CFTR-Intron10-2272 + GAUAUGGAGAAGAGGAUGACCA 22 21156 CFTR-Intron10-2273 + GGAUAUGGAGAAGAGGAUGACCA 23 21157 CFTR-Intron10-2274 + GGGAUAUGGAGAAGAGGAUGACCA 24 21158 CFTR-Intron10-2275 + GAAGUUCAGCCUGGGUGA 18 21159 CFTR-Intron10-2276 + GCAAAAAUUACAGAACCUAUA 21 21160 CFTR-Intron10-2277 + GAAGCAAAAAUUACAGAACCUAUA 24 21161 CFTR-Intron10-2278 + GCUUCCUCCCUUGUCUCCCUA 21 21162 CFTR-Intron10-2279 + GUCUUCUCAGACUUUUAUUUUA 22 21163 CFTR-Intron10-2280 + GUUUCCAAAUUUUUUUUA 18 21164 CFTR-Intron10-2281 + GACAAGUUUCCAAAUUUUUUUUA 23 21165 CFTR-Intron10-2282 + GUGUGGCUUAUAAACAAC 18 21166 CFTR-Intron10-2283 + GAACUGUGUGGCUUAUAAACAAC 23 21167 CFTR-Intron10-2284 + GAAGAUACUAAAAAAAGUUAC 21 21168 CFTR-Intron10-2285 + GGAAGAUACUAAAAAAAGUUAC 22 21169 CFTR-Intron10-2286 + GGGAAGAUACUAAAAAAAGUUAC 23 21170 CFTR-Intron10-2287 + GAAAGGUCAAUUGAGCCC 18 21171 CFTR-Intron10-2288 + GGAAAGGUCAAUUGAGCCC 19 21172 CFTR-Intron10-2289 + GCGGAAAGGUCAAUUGAGCCC 21 21173 CFTR-Intron10-2290 + GAAGCGGAAAGGUCAAUUGAGCCC 24 21174 CFTR-Intron10-2291 + GCUACUUGGAAGACUCUUCC 20 21175 CFTR-Intron10-2292 + GAUCACACCACUGAAGUUCAGC 22 21176 CFTR-Intron10-2293 + GAGUUUCACUGUGUUAGC 18 21177 CFTR-Intron10-2294 + GGAGUUUCACUGUGUUAGC 19 21178 CFTR-Intron10-2295 + GACGGAGUUUCACUGUGUUAGC 22 21179 CFTR-Intron10-2296 + GAGACGGAGUUUCACUGUGUUAGC 24 21180 CFTR-Intron10-2297 + GUCUCACUCUGUCACCCAGGC 21 21181 CFTR-Intron10-2298 + GAGUCUCACUCUGUCACCCAGGC 23 21182 CFTR-Intron10-2299 + GCCUCUGCCUCCAAAAGUGC 20 21183 CFTR-Intron10-2300 + GCCAUUCUCCUGCCUCAGCCUC 22 21184 CFTR-Intron10-2301 + GCUCACUGCAAGUUCUGCCUC 21 21185 CFTR-Intron10-2302 + GGCUCACUGCAAGUUCUGCCUC 22 21186 CFTR-Intron10-2303 + GAUCUUCCUUCAAAGCAUGUC 21 21187 CFTR-Intron10-2304 + GGAUCUUCCUUCAAAGCAUGUC 22 21188 CFTR-Intron10-2305 + GUGAUAUUUUUCAUUAUGAUUC 22 21189 CFTR-Intron10-2306 + GGUGAUAUUUUUCAUUAUGAUUC 23 21190 CFTR-Intron10-2307 + GCUACUUGGGAGGCUGAGGCAG 22 21191 CFTR-Intron10-2308 + GCUACUUGGGAGGGUGAGGCAG 22 21192 CFTR-Intron10-701 + GUUUGUGUUUUUUGUAGAGG 20 19587 CFTR-Intron10-2309 + GCACUUUGGGAGGCCGAGGCGG 22 21193 CFTR-Intron10-2310 + GAACAAAAAUUAAAACUAAUGG 22 21194 CFTR-Intron10-2311 + GUGAACAAAAAUUAAAACUAAUGG 24 21195 CFTR-Intron10-2312 + GUAGUCCCAGCUACUUGG 18 21196 CFTR-Intron10-2313 + GCCUGUAGUCCCAGCUACUUGG 22 21197 CFTR-Intron10-2314 + GUGCCUGUAGUCCCAGCUACUUGG 24 21198 CFTR-Intron10-2315 + GCAAUACCAUCACCUUGGGAAU 22 21199 CFTR-Intron10-2316 + GAAUUAGGAUUUCAACAU 18 21200 CFTR-Intron10-2317 + GGAAUUAGGAUUUCAACAU 19 21201 CFTR-Intron10-2318 + GGGAAUUAGGAUUUCAACAU 20 21202 CFTR-Intron10-2319 + GAUCAAGGUGCCAGCAGAU 19 21203 CFTR-Intron10-2320 + GUGAUAGUUGCACAACUAU 19 21204 CFTR-Intron10-2321 + GGUGAUAGUUGCACAACUAU 20 21205 CFTR-Intron10-2322 + GAGGUGAUAGUUGCACAACUAU 22 21206 CFTR-Intron10-2323 + GGAGGUGAUAGUUGCACAACUAU 23 21207 CFTR-Intron10-2324 + GUUUAUUUACAUUUCUCUUUACU 23 21208 CFTR-Intron10-2325 + GAAAAUGUUAAAUUUUCCCU 20 21209 CFTR-Intron10-2326 + GAAAUUUAAUUGCCAGUAAGUCU 23 21210 CFTR-Intron10-2327 + GUUCUCACAUGGCAGAAAGGGGU 23 21211 CFTR-Intron10-2328 + GCAUCACUAGUGGCACUUUGU 21 21212 CFTR-Intron10-2329 + GUGCAUCACUAGUGGCACUUUGU 23 21213 CFTR-Intron10-2330 + GACCCUUUAUCAACAUGAAGGUU 23 21214 CFTR-Intron10-2331 + GAAAUAUAGAUUUAAUCUUAUUU 23 21215 CFTR-Intron10-2332 + GGAAAUAUAGAUUUAAUCUUAUUU 24 21216 CFTR-Intron10-2333 + GUAUUUCUAGGCUAGACAGUUU 22 21217 CFTR-Intron10-2334 + GGUAUUUCUAGGCUAGACAGUUU 23 21218 CFTR-Intron10-2335 + GUUCAAGCCUGUAUUGUUU 19 21219 CFTR-Intron10-2336 + GCAGUUCAAGCCUGUAUUGUUU 22 21220 CFTR-Intron10-2337 GAAUAUUUAAACACUUCUGAGAAA 24 21221 CFTR-Intron10-2338 GACAUGCUUUGAAGGAAGAUCCAA 24 21222 CFTR-Intron10-2339 GAACCAUAUUUUGAAGAA 18 21223 CFTR-Intron10-2340 GAGAACCAUAUUUUGAAGAA 20 21224 CFTR-Intron10-2341 GUAUAUUAUAGAAAUUUAA 19 21225 CFTR-Intron10-2342 GGUAUAUUAUAGAAAUUUAA 20 21226 CFTR-Intron10-2343 GACAGGUAUAUUAUAGAAAUUUAA 24 21227 CFTR-Intron10-2344 GUGGAUUUUUGACUAUACA 19 21228 CFTR-Intron10-2345 GAGGUCACUGAGGCUGGCA 19 21229 CFTR-Intron10-2346 GGAGGUCACUGAGGCUGGCA 20 21230 CFTR-Intron10-2347 GUAAGGAGGUCACUGAGGCUGGCA 24 21231 CFTR-Intron10-2348 GAUAUGAAGUUAAAAACAUCA 21 21232 CFTR-Intron10-2349 GAGAUAUGAAGUUAAAAACAUCA 23 21233 CFTR-Intron10-2350 GGAGAUAUGAAGUUAAAAACAUCA 24 21234 CFTR-Intron10-2351 GACCAGAAUGAAAUUAGA 18 21235 CFTR-Intron10-2352 GAUGAUUCCAAGCUUUCUGGA 21 21236 CFTR-Intron10-2353 GAAAUAAAUUUAAAGACAUGA 21 21237 CFTR-Intron10-2354 GGAAAUAAAUUUAAAGACAUGA 22 21238 CFTR-Intron10-2355 GAGGAAAUAAAUUUAAAGACAUGA 24 21239 CFTR-Intron10-2356 GAGAAGACAAAGCUAGUGA 19 21240 CFTR-Intron10-2357 GUCUGAGAAGACAAAGCUAGUGA 23 21241 CFTR-Intron10-2358 GCACUCUAGCCUGGGUGA 18 21242 CFTR-Intron10-2359 GCCACUGCACUCUAGCCUGGGUGA 24 21243 CFTR-Intron10-2360 GCACCCCUAACCUUCAUGUUGAUA 24 21244 CFTR-Intron10-2361 GACUUGCAGGAGGUGAGGGAUUA 23 21245 CFTR-Intron10-2362 GCCAAUAAAAGGUUUGUUA 19 21246 CFTR-Intron10-2363 GCAUAUAUAUAUUUUUAAC 19 21247 CFTR-Intron10-2364 GUGGAGUCAAAAAUUAUAC 19 21248 CFTR-Intron10-2365 GUUUAGUGCAAUGCCAUAAACC 22 21249 CFTR-Intron10-2366 GAAAAAGUAAGAUAUGCC 18 21250 CFTR-Intron10-2367 GGUGAAUUGCUUGAGUCC 18 21251 CFTR-Intron10-2368 GCAGGUGAAUUGCUUGAGUCC 21 21252 CFTR-Intron10-2369 GGCAGGUGAAUUGCUUGAGUCC 22 21253 CFTR-Intron10-2370 GAGGCAGGUGAAUUGCUUGAGUCC 24 21254 CFTR-Intron10-2371 GAAAACAAAUUUUCUUUGUUUUCC 24 21255 CFTR-Intron10-2372 GCGCCACUGCACUCUAGC 18 21256 CFTR-Intron10-2373 GAUCGCGCCACUGCACUCUAGC 22 21257 CFTR-Intron10-2374 GAGAUCGCGCCACUGCACUCUAGC 24 21258 CFTR-Intron10-2375 GGGUUUCACCGUUUUAGC 18 21259 CFTR-Intron10-2376 GGGGUUUCACCGUUUUAGC 19 21260 CFTR-Intron10-2377 GACGGGGUUUCACCGUUUUAGC 22 21261 CFTR-Intron10-2378 GAGACGGGGUUUCACCGUUUUAGC 24 21262 CFTR-Intron10-2379 GUCUCGCUCUGUCGCCCAGGC 21 21263 CFTR-Intron10-2380 GAGUCUCGCUCUGUCGCCCAGGC 23 21264 CFTR-Intron10-2381 GGAGUCUCGCUCUGUCGCCCAGGC 24 21265 CFTR-Intron10-2382 GGGUUUCACCAUGUUGGC 18 21266 CFTR-Intron10-2383 GGGGUUUCACCAUGUUGGC 19 21267 CFTR-Intron10-2384 GACGGGGUUUCACCAUGUUGGC 22 21268 CFTR-Intron10-2385 GAGACGGGGUUUCACCAUGUUGGC 24 21269 CFTR-Intron10-686 GCCUCGGCCUCCCAAAGUGC 20 19572 CFTR-Intron10-2386 GCCCGCCUCGGCCUCCCAAAGUGC 24 21270 CFTR-Intron10-2387 GCAGAGGCAGGUGAAUUGC 19 21271 CFTR-Intron10-2388 GGCAGAGGCAGGUGAAUUGC 20 21272 CFTR-Intron10-2389 GAGGCAGAGGCAGGUGAAUUGC 22 21273 CFTR-Intron10-2390 GGAGGCAGAGGCAGGUGAAUUGC 23 21274 CFTR-Intron10-2391 GCUCACUGCAAGCUCCGCCUC 21 21275 CFTR-Intron10-2392 GGCUCACUGCAAGCUCCGCCUC 22 21276 CFTR-Intron10-2393 GUUGUAACAGUACAAGAAAAAAG 23 21277 CFTR-Intron10-2394 GCUUUGCCAUUAACAGAUAAAG 22 21278 CFTR-Intron10-2395 GCACUUUUGGAGGCAGAGGCAG 22 21279 CFTR-Intron10-2396 GCUACUCGGGAGGCUGAGGCAG 22 21280 CFTR-Intron10-2397 GACAAGGGAGGAAGCAAGGAG 21 21281 CFTR-Intron10-2398 GAGACAAGGGAGGAAGCAAGGAG 23 21282 CFTR-Intron10-2399 GGAGACAAGGGAGGAAGCAAGGAG 24 21283 CFTR-Intron10-2400 GACAUCCAAAUAGAGAUGUUAG 22 21284 CFTR-Intron10-2401 GCAUAGAGUAAGACAGGGAGGG 22 21285 CFTR-Intron10-2402 GGCAUAGAGUAAGACAGGGAGGG 23 21286 CFTR-Intron10-2403 GCAUAGUAUUCUAUCAUAUGG 21 21287 CFTR-Intron10-2404 GAUGCAUAGUAUUCUAUCAUAUGG 24 21288 CFTR-Intron10-2405 GCUUUCUGGACUGAGUAACUGG 22 21289 CFTR-Intron10-2406 GUAUAUAUGUGUGUCUGG 18 21290 CFTR-Intron10-2407 GUAUGUAUAUAUGUGUGUCUGG 22 21291 CFTR-Intron10-2408 GCCCAGGCUGGAGUGCAGUGG 21 21292 CFTR-Intron10-2409 GUCGCCCAGGCUGGAGUGCAGUGG 24 21293 CFTR-Intron10-2410 GCUACUUGGGAGGCUGAGGUGG 22 21294 CFTR-Intron10-2411 GGUGGGGGAGCCCCAUAAAUG 21 21295 CFTR-Intron10-2412 GGGUGGGGGAGCCCCAUAAAUG 22 21296 CFTR-Intron10-2413 GGGUGAGAUUAGAGGCCACUG 21 21297 CFTR-Intron10-2414 GCUUCAGCCUCCCAAAGUG 19 21298 CFTR-Intron10-2415 GAACAAAGACUUGCAGGAGGUG 22 21299 CFTR-Intron10-2416 GUUUGUUAAAGAAUGACUGUG 21 21300 CFTR-Intron10-2417 GGUUUGUUAAAGAAUGACUGUG 22 21301 CFTR-Intron10-2418 GCUAUUAGUAGUUAAGUUUUUG 22 21302 CFTR-Intron10-2419 GGCUAUUAGUAGUUAAGUUUUUG 23 21303 CFTR-Intron10-2420 GGGAGGUGAUUAGUCCAU 18 21304 CFTR-Intron10-2421 GCCUUUGGGAGGUGAUUAGUCCAU 24 21305 CFTR-Intron10-2422 GAUGCAUAGUAUUCUAUCAU 20 21306 CFTR-Intron10-2423 GAUGAGAAAGAGCUUUCUAGUAU 23 21307 CFTR-Intron10-2424 GUCUGUAGGCUAUAUGUAUCU 21 21308 CFTR-Intron10-716 GCCUCGGCCUCCCAAAGUGU 20 19602 CFTR-Intron10-2425 GCCUGCCUCGGCCUCCCAAAGUGU 24 21309 CFTR-Intron10-2426 GGAAGGCAGUGGUCCCUU 18 21310 CFTR-Intron10-127 GAGGAAGGCAGUGGUCCCUU 20 19013 CFTR-Intron10-2427 GAAGCAAGGAGAUGAGUU 18 21311 CFTR-Intron10-2428 GGAAGCAAGGAGAUGAGUU 19 21312 CFTR-Intron10-2429 GAGGAAGCAAGGAGAUGAGUU 21 21313 CFTR-Intron10-2430 GGAGGAAGCAAGGAGAUGAGUU 22 21314 CFTR-Intron10-2431 GGGAGGAAGCAAGGAGAUGAGUU 23 21315 CFTR-Intron10-2432 GAAAGAUAAUGGGAGAAACAGGUU 24 21316 CFTR-Intron10-2433 GCAUGGGUCCACUUAUUU 18 21317 CFTR-Intron10-2434 GAACUGCAUGGGUCCACUUAUUU 23 21318 CFTR-Intron10-2435 GCUUUUUUGUUGUUUUUCUAGUUU 24 21319 CFTR-Intron10-2436 GUUAAUACAUUGGAAAAUUUU 21 21320 CFTR-Intron10-2437 GUAUGUCCUCCACAAAUAUUUU 22 21321

Table 41D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 10, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 41D 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-2438 + CAAAAAAGCGAAGAAAAA 18 21322 CFTR-Intron10-2439 + ACAAAAAAGCGAAGAAAAA 19 21323 CFTR-Intron10-2440 + AACAAAAAAGCGAAGAAAAA 20 21324 CFTR-Intron10-2441 + CAACAAAAAAGCGAAGAAAAA 21 21325 CFTR-Intron10-2442 + ACAACAAAAAAGCGAAGAAAAA 22 21326 CFTR-Intron10-2443 + AACAACAAAAAAGCGAAGAAAAA 23 21327 CFTR-Intron10-2444 + AAACAACAAAAAAGCGAAGAAAAA 24 21328 CFTR-Intron10-2445 + AUACAUAUGAUUUUAUGAAAA 21 21329 CFTR-Intron10-2446 + CAUACAUAUGAUUUUAUGAAAA 22 21330 CFTR-Intron10-2447 + ACAUACAUAUGAUUUUAUGAAAA 23 21331 CFTR-Intron10-2448 + UACAUACAUAUGAUUUUAUGAAAA 24 21332 CFTR-Intron10-2449 + AGAUAAUACUACUGACUAAAA 21 21333 CFTR-Intron10-2450 + AAGAUAAUACUACUGACUAAAA 22 21334 CFTR-Intron10-2451 + AAAGAUAAUACUACUGACUAAAA 23 21335 CFTR-Intron10-2452 + AAAAGAUAAUACUACUGACUAAAA 24 21336 CFTR-Intron10-2453 + AUAAACAAACAAAGGAAA 18 21337 CFTR-Intron10-2454 + AAUAAACAAACAAAGGAAA 19 21338 CFTR-Intron10-1097 + AAAUAAACAAACAAAGGAAA 20 19982 CFTR-Intron10-2455 + CAAAUAAACAAACAAAGGAAA 21 21339 CFTR-Intron10-2456 + CCAAAUAAACAAACAAAGGAAA 22 21340 CFTR-Intron10-2457 + ACCAAAUAAACAAACAAAGGAAA 23 21341 CFTR-Intron10-2458 + AACCAAAUAAACAAACAAAGGAAA 24 21342 CFTR-Intron10-2459 + UAAGACCUAAUCUCUAAA 18 21343 CFTR-Intron10-2460 + AGUAAGACCUAAUCUCUAAA 20 21344 CFTR-Intron10-2461 + AGAGUAAGACCUAAUCUCUAAA 22 21345 CFTR-Intron10-2462 + CAGAGUAAGACCUAAUCUCUAAA 23 21346 CFTR-Intron10-2463 + ACAGAGUAAGACCUAAUCUCUAAA 24 21347 CFTR-Intron10-2464 + CAGAUGAGAGACAGUAAAGAA 21 21348 CFTR-Intron10-2465 + ACAGAUGAGAGACAGUAAAGAA 22 21349 CFTR-Intron10-2466 + UGUUCUCACAUGGCAGAA 18 21350 CFTR-Intron10-1106 + UGUGUUCUCACAUGGCAGAA 20 19991 CFTR-Intron10-2467 + CUGUGUUCUCACAUGGCAGAA 21 21351 CFTR-Intron10-2468 + UGCUGUGUUCUCACAUGGCAGAA 23 21352 CFTR-Intron10-2469 + CUGCUGUGUUCUCACAUGGCAGAA 24 21353 CFTR-Intron10-2470 + CUUAGGGUGGGAUAUGGAGAA 21 21354 CFTR-Intron10-2471 + UCUUAGGGUGGGAUAUGGAGAA 22 21355 CFTR-Intron10-2472 + UUCUUAGGGUGGGAUAUGGAGAA 23 21356 CFTR-Intron10-1110 + AGGAAGAAAAGUAUCAAUAA 20 19995 CFTR-Intron10-2473 + CAGGAAGAAAAGUAUCAAUAA 21 21357 CFTR-Intron10-2474 + UCAGGAAGAAAAGUAUCAAUAA 22 21358 CFTR-Intron10-2475 + AUCAGGAAGAAAAGUAUCAAUAA 23 21359 CFTR-Intron10-2476 + AAUCAGGAAGAAAAGUAUCAAUAA 24 21360 CFTR-Intron10-2477 + AGUUUUUACCAUUAUCUACACA 22 21361 CFTR-Intron10-2478 + AAGUUUUUACCAUUAUCUACACA 23 21362 CFTR-Intron10-2479 + CAAGUUUUUACCAUUAUCUACACA 24 21363 CFTR-Intron10-2480 + AUAUGGAGAAGAGGAUGACCA 21 21364 CFTR-Intron10-2481 + AAAAGAGACACACCUAAAGCA 21 21365 CFTR-Intron10-2482 + UAAAAGAGACACACCUAAAGCA 22 21366 CFTR-Intron10-2483 + CUAAAAGAGACACACCUAAAGCA 23 21367 CFTR-Intron10-2484 + ACUAAAAGAGACACACCUAAAGCA 24 21368 CFTR-Intron10-2485 + CAAUAGUGAUUCAUUAUAUCA 21 21369 CFTR-Intron10-2486 + UCAAUAGUGAUUCAUUAUAUCA 22 21370 CFTR-Intron10-2487 + AUCAAUAGUGAUUCAUUAUAUCA 23 21371 CFTR-Intron10-2488 + AAUCAAUAGUGAUUCAUUAUAUCA 24 21372 CFTR-Intron10-2489 + UUGUAUUUUUAGUAGAGA 18 21373 CFTR-Intron10-2490 + UUUGUAUUUUUAGUAGAGA 19 21374 CFTR-Intron10-1141 + UUUUGUAUUUUUAGUAGAGA 20 20026 CFTR-Intron10-2491 + UUUUUGUAUUUUUAGUAGAGA 21 21375 CFTR-Intron10-2492 + UUUUUUGUAUUUUUAGUAGAGA 22 21376 CFTR-Intron10-2493 + AUUUUUUGUAUUUUUAGUAGAGA 23 21377 CFTR-Intron10-2494 + AAUUUUUUGUAUUUUUAGUAGAGA 24 21378 CFTR-Intron10-2495 + UAUUUAUUUAUUUAGAGA 18 21379 CFTR-Intron10-2496 + UUAUUUAUUUAUUUAGAGA 19 21380 CFTR-Intron10-2497 + UUUAUUUAUUUAUUUAGAGA 20 21381 CFTR-Intron10-2498 + AUUUAUUUAUUUAUUUAGAGA 21 21382 CFTR-Intron10-2499 + UAUUUAUUUAUUUAUUUAGAGA 22 21383 CFTR-Intron10-2500 + UUAUUUAUUUAUUUAUUUAGAGA 23 21384 CFTR-Intron10-2501 + UUUAUUUAUUUAUUUAUUUAGAGA 24 21385 CFTR-Intron10-2502 + ACUAAAAGGCAGCCUCCUAGA 21 21386 CFTR-Intron10-2503 + UACUAAAAGGCAGCCUCCUAGA 22 21387 CFTR-Intron10-2504 + CUACUAAAAGGCAGCCUCCUAGA 23 21388 CFTR-Intron10-2505 + ACUACUAAAAGGCAGCCUCCUAGA 24 21389 CFTR-Intron10-2506 + UGAAGUUCAGCCUGGGUGA 19 21390 CFTR-Intron10-2507 + CUGAAGUUCAGCCUGGGUGA 20 21391 CFTR-Intron10-2508 + ACUGAAGUUCAGCCUGGGUGA 21 21392 CFTR-Intron10-2509 + CACUGAAGUUCAGCCUGGGUGA 22 21393 CFTR-Intron10-2510 + CCACUGAAGUUCAGCCUGGGUGA 23 21394 CFTR-Intron10-2511 + ACCACUGAAGUUCAGCCUGGGUGA 24 21395 CFTR-Intron10-2512 + CAAAUUACCAAAUUGUAUUGA 21 21396 CFTR-Intron10-2513 + ACAAAUUACCAAAUUGUAUUGA 22 21397 CFTR-Intron10-2514 + UACAAAUUACCAAAUUGUAUUGA 23 21398 CFTR-Intron10-2515 + AUACAAAUUACCAAAUUGUAUUGA 24 21399 CFTR-Intron10-2516 + AGCAAAAAUUACAGAACCUAUA 22 21400 CFTR-Intron10-2517 + AAGCAAAAAUUACAGAACCUAUA 23 21401 CFTR-Intron10-2518 + UUUGUUACAACAGUCUUUAUA 21 21402 CFTR-Intron10-2519 + UUUUGUUACAACAGUCUUUAUA 22 21403 CFTR-Intron10-2520 + CUUUUGUUACAACAGUCUUUAUA 23 21404 CFTR-Intron10-2521 + UCUUUUGUUACAACAGUCUUUAUA 24 21405 CFTR-Intron10-2522 + UGCUUCCUCCCUUGUCUCCCUA 22 21406 CFTR-Intron10-2523 + UUGCUUCCUCCCUUGUCUCCCUA 23 21407 CFTR-Intron10-2524 + CUUGCUUCCUCCCUUGUCUCCCUA 24 21408 CFTR-Intron10-2525 + CCUUUGUACAUUUUCCUA 18 21409 CFTR-Intron10-2526 + UCCUUUGUACAUUUUCCUA 19 21410 CFTR-Intron10-2527 + AUCCUUUGUACAUUUUCCUA 20 21411 CFTR-Intron10-2528 + AAUCCUUUGUACAUUUUCCUA 21 21412 CFTR-Intron10-2529 + CAAUCCUUUGUACAUUUUCCUA 22 21413 CFTR-Intron10-2530 + UCAAUCCUUUGUACAUUUUCCUA 23 21414 CFTR-Intron10-2531 + UUCAAUCCUUUGUACAUUUUCCUA 24 21415 CFTR-Intron10-2532 + AGAUAAAAUUAUAAAUUA 18 21416 CFTR-Intron10-2533 + AAGAUAAAAUUAUAAAUUA 19 21417 CFTR-Intron10-2534 + AAAGAUAAAAUUAUAAAUUA 20 21418 CFTR-Intron10-2535 + UAAAGAUAAAAUUAUAAAUUA 21 21419 CFTR-Intron10-2536 + AUAAAGAUAAAAUUAUAAAUUA 22 21420 CFTR-Intron10-2537 + AAUAAAGAUAAAAUUAUAAAUUA 23 21421 CFTR-Intron10-2538 + UAAUAAAGAUAAAAUUAUAAAUUA 24 21422 CFTR-Intron10-2539 + UCUCAGACUUUUAUUUUA 18 21423 CFTR-Intron10-2540 + UUCUCAGACUUUUAUUUUA 19 21424 CFTR-Intron10-2541 + CUUCUCAGACUUUUAUUUUA 20 21425 CFTR-Intron10-2542 + UCUUCUCAGACUUUUAUUUUA 21 21426 CFTR-Intron10-2543 + UGUCUUCUCAGACUUUUAUUUUA 23 21427 CFTR-Intron10-2544 + UUGUCUUCUCAGACUUUUAUUUUA 24 21428 CFTR-Intron10-2545 + AGUUUCCAAAUUUUUUUUA 19 21429 CFTR-Intron10-2546 + AAGUUUCCAAAUUUUUUUUA 20 21430 CFTR-Intron10-2547 + CAAGUUUCCAAAUUUUUUUUA 21 21431 CFTR-Intron10-2548 + ACAAGUUUCCAAAUUUUUUUUA 22 21432 CFTR-Intron10-2549 + AGACAAGUUUCCAAAUUUUUUUUA 24 21433 CFTR-Intron10-2550 + UGUGUGGCUUAUAAACAAC 19 21434 CFTR-Intron10-1180 + CUGUGUGGCUUAUAAACAAC 20 20065 CFTR-Intron10-2551 + ACUGUGUGGCUUAUAAACAAC 21 21435 CFTR-Intron10-2552 + AACUGUGUGGCUUAUAAACAAC 22 21436 CFTR-Intron10-2553 + UGAACUGUGUGGCUUAUAAACAAC 24 21437 CFTR-Intron10-2554 + UGGGAAGAUACUAAAAAAAGUUAC 24 21438 CFTR-Intron10-1194 + CGGAAAGGUCAAUUGAGCCC 20 20079 CFTR-Intron10-2555 + AGCGGAAAGGUCAAUUGAGCCC 22 21439 CFTR-Intron10-2556 + AAGCGGAAAGGUCAAUUGAGCCC 23 21440 CFTR-Intron10-2557 + UACUUGGAAGACUCUUCC 18 21441 CFTR-Intron10-2558 + CUACUUGGAAGACUCUUCC 19 21442 CFTR-Intron10-2559 + UGCUACUUGGAAGACUCUUCC 21 21443 CFTR-Intron10-2560 + CUGCUACUUGGAAGACUCUUCC 22 21444 CFTR-Intron10-2561 + CCUGCUACUUGGAAGACUCUUCC 23 21445 CFTR-Intron10-2562 + ACCUGCUACUUGGAAGACUCUUCC 24 21446 CFTR-Intron10-2563 + ACACCACUGAAGUUCAGC 18 21447 CFTR-Intron10-2564 + CACACCACUGAAGUUCAGC 19 21448 CFTR-Intron10-2565 + UCACACCACUGAAGUUCAGC 20 21449 CFTR-Intron10-2566 + AUCACACCACUGAAGUUCAGC 21 21450 CFTR-Intron10-2567 + UGAUCACACCACUGAAGUUCAGC 23 21451 CFTR-Intron10-2568 + AUGAUCACACCACUGAAGUUCAGC 24 21452 CFTR-Intron10-2569 + CGGAGUUUCACUGUGUUAGC 20 21453 CFTR-Intron10-2570 + ACGGAGUUUCACUGUGUUAGC 21 21454 CFTR-Intron10-2571 + AGACGGAGUUUCACUGUGUUAGC 23 21455 CFTR-Intron10-2572 + UCACUCUGUCACCCAGGC 18 21456 CFTR-Intron10-2573 + CUCACUCUGUCACCCAGGC 19 21457 CFTR-Intron10-2574 + UCUCACUCUGUCACCCAGGC 20 21458 CFTR-Intron10-2575 + AGUCUCACUCUGUCACCCAGGC 22 21459 CFTR-Intron10-2576 + AGAGUCUCACUCUGUCACCCAGGC 24 21460 CFTR-Intron10-2577 + UUUUGAGCCUAUCACCUAGGC 21 21461 CFTR-Intron10-2578 + UUUUUGAGCCUAUCACCUAGGC 22 21462 CFTR-Intron10-2579 + UUUUUUGAGCCUAUCACCUAGGC 23 21463 CFTR-Intron10-2580 + UUUUUUUGAGCCUAUCACCUAGGC 24 21464 CFTR-Intron10-2581 + CUCUGCCUCCAAAAGUGC 18 21465 CFTR-Intron10-2582 + CCUCUGCCUCCAAAAGUGC 19 21466 CFTR-Intron10-2583 + UGCCUCUGCCUCCAAAAGUGC 21 21467 CFTR-Intron10-2584 + CUGCCUCUGCCUCCAAAAGUGC 22 21468 CFTR-Intron10-2585 + CCUGCCUCUGCCUCCAAAAGUGC 23 21469 CFTR-Intron10-2586 + ACCUGCCUCUGCCUCCAAAAGUGC 24 21470 CFTR-Intron10-2587 + UUCUCCUGCCUCAGCCUC 18 16501 CFTR-Intron10-2588 + AUUCUCCUGCCUCAGCCUC 19 16502 CFTR-Intron10-2589 + CAUUCUCCUGCCUCAGCCUC 20 21471 CFTR-Intron10-2590 + CCAUUCUCCUGCCUCAGCCUC 21 21472 CFTR-Intron10-2591 + CGCCAUUCUCCUGCCUCAGCCUC 23 21473 CFTR-Intron10-2592 + ACGCCAUUCUCCUGCCUCAGCCUC 24 21474 CFTR-Intron10-2593 + CACUGCAAGUUCUGCCUC 18 21475 CFTR-Intron10-2594 + UCACUGCAAGUUCUGCCUC 19 21476 CFTR-Intron10-2595 + CUCACUGCAAGUUCUGCCUC 20 21477 CFTR-Intron10-2596 + CGGCUCACUGCAAGUUCUGCCUC 23 21478 CFTR-Intron10-2597 + UCGGCUCACUGCAAGUUCUGCCUC 24 21479 CFTR-Intron10-2598 + UAUUGCUUUCAUUAAGUC 18 21480 CFTR-Intron10-2599 + CUAUUGCUUUCAUUAAGUC 19 21481 CFTR-Intron10-2600 + ACUAUUGCUUUCAUUAAGUC 20 21482 CFTR-Intron10-2601 + CUUCCUUCAAAGCAUGUC 18 21483 CFTR-Intron10-2602 + UCUUCCUUCAAAGCAUGUC 19 21484 CFTR-Intron10-2603 + AUCUUCCUUCAAAGCAUGUC 20 21485 CFTR-Intron10-2604 + UGGAUCUUCCUUCAAAGCAUGUC 23 21486 CFTR-Intron10-2605 + UUGGAUCUUCCUUCAAAGCAUGUC 24 21487 CFTR-Intron10-2606 + UGAUAUUUUUCAUUAUGAUUC 21 21488 CFTR-Intron10-2607 + UGGUGAUAUUUUUCAUUAUGAUUC 24 21489 CFTR-Intron10-2608 + CUUGGGAGGCUGAGGCAG 18 21490 CFTR-Intron10-2609 + ACUUGGGAGGCUGAGGCAG 19 21491 CFTR-Intron10-2610 + UACUUGGGAGGCUGAGGCAG 20 21492 CFTR-Intron10-2611 + CUACUUGGGAGGCUGAGGCAG 21 21493 CFTR-Intron10-2612 + AGCUACUUGGGAGGCUGAGGCAG 23 21494 CFTR-Intron10-2613 + CAGCUACUUGGGAGGCUGAGGCAG 24 21495 CFTR-Intron10-2614 + CUUGGGAGGGUGAGGCAG 18 21496 CFTR-Intron10-2615 + ACUUGGGAGGGUGAGGCAG 19 21497 CFTR-Intron10-2616 + UACUUGGGAGGGUGAGGCAG 20 21498 CFTR-Intron10-2617 + CUACUUGGGAGGGUGAGGCAG 21 21499 CFTR-Intron10-2618 + AGCUACUUGGGAGGGUGAGGCAG 23 21500 CFTR-Intron10-2619 + CAGCUACUUGGGAGGGUGAGGCAG 24 21501 CFTR-Intron10-2620 + UAAAAAUACAAAAAUUAG 18 21502 CFTR-Intron10-2621 + CUAAAAAUACAAAAAUUAG 19 21503 CFTR-Intron10-2622 + ACUAAAAAUACAAAAAUUAG 20 21504 CFTR-Intron10-2623 + UACUAAAAAUACAAAAAUUAG 21 21505 CFTR-Intron10-2624 + CUACUAAAAAUACAAAAAUUAG 22 21506 CFTR-Intron10-2625 + UCUACUAAAAAUACAAAAAUUAG 23 21507 CFTR-Intron10-2626 + CUCUACUAAAAAUACAAAAAUUAG 24 21508 CFTR-Intron10-2627 + UGAUCUUGAAGACAUACG 18 21509 CFTR-Intron10-2628 + UUGAUCUUGAAGACAUACG 19 21510 CFTR-Intron10-2629 + AUUGAUCUUGAAGACAUACG 20 21511 CFTR-Intron10-2630 + UUGUGUUUUUUGUAGAGG 18 21512 CFTR-Intron10-2631 + UUUGUGUUUUUUGUAGAGG 19 21513 CFTR-Intron10-2632 + UGUUUGUGUUUUUUGUAGAGG 21 21514 CFTR-Intron10-2633 + UUGUUUGUGUUUUUUGUAGAGG 22 21515 CFTR-Intron10-2634 + UUUGUUUGUGUUUUUUGUAGAGG 23 21516 CFTR-Intron10-2635 + UUUUGUUUGUGUUUUUUGUAGAGG 24 21517 CFTR-Intron10-2636 + UUUGGGAGGCCGAGGCGG 18 21518 CFTR-Intron10-2637 + CUUUGGGAGGCCGAGGCGG 19 21519 CFTR-Intron10-2638 + ACUUUGGGAGGCCGAGGCGG 20 21520 CFTR-Intron10-2639 + CACUUUGGGAGGCCGAGGCGG 21 21521 CFTR-Intron10-2640 + AGCACUUUGGGAGGCCGAGGCGG 23 21522 CFTR-Intron10-2641 + CAGCACUUUGGGAGGCCGAGGCGG 24 21523 CFTR-Intron10-2642 + AAAAAUUAAAACUAAUGG 18 21524 CFTR-Intron10-2643 + CAAAAAUUAAAACUAAUGG 19 21525 CFTR-Intron10-2644 + ACAAAAAUUAAAACUAAUGG 20 21526 CFTR-Intron10-2645 + AACAAAAAUUAAAACUAAUGG 21 21527 CFTR-Intron10-2646 + UGAACAAAAAUUAAAACUAAUGG 23 21528 CFTR-Intron10-2647 + CUUUAACAAACCUUUUAUUGG 21 21529 CFTR-Intron10-2648 + UCUUUAACAAACCUUUUAUUGG 22 21530 CFTR-Intron10-2649 + UUCUUUAACAAACCUUUUAUUGG 23 21531 CFTR-Intron10-2650 + AUUCUUUAACAAACCUUUUAUUGG 24 21532 CFTR-Intron10-2651 + UGUAGUCCCAGCUACUUGG 19 21533 CFTR-Intron10-2652 + CUGUAGUCCCAGCUACUUGG 20 21534 CFTR-Intron10-2653 + CCUGUAGUCCCAGCUACUUGG 21 21535 CFTR-Intron10-2654 + UGCCUGUAGUCCCAGCUACUUGG 23 21536 CFTR-Intron10-2655 + AAAGGAAAUGGGGUAUAAGUG 21 21537 CFTR-Intron10-2656 + CAAAGGAAAUGGGGUAUAAGUG 22 21538 CFTR-Intron10-2657 + ACAAAGGAAAUGGGGUAUAAGUG 23 21539 CFTR-Intron10-2658 + AACAAAGGAAAUGGGGUAUAAGUG 24 21540 CFTR-Intron10-2659 + ACUACUAAUAGCCUAUUG 18 21541 CFTR-Intron10-2660 + AACUACUAAUAGCCUAUUG 19 21542 CFTR-Intron10-2661 + UAACUACUAAUAGCCUAUUG 20 21543 CFTR-Intron10-2662 + UUAACUACUAAUAGCCUAUUG 21 21544 CFTR-Intron10-2663 + CUUAACUACUAAUAGCCUAUUG 22 21545 CFTR-Intron10-2664 + ACUUAACUACUAAUAGCCUAUUG 23 21546 CFTR-Intron10-2665 + AACUUAACUACUAAUAGCCUAUUG 24 21547 CFTR-Intron10-2666 + UAAAACUAAUGGCAGAAU 18 21548 CFTR-Intron10-2667 + UUAAAACUAAUGGCAGAAU 19 21549 CFTR-Intron10-2668 + AUUAAAACUAAUGGCAGAAU 20 21550 CFTR-Intron10-2669 + AAUUAAAACUAAUGGCAGAAU 21 21551 CFTR-Intron10-2670 + AAAUUAAAACUAAUGGCAGAAU 22 21552 CFTR-Intron10-2671 + AAAAUUAAAACUAAUGGCAGAAU 23 21553 CFTR-Intron10-2672 + AAAAAUUAAAACUAAUGGCAGAAU 24 21554 CFTR-Intron10-2673 + UACCAUCACCUUGGGAAU 18 21555 CFTR-Intron10-2674 + AUACCAUCACCUUGGGAAU 19 21556 CFTR-Intron10-2675 + AAUACCAUCACCUUGGGAAU 20 21557 CFTR-Intron10-2676 + CAAUACCAUCACCUUGGGAAU 21 21558 CFTR-Intron10-2677 + UGCAAUACCAUCACCUUGGGAAU 23 21559 CFTR-Intron10-2678 + CUGCAAUACCAUCACCUUGGGAAU 24 21560 CFTR-Intron10-2679 + UGGGAAUUAGGAUUUCAACAU 21 21561 CFTR-Intron10-2680 + UUGGGAAUUAGGAUUUCAACAU 22 21562 CFTR-Intron10-2681 + CUUGGGAAUUAGGAUUUCAACAU 23 21563 CFTR-Intron10-2682 + CCUUGGGAAUUAGGAUUUCAACAU 24 21564 CFTR-Intron10-2683 + AUCAAGGUGCCAGCAGAU 18 21565 CFTR-Intron10-2684 + AGAUCAAGGUGCCAGCAGAU 20 21566 CFTR-Intron10-2685 + AAGAUCAAGGUGCCAGCAGAU 21 21567 CFTR-Intron10-2686 + CAAGAUCAAGGUGCCAGCAGAU 22 21568 CFTR-Intron10-2687 + CCAAGAUCAAGGUGCCAGCAGAU 23 21569 CFTR-Intron10-2688 + UCCAAGAUCAAGGUGCCAGCAGAU 24 21570 CFTR-Intron10-2689 + UGAUAGUUGCACAACUAU 18 21571 CFTR-Intron10-2690 + AGGUGAUAGUUGCACAACUAU 21 21572 CFTR-Intron10-2691 + AGGAGGUGAUAGUUGCACAACUAU 24 21573 CFTR-Intron10-2692 + UUUACAUUUCUCUUUACU 18 21574 CFTR-Intron10-2693 + AUUUACAUUUCUCUUUACU 19 21575 CFTR-Intron10-2694 + UAUUUACAUUUCUCUUUACU 20 21576 CFTR-Intron10-2695 + UUAUUUACAUUUCUCUUUACU 21 21577 CFTR-Intron10-2696 + UUUAUUUACAUUUCUCUUUACU 22 21578 CFTR-Intron10-2697 + UGUUUAUUUACAUUUCUCUUUACU 24 21579 CFTR-Intron10-2698 + AAAUGUUAAAUUUUCCCU 18 21580 CFTR-Intron10-2699 + AAAAUGUUAAAUUUUCCCU 19 21581 CFTR-Intron10-2700 + AGUUACUCAGUCCAGAAAGCU 21 21582 CFTR-Intron10-2701 + CAGUUACUCAGUCCAGAAAGCU 22 21583 CFTR-Intron10-2702 + CCAGUUACUCAGUCCAGAAAGCU 23 21584 CFTR-Intron10-2703 + UCCAGUUACUCAGUCCAGAAAGCU 24 21585 CFTR-Intron10-2704 + AAUUUAAUUGCCAGUAAGUCU 21 21586 CFTR-Intron10-2705 + AAAUUUAAUUGCCAGUAAGUCU 22 21587 CFTR-Intron10-2706 + UGAAAUUUAAUUGCCAGUAAGUCU 24 21588 CFTR-Intron10-2707 + UAUGCCAGGUUAAGUUGUUCU 21 21589 CFTR-Intron10-2708 + AUAUGCCAGGUUAAGUUGUUCU 22 21590 CFTR-Intron10-2709 + AAUAUGCCAGGUUAAGUUGUUCU 23 21591 CFTR-Intron10-2710 + AAAUAUGCCAGGUUAAGUUGUUCU 24 21592 CFTR-Intron10-2711 + CACAUGGCAGAAAGGGGU 18 21593 CFTR-Intron10-2712 + UCACAUGGCAGAAAGGGGU 19 21594 CFTR-Intron10-2713 + CUCACAUGGCAGAAAGGGGU 20 21595 CFTR-Intron10-2714 + UCUCACAUGGCAGAAAGGGGU 21 21596 CFTR-Intron10-2715 + UUCUCACAUGGCAGAAAGGGGU 22 21597 CFTR-Intron10-2716 + UGUUCUCACAUGGCAGAAAGGGGU 24 21598 CFTR-Intron10-2717 + UCACUAGUGGCACUUUGU 18 21599 CFTR-Intron10-2718 + AUCACUAGUGGCACUUUGU 19 21600 CFTR-Intron10-2719 + CAUCACUAGUGGCACUUUGU 20 21601 CFTR-Intron10-2720 + UGCAUCACUAGUGGCACUUUGU 22 21602 CFTR-Intron10-2721 + CGUGCAUCACUAGUGGCACUUUGU 24 21603 CFTR-Intron10-2722 + CUGCAAUACCAUCACCUU 18 21604 CFTR-Intron10-2723 + CCUGCAAUACCAUCACCUU 19 21605 CFTR-Intron10-1395 + CCCUGCAAUACCAUCACCUU 20 20279 CFTR-Intron10-2724 + ACCCUGCAAUACCAUCACCUU 21 21606 CFTR-Intron10-2725 + CACCCUGCAAUACCAUCACCUU 22 21607 CFTR-Intron10-2726 + CCACCCUGCAAUACCAUCACCUU 23 21608 CFTR-Intron10-2727 + CCCACCCUGCAAUACCAUCACCUU 24 21609 CFTR-Intron10-2728 + AUAAAAGAAAUGCAAGUU 18 21610 CFTR-Intron10-2729 + AAUAAAAGAAAUGCAAGUU 19 21611 CFTR-Intron10-2730 + UAAUAAAAGAAAUGCAAGUU 20 21612 CFTR-Intron10-2731 + AUAAUAAAAGAAAUGCAAGUU 21 21613 CFTR-Intron10-2732 + UAUAAUAAAAGAAAUGCAAGUU 22 21614 CFTR-Intron10-2733 + UUAUAAUAAAAGAAAUGCAAGUU 23 21615 CFTR-Intron10-2734 + CUUAUAAUAAAAGAAAUGCAAGUU 24 21616 CFTR-Intron10-2735 + CCCUUUAUCAACAUGAAGGUU 21 21617 CFTR-Intron10-2736 + ACCCUUUAUCAACAUGAAGGUU 22 21618 CFTR-Intron10-2737 + UGACCCUUUAUCAACAUGAAGGUU 24 21619 CFTR-Intron10-2738 + AUAGAUUUAAUCUUAUUU 18 21620 CFTR-Intron10-2739 + UAUAGAUUUAAUCUUAUUU 19 21621 CFTR-Intron10-2740 + AUAUAGAUUUAAUCUUAUUU 20 21622 CFTR-Intron10-2741 + AAUAUAGAUUUAAUCUUAUUU 21 21623 CFTR-Intron10-2742 + AAAUAUAGAUUUAAUCUUAUUU 22 21624 CFTR-Intron10-2743 + UUCUAGGCUAGACAGUUU 18 21625 CFTR-Intron10-2744 + UUUCUAGGCUAGACAGUUU 19 21626 CFTR-Intron10-2745 + AUUUCUAGGCUAGACAGUUU 20 21627 CFTR-Intron10-2746 + UAUUUCUAGGCUAGACAGUUU 21 21628 CFTR-Intron10-2747 + CGGUAUUUCUAGGCUAGACAGUUU 24 21629 CFTR-Intron10-2748 + UUCAAGCCUGUAUUGUUU 18 21630 CFTR-Intron10-2749 + AGUUCAAGCCUGUAUUGUUU 20 21631 CFTR-Intron10-2750 + CAGUUCAAGCCUGUAUUGUUU 21 21632 CFTR-Intron10-2751 + UGCAGUUCAAGCCUGUAUUGUUU 23 21633 CFTR-Intron10-2752 + AUGCAGUUCAAGCCUGUAUUGUUU 24 21634 CFTR-Intron10-2753 UAUUUAAACACUUCUGAGAAA 21 21635 CFTR-Intron10-2754 AUAUUUAAACACUUCUGAGAAA 22 21636 CFTR-Intron10-2755 AAUAUUUAAACACUUCUGAGAAA 23 21637 CFTR-Intron10-2756 AUGCUUUGAAGGAAGAUCCAA 21 21638 CFTR-Intron10-2757 CAUGCUUUGAAGGAAGAUCCAA 22 21639 CFTR-Intron10-2758 ACAUGCUUUGAAGGAAGAUCCAA 23 21640 CFTR-Intron10-2759 AGAACCAUAUUUUGAAGAA 19 21641 CFTR-Intron10-2760 UAUAUUAUAGAAAUUUAA 18 21642 CFTR-Intron10-2761 AGGUAUAUUAUAGAAAUUUAA 21 21643 CFTR-Intron10-2762 CAGGUAUAUUAUAGAAAUUUAA 22 21644 CFTR-Intron10-2763 ACAGGUAUAUUAUAGAAAUUUAA 23 21645 CFTR-Intron10-2764 UGGAUUUUUGACUAUACA 18 21646 CFTR-Intron10-2765 CGUGGAUUUUUGACUAUACA 20 21647 CFTR-Intron10-2766 ACGUGGAUUUUUGACUAUACA 21 21648 CFTR-Intron10-2767 UACGUGGAUUUUUGACUAUACA 22 21649 CFTR-Intron10-2768 AUACGUGGAUUUUUGACUAUACA 23 21650 CFTR-Intron10-2769 UAUACGUGGAUUUUUGACUAUACA 24 21651 CFTR-Intron10-2770 UCAUUAGGAAAAUGUACA 18 21652 CFTR-Intron10-2771 CUCAUUAGGAAAAUGUACA 19 21653 CFTR-Intron10-2772 ACUCAUUAGGAAAAUGUACA 20 21654 CFTR-Intron10-2773 AGGUCACUGAGGCUGGCA 18 21655 CFTR-Intron10-2774 AGGAGGUCACUGAGGCUGGCA 21 21656 CFTR-Intron10-2775 AAGGAGGUCACUGAGGCUGGCA 22 21657 CFTR-Intron10-2776 UAAGGAGGUCACUGAGGCUGGCA 23 21658 CFTR-Intron10-2777 AGAUAUGAAGUUAAAAACAUCA 22 21659 CFTR-Intron10-2778 UUAGUAUAGAAUUUUGCAUCA 21 21660 CFTR-Intron10-2779 AUUAGUAUAGAAUUUUGCAUCA 22 21661 CFTR-Intron10-2780 UAUUAGUAUAGAAUUUUGCAUCA 23 21662 CFTR-Intron10-2781 AUAUUAGUAUAGAAUUUUGCAUCA 24 21663 CFTR-Intron10-2782 UAAAGAGCCUUUUCUUUUUCA 21 21664 CFTR-Intron10-2783 AUAAAGAGCCUUUUCUUUUUCA 22 21665 CFTR-Intron10-2784 UAUAAAGAGCCUUUUCUUUUUCA 23 21666 CFTR-Intron10-2785 UUAUAAAGAGCCUUUUCUUUUUCA 24 21667 CFTR-Intron10-2786 AGAUCUAGCUAAAAUAUAAGA 21 21668 CFTR-Intron10-2787 AAGAUCUAGCUAAAAUAUAAGA 22 21669 CFTR-Intron10-2788 AAAGAUCUAGCUAAAAUAUAAGA 23 21670 CFTR-Intron10-2789 AAAAGAUCUAGCUAAAAUAUAAGA 24 21671 CFTR-Intron10-2790 AUUUUUGUAUUUUUAGUAGAGA 22 21672 CFTR-Intron10-2791 AAUUUUUGUAUUUUUAGUAGAGA 23 21673 CFTR-Intron10-2792 UAAUUUUUGUAUUUUUAGUAGAGA 24 21674 CFTR-Intron10-2793 UUACUAUUAUUUUUGAGA 18 21675 CFTR-Intron10-2794 AUUACUAUUAUUUUUGAGA 19 21676 CFTR-Intron10-2795 UAUUACUAUUAUUUUUGAGA 20 21677 CFTR-Intron10-2796 AUAUUACUAUUAUUUUUGAGA 21 21678 CFTR-Intron10-2797 AAUAUUACUAUUAUUUUUGAGA 22 21679 CFTR-Intron10-2798 UAAUAUUACUAUUAUUUUUGAGA 23 21680 CFTR-Intron10-2799 UUAAUAUUACUAUUAUUUUUGAGA 24 21681 CFTR-Intron10-2800 UUUUUUUUUUUUUUGAGA 18 21682 CFTR-Intron10-2801 UUUUUUUUUUUUUUUGAGA 19 21683 CFTR-Intron10-1142 UUUUUUUUUUUUUUUUGAGA 20 20027 CFTR-Intron10-2802 UUUUUUUUUUUUUUUUUGAGA 21 21684 CFTR-Intron10-2803 UUUUUUUUUUUUUUUUUUGAGA 22 21685 CFTR-Intron10-2804 UUUUUUUUUUUUUUUUUUUGAGA 23 21686 CFTR-Intron10-2805 UUUUUUUUUUUUUUUUUUUUGAGA 24 21687 CFTR-Intron10-2806 UGACCAGAAUGAAAUUAGA 19 21688 CFTR-Intron10-2807 UUGACCAGAAUGAAAUUAGA 20 21689 CFTR-Intron10-2808 AUUAGGAAAAUGUACAAAGGA 21 21690 CFTR-Intron10-2809 CAUUAGGAAAAUGUACAAAGGA 22 21691 CFTR-Intron10-2810 UCAUUAGGAAAAUGUACAAAGGA 23 21692 CFTR-Intron10-2811 CUCAUUAGGAAAAUGUACAAAGGA 24 21693 CFTR-Intron10-2812 AGAUGAUUCCAAGCUUUCUGGA 22 21694 CFTR-Intron10-2813 AAGAUGAUUCCAAGCUUUCUGGA 23 21695 CFTR-Intron10-2814 AAAGAUGAUUCCAAGCUUUCUGGA 24 21696 CFTR-Intron10-2815 AUAAAUUUAAAGACAUGA 18 21697 CFTR-Intron10-2816 AAUAAAUUUAAAGACAUGA 19 21698 CFTR-Intron10-2817 AAAUAAAUUUAAAGACAUGA 20 21699 CFTR-Intron10-2818 AGGAAAUAAAUUUAAAGACAUGA 23 21700 CFTR-Intron10-2819 AGAAGACAAAGCUAGUGA 18 21701 CFTR-Intron10-2820 UGAGAAGACAAAGCUAGUGA 20 21702 CFTR-Intron10-2821 CUGAGAAGACAAAGCUAGUGA 21 21703 CFTR-Intron10-2822 UCUGAGAAGACAAAGCUAGUGA 22 21704 CFTR-Intron10-2823 AGUCUGAGAAGACAAAGCUAGUGA 24 21705 CFTR-Intron10-2824 UGCACUCUAGCCUGGGUGA 19 21706 CFTR-Intron10-2825 CUGCACUCUAGCCUGGGUGA 20 21707 CFTR-Intron10-2826 ACUGCACUCUAGCCUGGGUGA 21 21708 CFTR-Intron10-2827 CACUGCACUCUAGCCUGGGUGA 22 21709 CFTR-Intron10-2828 CCACUGCACUCUAGCCUGGGUGA 23 21710 CFTR-Intron10-2829 CCCCUAACCUUCAUGUUGAUA 21 21711 CFTR-Intron10-2830 ACCCCUAACCUUCAUGUUGAUA 22 21712 CFTR-Intron10-2831 CACCCCUAACCUUCAUGUUGAUA 23 21713 CFTR-Intron10-2832 AAAAUACUUUCUAGAAUUAUA 21 21714 CFTR-Intron10-2833 CAAAAUACUUUCUAGAAUUAUA 22 21715 CFTR-Intron10-2834 UCAAAAUACUUUCUAGAAUUAUA 23 21716 CFTR-Intron10-2835 UUCAAAAUACUUUCUAGAAUUAUA 24 21717 CFTR-Intron10-2836 CGUUUUUGCUUGCUUUUUAUA 21 21718 CFTR-Intron10-2837 ACGUUUUUGCUUGCUUUUUAUA 22 21719 CFTR-Intron10-2838 CACGUUUUUGCUUGCUUUUUAUA 23 21720 CFTR-Intron10-2839 UCACGUUUUUGCUUGCUUUUUAUA 24 21721 CFTR-Intron10-2840 CUUGCAGGAGGUGAGGGAUUA 21 21722 CFTR-Intron10-2841 ACUUGCAGGAGGUGAGGGAUUA 22 21723 CFTR-Intron10-2842 AGACUUGCAGGAGGUGAGGGAUUA 24 21724 CFTR-Intron10-2843 CCAAUAAAAGGUUUGUUA 18 21725 CFTR-Intron10-2844 AGCCAAUAAAAGGUUUGUUA 20 21726 CFTR-Intron10-2845 UAAGUUAGCAAUGGUCUAAAC 21 21727 CFTR-Intron10-2846 AUAAGUUAGCAAUGGUCUAAAC 22 21728 CFTR-Intron10-2847 AAUAAGUUAGCAAUGGUCUAAAC 23 21729 CFTR-Intron10-2848 AAAUAAGUUAGCAAUGGUCUAAAC 24 21730 CFTR-Intron10-2849 UAAACUUUGUUUUUCAAC 18 21731 CFTR-Intron10-2850 UUAAACUUUGUUUUUCAAC 19 21732 CFTR-Intron10-2851 UUUAAACUUUGUUUUUCAAC 20 21733 CFTR-Intron10-2852 AUUUAAACUUUGUUUUUCAAC 21 21734 CFTR-Intron10-2853 UAUUUAAACUUUGUUUUUCAAC 22 21735 CFTR-Intron10-2854 AUAUUUAAACUUUGUUUUUCAAC 23 21736 CFTR-Intron10-2855 CAUAUUUAAACUUUGUUUUUCAAC 24 21737 CFTR-Intron10-2856 CAUAUAUAUAUUUUUAAC 18 21738 CFTR-Intron10-2857 UGCAUAUAUAUAUUUUUAAC 20 21739 CFTR-Intron10-2858 AUGCAUAUAUAUAUUUUUAAC 21 21740 CFTR-Intron10-2859 UAUGCAUAUAUAUAUUUUUAAC 22 21741 CFTR-Intron10-2860 AUAUGCAUAUAUAUAUUUUUAAC 23 21742 CFTR-Intron10-2861 AAUAUGCAUAUAUAUAUUUUUAAC 24 21743 CFTR-Intron10-2862 UGGAGUCAAAAAUUAUAC 18 21744 CFTR-Intron10-2863 UGUGGAGUCAAAAAUUAUAC 20 21745 CFTR-Intron10-2864 UUGUGGAGUCAAAAAUUAUAC 21 21746 CFTR-Intron10-2865 UUUGUGGAGUCAAAAAUUAUAC 22 21747 CFTR-Intron10-2866 UUUUGUGGAGUCAAAAAUUAUAC 23 21748 CFTR-Intron10-2867 UUUUUGUGGAGUCAAAAAUUAUAC 24 21749 CFTR-Intron10-2868 AGUGCAAUGCCAUAAACC 18 21750 CFTR-Intron10-2869 UAGUGCAAUGCCAUAAACC 19 21751 CFTR-Intron10-2870 UUAGUGCAAUGCCAUAAACC 20 21752 CFTR-Intron10-2871 UUUAGUGCAAUGCCAUAAACC 21 21753 CFTR-Intron10-2872 UGUUUAGUGCAAUGCCAUAAACC 23 21754 CFTR-Intron10-2873 AUGUUUAGUGCAAUGCCAUAAACC 24 21755 CFTR-Intron10-2874 AGAAAAAGUAAGAUAUGCC 19 21756 CFTR-Intron10-2875 AAGAAAAAGUAAGAUAUGCC 20 21757 CFTR-Intron10-2876 UAAGAAAAAGUAAGAUAUGCC 21 21758 CFTR-Intron10-2877 UUAAGAAAAAGUAAGAUAUGCC 22 21759 CFTR-Intron10-2878 AUUAAGAAAAAGUAAGAUAUGCC 23 21760 CFTR-Intron10-2879 AAUUAAGAAAAAGUAAGAUAUGCC 24 21761 CFTR-Intron10-2880 AGGUGAAUUGCUUGAGUCC 19 21762 CFTR-Intron10-1217 CAGGUGAAUUGCUUGAGUCC 20 20102 CFTR-Intron10-2881 AGGCAGGUGAAUUGCUUGAGUCC 23 21763 CFTR-Intron10-2882 CUAAAACCAAACAAGCUUUCC 21 21764 CFTR-Intron10-2883 ACUAAAACCAAACAAGCUUUCC 22 21765 CFTR-Intron10-2884 UACUAAAACCAAACAAGCUUUCC 23 21766 CFTR-Intron10-2885 CUACUAAAACCAAACAAGCUUUCC 24 21767 CFTR-Intron10-2886 AAAUUUUCUUUGUUUUCC 18 21768 CFTR-Intron10-2887 CAAAUUUUCUUUGUUUUCC 19 21769 CFTR-Intron10-2888 ACAAAUUUUCUUUGUUUUCC 20 21770 CFTR-Intron10-2889 AACAAAUUUUCUUUGUUUUCC 21 21771 CFTR-Intron10-2890 AAACAAAUUUUCUUUGUUUUCC 22 21772 CFTR-Intron10-2891 AAAACAAAUUUUCUUUGUUUUCC 23 21773 CFTR-Intron10-2892 CAGCUUUUAAAACAAAAUAGC 21 21774 CFTR-Intron10-2893 ACAGCUUUUAAAACAAAAUAGC 22 21775 CFTR-Intron10-2894 AACAGCUUUUAAAACAAAAUAGC 23 21776 CFTR-Intron10-2895 AAACAGCUUUUAAAACAAAAUAGC 24 21777 CFTR-Intron10-2896 CGCGCCACUGCACUCUAGC 19 21778 CFTR-Intron10-2897 UCGCGCCACUGCACUCUAGC 20 21779 CFTR-Intron10-2898 AUCGCGCCACUGCACUCUAGC 21 21780 CFTR-Intron10-2899 AGAUCGCGCCACUGCACUCUAGC 23 21781 CFTR-Intron10-1224 CGGGGUUUCACCGUUUUAGC 20 20109 CFTR-Intron10-2900 ACGGGGUUUCACCGUUUUAGC 21 21782 CFTR-Intron10-2901 AGACGGGGUUUCACCGUUUUAGC 23 21783 CFTR-Intron10-2902 UCGCUCUGUCGCCCAGGC 18 21784 CFTR-Intron10-2903 CUCGCUCUGUCGCCCAGGC 19 21785 CFTR-Intron10-1226 UCUCGCUCUGUCGCCCAGGC 20 20111 CFTR-Intron10-2904 AGUCUCGCUCUGUCGCCCAGGC 22 21786 CFTR-Intron10-2905 CGGGGUUUCACCAUGUUGGC 20 21787 CFTR-Intron10-2906 ACGGGGUUUCACCAUGUUGGC 21 21788 CFTR-Intron10-2907 AGACGGGGUUUCACCAUGUUGGC 23 21789 CFTR-Intron10-2908 AAUACAGGCUUGAACUGC 18 21790 CFTR-Intron10-2909 CAAUACAGGCUUGAACUGC 19 21791 CFTR-Intron10-2910 ACAAUACAGGCUUGAACUGC 20 21792 CFTR-Intron10-2911 AACAAUACAGGCUUGAACUGC 21 21793 CFTR-Intron10-2912 AAACAAUACAGGCUUGAACUGC 22 21794 CFTR-Intron10-2913 UAAACAAUACAGGCUUGAACUGC 23 21795 CFTR-Intron10-2914 UUAAACAAUACAGGCUUGAACUGC 24 21796 CFTR-Intron10-2915 CUCGGCCUCCCAAAGUGC 18 21797 CFTR-Intron10-2916 CCUCGGCCUCCCAAAGUGC 19 21798 CFTR-Intron10-2917 CGCCUCGGCCUCCCAAAGUGC 21 21799 CFTR-Intron10-2918 CCGCCUCGGCCUCCCAAAGUGC 22 21800 CFTR-Intron10-2919 CCCGCCUCGGCCUCCCAAAGUGC 23 21801 CFTR-Intron10-2920 CAGAGGCAGGUGAAUUGC 18 21802 CFTR-Intron10-2921 AGGCAGAGGCAGGUGAAUUGC 21 21803 CFTR-Intron10-2922 UGGAGGCAGAGGCAGGUGAAUUGC 24 21804 CFTR-Intron10-2923 CACUGCAAGCUCCGCCUC 18 21805 CFTR-Intron10-2924 UCACUGCAAGCUCCGCCUC 19 21806 CFTR-Intron10-2925 CUCACUGCAAGCUCCGCCUC 20 21807 CFTR-Intron10-2926 CGGCUCACUGCAAGCUCCGCCUC 23 21808 CFTR-Intron10-2927 UCGGCUCACUGCAAGCUCCGCCUC 24 21809 CFTR-Intron10-2928 AGGUUCUGUAAUUUUUGCUUC 21 21810 CFTR-Intron10-2929 UAGGUUCUGUAAUUUUUGCUUC 22 21811 CFTR-Intron10-2930 AUAGGUUCUGUAAUUUUUGCUUC 23 21812 CFTR-Intron10-2931 UAUAGGUUCUGUAAUUUUUGCUUC 24 21813 CFTR-Intron10-2932 UGUAACAGUACAAGAAAAAAG 21 21814 CFTR-Intron10-2933 UUGUAACAGUACAAGAAAAAAG 22 21815 CFTR-Intron10-2934 AGUUGUAACAGUACAAGAAAAAAG 24 21816 CFTR-Intron10-2935 CUUUGCCAUUAACAGAUAAAG 21 21817 CFTR-Intron10-2936 UGCUUUGCCAUUAACAGAUAAAG 23 21818 CFTR-Intron10-2937 UUGCUUUGCCAUUAACAGAUAAAG 24 21819 CFTR-Intron10-2938 UUUUGGAGGCAGAGGCAG 18 21820 CFTR-Intron10-2939 CUUUUGGAGGCAGAGGCAG 19 21821 CFTR-Intron10-2940 ACUUUUGGAGGCAGAGGCAG 20 21822 CFTR-Intron10-2941 CACUUUUGGAGGCAGAGGCAG 21 21823 CFTR-Intron10-2942 AGCACUUUUGGAGGCAGAGGCAG 23 21824 CFTR-Intron10-2943 UAGCACUUUUGGAGGCAGAGGCAG 24 21825 CFTR-Intron10-2944 CUCGGGAGGCUGAGGCAG 18 21826 CFTR-Intron10-2945 ACUCGGGAGGCUGAGGCAG 19 21827 CFTR-Intron10-2946 UACUCGGGAGGCUGAGGCAG 20 21828 CFTR-Intron10-2947 CUACUCGGGAGGCUGAGGCAG 21 21829 CFTR-Intron10-2948 AGCUACUCGGGAGGCUGAGGCAG 23 21830 CFTR-Intron10-2949 CAGCUACUCGGGAGGCUGAGGCAG 24 21831 CFTR-Intron10-2950 AAGGGAGGAAGCAAGGAG 18 21832 CFTR-Intron10-2951 CAAGGGAGGAAGCAAGGAG 19 21833 CFTR-Intron10-2952 ACAAGGGAGGAAGCAAGGAG 20 21834 CFTR-Intron10-2953 AGACAAGGGAGGAAGCAAGGAG 22 21835 CFTR-Intron10-2954 ACAAACAAAAGAAAAUAG 18 21836 CFTR-Intron10-2955 CACAAACAAAAGAAAAUAG 19 21837 CFTR-Intron10-2956 ACACAAACAAAAGAAAAUAG 20 21838 CFTR-Intron10-2957 AACACAAACAAAAGAAAAUAG 21 21839 CFTR-Intron10-2958 AAACACAAACAAAAGAAAAUAG 22 21840 CFTR-Intron10-2959 AAAACACAAACAAAAGAAAAUAG 23 21841 CFTR-Intron10-2960 AAAAACACAAACAAAAGAAAAUAG 24 21842 CFTR-Intron10-2961 UCCAAAUAGAGAUGUUAG 18 21843 CFTR-Intron10-2962 AUCCAAAUAGAGAUGUUAG 19 21844 CFTR-Intron10-2963 CAUCCAAAUAGAGAUGUUAG 20 21845 CFTR-Intron10-2964 ACAUCCAAAUAGAGAUGUUAG 21 21846 CFTR-Intron10-2965 UGACAUCCAAAUAGAGAUGUUAG 23 21847 CFTR-Intron10-2966 UUGACAUCCAAAUAGAGAUGUUAG 24 21848 CFTR-Intron10-2967 AGAGUAAGACAGGGAGGG 18 21849 CFTR-Intron10-2968 UAGAGUAAGACAGGGAGGG 19 21850 CFTR-Intron10-2969 AUAGAGUAAGACAGGGAGGG 20 21851 CFTR-Intron10-2970 CAUAGAGUAAGACAGGGAGGG 21 21852 CFTR-Intron10-2971 UGGCAUAGAGUAAGACAGGGAGGG 24 21853 CFTR-Intron10-2972 UAGUAUUCUAUCAUAUGG 18 21854 CFTR-Intron10-2973 AUAGUAUUCUAUCAUAUGG 19 21855 CFTR-Intron10-2974 CAUAGUAUUCUAUCAUAUGG 20 21856 CFTR-Intron10-2975 UGCAUAGUAUUCUAUCAUAUGG 22 21857 CFTR-Intron10-2976 AUGCAUAGUAUUCUAUCAUAUGG 23 21858 CFTR-Intron10-2977 UCUGGACUGAGUAACUGG 18 21859 CFTR-Intron10-2978 UUCUGGACUGAGUAACUGG 19 21860 CFTR-Intron10-2979 UUUCUGGACUGAGUAACUGG 20 21861 CFTR-Intron10-2980 CUUUCUGGACUGAGUAACUGG 21 21862 CFTR-Intron10-2981 AGCUUUCUGGACUGAGUAACUGG 23 21863 CFTR-Intron10-2982 AAGCUUUCUGGACUGAGUAACUGG 24 21864 CFTR-Intron10-2983 UGUAUAUAUGUGUGUCUGG 19 21865 CFTR-Intron10-2984 AUGUAUAUAUGUGUGUCUGG 20 21866 CFTR-Intron10-2985 UAUGUAUAUAUGUGUGUCUGG 21 21867 CFTR-Intron10-2986 UGUAUGUAUAUAUGUGUGUCUGG 23 21868 CFTR-Intron10-2987 AUGUAUGUAUAUAUGUGUGUCUGG 24 21869 CFTR-Intron10-2988 CAGGCUGGAGUGCAGUGG 18 21870 CFTR-Intron10-2989 CCAGGCUGGAGUGCAGUGG 19 21871 CFTR-Intron10-1304 CCCAGGCUGGAGUGCAGUGG 20 20189 CFTR-Intron10-2990 CGCCCAGGCUGGAGUGCAGUGG 22 21872 CFTR-Intron10-2991 UCGCCCAGGCUGGAGUGCAGUGG 23 21873 CFTR-Intron10-2992 CUUGGGAGGCUGAGGUGG 18 21874 CFTR-Intron10-2993 ACUUGGGAGGCUGAGGUGG 19 21875 CFTR-Intron10-2994 UACUUGGGAGGCUGAGGUGG 20 21876 CFTR-Intron10-2995 CUACUUGGGAGGCUGAGGUGG 21 21877 CFTR-Intron10-2996 AGCUACUUGGGAGGCUGAGGUGG 23 21878 CFTR-Intron10-2997 CAGCUACUUGGGAGGCUGAGGUGG 24 21879 CFTR-Intron10-2998 UGGGUGGGGGAGCCCCAUAAAUG 23 21880 CFTR-Intron10-2999 UUGGGUGGGGGAGCCCCAUAAAUG 24 21881 CFTR-Intron10-3000 AAUUAGCCAGACGUGAUG 18 21882 CFTR-Intron10-3001 AAAUUAGCCAGACGUGAUG 19 21883 CFTR-Intron10-3002 AAAAUUAGCCAGACGUGAUG 20 21884 CFTR-Intron10-3003 AAAAAUUAGCCAGACGUGAUG 21 21885 CFTR-Intron10-3004 AAAAAAUUAGCCAGACGUGAUG 22 21886 CFTR-Intron10-3005 CAAAAAAUUAGCCAGACGUGAUG 23 21887 CFTR-Intron10-3006 ACAAAAAAUUAGCCAGACGUGAUG 24 21888 CFTR-Intron10-3007 UGGGUGAGAUUAGAGGCCACUG 22 21889 CFTR-Intron10-3008 CUGGGUGAGAUUAGAGGCCACUG 23 21890 CFTR-Intron10-3009 UCUGGGUGAGAUUAGAGGCCACUG 24 21891 CFTR-Intron10-3010 CUUCAGCCUCCCAAAGUG 18 21892 CFTR-Intron10-3011 CGCUUCAGCCUCCCAAAGUG 20 21893 CFTR-Intron10-3012 CCGCUUCAGCCUCCCAAAGUG 21 21894 CFTR-Intron10-3013 UCCGCUUCAGCCUCCCAAAGUG 22 21895 CFTR-Intron10-3014 UUCCGCUUCAGCCUCCCAAAGUG 23 21896 CFTR-Intron10-3015 UUUCCGCUUCAGCCUCCCAAAGUG 24 21897 CFTR-Intron10-3016 AAAGACUUGCAGGAGGUG 18 21898 CFTR-Intron10-3017 CAAAGACUUGCAGGAGGUG 19 21899 CFTR-Intron10-1317 ACAAAGACUUGCAGGAGGUG 20 20202 CFTR-Intron10-3018 AACAAAGACUUGCAGGAGGUG 21 21900 CFTR-Intron10-3019 UGAACAAAGACUUGCAGGAGGUG 23 21901 CFTR-Intron10-3020 UUGAACAAAGACUUGCAGGAGGUG 24 21902 CFTR-Intron10-3021 AGGUUUGUUAAAGAAUGACUGUG 23 21903 CFTR-Intron10-3022 AAGGUUUGUUAAAGAAUGACUGUG 24 21904 CFTR-Intron10-3023 CCCAAGGUGAUGGUAUUG 18 21905 CFTR-Intron10-3024 UCCCAAGGUGAUGGUAUUG 19 21906 CFTR-Intron10-3025 UUCCCAAGGUGAUGGUAUUG 20 21907 CFTR-Intron10-3026 AUUCCCAAGGUGAUGGUAUUG 21 21908 CFTR-Intron10-3027 AAUUCCCAAGGUGAUGGUAUUG 22 21909 CFTR-Intron10-3028 UAAUUCCCAAGGUGAUGGUAUUG 23 21910 CFTR-Intron10-3029 CUAAUUCCCAAGGUGAUGGUAUUG 24 21911 CFTR-Intron10-3030 UUAGUAGUUAAGUUUUUG 18 21912 CFTR-Intron10-3031 AUUAGUAGUUAAGUUUUUG 19 21913 CFTR-Intron10-1325 UAUUAGUAGUUAAGUUUUUG 20 20210 CFTR-Intron10-3032 CUAUUAGUAGUUAAGUUUUUG 21 21914 CFTR-Intron10-3033 AGGCUAUUAGUAGUUAAGUUUUUG 24 21915 CFTR-Intron10-3034 UCAGAUUUUUUCCCAUGUAAU 21 21916 CFTR-Intron10-3035 UUCAGAUUUUUUCCCAUGUAAU 22 21917 CFTR-Intron10-3036 AUUCAGAUUUUUUCCCAUGUAAU 23 21918 CFTR-Intron10-3037 AAUUCAGAUUUUUUCCCAUGUAAU 24 21919 CFTR-Intron10-3038 UGGGAGGUGAUUAGUCCAU 19 21920 CFTR-Intron10-3039 UUGGGAGGUGAUUAGUCCAU 20 21921 CFTR-Intron10-3040 UUUGGGAGGUGAUUAGUCCAU 21 21922 CFTR-Intron10-3041 CUUUGGGAGGUGAUUAGUCCAU 22 21923 CFTR-Intron10-3042 CCUUUGGGAGGUGAUUAGUCCAU 23 21924 CFTR-Intron10-3043 UGCAUAGUAUUCUAUCAU 18 21925 CFTR-Intron10-3044 AUGCAUAGUAUUCUAUCAU 19 21926 CFTR-Intron10-3045 AGAUGCAUAGUAUUCUAUCAU 21 21927 CFTR-Intron10-3046 UAGAUGCAUAGUAUUCUAUCAU 22 21928 CFTR-Intron10-3047 AUAGAUGCAUAGUAUUCUAUCAU 23 21929 CFTR-Intron10-3048 AAUAGAUGCAUAGUAUUCUAUCAU 24 21930 CFTR-Intron10-3049 UGAGAAAGAGCUUUCUAGUAU 21 21931 CFTR-Intron10-3050 AUGAGAAAGAGCUUUCUAGUAU 22 21932 CFTR-Intron10-3051 AGAUGAGAAAGAGCUUUCUAGUAU 24 21933 CFTR-Intron10-3052 UAAAAAGCUGUGCAUUUUCCU 21 21934 CFTR-Intron10-3053 UUAAAAAGCUGUGCAUUUUCCU 22 21935 CFTR-Intron10-3054 UUUAAAAAGCUGUGCAUUUUCCU 23 21936 CFTR-Intron10-3055 UUUUAAAAAGCUGUGCAUUUUCCU 24 21937 CFTR-Intron10-3056 CAAAUUAUUUCUACUGCU 18 21938 CFTR-Intron10-3057 UCAAAUUAUUUCUACUGCU 19 21939 CFTR-Intron10-521 UUCAAAUUAUUUCUACUGCU 20 19407 CFTR-Intron10-3058 UGUCUGUAGGCUAUAUGUAUCU 22 21940 CFTR-Intron10-3059 UUGUCUGUAGGCUAUAUGUAUCU 23 21941 CFTR-Intron10-3060 AUUGUCUGUAGGCUAUAUGUAUCU 24 21942 CFTR-Intron10-3061 CUCGGCCUCCCAAAGUGU 18 21943 CFTR-Intron10-3062 CCUCGGCCUCCCAAAGUGU 19 21944 CFTR-Intron10-3063 UGCCUCGGCCUCCCAAAGUGU 21 21945 CFTR-Intron10-3064 CUGCCUCGGCCUCCCAAAGUGU 22 21946 CFTR-Intron10-3065 CCUGCCUCGGCCUCCCAAAGUGU 23 21947 CFTR-Intron10-3066 AGGAAGGCAGUGGUCCCUU 19 21948 CFTR-Intron10-1399 AGGAAGCAAGGAGAUGAGUU 20 20283 CFTR-Intron10-3067 AGGGAGGAAGCAAGGAGAUGAGUU 24 21949 CFTR-Intron10-3068 AGAUAAUGGGAGAAACAGGUU 21 21950 CFTR-Intron10-3069 AAGAUAAUGGGAGAAACAGGUU 22 21951 CFTR-Intron10-3070 AAAGAUAAUGGGAGAAACAGGUU 23 21952 CFTR-Intron10-3071 AUAGUUUUAUCAAUAUUU 18 21953 CFTR-Intron10-3072 AAUAGUUUUAUCAAUAUUU 19 21954 CFTR-Intron10-1405 AAAUAGUUUUAUCAAUAUUU 20 20289 CFTR-Intron10-3073 UGCAUGGGUCCACUUAUUU 19 21955 CFTR-Intron10-3074 CUGCAUGGGUCCACUUAUUU 20 21956 CFTR-Intron10-3075 ACUGCAUGGGUCCACUUAUUU 21 21957 CFTR-Intron10-3076 AACUGCAUGGGUCCACUUAUUU 22 21958 CFTR-Intron10-3077 UGAACUGCAUGGGUCCACUUAUUU 24 21959 CFTR-Intron10-3078 UUGUUGUUUUUCUAGUUU 18 21960 CFTR-Intron10-3079 UUUGUUGUUUUUCUAGUUU 19 21961 CFTR-Intron10-3080 UUUUGUUGUUUUUCUAGUUU 20 21962 CFTR-Intron10-3081 UUUUUGUUGUUUUUCUAGUUU 21 21963 CFTR-Intron10-3082 UUUUUUGUUGUUUUUCUAGUUU 22 21964 CFTR-Intron10-3083 CUUUUUUGUUGUUUUUCUAGUUU 23 21965 CFTR-Intron10-3084 AAUACAUUGGAAAAUUUU 18 21966 CFTR-Intron10-3085 UAAUACAUUGGAAAAUUUU 19 21967 CFTR-Intron10-1411 UUAAUACAUUGGAAAAUUUU 20 20295 CFTR-Intron10-3086 AGUUAAUACAUUGGAAAAUUUU 22 21968 CFTR-Intron10-3087 CAGUUAAUACAUUGGAAAAUUUU 23 21969 CFTR-Intron10-3088 UCAGUUAAUACAUUGGAAAAUUUU 24 21970 CFTR-Intron10-3089 UAUGUCCUCCACAAAUAUUUU 21 21971 CFTR-Intron10-3090 AGUAUGUCCUCCACAAAUAUUUU 23 21972 CFTR-Intron10-3091 AAGUAUGUCCUCCACAAAUAUUUU 24 21973

Table 41E provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fifth tier parameters. The targeting domains bind within intron 10, and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 41E 5th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-3092 + AAAAAAAAAAAAAAAAAA 18 21974 CFTR-Intron10-3093 + AAAAAAAAAAAAAAAAAAA 19 21975 CFTR-Intron10-3094 + AAAAAAAAAAAAAAAAAAAA 20 21976 CFTR-Intron10-3095 + AAAAAAAAAAAAAAAAAAAAA 21 21977 CFTR-Intron10-3096 + AAAAAAAAAAAAAAAAAAAAAA 22 21978 CFTR-Intron10-3097 + AAAAAAAAAAAAAAAAAAAAAAA 23 21979 CFTR-Intron10-3098 + CAAAAAAAAAAAAAAAAAAAAAAA 24 21980 CFTR-Intron10-3099 + UAGAAAAACAACAAAAAA 18 21981 CFTR-Intron10-3100 + CUAGAAAAACAACAAAAAA 19 21982 CFTR-Intron10-3101 + ACUAGAAAAACAACAAAAAA 20 21983 CFTR-Intron10-3102 + AACUAGAAAAACAACAAAAAA 21 21984 CFTR-Intron10-3103 + AAACUAGAAAAACAACAAAAAA 22 21985 CFTR-Intron10-3104 + AAAACUAGAAAAACAACAAAAAA 23 21986 CFTR-Intron10-3105 + AAAAACUAGAAAAACAACAAAAAA 24 21987 CFTR-Intron10-3106 + CAAACAAAGAAACAAAAA 18 21988 CFTR-Intron10-3107 + ACAAACAAAGAAACAAAAA 19 21989 CFTR-Intron10-3108 + UACAAACAAAGAAACAAAAA 20 21990 CFTR-Intron10-3109 + AUACAAACAAAGAAACAAAAA 21 21991 CFTR-Intron10-3110 + AAUACAAACAAAGAAACAAAAA 22 21992 CFTR-Intron10-3111 + AAAUACAAACAAAGAAACAAAAA 23 21993 CFTR-Intron10-3112 + UAAAUACAAACAAAGAAACAAAAA 24 21994 CFTR-Intron10-3113 + CAUAUUGUUACAUAAAAA 18 21995 CFTR-Intron10-3114 + GCAUAUUGUUACAUAAAAA 19 21996 CFTR-Intron10-3115 + UGCAUAUUGUUACAUAAAAA 20 21997 CFTR-Intron10-3116 + CUGCAUAUUGUUACAUAAAAA 21 21998 CFTR-Intron10-3117 + UCUGCAUAUUGUUACAUAAAAA 22 21999 CFTR-Intron10-3118 + CUCUGCAUAUUGUUACAUAAAAA 23 22000 CFTR-Intron10-3119 + ACUCUGCAUAUUGUUACAUAAAAA 24 22001 CFTR-Intron10-3120 + GUGCAUAAAGGUUGAAAA 18 22002 CFTR-Intron10-3121 + AGUGCAUAAAGGUUGAAAA 19 22003 CFTR-Intron10-65 + GAGUGCAUAAAGGUUGAAAA 20 18951 CFTR-Intron10-3122 + AGAGUGCAUAAAGGUUGAAAA 21 22004 CFTR-Intron10-3123 + AAGAGUGCAUAAAGGUUGAAAA 22 22005 CFTR-Intron10-3124 + AAAGAGUGCAUAAAGGUUGAAAA 23 22006 CFTR-Intron10-3125 + CAAAGAGUGCAUAAAGGUUGAAAA 24 22007 CFTR-Intron10-3126 + UUUCCUCAAUAGUUAAAA 18 22008 CFTR-Intron10-3127 + AUUUCCUCAAUAGUUAAAA 19 22009 CFTR-Intron10-3128 + UAUUUCCUCAAUAGUUAAAA 20 22010 CFTR-Intron10-3129 + UUAUUUCCUCAAUAGUUAAAA 21 22011 CFTR-Intron10-3130 + UUUAUUUCCUCAAUAGUUAAAA 22 22012 CFTR-Intron10-3131 + AUUUAUUUCCUCAAUAGUUAAAA 23 22013 CFTR-Intron10-3132 + AAUUUAUUUCCUCAAUAGUUAAAA 24 22014 CFTR-Intron10-3133 + UAGUAAAAAAAAAUCAAA 18 22015 CFTR-Intron10-3134 + UUAGUAAAAAAAAAUCAAA 19 22016 CFTR-Intron10-1092 + AUUAGUAAAAAAAAAUCAAA 20 19977 CFTR-Intron10-3135 + AAUUAGUAAAAAAAAAUCAAA 21 22017 CFTR-Intron10-3136 + AAAUUAGUAAAAAAAAAUCAAA 22 22018 CFTR-Intron10-3137 + AAAAUUAGUAAAAAAAAAUCAAA 23 22019 CFTR-Intron10-3138 + CAAAAUUAGUAAAAAAAAAUCAAA 24 22020 CFTR-Intron10-3139 + GCUAAAAUGACAAUCAAA 18 22021 CFTR-Intron10-3140 + AGCUAAAAUGACAAUCAAA 19 22022 CFTR-Intron10-335 + CAGCUAAAAUGACAAUCAAA 20 19221 CFTR-Intron10-3141 + ACAGCUAAAAUGACAAUCAAA 21 22023 CFTR-Intron10-3142 + CACAGCUAAAAUGACAAUCAAA 22 22024 CFTR-Intron10-3143 + CCACAGCUAAAAUGACAAUCAAA 23 22025 CFTR-Intron10-3144 + ACCACAGCUAAAAUGACAAUCAAA 24 22026 CFTR-Intron10-3145 + AGGAUAUCUUAGGUCAAA 18 22027 CFTR-Intron10-3146 + UAGGAUAUCUUAGGUCAAA 19 22028 CFTR-Intron10-3147 + UUAGGAUAUCUUAGGUCAAA 20 22029 CFTR-Intron10-3148 + CUUAGGAUAUCUUAGGUCAAA 21 22030 CFTR-Intron10-3149 + CCUUAGGAUAUCUUAGGUCAAA 22 22031 CFTR-Intron10-3150 + CCCUUAGGAUAUCUUAGGUCAAA 23 22032 CFTR-Intron10-3151 + UCCCUUAGGAUAUCUUAGGUCAAA 24 22033 CFTR-Intron10-3152 + AAUGCAGGAGAAUGGAAA 18 22034 CFTR-Intron10-3153 + GAAUGCAGGAGAAUGGAAA 19 22035 CFTR-Intron10-3154 + GGAAUGCAGGAGAAUGGAAA 20 22036 CFTR-Intron10-3155 + GGGAAUGCAGGAGAAUGGAAA 21 22037 CFTR-Intron10-3156 + AGGGAAUGCAGGAGAAUGGAAA 22 22038 CFTR-Intron10-3157 + GAGGGAAUGCAGGAGAAUGGAAA 23 22039 CFTR-Intron10-3158 + UGAGGGAAUGCAGGAGAAUGGAAA 24 22040 CFTR-Intron10-3159 + CAAAUACAUUCAAUGAAA 18 22041 CFTR-Intron10-3160 + CCAAAUACAUUCAAUGAAA 19 22042 CFTR-Intron10-3161 + CCCAAAUACAUUCAAUGAAA 20 22043 CFTR-Intron10-3162 + GCCCAAAUACAUUCAAUGAAA 21 22044 CFTR-Intron10-3163 + GGCCCAAAUACAUUCAAUGAAA 22 22045 CFTR-Intron10-3164 + AGGCCCAAAUACAUUCAAUGAAA 23 22046 CFTR-Intron10-3165 + CAGGCCCAAAUACAUUCAAUGAAA 24 22047 CFTR-Intron10-3166 + AGUGCAUAAAGGUUGAAA 18 22048 CFTR-Intron10-3167 + GAGUGCAUAAAGGUUGAAA 19 22049 CFTR-Intron10-3168 + AGAGUGCAUAAAGGUUGAAA 20 22050 CFTR-Intron10-3169 + AAGAGUGCAUAAAGGUUGAAA 21 22051 CFTR-Intron10-3170 + AAAGAGUGCAUAAAGGUUGAAA 22 22052 CFTR-Intron10-3171 + CAAAGAGUGCAUAAAGGUUGAAA 23 22053 CFTR-Intron10-3172 + GCAAAGAGUGCAUAAAGGUUGAAA 24 22054 CFTR-Intron10-3173 + UGCAUAUUGUUACAUAAA 18 22055 CFTR-Intron10-3174 + CUGCAUAUUGUUACAUAAA 19 22056 CFTR-Intron10-3175 + UCUGCAUAUUGUUACAUAAA 20 22057 CFTR-Intron10-3176 + CUCUGCAUAUUGUUACAUAAA 21 22058 CFTR-Intron10-3177 + ACUCUGCAUAUUGUUACAUAAA 22 22059 CFTR-Intron10-3178 + AACUCUGCAUAUUGUUACAUAAA 23 22060 CFTR-Intron10-3179 + AAACUCUGCAUAUUGUUACAUAAA 24 22061 CFTR-Intron10-3180 + UCGUAUGUAGGAAAACAA 18 22062 CFTR-Intron10-3181 + UUCGUAUGUAGGAAAACAA 19 22063 CFTR-Intron10-3182 + UUUCGUAUGUAGGAAAACAA 20 22064 CFTR-Intron10-3183 + GUUUCGUAUGUAGGAAAACAA 21 22065 CFTR-Intron10-3184 + UGUUUCGUAUGUAGGAAAACAA 22 22066 CFTR-Intron10-3185 + CUGUUUCGUAUGUAGGAAAACAA 23 22067 CFTR-Intron10-3186 + GCUGUUUCGUAUGUAGGAAAACAA 24 22068 CFTR-Intron10-3187 + AACCAAAUAAACAAACAA 18 22069 CFTR-Intron10-3188 + AAACCAAAUAAACAAACAA 19 22070 CFTR-Intron10-1099 + AAAACCAAAUAAACAAACAA 20 19984 CFTR-Intron10-3189 + AAAAACCAAAUAAACAAACAA 21 22071 CFTR-Intron10-3190 + UAAAAACCAAAUAAACAAACAA 22 22072 CFTR-Intron10-3191 + GUAAAAACCAAAUAAACAAACAA 23 22073 CFTR-Intron10-3192 + AGUAAAAACCAAAUAAACAAACAA 24 22074 CFTR-Intron10-3193 + UGUGUGGCUUAUAAACAA 18 22075 CFTR-Intron10-3194 + CUGUGUGGCUUAUAAACAA 19 22076 CFTR-Intron10-3195 + ACUGUGUGGCUUAUAAACAA 20 22077 CFTR-Intron10-3196 + AACUGUGUGGCUUAUAAACAA 21 22078 CFTR-Intron10-3197 + GAACUGUGUGGCUUAUAAACAA 22 22079 CFTR-Intron10-3198 + UGAACUGUGUGGCUUAUAAACAA 23 22080 CFTR-Intron10-3199 + AUGAACUGUGUGGCUUAUAAACAA 24 22081 CFTR-Intron10-3200 + CAGCUGUGAUGCAGACAA 18 22082 CFTR-Intron10-3201 + UCAGCUGUGAUGCAGACAA 19 22083 CFTR-Intron10-3202 + UUCAGCUGUGAUGCAGACAA 20 22084 CFTR-Intron10-3203 + CUUCAGCUGUGAUGCAGACAA 21 22085 CFTR-Intron10-3204 + GCUUCAGCUGUGAUGCAGACAA 22 22086 CFTR-Intron10-3205 + UGCUUCAGCUGUGAUGCAGACAA 23 22087 CFTR-Intron10-3206 + CUGCUUCAGCUGUGAUGCAGACAA 24 22088 CFTR-Intron10-3207 + UAAUGAGUUACAAUACAA 18 22089 CFTR-Intron10-3208 + UUAAUGAGUUACAAUACAA 19 22090 CFTR-Intron10-3209 + AUUAAUGAGUUACAAUACAA 20 22091 CFTR-Intron10-3210 + AAUUAAUGAGUUACAAUACAA 21 22092 CFTR-Intron10-3211 + AAAUUAAUGAGUUACAAUACAA 22 22093 CFTR-Intron10-3212 + UAAAUUAAUGAGUUACAAUACAA 23 22094 CFTR-Intron10-3213 + AUAAAUUAAUGAGUUACAAUACAA 24 22095 CFTR-Intron10-3214 + AGCUUACCGUAAUAGCAA 18 22096 CFTR-Intron10-3215 + GAGCUUACCGUAAUAGCAA 19 22097 CFTR-Intron10-3216 + UGAGCUUACCGUAAUAGCAA 20 22098 CFTR-Intron10-3217 + UUGAGCUUACCGUAAUAGCAA 21 22099 CFTR-Intron10-3218 + CUUGAGCUUACCGUAAUAGCAA 22 22100 CFTR-Intron10-3219 + GCUUGAGCUUACCGUAAUAGCAA 23 22101 CFTR-Intron10-3220 + UGCUUGAGCUUACCGUAAUAGCAA 24 22102 CFTR-Intron10-3221 + GGUCAAUUGUAUUAGCAA 18 22103 CFTR-Intron10-3222 + GGGUCAAUUGUAUUAGCAA 19 22104 CFTR-Intron10-3223 + AGGGUCAAUUGUAUUAGCAA 20 22105 CFTR-Intron10-3224 + AAGGGUCAAUUGUAUUAGCAA 21 22106 CFTR-Intron10-3225 + UAAGGGUCAAUUGUAUUAGCAA 22 22107 CFTR-Intron10-3226 + UUAAGGGUCAAUUGUAUUAGCAA 23 22108 CFTR-Intron10-3227 + UUUAAGGGUCAAUUGUAUUAGCAA 24 22109 CFTR-Intron10-3228 + UUAGUAAAAAAAAAUCAA 18 22110 CFTR-Intron10-3229 + AUUAGUAAAAAAAAAUCAA 19 22111 CFTR-Intron10-3230 + AAUUAGUAAAAAAAAAUCAA 20 22112 CFTR-Intron10-3231 + AAAUUAGUAAAAAAAAAUCAA 21 22113 CFTR-Intron10-3232 + AAAAUUAGUAAAAAAAAAUCAA 22 22114 CFTR-Intron10-3233 + CAAAAUUAGUAAAAAAAAAUCAA 23 22115 CFTR-Intron10-3234 + ACAAAAUUAGUAAAAAAAAAUCAA 24 22116 CFTR-Intron10-3235 + AGCUAAAAUGACAAUCAA 18 22117 CFTR-Intron10-3236 + CAGCUAAAAUGACAAUCAA 19 22118 CFTR-Intron10-3237 + ACAGCUAAAAUGACAAUCAA 20 22119 CFTR-Intron10-3238 + CACAGCUAAAAUGACAAUCAA 21 22120 CFTR-Intron10-3239 + CCACAGCUAAAAUGACAAUCAA 22 22121 CFTR-Intron10-3240 + ACCACAGCUAAAAUGACAAUCAA 23 22122 CFTR-Intron10-3241 + UACCACAGCUAAAAUGACAAUCAA 24 22123 CFTR-Intron10-3242 + CUGAAGCGGAAAGGUCAA 18 22124 CFTR-Intron10-3243 + GCUGAAGCGGAAAGGUCAA 19 22125 CFTR-Intron10-3244 + GGCUGAAGCGGAAAGGUCAA 20 22126 CFTR-Intron10-3245 + AGGCUGAAGCGGAAAGGUCAA 21 22127 CFTR-Intron10-3246 + GAGGCUGAAGCGGAAAGGUCAA 22 22128 CFTR-Intron10-3247 + GGAGGCUGAAGCGGAAAGGUCAA 23 22129 CFTR-Intron10-3248 + GGGAGGCUGAAGCGGAAAGGUCAA 24 22130 CFTR-Intron10-3249 + CACCUGAAAUAUAUUCAA 18 22131 CFTR-Intron10-3250 + UCACCUGAAAUAUAUUCAA 19 22132 CFTR-Intron10-3251 + AUCACCUGAAAUAUAUUCAA 20 22133 CFTR-Intron10-3252 + UAUCACCUGAAAUAUAUUCAA 21 22134 CFTR-Intron10-3253 + AUAUCACCUGAAAUAUAUUCAA 22 22135 CFTR-Intron10-3254 + AAUAUCACCUGAAAUAUAUUCAA 23 22136 CFTR-Intron10-3255 + UAAUAUCACCUGAAAUAUAUUCAA 24 22137 CFTR-Intron10-3256 + AAAAAAAAAAAAAAAGAA 18 22138 CFTR-Intron10-3257 + AAAAAAAAAAAAAAAAGAA 19 22139 CFTR-Intron10-3258 + AAAAAAAAAAAAAAAAAGAA 20 22140 CFTR-Intron10-3259 + AAAAAAAAAAAAAAAAAAGAA 21 22141 CFTR-Intron10-3260 + AAAAAAAAAAAAAAAAAAAGAA 22 22142 CFTR-Intron10-3261 + AAAAAAAAAAAAAAAAAAAAGAA 23 22143 CFTR-Intron10-3262 + AAAAAAAAAAAAAAAAAAAAAGAA 24 22144 CFTR-Intron10-3263 + GAAAUAUAUUCAAAAGAA 18 22145 CFTR-Intron10-3264 + UGAAAUAUAUUCAAAAGAA 19 22146 CFTR-Intron10-1103 + CUGAAAUAUAUUCAAAAGAA 20 19988 CFTR-Intron10-3265 + CCUGAAAUAUAUUCAAAAGAA 21 22147 CFTR-Intron10-3266 + ACCUGAAAUAUAUUCAAAAGAA 22 22148 CFTR-Intron10-3267 + CACCUGAAAUAUAUUCAAAAGAA 23 22149 CFTR-Intron10-3268 + UCACCUGAAAUAUAUUCAAAAGAA 24 22150 CFTR-Intron10-3269 + AAAAAUACGAUAUAAGAA 18 22151 CFTR-Intron10-3270 + CAAAAAUACGAUAUAAGAA 19 22152 CFTR-Intron10-3271 + GCAAAAAUACGAUAUAAGAA 20 22153 CFTR-Intron10-3272 + UGCAAAAAUACGAUAUAAGAA 21 22154 CFTR-Intron10-3273 + UUGCAAAAAUACGAUAUAAGAA 22 22155 CFTR-Intron10-3274 + GUUGCAAAAAUACGAUAUAAGAA 23 22156 CFTR-Intron10-3275 + AGUUGCAAAAAUACGAUAUAAGAA 24 22157 CFTR-Intron10-3276 + UGAGGGAAUGCAGGAGAA 18 22158 CFTR-Intron10-3277 + AUGAGGGAAUGCAGGAGAA 19 22159 CFTR-Intron10-649 + GAUGAGGGAAUGCAGGAGAA 20 19535 CFTR-Intron10-3278 + GGAUGAGGGAAUGCAGGAGAA 21 22160 CFTR-Intron10-3279 + UGGAUGAGGGAAUGCAGGAGAA 22 22161 CFTR-Intron10-3280 + UUGGAUGAGGGAAUGCAGGAGAA 23 22162 CFTR-Intron10-3281 + GUUGGAUGAGGGAAUGCAGGAGAA 24 22163 CFTR-Intron10-3282 + AAUAAACAAACAAAGGAA 18 22164 CFTR-Intron10-3283 + AAAUAAACAAACAAAGGAA 19 22165 CFTR-Intron10-3284 + CAAAUAAACAAACAAAGGAA 20 22166 CFTR-Intron10-3285 + CCAAAUAAACAAACAAAGGAA 21 22167 CFTR-Intron10-3286 + ACCAAAUAAACAAACAAAGGAA 22 22168 CFTR-Intron10-3287 + AACCAAAUAAACAAACAAAGGAA 23 22169 CFTR-Intron10-3288 + AAACCAAAUAAACAAACAAAGGAA 24 22170 CFTR-Intron10-3289 + AAAACUGAGUAGAAGGAA 18 22171 CFTR-Intron10-3290 + UAAAACUGAGUAGAAGGAA 19 22172 CFTR-Intron10-349 + CUAAAACUGAGUAGAAGGAA 20 19235 CFTR-Intron10-3291 + ACUAAAACUGAGUAGAAGGAA 21 22173 CFTR-Intron10-3292 + GACUAAAACUGAGUAGAAGGAA 22 22174 CFTR-Intron10-3293 + UGACUAAAACUGAGUAGAAGGAA 23 22175 CFTR-Intron10-3294 + CUGACUAAAACUGAGUAGAAGGAA 24 22176 CFTR-Intron10-3295 + UAAACAGAAUCAGGGGAA 18 22177 CFTR-Intron10-3296 + UUAAACAGAAUCAGGGGAA 19 22178 CFTR-Intron10-3297 + UUUAAACAGAAUCAGGGGAA 20 22179 CFTR-Intron10-3298 + AUUUAAACAGAAUCAGGGGAA 21 22180 CFTR-Intron10-3299 + UAUUUAAACAGAAUCAGGGGAA 22 22181 CFTR-Intron10-3300 + CUAUUUAAACAGAAUCAGGGGAA 23 22182 CFTR-Intron10-3301 + GCUAUUUAAACAGAAUCAGGGGAA 24 22183 CFTR-Intron10-3302 + GCACUUUGGGAGGCUGAA 18 22184 CFTR-Intron10-3303 + AGCACUUUGGGAGGCUGAA 19 22185 CFTR-Intron10-3304 + CAGCACUUUGGGAGGCUGAA 20 22186 CFTR-Intron10-3305 + CCAGCACUUUGGGAGGCUGAA 21 22187 CFTR-Intron10-3306 + CCCAGCACUUUGGGAGGCUGAA 22 22188 CFTR-Intron10-3307 + ACCCAGCACUUUGGGAGGCUGAA 23 22189 CFTR-Intron10-3308 + AACCCAGCACUUUGGGAGGCUGAA 24 22190 CFTR-Intron10-3309 + GUACAUUUAAUAUCUGAA 18 22191 CFTR-Intron10-3310 + UGUACAUUUAAUAUCUGAA 19 22192 CFTR-Intron10-3311 + AUGUACAUUUAAUAUCUGAA 20 22193 CFTR-Intron10-3312 + GAUGUACAUUUAAUAUCUGAA 21 22194 CFTR-Intron10-3313 + UGAUGUACAUUUAAUAUCUGAA 22 22195 CFTR-Intron10-3314 + AUGAUGUACAUUUAAUAUCUGAA 23 22196 CFTR-Intron10-3315 + AAUGAUGUACAUUUAAUAUCUGAA 24 22197 CFTR-Intron10-3316 + AAAAAAAUUCACAAAUAA 18 22198 CFTR-Intron10-3317 + AAAAAAAAUUCACAAAUAA 19 22199 CFTR-Intron10-3318 + GAAAAAAAAUUCACAAAUAA 20 22200 CFTR-Intron10-3319 + UGAAAAAAAAUUCACAAAUAA 21 22201 CFTR-Intron10-3320 + CUGAAAAAAAAUUCACAAAUAA 22 22202 CFTR-Intron10-3321 + ACUGAAAAAAAAUUCACAAAUAA 23 22203 CFTR-Intron10-3322 + AACUGAAAAAAAAUUCACAAAUAA 24 22204 CFTR-Intron10-3323 + UGAGGCAAUGAUCAAUAA 18 22205 CFTR-Intron10-3324 + GUGAGGCAAUGAUCAAUAA 19 22206 CFTR-Intron10-3325 + AGUGAGGCAAUGAUCAAUAA 20 22207 CFTR-Intron10-3326 + UAGUGAGGCAAUGAUCAAUAA 21 22208 CFTR-Intron10-3327 + AUAGUGAGGCAAUGAUCAAUAA 22 22209 CFTR-Intron10-3328 + CAUAGUGAGGCAAUGAUCAAUAA 23 22210 CFTR-Intron10-3329 + CCAUAGUGAGGCAAUGAUCAAUAA 24 22211 CFTR-Intron10-3330 + AGAACCUAUAAGGAAUAA 18 22212 CFTR-Intron10-3331 + CAGAACCUAUAAGGAAUAA 19 22213 CFTR-Intron10-3332 + ACAGAACCUAUAAGGAAUAA 20 22214 CFTR-Intron10-3333 + UACAGAACCUAUAAGGAAUAA 21 22215 CFTR-Intron10-3334 + UUACAGAACCUAUAAGGAAUAA 22 22216 CFTR-Intron10-3335 + AUUACAGAACCUAUAAGGAAUAA 23 22217 CFTR-Intron10-3336 + AAUUACAGAACCUAUAAGGAAUAA 24 22218 CFTR-Intron10-3337 + ACAGUGACUUCAUAAUAA 18 22219 CFTR-Intron10-3338 + UACAGUGACUUCAUAAUAA 19 22220 CFTR-Intron10-1111 + AUACAGUGACUUCAUAAUAA 20 19996 CFTR-Intron10-3339 + AAUACAGUGACUUCAUAAUAA 21 22221 CFTR-Intron10-3340 + CAAUACAGUGACUUCAUAAUAA 22 22222 CFTR-Intron10-3341 + ACAAUACAGUGACUUCAUAAUAA 23 22223 CFTR-Intron10-3342 + GACAAUACAGUGACUUCAUAAUAA 24 22224 CFTR-Intron10-3343 + UUACACUACUUAUAAUAA 18 22225 CFTR-Intron10-3344 + UUUACACUACUUAUAAUAA 19 22226 CFTR-Intron10-3345 + UUUUACACUACUUAUAAUAA 20 22227 CFTR-Intron10-3346 + AUUUUACACUACUUAUAAUAA 21 22228 CFTR-Intron10-3347 + UAUUUUACACUACUUAUAAUAA 22 22229 CFTR-Intron10-3348 + AUAUUUUACACUACUUAUAAUAA 23 22230 CFTR-Intron10-3349 + GAUAUUUUACACUACUUAUAAUAA 24 22231 CFTR-Intron10-3350 + CAAGUAGAAAAAAGAUAA 18 22232 CFTR-Intron10-3351 + GCAAGUAGAAAAAAGAUAA 19 22233 CFTR-Intron10-3352 + AGCAAGUAGAAAAAAGAUAA 20 22234 CFTR-Intron10-3353 + AAGCAAGUAGAAAAAAGAUAA 21 22235 CFTR-Intron10-3354 + AAAGCAAGUAGAAAAAAGAUAA 22 22236 CFTR-Intron10-3355 + CAAAGCAAGUAGAAAAAAGAUAA 23 22237 CFTR-Intron10-3356 + GCAAAGCAAGUAGAAAAAAGAUAA 24 22238 CFTR-Intron10-3357 + AUAAUAUACAAGAUAUAA 18 22239 CFTR-Intron10-3358 + AAUAAUAUACAAGAUAUAA 19 22240 CFTR-Intron10-3359 + UAAUAAUAUACAAGAUAUAA 20 22241 CFTR-Intron10-3360 + GUAAUAAUAUACAAGAUAUAA 21 22242 CFTR-Intron10-3361 + AGUAAUAAUAUACAAGAUAUAA 22 22243 CFTR-Intron10-3362 + UAGUAAUAAUAUACAAGAUAUAA 23 22244 CFTR-Intron10-3363 + CUAGUAAUAAUAUACAAGAUAUAA 24 22245 CFTR-Intron10-3364 + UAACUUUAUGCUAACUAA 18 22246 CFTR-Intron10-3365 + CUAACUUUAUGCUAACUAA 19 22247 CFTR-Intron10-3366 + CCUAACUUUAUGCUAACUAA 20 22248 CFTR-Intron10-3367 + ACCUAACUUUAUGCUAACUAA 21 22249 CFTR-Intron10-3368 + AACCUAACUUUAUGCUAACUAA 22 22250 CFTR-Intron10-3369 + AAACCUAACUUUAUGCUAACUAA 23 22251 CFTR-Intron10-3370 + CAAACCUAACUUUAUGCUAACUAA 24 22252 CFTR-Intron10-3371 + AGUAAAGUAACAAAGUAA 18 22253 CFTR-Intron10-3372 + CAGUAAAGUAACAAAGUAA 19 22254 CFTR-Intron10-3373 + UCAGUAAAGUAACAAAGUAA 20 22255 CFTR-Intron10-3374 + AUCAGUAAAGUAACAAAGUAA 21 22256 CFTR-Intron10-3375 + UAUCAGUAAAGUAACAAAGUAA 22 22257 CFTR-Intron10-3376 + UUAUCAGUAAAGUAACAAAGUAA 23 22258 CFTR-Intron10-3377 + UUUAUCAGUAAAGUAACAAAGUAA 24 22259 CFTR-Intron10-3378 + AGCUAAUAAAUAAAGUAA 18 22260 CFTR-Intron10-3379 + AAGCUAAUAAAUAAAGUAA 19 22261 CFTR-Intron10-3380 + AAAGCUAAUAAAUAAAGUAA 20 22262 CFTR-Intron10-3381 + UAAAGCUAAUAAAUAAAGUAA 21 22263 CFTR-Intron10-3382 + UUAAAGCUAAUAAAUAAAGUAA 22 22264 CFTR-Intron10-3383 + UUUAAAGCUAAUAAAUAAAGUAA 23 22265 CFTR-Intron10-3384 + AUUUAAAGCUAAUAAAUAAAGUAA 24 22266 CFTR-Intron10-3385 + UUCUAGAAAACAAUGUAA 18 22267 CFTR-Intron10-3386 + UUUCUAGAAAACAAUGUAA 19 22268 CFTR-Intron10-1114 + UUUUCUAGAAAACAAUGUAA 20 19999 CFTR-Intron10-3387 + AUUUUCUAGAAAACAAUGUAA 21 22269 CFTR-Intron10-3388 + GAUUUUCUAGAAAACAAUGUAA 22 22270 CFTR-Intron10-3389 + AGAUUUUCUAGAAAACAAUGUAA 23 22271 CFTR-Intron10-3390 + CAGAUUUUCUAGAAAACAAUGUAA 24 22272 CFTR-Intron10-3391 + UAUAAGUGUGGAGUGUAA 18 22273 CFTR-Intron10-3392 + GUAUAAGUGUGGAGUGUAA 19 22274 CFTR-Intron10-72 + GGUAUAAGUGUGGAGUGUAA 20 18958 CFTR-Intron10-3393 + GGGUAUAAGUGUGGAGUGUAA 21 22275 CFTR-Intron10-3394 + GGGGUAUAAGUGUGGAGUGUAA 22 22276 CFTR-Intron10-3395 + UGGGGUAUAAGUGUGGAGUGUAA 23 22277 CFTR-Intron10-3396 + AUGGGGUAUAAGUGUGGAGUGUAA 24 22278 CFTR-Intron10-3397 + UGAACUCUAAUCUAUUAA 18 22279 CFTR-Intron10-3398 + UUGAACUCUAAUCUAUUAA 19 22280 CFTR-Intron10-3399 + AUUGAACUCUAAUCUAUUAA 20 22281 CFTR-Intron10-3400 + AAUUGAACUCUAAUCUAUUAA 21 22282 CFTR-Intron10-3401 + GAAUUGAACUCUAAUCUAUUAA 22 22283 CFTR-Intron10-3402 + UGAAUUGAACUCUAAUCUAUUAA 23 22284 CFTR-Intron10-3403 + CUGAAUUGAACUCUAAUCUAUUAA 24 22285 CFTR-Intron10-3404 + GCUUAACCCAUCUAUUAA 18 22286 CFTR-Intron10-3405 + GGCUUAACCCAUCUAUUAA 19 22287 CFTR-Intron10-3406 + UGGCUUAACCCAUCUAUUAA 20 22288 CFTR-Intron10-3407 + UUGGCUUAACCCAUCUAUUAA 21 22289 CFTR-Intron10-3408 + GUUGGCUUAACCCAUCUAUUAA 22 22290 CFTR-Intron10-3409 + AGUUGGCUUAACCCAUCUAUUAA 23 22291 CFTR-Intron10-3410 + CAGUUGGCUUAACCCAUCUAUUAA 24 22292 CFTR-Intron10-3411 + AAUUUUCCAAUGUAUUAA 18 22293 CFTR-Intron10-3412 + AAAUUUUCCAAUGUAUUAA 19 22294 CFTR-Intron10-3413 + AAAAUUUUCCAAUGUAUUAA 20 22295 CFTR-Intron10-3414 + AAAAAUUUUCCAAUGUAUUAA 21 22296 CFTR-Intron10-3415 + CAAAAAUUUUCCAAUGUAUUAA 22 22297 CFTR-Intron10-3416 + CCAAAAAUUUUCCAAUGUAUUAA 23 22298 CFTR-Intron10-3417 + CCCAAAAAUUUUCCAAUGUAUUAA 24 22299 CFTR-Intron10-3418 + AGCCUAGAUGAUUAUUAA 18 22300 CFTR-Intron10-3419 + CAGCCUAGAUGAUUAUUAA 19 22301 CFTR-Intron10-3420 + GCAGCCUAGAUGAUUAUUAA 20 22302 CFTR-Intron10-3421 + UGCAGCCUAGAUGAUUAUUAA 21 22303 CFTR-Intron10-3422 + UUGCAGCCUAGAUGAUUAUUAA 22 22304 CFTR-Intron10-3423 + UUUGCAGCCUAGAUGAUUAUUAA 23 22305 CFTR-Intron10-3424 + UUUUGCAGCCUAGAUGAUUAUUAA 24 22306 CFTR-Intron10-3425 + UAUUUCCUCAAUAGUUAA 18 22307 CFTR-Intron10-3426 + UUAUUUCCUCAAUAGUUAA 19 22308 CFTR-Intron10-3427 + UUUAUUUCCUCAAUAGUUAA 20 22309 CFTR-Intron10-3428 + AUUUAUUUCCUCAAUAGUUAA 21 22310 CFTR-Intron10-3429 + AAUUUAUUUCCUCAAUAGUUAA 22 22311 CFTR-Intron10-3430 + AAAUUUAUUUCCUCAAUAGUUAA 23 22312 CFTR-Intron10-3431 + UAAAUUUAUUUCCUCAAUAGUUAA 24 22313 CFTR-Intron10-3432 + CAACAUUCUUGGAAAACA 18 22314 CFTR-Intron10-3433 + ACAACAUUCUUGGAAAACA 19 22315 CFTR-Intron10-3434 + AACAACAUUCUUGGAAAACA 20 22316 CFTR-Intron10-3435 + GAACAACAUUCUUGGAAAACA 21 22317 CFTR-Intron10-3436 + UGAACAACAUUCUUGGAAAACA 22 22318 CFTR-Intron10-3437 + UUGAACAACAUUCUUGGAAAACA 23 22319 CFTR-Intron10-3438 + UUUGAACAACAUUCUUGGAAAACA 24 22320 CFTR-Intron10-3439 + AAUGAAACAAAUAAAACA 18 22321 CFTR-Intron10-3440 + AAAUGAAACAAAUAAAACA 19 22322 CFTR-Intron10-3441 + GAAAUGAAACAAAUAAAACA 20 22323 CFTR-Intron10-3442 + AGAAAUGAAACAAAUAAAACA 21 22324 CFTR-Intron10-3443 + AAGAAAUGAAACAAAUAAAACA 22 22325 CFTR-Intron10-3444 + AAAGAAAUGAAACAAAUAAAACA 23 22326 CFTR-Intron10-3445 + AAAAGAAAUGAAACAAAUAAAACA 24 22327 CFTR-Intron10-3446 + AAACCAAAUAAACAAACA 18 22328 CFTR-Intron10-3447 + AAAACCAAAUAAACAAACA 19 22329 CFTR-Intron10-3448 + AAAAACCAAAUAAACAAACA 20 22330 CFTR-Intron10-3449 + UAAAAACCAAAUAAACAAACA 21 22331 CFTR-Intron10-3450 + GUAAAAACCAAAUAAACAAACA 22 22332 CFTR-Intron10-3451 + AGUAAAAACCAAAUAAACAAACA 23 22333 CFTR-Intron10-3452 + AAGUAAAAACCAAAUAAACAAACA 24 22334 CFTR-Intron10-3453 + AAACUGUAAAUACAAACA 18 22335 CFTR-Intron10-3454 + AAAACUGUAAAUACAAACA 19 22336 CFTR-Intron10-3455 + UAAAACUGUAAAUACAAACA 20 22337 CFTR-Intron10-3456 + UUAAAACUGUAAAUACAAACA 21 22338 CFTR-Intron10-3457 + CUUAAAACUGUAAAUACAAACA 22 22339 CFTR-Intron10-3458 + ACUUAAAACUGUAAAUACAAACA 23 22340 CFTR-Intron10-3459 + AACUUAAAACUGUAAAUACAAACA 24 22341 CFTR-Intron10-3460 + GACAAUCAAAUGGGAACA 18 22342 CFTR-Intron10-3461 + UGACAAUCAAAUGGGAACA 19 22343 CFTR-Intron10-363 + AUGACAAUCAAAUGGGAACA 20 19249 CFTR-Intron10-3462 + AAUGACAAUCAAAUGGGAACA 21 22344 CFTR-Intron10-3463 + AAAUGACAAUCAAAUGGGAACA 22 22345 CFTR-Intron10-3464 + AAAAUGACAAUCAAAUGGGAACA 23 22346 CFTR-Intron10-3465 + UAAAAUGACAAUCAAAUGGGAACA 24 22347 CFTR-Intron10-3466 + AACCUAUAAGGAAUAACA 18 22348 CFTR-Intron10-3467 + GAACCUAUAAGGAAUAACA 19 22349 CFTR-Intron10-364 + AGAACCUAUAAGGAAUAACA 20 19250 CFTR-Intron10-3468 + CAGAACCUAUAAGGAAUAACA 21 22350 CFTR-Intron10-3469 + ACAGAACCUAUAAGGAAUAACA 22 22351 CFTR-Intron10-3470 + UACAGAACCUAUAAGGAAUAACA 23 22352 CFTR-Intron10-3471 + UUACAGAACCUAUAAGGAAUAACA 24 22353 CFTR-Intron10-3472 + GAGAGAGAACUGCUCACA 18 22354 CFTR-Intron10-3473 + GGAGAGAGAACUGCUCACA 19 22355 CFTR-Intron10-1122 + UGGAGAGAGAACUGCUCACA 20 20007 CFTR-Intron10-3474 + CUGGAGAGAGAACUGCUCACA 21 22356 CFTR-Intron10-3475 + ACUGGAGAGAGAACUGCUCACA 22 22357 CFTR-Intron10-3476 + UACUGGAGAGAGAACUGCUCACA 23 22358 CFTR-Intron10-3477 + UUACUGGAGAGAGAACUGCUCACA 24 22359 CFTR-Intron10-3478 + UUUACAAUUCUUAUUACA 18 22360 CFTR-Intron10-3479 + UUUUACAAUUCUUAUUACA 19 22361 CFTR-Intron10-1125 + AUUUUACAAUUCUUAUUACA 20 20010 CFTR-Intron10-3480 + AAUUUUACAAUUCUUAUUACA 21 22362 CFTR-Intron10-3481 + AAAUUUUACAAUUCUUAUUACA 22 22363 CFTR-Intron10-3482 + UAAAUUUUACAAUUCUUAUUACA 23 22364 CFTR-Intron10-3483 + GUAAAUUUUACAAUUCUUAUUACA 24 22365 CFTR-Intron10-3484 + CAGGAGUUCAAGGUUACA 18 22366 CFTR-Intron10-3485 + CCAGGAGUUCAAGGUUACA 19 22367 CFTR-Intron10-3486 + CCCAGGAGUUCAAGGUUACA 20 22368 CFTR-Intron10-3487 + GCCCAGGAGUUCAAGGUUACA 21 22369 CFTR-Intron10-3488 + AGCCCAGGAGUUCAAGGUUACA 22 22370 CFTR-Intron10-3489 + GAGCCCAGGAGUUCAAGGUUACA 23 22371 CFTR-Intron10-3490 + UGAGCCCAGGAGUUCAAGGUUACA 24 22372 CFTR-Intron10-3491 + UGAGCUAUGAUCACACCA 18 22373 CFTR-Intron10-3492 + GUGAGCUAUGAUCACACCA 19 22374 CFTR-Intron10-3493 + AGUGAGCUAUGAUCACACCA 20 22375 CFTR-Intron10-3494 + CAGUGAGCUAUGAUCACACCA 21 22376 CFTR-Intron10-3495 + ACAGUGAGCUAUGAUCACACCA 22 22377 CFTR-Intron10-3496 + UACAGUGAGCUAUGAUCACACCA 23 22378 CFTR-Intron10-3497 + UUACAGUGAGCUAUGAUCACACCA 24 22379 CFTR-Intron10-3498 + GGCCUCUAAUCUCACCCA 18 22380 CFTR-Intron10-3499 + UGGCCUCUAAUCUCACCCA 19 22381 CFTR-Intron10-3500 + GUGGCCUCUAAUCUCACCCA 20 22382 CFTR-Intron10-3501 + AGUGGCCUCUAAUCUCACCCA 21 22383 CFTR-Intron10-3502 + CAGUGGCCUCUAAUCUCACCCA 22 22384 CFTR-Intron10-3503 + CCAGUGGCCUCUAAUCUCACCCA 23 22385 CFTR-Intron10-3504 + UCCAGUGGCCUCUAAUCUCACCCA 24 22386 CFTR-Intron10-3505 + CAGCUAAAGUAUUACCCA 18 22387 CFTR-Intron10-3506 + ACAGCUAAAGUAUUACCCA 19 22388 CFTR-Intron10-3507 + UACAGCUAAAGUAUUACCCA 20 22389 CFTR-Intron10-3508 + AUACAGCUAAAGUAUUACCCA 21 22390 CFTR-Intron10-3509 + UAUACAGCUAAAGUAUUACCCA 22 22391 CFTR-Intron10-3510 + AUAUACAGCUAAAGUAUUACCCA 23 22392 CFTR-Intron10-3511 + AAUAUACAGCUAAAGUAUUACCCA 24 22393 CFTR-Intron10-3512 + AGUGUUUAAAUAUUCCCA 18 22394 CFTR-Intron10-3513 + AAGUGUUUAAAUAUUCCCA 19 22395 CFTR-Intron10-76 + GAAGUGUUUAAAUAUUCCCA 20 18962 CFTR-Intron10-3514 + AGAAGUGUUUAAAUAUUCCCA 21 22396 CFTR-Intron10-3515 + CAGAAGUGUUUAAAUAUUCCCA 22 22397 CFTR-Intron10-3516 + UCAGAAGUGUUUAAAUAUUCCCA 23 22398 CFTR-Intron10-3517 + CUCAGAAGUGUUUAAAUAUUCCCA 24 22399 CFTR-Intron10-3518 + UAGUAUUAAGUAUAGCCA 18 22400 CFTR-Intron10-3519 + UUAGUAUUAAGUAUAGCCA 19 22401 CFTR-Intron10-3520 + AUUAGUAUUAAGUAUAGCCA 20 22402 CFTR-Intron10-3521 + UAUUAGUAUUAAGUAUAGCCA 21 22403 CFTR-Intron10-3522 + UUAUUAGUAUUAAGUAUAGCCA 22 22404 CFTR-Intron10-3523 + GUUAUUAGUAUUAAGUAUAGCCA 23 22405 CFTR-Intron10-3524 + AGUUAUUAGUAUUAAGUAUAGCCA 24 22406 CFTR-Intron10-3525 + UGAGUAUACUUUAUGCCA 18 22407 CFTR-Intron10-3526 + GUGAGUAUACUUUAUGCCA 19 22408 CFTR-Intron10-3527 + UGUGAGUAUACUUUAUGCCA 20 22409 CFTR-Intron10-3528 + AUGUGAGUAUACUUUAUGCCA 21 22410 CFTR-Intron10-3529 + UAUGUGAGUAUACUUUAUGCCA 22 22411 CFTR-Intron10-3530 + CUAUGUGAGUAUACUUUAUGCCA 23 22412 CFTR-Intron10-3531 + ACUAUGUGAGUAUACUUUAUGCCA 24 22413 CFTR-Intron10-3532 + GAAGGAAAGGAGGUAGCA 18 22414 CFTR-Intron10-3533 + AGAAGGAAAGGAGGUAGCA 19 22415 CFTR-Intron10-3534 + UAGAAGGAAAGGAGGUAGCA 20 22416 CFTR-Intron10-3535 + GUAGAAGGAAAGGAGGUAGCA 21 22417 CFTR-Intron10-3536 + AGUAGAAGGAAAGGAGGUAGCA 22 22418 CFTR-Intron10-3537 + GAGUAGAAGGAAAGGAGGUAGCA 23 22419 CFTR-Intron10-3538 + UGAGUAGAAGGAAAGGAGGUAGCA 24 22420 CFTR-Intron10-3539 + UUCAACAUAUGAAUGGCA 18 22421 CFTR-Intron10-3540 + UUUCAACAUAUGAAUGGCA 19 22422 CFTR-Intron10-1128 + AUUUCAACAUAUGAAUGGCA 20 20013 CFTR-Intron10-3541 + GAUUUCAACAUAUGAAUGGCA 21 22423 CFTR-Intron10-3542 + GGAUUUCAACAUAUGAAUGGCA 22 22424 CFTR-Intron10-3543 + AGGAUUUCAACAUAUGAAUGGCA 23 22425 CFTR-Intron10-3544 + UAGGAUUUCAACAUAUGAAUGGCA 24 22426 CFTR-Intron10-3545 + CGGGAGGCGGAGCUUGCA 18 22427 CFTR-Intron10-3546 + CCGGGAGGCGGAGCUUGCA 19 22428 CFTR-Intron10-3547 + CCCGGGAGGCGGAGCUUGCA 20 22429 CFTR-Intron10-3548 + ACCCGGGAGGCGGAGCUUGCA 21 22430 CFTR-Intron10-3549 + AACCCGGGAGGCGGAGCUUGCA 22 22431 CFTR-Intron10-3550 + GAACCCGGGAGGCGGAGCUUGCA 23 22432 CFTR-Intron10-3551 + UGAACCCGGGAGGCGGAGCUUGCA 24 22433 CFTR-Intron10-3552 + CGGGAGGCAGAGGUUGCA 18 22434 CFTR-Intron10-3553 + CCGGGAGGCAGAGGUUGCA 19 22435 CFTR-Intron10-3554 + CCCGGGAGGCAGAGGUUGCA 20 22436 CFTR-Intron10-3555 + GCCCGGGAGGCAGAGGUUGCA 21 22437 CFTR-Intron10-3556 + AGCCCGGGAGGCAGAGGUUGCA 22 22438 CFTR-Intron10-3557 + GAGCCCGGGAGGCAGAGGUUGCA 23 22439 CFTR-Intron10-3558 + UGAGCCCGGGAGGCAGAGGUUGCA 24 22440 CFTR-Intron10-3559 + GCUAUUUAAACAGAAUCA 18 22441 CFTR-Intron10-3560 + UGCUAUUUAAACAGAAUCA 19 22442 CFTR-Intron10-77 + GUGCUAUUUAAACAGAAUCA 20 18963 CFTR-Intron10-3561 + AGUGCUAUUUAAACAGAAUCA 21 22443 CFTR-Intron10-3562 + CAGUGCUAUUUAAACAGAAUCA 22 22444 CFTR-Intron10-3563 + CCAGUGCUAUUUAAACAGAAUCA 23 22445 CFTR-Intron10-3564 + UCCAGUGCUAUUUAAACAGAAUCA 24 22446 CFTR-Intron10-3565 + AGUACAAAAGGACUAUCA 18 22447 CFTR-Intron10-3566 + UAGUACAAAAGGACUAUCA 19 22448 CFTR-Intron10-3567 + AUAGUACAAAAGGACUAUCA 20 22449 CFTR-Intron10-3568 + GAUAGUACAAAAGGACUAUCA 21 22450 CFTR-Intron10-3569 + UGAUAGUACAAAAGGACUAUCA 22 22451 CFTR-Intron10-3570 + AUGAUAGUACAAAAGGACUAUCA 23 22452 CFTR-Intron10-3571 + GAUGAUAGUACAAAAGGACUAUCA 24 22453 CFTR-Intron10-3572 + UUAGGAUAUCUUAGGUCA 18 22454 CFTR-Intron10-3573 + CUUAGGAUAUCUUAGGUCA 19 22455 CFTR-Intron10-3574 + CCUUAGGAUAUCUUAGGUCA 20 22456 CFTR-Intron10-3575 + CCCUUAGGAUAUCUUAGGUCA 21 22457 CFTR-Intron10-3576 + UCCCUUAGGAUAUCUUAGGUCA 22 22458 CFTR-Intron10-3577 + UUCCCUUAGGAUAUCUUAGGUCA 23 22459 CFTR-Intron10-3578 + UUUCCCUUAGGAUAUCUUAGGUCA 24 22460 CFTR-Intron10-3579 + UAUUCUUUUAUGUGGUCA 18 22461 CFTR-Intron10-3580 + AUAUUCUUUUAUGUGGUCA 19 22462 CFTR-Intron10-3581 + UAUAUUCUUUUAUGUGGUCA 20 22463 CFTR-Intron10-3582 + AUAUAUUCUUUUAUGUGGUCA 21 22464 CFTR-Intron10-3583 + AAUAUAUUCUUUUAUGUGGUCA 22 22465 CFTR-Intron10-3584 + GAAUAUAUUCUUUUAUGUGGUCA 23 22466 CFTR-Intron10-3585 + CGAAUAUAUUCUUUUAUGUGGUCA 24 22467 CFTR-Intron10-3586 + CUUCACUAAAAUAAUUCA 18 22468 CFTR-Intron10-3587 + GCUUCACUAAAAUAAUUCA 19 22469 CFTR-Intron10-1133 + UGCUUCACUAAAAUAAUUCA 20 20018 CFTR-Intron10-3588 + UUGCUUCACUAAAAUAAUUCA 21 22470 CFTR-Intron10-3589 + AUUGCUUCACUAAAAUAAUUCA 22 22471 CFTR-Intron10-3590 + UAUUGCUUCACUAAAAUAAUUCA 23 22472 CFTR-Intron10-3591 + AUAUUGCUUCACUAAAAUAAUUCA 24 22473 CFTR-Intron10-3592 + AAUCUAAAAGCUAAUUCA 18 22474 CFTR-Intron10-3593 + AAAUCUAAAAGCUAAUUCA 19 22475 CFTR-Intron10-369 + UAAAUCUAAAAGCUAAUUCA 20 19255 CFTR-Intron10-3594 + GUAAAUCUAAAAGCUAAUUCA 21 22476 CFTR-Intron10-3595 + AGUAAAUCUAAAAGCUAAUUCA 22 22477 CFTR-Intron10-3596 + AAGUAAAUCUAAAAGCUAAUUCA 23 22478 CFTR-Intron10-3597 + UAAGUAAAUCUAAAAGCUAAUUCA 24 22479 CFTR-Intron10-3598 + CAGGCCCAAAUACAUUCA 18 22480 CFTR-Intron10-3599 + GCAGGCCCAAAUACAUUCA 19 22481 CFTR-Intron10-3600 + UGCAGGCCCAAAUACAUUCA 20 22482 CFTR-Intron10-3601 + AUGCAGGCCCAAAUACAUUCA 21 22483 CFTR-Intron10-3602 + UAUGCAGGCCCAAAUACAUUCA 22 22484 CFTR-Intron10-3603 + AUAUGCAGGCCCAAAUACAUUCA 23 22485 CFTR-Intron10-3604 + CAUAUGCAGGCCCAAAUACAUUCA 24 22486 CFTR-Intron10-3605 + GAAUUGGUACAAAUUUCA 18 22487 CFTR-Intron10-3606 + CGAAUUGGUACAAAUUUCA 19 22488 CFTR-Intron10-370 + ACGAAUUGGUACAAAUUUCA 20 19256 CFTR-Intron10-3607 + UACGAAUUGGUACAAAUUUCA 21 22489 CFTR-Intron10-3608 + GUACGAAUUGGUACAAAUUUCA 22 22490 CFTR-Intron10-3609 + AGUACGAAUUGGUACAAAUUUCA 23 22491 CFTR-Intron10-3610 + GAGUACGAAUUGGUACAAAUUUCA 24 22492 CFTR-Intron10-3611 + UGAAAUAUAUUCAAAAGA 18 22493 CFTR-Intron10-3612 + CUGAAAUAUAUUCAAAAGA 19 22494 CFTR-Intron10-3613 + CCUGAAAUAUAUUCAAAAGA 20 22495 CFTR-Intron10-3614 + ACCUGAAAUAUAUUCAAAAGA 21 22496 CFTR-Intron10-3615 + CACCUGAAAUAUAUUCAAAAGA 22 22497 CFTR-Intron10-3616 + UCACCUGAAAUAUAUUCAAAAGA 23 22498 CFTR-Intron10-3617 + AUCACCUGAAAUAUAUUCAAAAGA 24 22499 CFTR-Intron10-3618 + GAUGAGAGACAGUAAAGA 18 22500 CFTR-Intron10-3619 + AGAUGAGAGACAGUAAAGA 19 22501 CFTR-Intron10-3620 + CAGAUGAGAGACAGUAAAGA 20 22502 CFTR-Intron10-3621 + ACAGAUGAGAGACAGUAAAGA 21 22503 CFTR-Intron10-3622 + GACAGAUGAGAGACAGUAAAGA 22 22504 CFTR-Intron10-3623 + GGACAGAUGAGAGACAGUAAAGA 23 22505 CFTR-Intron10-3624 + UGGACAGAUGAGAGACAGUAAAGA 24 22506 CFTR-Intron10-3625 + AAUAAUAACAUUUUAAGA 18 22507 CFTR-Intron10-3626 + AAAUAAUAACAUUUUAAGA 19 22508 CFTR-Intron10-3627 + AAAAUAAUAACAUUUUAAGA 20 22509 CFTR-Intron10-3628 + AAAAAUAAUAACAUUUUAAGA 21 22510 CFTR-Intron10-3629 + GAAAAAUAAUAACAUUUUAAGA 22 22511 CFTR-Intron10-3630 + AGAAAAAUAAUAACAUUUUAAGA 23 22512 CFTR-Intron10-3631 + AAGAAAAAUAAUAACAUUUUAAGA 24 22513 CFTR-Intron10-3632 + UCCAGCCUGGGCGACAGA 18 22514 CFTR-Intron10-3633 + CUCCAGCCUGGGCGACAGA 19 22515 CFTR-Intron10-3634 + ACUCCAGCCUGGGCGACAGA 20 22516 CFTR-Intron10-3635 + CACUCCAGCCUGGGCGACAGA 21 22517 CFTR-Intron10-3636 + GCACUCCAGCCUGGGCGACAGA 22 22518 CFTR-Intron10-3637 + UGCACUCCAGCCUGGGCGACAGA 23 22519 CFTR-Intron10-3638 + CUGCACUCCAGCCUGGGCGACAGA 24 22520 CFTR-Intron10-3639 + GUGUUCUCACAUGGCAGA 18 22521 CFTR-Intron10-3640 + UGUGUUCUCACAUGGCAGA 19 22522 CFTR-Intron10-3641 + CUGUGUUCUCACAUGGCAGA 20 22523 CFTR-Intron10-3642 + GCUGUGUUCUCACAUGGCAGA 21 22524 CFTR-Intron10-3643 + UGCUGUGUUCUCACAUGGCAGA 22 22525 CFTR-Intron10-3644 + CUGCUGUGUUCUCACAUGGCAGA 23 22526 CFTR-Intron10-3645 + CCUGCUGUGUUCUCACAUGGCAGA 24 22527 CFTR-Intron10-3646 + UGAAUGGCAGGGGAGAGA 18 22528 CFTR-Intron10-3647 + AUGAAUGGCAGGGGAGAGA 19 22529 CFTR-Intron10-3648 + UAUGAAUGGCAGGGGAGAGA 20 22530 CFTR-Intron10-3649 + AUAUGAAUGGCAGGGGAGAGA 21 22531 CFTR-Intron10-3650 + CAUAUGAAUGGCAGGGGAGAGA 22 22532 CFTR-Intron10-3651 + ACAUAUGAAUGGCAGGGGAGAGA 23 22533 CFTR-Intron10-3652 + AACAUAUGAAUGGCAGGGGAGAGA 24 22534 CFTR-Intron10-3653 + AUGAGGGAAUGCAGGAGA 18 22535 CFTR-Intron10-3654 + GAUGAGGGAAUGCAGGAGA 19 22536 CFTR-Intron10-3655 + GGAUGAGGGAAUGCAGGAGA 20 22537 CFTR-Intron10-3656 + UGGAUGAGGGAAUGCAGGAGA 21 22538 CFTR-Intron10-3657 + UUGGAUGAGGGAAUGCAGGAGA 22 22539 CFTR-Intron10-3658 + GUUGGAUGAGGGAAUGCAGGAGA 23 22540 CFTR-Intron10-3659 + GGUUGGAUGAGGGAAUGCAGGAGA 24 22541 CFTR-Intron10-3660 + GAUCACGAGGUCAGGAGA 18 22542 CFTR-Intron10-3661 + GGAUCACGAGGUCAGGAGA 19 22543 CFTR-Intron10-3662 + CGGAUCACGAGGUCAGGAGA 20 22544 CFTR-Intron10-3663 + GCGGAUCACGAGGUCAGGAGA 21 22545 CFTR-Intron10-3664 + GGCGGAUCACGAGGUCAGGAGA 22 22546 CFTR-Intron10-3665 + GGGCGGAUCACGAGGUCAGGAGA 23 22547 CFTR-Intron10-3666 + CGGGCGGAUCACGAGGUCAGGAGA 24 22548 CFTR-Intron10-3667 + UAGGAAAACAACUGGAGA 18 22549 CFTR-Intron10-3668 + GUAGGAAAACAACUGGAGA 19 22550 CFTR-Intron10-3669 + UGUAGGAAAACAACUGGAGA 20 22551 CFTR-Intron10-3670 + AUGUAGGAAAACAACUGGAGA 21 22552 CFTR-Intron10-3671 + UAUGUAGGAAAACAACUGGAGA 22 22553 CFTR-Intron10-3672 + GUAUGUAGGAAAACAACUGGAGA 23 22554 CFTR-Intron10-3673 + CGUAUGUAGGAAAACAACUGGAGA 24 22555 CFTR-Intron10-3674 + UAUGCAAUUUACUGGAGA 18 22556 CFTR-Intron10-3675 + AUAUGCAAUUUACUGGAGA 19 22557 CFTR-Intron10-3676 + AAUAUGCAAUUUACUGGAGA 20 22558 CFTR-Intron10-3677 + CAAUAUGCAAUUUACUGGAGA 21 22559 CFTR-Intron10-3678 + GCAAUAUGCAAUUUACUGGAGA 22 22560 CFTR-Intron10-3679 + UGCAAUAUGCAAUUUACUGGAGA 23 22561 CFTR-Intron10-3680 + CUGCAAUAUGCAAUUUACUGGAGA 24 22562 CFTR-Intron10-3681 + GAACUAGAGUCACAUAGA 18 22563 CFTR-Intron10-3682 + UGAACUAGAGUCACAUAGA 19 22564 CFTR-Intron10-3683 + GUGAACUAGAGUCACAUAGA 20 22565 CFTR-Intron10-3684 + AGUGAACUAGAGUCACAUAGA 21 22566 CFTR-Intron10-3685 + UAGUGAACUAGAGUCACAUAGA 22 22567 CFTR-Intron10-3686 + UUAGUGAACUAGAGUCACAUAGA 23 22568 CFTR-Intron10-3687 + AUUAGUGAACUAGAGUCACAUAGA 24 22569 CFTR-Intron10-3688 + AUUGAUUAUAUAUAUAGA 18 22570 CFTR-Intron10-3689 + UAUUGAUUAUAUAUAUAGA 19 22571 CFTR-Intron10-3690 + AUAUUGAUUAUAUAUAUAGA 20 22572 CFTR-Intron10-3691 + UAUAUUGAUUAUAUAUAUAGA 21 22573 CFTR-Intron10-3692 + GUAUAUUGAUUAUAUAUAUAGA 22 22574 CFTR-Intron10-3693 + UGUAUAUUGAUUAUAUAUAUAGA 23 22575 CFTR-Intron10-3694 + AUGUAUAUUGAUUAUAUAUAUAGA 24 22576 CFTR-Intron10-3695 + AGGAUCACUUUAUAUAGA 18 22577 CFTR-Intron10-3696 + UAGGAUCACUUUAUAUAGA 19 22578 CFTR-Intron10-3697 + CUAGGAUCACUUUAUAUAGA 20 22579 CFTR-Intron10-3698 + UCUAGGAUCACUUUAUAUAGA 21 22580 CFTR-Intron10-3699 + UUCUAGGAUCACUUUAUAUAGA 22 22581 CFTR-Intron10-3700 + AUUCUAGGAUCACUUUAUAUAGA 23 22582 CFTR-Intron10-3701 + GAUUCUAGGAUCACUUUAUAUAGA 24 22583 CFTR-Intron10-3702 + UGACUAAAACUGAGUAGA 18 22584 CFTR-Intron10-3703 + CUGACUAAAACUGAGUAGA 19 22585 CFTR-Intron10-374 + ACUGACUAAAACUGAGUAGA 20 19260 CFTR-Intron10-3704 + UACUGACUAAAACUGAGUAGA 21 22586 CFTR-Intron10-3705 + CUACUGACUAAAACUGAGUAGA 22 22587 CFTR-Intron10-3706 + ACUACUGACUAAAACUGAGUAGA 23 22588 CFTR-Intron10-3707 + UACUACUGACUAAAACUGAGUAGA 24 22589 CFTR-Intron10-3708 + GCACUCCAGCCUGGGCGA 18 22590 CFTR-Intron10-3709 + UGCACUCCAGCCUGGGCGA 19 22591 CFTR-Intron10-3710 + CUGCACUCCAGCCUGGGCGA 20 22592 CFTR-Intron10-3711 + ACUGCACUCCAGCCUGGGCGA 21 22593 CFTR-Intron10-3712 + CACUGCACUCCAGCCUGGGCGA 22 22594 CFTR-Intron10-3713 + CCACUGCACUCCAGCCUGGGCGA 23 22595 CFTR-Intron10-3714 + GCCACUGCACUCCAGCCUGGGCGA 24 22596 CFTR-Intron10-3715 + UGACUUCAUAAUAAAGGA 18 22597 CFTR-Intron10-3716 + GUGACUUCAUAAUAAAGGA 19 22598 CFTR-Intron10-3717 + AGUGACUUCAUAAUAAAGGA 20 22599 CFTR-Intron10-3718 + CAGUGACUUCAUAAUAAAGGA 21 22600 CFTR-Intron10-3719 + ACAGUGACUUCAUAAUAAAGGA 22 22601 CFTR-Intron10-3720 + UACAGUGACUUCAUAAUAAAGGA 23 22602 CFTR-Intron10-3721 + AUACAGUGACUUCAUAAUAAAGGA 24 22603 CFTR-Intron10-3722 + AUGCAGACAACAGAAGGA 18 22604 CFTR-Intron10-3723 + GAUGCAGACAACAGAAGGA 19 22605 CFTR-Intron10-3724 + UGAUGCAGACAACAGAAGGA 20 22606 CFTR-Intron10-3725 + GUGAUGCAGACAACAGAAGGA 21 22607 CFTR-Intron10-3726 + UGUGAUGCAGACAACAGAAGGA 22 22608 CFTR-Intron10-3727 + CUGUGAUGCAGACAACAGAAGGA 23 22609 CFTR-Intron10-3728 + GCUGUGAUGCAGACAACAGAAGGA 24 22610 CFTR-Intron10-3729 + UAAAACUGAGUAGAAGGA 18 22611 CFTR-Intron10-3730 + CUAAAACUGAGUAGAAGGA 19 22612 CFTR-Intron10-3731 + ACUAAAACUGAGUAGAAGGA 20 22613 CFTR-Intron10-3732 + GACUAAAACUGAGUAGAAGGA 21 22614 CFTR-Intron10-3733 + UGACUAAAACUGAGUAGAAGGA 22 22615 CFTR-Intron10-3734 + CUGACUAAAACUGAGUAGAAGGA 23 22616 CFTR-Intron10-3735 + ACUGACUAAAACUGAGUAGAAGGA 24 22617 CFTR-Intron10-3736 + UGUAGGAAAACAACUGGA 18 22618 CFTR-Intron10-3737 + AUGUAGGAAAACAACUGGA 19 22619 CFTR-Intron10-3738 + UAUGUAGGAAAACAACUGGA 20 22620 CFTR-Intron10-3739 + GUAUGUAGGAAAACAACUGGA 21 22621 CFTR-Intron10-3740 + CGUAUGUAGGAAAACAACUGGA 22 22622 CFTR-Intron10-3741 + UCGUAUGUAGGAAAACAACUGGA 23 22623 CFTR-Intron10-3742 + UUCGUAUGUAGGAAAACAACUGGA 24 22624 CFTR-Intron10-3743 + AAUAUGCAAUUUACUGGA 18 22625 CFTR-Intron10-3744 + CAAUAUGCAAUUUACUGGA 19 22626 CFTR-Intron10-3745 + GCAAUAUGCAAUUUACUGGA 20 22627 CFTR-Intron10-3746 + UGCAAUAUGCAAUUUACUGGA 21 22628 CFTR-Intron10-3747 + CUGCAAUAUGCAAUUUACUGGA 22 22629 CFTR-Intron10-3748 + ACUGCAAUAUGCAAUUUACUGGA 23 22630 CFTR-Intron10-3749 + UACUGCAAUAUGCAAUUUACUGGA 24 22631 CFTR-Intron10-3750 + UUUCAUCUUACUUGAUGA 18 22632 CFTR-Intron10-3751 + GUUUCAUCUUACUUGAUGA 19 22633 CFTR-Intron10-3752 + AGUUUCAUCUUACUUGAUGA 20 22634 CFTR-Intron10-3753 + CAGUUUCAUCUUACUUGAUGA 21 22635 CFTR-Intron10-3754 + ACAGUUUCAUCUUACUUGAUGA 22 22636 CFTR-Intron10-3755 + AACAGUUUCAUCUUACUUGAUGA 23 22637 CFTR-Intron10-3756 + UAACAGUUUCAUCUUACUUGAUGA 24 22638 CFTR-Intron10-3757 + UGACACCAAAUUUAUUGA 18 22639 CFTR-Intron10-3758 + CUGACACCAAAUUUAUUGA 19 22640 CFTR-Intron10-3759 + CCUGACACCAAAUUUAUUGA 20 22641 CFTR-Intron10-3760 + GCCUGACACCAAAUUUAUUGA 21 22642 CFTR-Intron10-3761 + AGCCUGACACCAAAUUUAUUGA 22 22643 CFTR-Intron10-3762 + CAGCCUGACACCAAAUUUAUUGA 23 22644 CFTR-Intron10-3763 + CCAGCCUGACACCAAAUUUAUUGA 24 22645 CFTR-Intron10-3764 + CUAAUAGCCUAUUGUUGA 18 22646 CFTR-Intron10-3765 + ACUAAUAGCCUAUUGUUGA 19 22647 CFTR-Intron10-3766 + UACUAAUAGCCUAUUGUUGA 20 22648 CFTR-Intron10-3767 + CUACUAAUAGCCUAUUGUUGA 21 22649 CFTR-Intron10-3768 + ACUACUAAUAGCCUAUUGUUGA 22 22650 CFTR-Intron10-3769 + AACUACUAAUAGCCUAUUGUUGA 23 22651 CFTR-Intron10-3770 + UAACUACUAAUAGCCUAUUGUUGA 24 22652 CFTR-Intron10-3771 + CCUUGGAAUAUAAAAAUA 18 22653 CFTR-Intron10-3772 + UCCUUGGAAUAUAAAAAUA 19 22654 CFTR-Intron10-3773 + GUCCUUGGAAUAUAAAAAUA 20 22655 CFTR-Intron10-3774 + AGUCCUUGGAAUAUAAAAAUA 21 22656 CFTR-Intron10-3775 + CAGUCCUUGGAAUAUAAAAAUA 22 22657 CFTR-Intron10-3776 + ACAGUCCUUGGAAUAUAAAAAUA 23 22658 CFTR-Intron10-3777 + GACAGUCCUUGGAAUAUAAAAAUA 24 22659 CFTR-Intron10-3778 + CUUUGUGUUAACAAAAUA 18 22660 CFTR-Intron10-3779 + UCUUUGUGUUAACAAAAUA 19 22661 CFTR-Intron10-3780 + UUCUUUGUGUUAACAAAAUA 20 22662 CFTR-Intron10-3781 + GUUCUUUGUGUUAACAAAAUA 21 22663 CFTR-Intron10-3782 + UGUUCUUUGUGUUAACAAAAUA 22 22664 CFTR-Intron10-3783 + UUGUUCUUUGUGUUAACAAAAUA 23 22665 CFTR-Intron10-3784 + GUUGUUCUUUGUGUUAACAAAAUA 24 22666 CFTR-Intron10-3785 + GGAAGAAAAGUAUCAAUA 18 22667 CFTR-Intron10-3786 + AGGAAGAAAAGUAUCAAUA 19 22668 CFTR-Intron10-3787 + CAGGAAGAAAAGUAUCAAUA 20 22669 CFTR-Intron10-3788 + UCAGGAAGAAAAGUAUCAAUA 21 22670 CFTR-Intron10-3789 + AUCAGGAAGAAAAGUAUCAAUA 22 22671 CFTR-Intron10-3790 + AAUCAGGAAGAAAAGUAUCAAUA 23 22672 CFTR-Intron10-3791 + UAAUCAGGAAGAAAAGUAUCAAUA 24 22673 CFTR-Intron10-3792 + UCCUCUGUGCUUUGAAUA 18 22674 CFTR-Intron10-3793 + GUCCUCUGUGCUUUGAAUA 19 22675 CFTR-Intron10-382 + AGUCCUCUGUGCUUUGAAUA 20 19268 CFTR-Intron10-3794 + AAGUCCUCUGUGCUUUGAAUA 21 22676 CFTR-Intron10-3795 + CAAGUCCUCUGUGCUUUGAAUA 22 22677 CFTR-Intron10-3796 + GCAAGUCCUCUGUGCUUUGAAUA 23 22678 CFTR-Intron10-3797 + UGCAAGUCCUCUGUGCUUUGAAUA 24 22679 CFTR-Intron10-3798 + UACAGUGACUUCAUAAUA 18 22680 CFTR-Intron10-3799 + AUACAGUGACUUCAUAAUA 19 22681 CFTR-Intron10-3800 + AAUACAGUGACUUCAUAAUA 20 22682 CFTR-Intron10-3801 + CAAUACAGUGACUUCAUAAUA 21 22683 CFTR-Intron10-3802 + ACAAUACAGUGACUUCAUAAUA 22 22684 CFTR-Intron10-3803 + GACAAUACAGUGACUUCAUAAUA 23 22685 CFTR-Intron10-3804 + AGACAAUACAGUGACUUCAUAAUA 24 22686 CFTR-Intron10-3805 + CCUAGAUGAUUAUUAAUA 18 22687 CFTR-Intron10-3806 + GCCUAGAUGAUUAUUAAUA 19 22688 CFTR-Intron10-384 + AGCCUAGAUGAUUAUUAAUA 20 19270 CFTR-Intron10-3807 + CAGCCUAGAUGAUUAUUAAUA 21 22689 CFTR-Intron10-3808 + GCAGCCUAGAUGAUUAUUAAUA 22 22690 CFTR-Intron10-3809 + UGCAGCCUAGAUGAUUAUUAAUA 23 22691 CFTR-Intron10-3810 + UUGCAGCCUAGAUGAUUAUUAAUA 24 22692 CFTR-Intron10-3811 + UAGUAUAAUUUUUUAAUA 18 22693 CFTR-Intron10-3812 + AUAGUAUAAUUUUUUAAUA 19 22694 CFTR-Intron10-3813 + UAUAGUAUAAUUUUUUAAUA 20 22695 CFTR-Intron10-3814 + CUAUAGUAUAAUUUUUUAAUA 21 22696 CFTR-Intron10-3815 + CCUAUAGUAUAAUUUUUUAAUA 22 22697 CFTR-Intron10-3816 + UCCUAUAGUAUAAUUUUUUAAUA 23 22698 CFTR-Intron10-3817 + CUCCUAUAGUAUAAUUUUUUAAUA 24 22699 CFTR-Intron10-3818 + UGAAACAAAUAAAACAUA 18 22700 CFTR-Intron10-3819 + AUGAAACAAAUAAAACAUA 19 22701 CFTR-Intron10-3820 + AAUGAAACAAAUAAAACAUA 20 22702 CFTR-Intron10-3821 + AAAUGAAACAAAUAAAACAUA 21 22703 CFTR-Intron10-3822 + GAAAUGAAACAAAUAAAACAUA 22 22704 CFTR-Intron10-3823 + AGAAAUGAAACAAAUAAAACAUA 23 22705 CFTR-Intron10-3824 + AAGAAAUGAAACAAAUAAAACAUA 24 22706 CFTR-Intron10-3825 + CUAAAACUCAGUACCAUA 18 22707 CFTR-Intron10-3826 + GCUAAAACUCAGUACCAUA 19 22708 CFTR-Intron10-3827 + AGCUAAAACUCAGUACCAUA 20 22709 CFTR-Intron10-3828 + AAGCUAAAACUCAGUACCAUA 21 22710 CFTR-Intron10-3829 + UAAGCUAAAACUCAGUACCAUA 22 22711 CFTR-Intron10-3830 + AUAAGCUAAAACUCAGUACCAUA 23 22712 CFTR-Intron10-3831 + AAUAAGCUAAAACUCAGUACCAUA 24 22713 CFTR-Intron10-3832 + AAAAUAUAUAUAUGCAUA 18 22714 CFTR-Intron10-3833 + AAAAAUAUAUAUAUGCAUA 19 22715 CFTR-Intron10-3834 + UAAAAAUAUAUAUAUGCAUA 20 22716 CFTR-Intron10-3835 + UUAAAAAUAUAUAUAUGCAUA 21 22717 CFTR-Intron10-3836 + GUUAAAAAUAUAUAUAUGCAUA 22 22718 CFTR-Intron10-3837 + GGUUAAAAAUAUAUAUAUGCAUA 23 22719 CFTR-Intron10-3838 + AGGUUAAAAAUAUAUAUAUGCAUA 24 22720 CFTR-Intron10-3839 + ACAUAGAGAAAACUCAUA 18 22721 CFTR-Intron10-3840 + AACAUAGAGAAAACUCAUA 19 22722 CFTR-Intron10-1168 + AAACAUAGAGAAAACUCAUA 20 20053 CFTR-Intron10-3841 + AAAACAUAGAGAAAACUCAUA 21 22723 CFTR-Intron10-3842 + UAAAACAUAGAGAAAACUCAUA 22 22724 CFTR-Intron10-3843 + AUAAAACAUAGAGAAAACUCAUA 23 22725 CFTR-Intron10-3844 + AAUAAAACAUAGAGAAAACUCAUA 24 22726 CFTR-Intron10-3845 + GGAAAGUUGUCCAAGAUA 18 22727 CFTR-Intron10-3846 + UGGAAAGUUGUCCAAGAUA 19 22728 CFTR-Intron10-3847 + AUGGAAAGUUGUCCAAGAUA 20 22729 CFTR-Intron10-3848 + UAUGGAAAGUUGUCCAAGAUA 21 22730 CFTR-Intron10-3849 + AUAUGGAAAGUUGUCCAAGAUA 22 22731 CFTR-Intron10-3850 + AAUAUGGAAAGUUGUCCAAGAUA 23 22732 CFTR-Intron10-3851 + GAAUAUGGAAAGUUGUCCAAGAUA 24 22733 CFTR-Intron10-3852 + UGUUCUUAGGGUGGGAUA 18 22734 CFTR-Intron10-3853 + UUGUUCUUAGGGUGGGAUA 19 22735 CFTR-Intron10-84 + GUUGUUCUUAGGGUGGGAUA 20 18970 CFTR-Intron10-3854 + AGUUGUUCUUAGGGUGGGAUA 21 22736 CFTR-Intron10-3855 + AAGUUGUUCUUAGGGUGGGAUA 22 22737 CFTR-Intron10-3856 + UAAGUUGUUCUUAGGGUGGGAUA 23 22738 CFTR-Intron10-3857 + UUAAGUUGUUCUUAGGGUGGGAUA 24 22739 CFTR-Intron10-3858 + AUAUUGAUUAUAUAUAUA 18 22740 CFTR-Intron10-3859 + UAUAUUGAUUAUAUAUAUA 19 22741 CFTR-Intron10-3860 + GUAUAUUGAUUAUAUAUAUA 20 22742 CFTR-Intron10-3861 + UGUAUAUUGAUUAUAUAUAUA 21 22743 CFTR-Intron10-3862 + AUGUAUAUUGAUUAUAUAUAUA 22 22744 CFTR-Intron10-3863 + AAUGUAUAUUGAUUAUAUAUAUA 23 22745 CFTR-Intron10-3864 + AAAUGUAUAUUGAUUAUAUAUAUA 24 22746 CFTR-Intron10-3865 + GUAUAUUGAUUAUAUAUA 18 22747 CFTR-Intron10-3866 + UGUAUAUUGAUUAUAUAUA 19 22748 CFTR-Intron10-3867 + AUGUAUAUUGAUUAUAUAUA 20 22749 CFTR-Intron10-3868 + AAUGUAUAUUGAUUAUAUAUA 21 22750 CFTR-Intron10-3869 + AAAUGUAUAUUGAUUAUAUAUA 22 22751 CFTR-Intron10-3870 + AAAAUGUAUAUUGAUUAUAUAUA 23 22752 CFTR-Intron10-3871 + AAAAAUGUAUAUUGAUUAUAUAUA 24 22753 CFTR-Intron10-3872 + CUAGGAUCACUUUAUAUA 18 22754 CFTR-Intron10-3873 + UCUAGGAUCACUUUAUAUA 19 22755 CFTR-Intron10-3874 + UUCUAGGAUCACUUUAUAUA 20 22756 CFTR-Intron10-3875 + AUUCUAGGAUCACUUUAUAUA 21 22757 CFTR-Intron10-3876 + GAUUCUAGGAUCACUUUAUAUA 22 22758 CFTR-Intron10-3877 + UGAUUCUAGGAUCACUUUAUAUA 23 22759 CFTR-Intron10-3878 + AUGAUUCUAGGAUCACUUUAUAUA 24 22760 CFTR-Intron10-3879 + CCUGAAAGCAGUGUUAUA 18 22761 CFTR-Intron10-3880 + UCCUGAAAGCAGUGUUAUA 19 22762 CFTR-Intron10-3881 + CUCCUGAAAGCAGUGUUAUA 20 22763 CFTR-Intron10-3882 + GCUCCUGAAAGCAGUGUUAUA 21 22764 CFTR-Intron10-3883 + GGCUCCUGAAAGCAGUGUUAUA 22 22765 CFTR-Intron10-3884 + UGGCUCCUGAAAGCAGUGUUAUA 23 22766 CFTR-Intron10-3885 + UUGGCUCCUGAAAGCAGUGUUAUA 24 22767 CFTR-Intron10-3886 + UUCUAGGAUCACUUUAUA 18 22768 CFTR-Intron10-3887 + AUUCUAGGAUCACUUUAUA 19 22769 CFTR-Intron10-3888 + GAUUCUAGGAUCACUUUAUA 20 22770 CFTR-Intron10-3889 + UGAUUCUAGGAUCACUUUAUA 21 22771 CFTR-Intron10-3890 + AUGAUUCUAGGAUCACUUUAUA 22 22772 CFTR-Intron10-3891 + UAUGAUUCUAGGAUCACUUUAUA 23 22773 CFTR-Intron10-3892 + UUAUGAUUCUAGGAUCACUUUAUA 24 22774 CFTR-Intron10-3893 + GACAGAUGAGAGACAGUA 18 22775 CFTR-Intron10-3894 + GGACAGAUGAGAGACAGUA 19 22776 CFTR-Intron10-3895 + UGGACAGAUGAGAGACAGUA 20 22777 CFTR-Intron10-3896 + AUGGACAGAUGAGAGACAGUA 21 22778 CFTR-Intron10-3897 + AAUGGACAGAUGAGAGACAGUA 22 22779 CFTR-Intron10-3898 + AAAUGGACAGAUGAGAGACAGUA 23 22780 CFTR-Intron10-3899 + AAAAUGGACAGAUGAGAGACAGUA 24 22781 CFTR-Intron10-3900 + UUUCUAGAAAACAAUGUA 18 22782 CFTR-Intron10-3901 + UUUUCUAGAAAACAAUGUA 19 22783 CFTR-Intron10-3902 + AUUUUCUAGAAAACAAUGUA 20 22784 CFTR-Intron10-3903 + GAUUUUCUAGAAAACAAUGUA 21 22785 CFTR-Intron10-3904 + AGAUUUUCUAGAAAACAAUGUA 22 22786 CFTR-Intron10-3905 + CAGAUUUUCUAGAAAACAAUGUA 23 22787 CFTR-Intron10-3906 + ACAGAUUUUCUAGAAAACAAUGUA 24 22788 CFTR-Intron10-3907 + GUAUAAGUGUGGAGUGUA 18 22789 CFTR-Intron10-3908 + GGUAUAAGUGUGGAGUGUA 19 22790 CFTR-Intron10-3909 + GGGUAUAAGUGUGGAGUGUA 20 22791 CFTR-Intron10-3910 + GGGGUAUAAGUGUGGAGUGUA 21 22792 CFTR-Intron10-3911 + UGGGGUAUAAGUGUGGAGUGUA 22 22793 CFTR-Intron10-3912 + AUGGGGUAUAAGUGUGGAGUGUA 23 22794 CFTR-Intron10-3913 + AAUGGGGUAUAAGUGUGGAGUGUA 24 22795 CFTR-Intron10-3914 + UUCUUGAAGCAAAAAUUA 18 22796 CFTR-Intron10-3915 + AUUCUUGAAGCAAAAAUUA 19 22797 CFTR-Intron10-3916 + UAUUCUUGAAGCAAAAAUUA 20 22798 CFTR-Intron10-3917 + AUAUUCUUGAAGCAAAAAUUA 21 22799 CFTR-Intron10-3918 + AAUAUUCUUGAAGCAAAAAUUA 22 22800 CFTR-Intron10-3919 + CAAUAUUCUUGAAGCAAAAAUUA 23 22801 CFTR-Intron10-3920 + GCAAUAUUCUUGAAGCAAAAAUUA 24 22802 CFTR-Intron10-3921 + CUGAAUAACACGCCAUUA 18 22803 CFTR-Intron10-3922 + GCUGAAUAACACGCCAUUA 19 22804 CFTR-Intron10-3923 + GGCUGAAUAACACGCCAUUA 20 22805 CFTR-Intron10-3924 + UGGCUGAAUAACACGCCAUUA 21 22806 CFTR-Intron10-3925 + UUGGCUGAAUAACACGCCAUUA 22 22807 CFTR-Intron10-3926 + AUUGGCUGAAUAACACGCCAUUA 23 22808 CFTR-Intron10-3927 + UAUUGGCUGAAUAACACGCCAUUA 24 22809 CFTR-Intron10-3928 + UUAUCAGAGCUCAUAUUA 18 22810 CFTR-Intron10-3929 + UUUAUCAGAGCUCAUAUUA 19 22811 CFTR-Intron10-3930 + UUUUAUCAGAGCUCAUAUUA 20 22812 CFTR-Intron10-3931 + AUUUUAUCAGAGCUCAUAUUA 21 22813 CFTR-Intron10-3932 + GAUUUUAUCAGAGCUCAUAUUA 22 22814 CFTR-Intron10-3933 + UGAUUUUAUCAGAGCUCAUAUUA 23 22815 CFTR-Intron10-3934 + CUGAUUUUAUCAGAGCUCAUAUUA 24 22816 CFTR-Intron10-3935 + CAAAUGCUUGACCACUUA 18 22817 CFTR-Intron10-3936 + ACAAAUGCUUGACCACUUA 19 22818 CFTR-Intron10-3937 + CACAAAUGCUUGACCACUUA 20 22819 CFTR-Intron10-3938 + ACACAAAUGCUUGACCACUUA 21 22820 CFTR-Intron10-3939 + UACACAAAUGCUUGACCACUUA 22 22821 CFTR-Intron10-3940 + GUACACAAAUGCUUGACCACUUA 23 22822 CFTR-Intron10-3941 + AGUACACAAAUGCUUGACCACUUA 24 22823 CFTR-Intron10-3942 + AUUAAUAACAAAAUCUUA 18 22824 CFTR-Intron10-3943 + UAUUAAUAACAAAAUCUUA 19 22825 CFTR-Intron10-3944 + AUAUUAAUAACAAAAUCUUA 20 22826 CFTR-Intron10-3945 + AAUAUUAAUAACAAAAUCUUA 21 22827 CFTR-Intron10-3946 + UAAUAUUAAUAACAAAAUCUUA 22 22828 CFTR-Intron10-3947 + GUAAUAUUAAUAACAAAAUCUUA 23 22829 CFTR-Intron10-3948 + AGUAAUAUUAAUAACAAAAUCUUA 24 22830 CFTR-Intron10-3949 + ACAUAUUUGGGUAAGUUA 18 22831 CFTR-Intron10-3950 + AACAUAUUUGGGUAAGUUA 19 22832 CFTR-Intron10-3951 + AAACAUAUUUGGGUAAGUUA 20 22833 CFTR-Intron10-3952 + CAAACAUAUUUGGGUAAGUUA 21 22834 CFTR-Intron10-3953 + GCAAACAUAUUUGGGUAAGUUA 22 22835 CFTR-Intron10-3954 + UGCAAACAUAUUUGGGUAAGUUA 23 22836 CFTR-Intron10-3955 + CUGCAAACAUAUUUGGGUAAGUUA 24 22837 CFTR-Intron10-3956 + ACUGCAAUAUGCAAUUUA 18 22838 CFTR-Intron10-3957 + UACUGCAAUAUGCAAUUUA 19 22839 CFTR-Intron10-3958 + UUACUGCAAUAUGCAAUUUA 20 22840 CFTR-Intron10-3959 + UUUACUGCAAUAUGCAAUUUA 21 22841 CFTR-Intron10-3960 + UUUUACUGCAAUAUGCAAUUUA 22 22842 CFTR-Intron10-3961 + UUUUUACUGCAAUAUGCAAUUUA 23 22843 CFTR-Intron10-3962 + CUUUUUACUGCAAUAUGCAAUUUA 24 22844 CFTR-Intron10-3963 + CCUAUUAUUCAACAUUUA 18 22845 CFTR-Intron10-3964 + CCCUAUUAUUCAACAUUUA 19 22846 CFTR-Intron10-398 + CCCCUAUUAUUCAACAUUUA 20 19284 CFTR-Intron10-3965 + ACCCCUAUUAUUCAACAUUUA 21 22847 CFTR-Intron10-3966 + AACCCCUAUUAUUCAACAUUUA 22 22848 CFTR-Intron10-3967 + AAACCCCUAUUAUUCAACAUUUA 23 22849 CFTR-Intron10-3968 + CAAACCCCUAUUAUUCAACAUUUA 24 22850 CFTR-Intron10-3969 + UAAAAAGCAAGCAAAAAC 18 22851 CFTR-Intron10-3970 + AUAAAAAGCAAGCAAAAAC 19 22852 CFTR-Intron10-3971 + UAUAAAAAGCAAGCAAAAAC 20 22853 CFTR-Intron10-3972 + GUAUAAAAAGCAAGCAAAAAC 21 22854 CFTR-Intron10-3973 + UGUAUAAAAAGCAAGCAAAAAC 22 22855 CFTR-Intron10-3974 + CUGUAUAAAAAGCAAGCAAAAAC 23 22856 CFTR-Intron10-3975 + UCUGUAUAAAAAGCAAGCAAAAAC 24 22857 CFTR-Intron10-3976 + AACAUCUAACUCAAAAAC 18 22858 CFTR-Intron10-3977 + AAACAUCUAACUCAAAAAC 19 22859 CFTR-Intron10-3978 + CAAACAUCUAACUCAAAAAC 20 22860 CFTR-Intron10-3979 + UCAAACAUCUAACUCAAAAAC 21 22861 CFTR-Intron10-3980 + GUCAAACAUCUAACUCAAAAAC 22 22862 CFTR-Intron10-3981 + CGUCAAACAUCUAACUCAAAAAC 23 22863 CFTR-Intron10-3982 + GCGUCAAACAUCUAACUCAAAAAC 24 22864 CFTR-Intron10-3983 + CGUAUGUAGGAAAACAAC 18 22865 CFTR-Intron10-3984 + UCGUAUGUAGGAAAACAAC 19 22866 CFTR-Intron10-402 + UUCGUAUGUAGGAAAACAAC 20 19288 CFTR-Intron10-3985 + UUUCGUAUGUAGGAAAACAAC 21 22867 CFTR-Intron10-3986 + GUUUCGUAUGUAGGAAAACAAC 22 22868 CFTR-Intron10-3987 + UGUUUCGUAUGUAGGAAAACAAC 23 22869 CFTR-Intron10-3988 + CUGUUUCGUAUGUAGGAAAACAAC 24 22870 CFTR-Intron10-3989 + GCUUACCGUAAUAGCAAC 18 22871 CFTR-Intron10-3990 + AGCUUACCGUAAUAGCAAC 19 22872 CFTR-Intron10-660 + GAGCUUACCGUAAUAGCAAC 20 19546 CFTR-Intron10-3991 + UGAGCUUACCGUAAUAGCAAC 21 22873 CFTR-Intron10-3992 + UUGAGCUUACCGUAAUAGCAAC 22 22874 CFTR-Intron10-3993 + CUUGAGCUUACCGUAAUAGCAAC 23 22875 CFTR-Intron10-3994 + GCUUGAGCUUACCGUAAUAGCAAC 24 22876 CFTR-Intron10-3995 + CAUUGACCCUUUAUCAAC 18 22877 CFTR-Intron10-3996 + CCAUUGACCCUUUAUCAAC 19 22878 CFTR-Intron10-3997 + ACCAUUGACCCUUUAUCAAC 20 22879 CFTR-Intron10-3998 + UACCAUUGACCCUUUAUCAAC 21 22880 CFTR-Intron10-3999 + AUACCAUUGACCCUUUAUCAAC 22 22881 CFTR-Intron10-4000 + UAUACCAUUGACCCUUUAUCAAC 23 22882 CFTR-Intron10-4001 + AUAUACCAUUGACCCUUUAUCAAC 24 22883 CFTR-Intron10-4002 + UGACAAUCAAAUGGGAAC 18 22884 CFTR-Intron10-4003 + AUGACAAUCAAAUGGGAAC 19 22885 CFTR-Intron10-4004 + AAUGACAAUCAAAUGGGAAC 20 22886 CFTR-Intron10-4005 + AAAUGACAAUCAAAUGGGAAC 21 22887 CFTR-Intron10-4006 + AAAAUGACAAUCAAAUGGGAAC 22 22888 CFTR-Intron10-4007 + UAAAAUGACAAUCAAAUGGGAAC 23 22889 CFTR-Intron10-4008 + CUAAAAUGACAAUCAAAUGGGAAC 24 22890 CFTR-Intron10-4009 + CAGGAGAAUGGCGUGAAC 18 22891 CFTR-Intron10-4010 + GCAGGAGAAUGGCGUGAAC 19 22892 CFTR-Intron10-4011 + GGCAGGAGAAUGGCGUGAAC 20 22893 CFTR-Intron10-4012 + AGGCAGGAGAAUGGCGUGAAC 21 22894 CFTR-Intron10-4013 + GAGGCAGGAGAAUGGCGUGAAC 22 22895 CFTR-Intron10-4014 + UGAGGCAGGAGAAUGGCGUGAAC 23 22896 CFTR-Intron10-4015 + CUGAGGCAGGAGAAUGGCGUGAAC 24 22897 CFTR-Intron10-4016 + GAACCUAUAAGGAAUAAC 18 22898 CFTR-Intron10-4017 + AGAACCUAUAAGGAAUAAC 19 22899 CFTR-Intron10-403 + CAGAACCUAUAAGGAAUAAC 20 19289 CFTR-Intron10-4018 + ACAGAACCUAUAAGGAAUAAC 21 22900 CFTR-Intron10-4019 + UACAGAACCUAUAAGGAAUAAC 22 22901 CFTR-Intron10-4020 + UUACAGAACCUAUAAGGAAUAAC 23 22902 CFTR-Intron10-4021 + AUUACAGAACCUAUAAGGAAUAAC 24 22903 CFTR-Intron10-4022 + AAAAUAUGCGAGAACCAC 18 22904 CFTR-Intron10-4023 + AAAAAUAUGCGAGAACCAC 19 22905 CFTR-Intron10-4024 + GAAAAAUAUGCGAGAACCAC 20 22906 CFTR-Intron10-4025 + UGAAAAAUAUGCGAGAACCAC 21 22907 CFTR-Intron10-4026 + AUGAAAAAUAUGCGAGAACCAC 22 22908 CFTR-Intron10-4027 + GAUGAAAAAUAUGCGAGAACCAC 23 22909 CFTR-Intron10-4028 + UGAUGAAAAAUAUGCGAGAACCAC 24 22910 CFTR-Intron10-4029 + AGUAUUAAGUAUAGCCAC 18 22911 CFTR-Intron10-4030 + UAGUAUUAAGUAUAGCCAC 19 22912 CFTR-Intron10-408 + UUAGUAUUAAGUAUAGCCAC 20 19294 CFTR-Intron10-4031 + AUUAGUAUUAAGUAUAGCCAC 21 22913 CFTR-Intron10-4032 + UAUUAGUAUUAAGUAUAGCCAC 22 22914 CFTR-Intron10-4033 + UUAUUAGUAUUAAGUAUAGCCAC 23 22915 CFTR-Intron10-4034 + GUUAUUAGUAUUAAGUAUAGCCAC 24 22916 CFTR-Intron10-4035 + UUUAAUAAAUAAUAUCAC 18 22917 CFTR-Intron10-4036 + UUUUAAUAAAUAAUAUCAC 19 22918 CFTR-Intron10-4037 + AUUUUAAUAAAUAAUAUCAC 20 22919 CFTR-Intron10-4038 + AAUUUUAAUAAAUAAUAUCAC 21 22920 CFTR-Intron10-4039 + AAAUUUUAAUAAAUAAUAUCAC 22 22921 CFTR-Intron10-4040 + UAAAUUUUAAUAAAUAAUAUCAC 23 22922 CFTR-Intron10-4041 + UUAAAUUUUAAUAAAUAAUAUCAC 24 22923 CFTR-Intron10-4042 + GGAGAGAGAACUGCUCAC 18 22924 CFTR-Intron10-4043 + UGGAGAGAGAACUGCUCAC 19 22925 CFTR-Intron10-4044 + CUGGAGAGAGAACUGCUCAC 20 22926 CFTR-Intron10-4045 + ACUGGAGAGAGAACUGCUCAC 21 22927 CFTR-Intron10-4046 + UACUGGAGAGAGAACUGCUCAC 22 22928 CFTR-Intron10-4047 + UUACUGGAGAGAGAACUGCUCAC 23 22929 CFTR-Intron10-4048 + UUUACUGGAGAGAGAACUGCUCAC 24 22930 CFTR-Intron10-4049 + AAGACAUUUAAUGUAGAC 18 22931 CFTR-Intron10-4050 + CAAGACAUUUAAUGUAGAC 19 22932 CFTR-Intron10-4051 + GCAAGACAUUUAAUGUAGAC 20 22933 CFTR-Intron10-4052 + CGCAAGACAUUUAAUGUAGAC 21 22934 CFTR-Intron10-4053 + GCGCAAGACAUUUAAUGUAGAC 22 22935 CFTR-Intron10-4054 + AGCGCAAGACAUUUAAUGUAGAC 23 22936 CFTR-Intron10-4055 + AAGCGCAAGACAUUUAAUGUAGAC 24 22937 CFTR-Intron10-4056 + UUUAGCCCAUUCUAAUAC 18 22938 CFTR-Intron10-4057 + CUUUAGCCCAUUCUAAUAC 19 22939 CFTR-Intron10-4058 + CCUUUAGCCCAUUCUAAUAC 20 22940 CFTR-Intron10-4059 + CCCUUUAGCCCAUUCUAAUAC 21 22941 CFTR-Intron10-4060 + GCCCUUUAGCCCAUUCUAAUAC 22 22942 CFTR-Intron10-4061 + UGCCCUUUAGCCCAUUCUAAUAC 23 22943 CFTR-Intron10-4062 + UUGCCCUUUAGCCCAUUCUAAUAC 24 22944 CFTR-Intron10-4063 + UAUUUGUGGAGGACAUAC 18 22945 CFTR-Intron10-4064 + AUAUUUGUGGAGGACAUAC 19 22946 CFTR-Intron10-4065 + AAUAUUUGUGGAGGACAUAC 20 22947 CFTR-Intron10-4066 + AAAUAUUUGUGGAGGACAUAC 21 22948 CFTR-Intron10-4067 + AAAAUAUUUGUGGAGGACAUAC 22 22949 CFTR-Intron10-4068 + AAAAAUAUUUGUGGAGGACAUAC 23 22950 CFTR-Intron10-4069 + AAAAAAUAUUUGUGGAGGACAUAC 24 22951 CFTR-Intron10-4070 + GCCUGUAGUCCCAGCUAC 18 22952 CFTR-Intron10-4071 + CGCCUGUAGUCCCAGCUAC 19 22953 CFTR-Intron10-4072 + GCGCCUGUAGUCCCAGCUAC 20 22954 CFTR-Intron10-4073 + GGCGCCUGUAGUCCCAGCUAC 21 22955 CFTR-Intron10-4074 + GGGCGCCUGUAGUCCCAGCUAC 22 22956 CFTR-Intron10-4075 + CGGGCGCCUGUAGUCCCAGCUAC 23 22957 CFTR-Intron10-4076 + GCGGGCGCCUGUAGUCCCAGCUAC 24 22958 CFTR-Intron10-4077 + UGCCUGUAGUCCCAGCUAC 19 22959 CFTR-Intron10-4078 + GUGCCUGUAGUCCCAGCUAC 20 22960 CFTR-Intron10-4079 + CGUGCCUGUAGUCCCAGCUAC 21 22961 CFTR-Intron10-4080 + GCGUGCCUGUAGUCCCAGCUAC 22 22962 CFTR-Intron10-4081 + UGCGUGCCUGUAGUCCCAGCUAC 23 22963 CFTR-Intron10-4082 + GUGCGUGCCUGUAGUCCCAGCUAC 24 22964 CFTR-Intron10-4083 + ACUUGCUUCACCUGCUAC 18 22965 CFTR-Intron10-4084 + CACUUGCUUCACCUGCUAC 19 22966 CFTR-Intron10-4085 + GCACUUGCUUCACCUGCUAC 20 22967 CFTR-Intron10-4086 + UGCACUUGCUUCACCUGCUAC 21 22968 CFTR-Intron10-4087 + UUGCACUUGCUUCACCUGCUAC 22 22969 CFTR-Intron10-4088 + UUUGCACUUGCUUCACCUGCUAC 23 22970 CFTR-Intron10-4089 + CUUUGCACUUGCUUCACCUGCUAC 24 22971 CFTR-Intron10-4090 + AAAUCUUAUAGAGAUUAC 18 22972 CFTR-Intron10-4091 + AAAAUCUUAUAGAGAUUAC 19 22973 CFTR-Intron10-4092 + CAAAAUCUUAUAGAGAUUAC 20 22974 CFTR-Intron10-4093 + ACAAAAUCUUAUAGAGAUUAC 21 22975 CFTR-Intron10-4094 + AACAAAAUCUUAUAGAGAUUAC 22 22976 CFTR-Intron10-4095 + UAACAAAAUCUUAUAGAGAUUAC 23 22977 CFTR-Intron10-4096 + AUAACAAAAUCUUAUAGAGAUUAC 24 22978 CFTR-Intron10-4097 + UUUUACAAUUCUUAUUAC 18 22979 CFTR-Intron10-4098 + AUUUUACAAUUCUUAUUAC 19 22980 CFTR-Intron10-4099 + AAUUUUACAAUUCUUAUUAC 20 22981 CFTR-Intron10-4100 + AAAUUUUACAAUUCUUAUUAC 21 22982 CFTR-Intron10-4101 + UAAAUUUUACAAUUCUUAUUAC 22 22983 CFTR-Intron10-4102 + GUAAAUUUUACAAUUCUUAUUAC 23 22984 CFTR-Intron10-4103 + AGUAAAUUUUACAAUUCUUAUUAC 24 22985 CFTR-Intron10-4104 + CUGCAAUAUGCAAUUUAC 18 22986 CFTR-Intron10-4105 + ACUGCAAUAUGCAAUUUAC 19 22987 CFTR-Intron10-1190 + UACUGCAAUAUGCAAUUUAC 20 20075 CFTR-Intron10-4106 + UUACUGCAAUAUGCAAUUUAC 21 22988 CFTR-Intron10-4107 + UUUACUGCAAUAUGCAAUUUAC 22 22989 CFTR-Intron10-4108 + UUUUACUGCAAUAUGCAAUUUAC 23 22990 CFTR-Intron10-4109 + UUUUUACUGCAAUAUGCAAUUUAC 24 22991 CFTR-Intron10-4110 + UUUGUACAAAAUUAAACC 18 22992 CFTR-Intron10-4111 + CUUUGUACAAAAUUAAACC 19 22993 CFTR-Intron10-4112 + CCUUUGUACAAAAUUAAACC 20 22994 CFTR-Intron10-4113 + UCCUUUGUACAAAAUUAAACC 21 22995 CFTR-Intron10-4114 + UUCCUUUGUACAAAAUUAAACC 22 22996 CFTR-Intron10-4115 + AUUCCUUUGUACAAAAUUAAACC 23 22997 CFTR-Intron10-4116 + AAUUCCUUUGUACAAAAUUAAACC 24 22998 CFTR-Intron10-4117 + AGGAGAAUGGCGUGAACC 18 22999 CFTR-Intron10-4118 + CAGGAGAAUGGCGUGAACC 19 23000 CFTR-Intron10-661 + GCAGGAGAAUGGCGUGAACC 20 19547 CFTR-Intron10-4119 + GGCAGGAGAAUGGCGUGAACC 21 23001 CFTR-Intron10-4120 + AGGCAGGAGAAUGGCGUGAACC 22 23002 CFTR-Intron10-4121 + GAGGCAGGAGAAUGGCGUGAACC 23 23003 CFTR-Intron10-4122 + UGAGGCAGGAGAAUGGCGUGAACC 24 23004 CFTR-Intron10-4123 + GGUCUUGAUCUCCUAACC 18 23005 CFTR-Intron10-4124 + UGGUCUUGAUCUCCUAACC 19 23006 CFTR-Intron10-4125 + AUGGUCUUGAUCUCCUAACC 20 23007 CFTR-Intron10-4126 + GAUGGUCUUGAUCUCCUAACC 21 23008 CFTR-Intron10-4127 + GGAUGGUCUUGAUCUCCUAACC 22 23009 CFTR-Intron10-4128 + AGGAUGGUCUUGAUCUCCUAACC 23 23010 CFTR-Intron10-4129 + CAGGAUGGUCUUGAUCUCCUAACC 24 23011 CFTR-Intron10-4130 + CCCUGCAAUACCAUCACC 18 23012 CFTR-Intron10-4131 + ACCCUGCAAUACCAUCACC 19 23013 CFTR-Intron10-4132 + CACCCUGCAAUACCAUCACC 20 23014 CFTR-Intron10-4133 + CCACCCUGCAAUACCAUCACC 21 23015 CFTR-Intron10-4134 + CCCACCCUGCAAUACCAUCACC 22 23016 CFTR-Intron10-4135 + CCCCACCCUGCAAUACCAUCACC 23 23017 CFTR-Intron10-4136 + GCCCCACCCUGCAAUACCAUCACC 24 23018 CFTR-Intron10-4137 + GUGGCCUCUAAUCUCACC 18 23019 CFTR-Intron10-4138 + AGUGGCCUCUAAUCUCACC 19 23020 CFTR-Intron10-4139 + CAGUGGCCUCUAAUCUCACC 20 23021 CFTR-Intron10-4140 + CCAGUGGCCUCUAAUCUCACC 21 23022 CFTR-Intron10-4141 + UCCAGUGGCCUCUAAUCUCACC 22 23023 CFTR-Intron10-4142 + CUCCAGUGGCCUCUAAUCUCACC 23 23024 CFTR-Intron10-4143 + UCUCCAGUGGCCUCUAAUCUCACC 24 23025 CFTR-Intron10-4144 + CUGCUAUAACAAAAUACC 18 23026 CFTR-Intron10-4145 + GCUGCUAUAACAAAAUACC 19 23027 CFTR-Intron10-4146 + GGCUGCUAUAACAAAAUACC 20 23028 CFTR-Intron10-4147 + AGGCUGCUAUAACAAAAUACC 21 23029 CFTR-Intron10-4148 + CAGGCUGCUAUAACAAAAUACC 22 23030 CFTR-Intron10-4149 + UCAGGCUGCUAUAACAAAAUACC 23 23031 CFTR-Intron10-4150 + UUCAGGCUGCUAUAACAAAAUACC 24 23032 CFTR-Intron10-4151 + UACAGCUAAAGUAUUACC 18 23033 CFTR-Intron10-4152 + AUACAGCUAAAGUAUUACC 19 23034 CFTR-Intron10-4153 + UAUACAGCUAAAGUAUUACC 20 23035 CFTR-Intron10-4154 + AUAUACAGCUAAAGUAUUACC 21 23036 CFTR-Intron10-4155 + AAUAUACAGCUAAAGUAUUACC 22 23037 CFTR-Intron10-4156 + UAAUAUACAGCUAAAGUAUUACC 23 23038 CFTR-Intron10-4157 + AUAAUAUACAGCUAAAGUAUUACC 24 23039 CFTR-Intron10-4158 + GGAGAAUGGCGUGAACCC 18 23040 CFTR-Intron10-4159 + AGGAGAAUGGCGUGAACCC 19 23041 CFTR-Intron10-1191 + CAGGAGAAUGGCGUGAACCC 20 20076 CFTR-Intron10-4160 + GCAGGAGAAUGGCGUGAACCC 21 23042 CFTR-Intron10-4161 + GGCAGGAGAAUGGCGUGAACCC 22 23043 CFTR-Intron10-4162 + AGGCAGGAGAAUGGCGUGAACCC 23 23044 CFTR-Intron10-4163 + GAGGCAGGAGAAUGGCGUGAACCC 24 23045 CFTR-Intron10-4164 + GGAGAAUUGCUUGAGCCC 18 23046 CFTR-Intron10-4165 + AGGAGAAUUGCUUGAGCCC 19 23047 CFTR-Intron10-1195 + CAGGAGAAUUGCUUGAGCCC 20 20080 CFTR-Intron10-4166 + GCAGGAGAAUUGCUUGAGCCC 21 23048 CFTR-Intron10-4167 + GGCAGGAGAAUUGCUUGAGCCC 22 23049 CFTR-Intron10-4168 + AGGCAGGAGAAUUGCUUGAGCCC 23 23050 CFTR-Intron10-4169 + GAGGCAGGAGAAUUGCUUGAGCCC 24 23051 CFTR-Intron10-4170 + AAGUGUUUAAAUAUUCCC 18 23052 CFTR-Intron10-4171 + GAAGUGUUUAAAUAUUCCC 19 23053 CFTR-Intron10-4172 + AGAAGUGUUUAAAUAUUCCC 20 23054 CFTR-Intron10-4173 + CAGAAGUGUUUAAAUAUUCCC 21 23055 CFTR-Intron10-4174 + UCAGAAGUGUUUAAAUAUUCCC 22 23056 CFTR-Intron10-4175 + CUCAGAAGUGUUUAAAUAUUCCC 23 23057 CFTR-Intron10-4176 + UCUCAGAAGUGUUUAAAUAUUCCC 24 23058 CFTR-Intron10-4177 + GGAAAGGUCAAUUGAGCC 18 23059 CFTR-Intron10-4178 + CGGAAAGGUCAAUUGAGCC 19 23060 CFTR-Intron10-4179 + GCGGAAAGGUCAAUUGAGCC 20 23061 CFTR-Intron10-4180 + AGCGGAAAGGUCAAUUGAGCC 21 23062 CFTR-Intron10-4181 + AAGCGGAAAGGUCAAUUGAGCC 22 23063 CFTR-Intron10-4182 + GAAGCGGAAAGGUCAAUUGAGCC 23 23064 CFTR-Intron10-4183 + UGAAGCGGAAAGGUCAAUUGAGCC 24 23065 CFTR-Intron10-4184 + AGGAGAAUUGCUUGAGCC 18 23066 CFTR-Intron10-4185 + CAGGAGAAUUGCUUGAGCC 19 23067 CFTR-Intron10-665 + GCAGGAGAAUUGCUUGAGCC 20 19551 CFTR-Intron10-4186 + GGCAGGAGAAUUGCUUGAGCC 21 23068 CFTR-Intron10-4187 + AGGCAGGAGAAUUGCUUGAGCC 22 23069 CFTR-Intron10-4188 + GAGGCAGGAGAAUUGCUUGAGCC 23 23070 CFTR-Intron10-4189 + UGAGGCAGGAGAAUUGCUUGAGCC 24 23071 CFTR-Intron10-4190 + GGCACUUGUUGACAGUCC 18 23072 CFTR-Intron10-4191 + AGGCACUUGUUGACAGUCC 19 23073 CFTR-Intron10-4192 + UAGGCACUUGUUGACAGUCC 20 23074 CFTR-Intron10-4193 + CUAGGCACUUGUUGACAGUCC 21 23075 CFTR-Intron10-4194 + GCUAGGCACUUGUUGACAGUCC 22 23076 CFTR-Intron10-4195 + UGCUAGGCACUUGUUGACAGUCC 23 23077 CFTR-Intron10-4196 + GUGCUAGGCACUUGUUGACAGUCC 24 23078 CFTR-Intron10-4197 + CUACCAGCCCCCUCUUCC 18 23079 CFTR-Intron10-4198 + ACUACCAGCCCCCUCUUCC 19 23080 CFTR-Intron10-4199 + CACUACCAGCCCCCUCUUCC 20 23081 CFTR-Intron10-4200 + ACACUACCAGCCCCCUCUUCC 21 23082 CFTR-Intron10-4201 + CACACUACCAGCCCCCUCUUCC 22 23083 CFTR-Intron10-4202 + UCACACUACCAGCCCCCUCUUCC 23 23084 CFTR-Intron10-4203 + UUCACACUACCAGCCCCCUCUUCC 24 23085 CFTR-Intron10-4204 + CAAGAUAGUGGGAAAAGC 18 23086 CFTR-Intron10-4205 + CCAAGAUAGUGGGAAAAGC 19 23087 CFTR-Intron10-4206 + UCCAAGAUAGUGGGAAAAGC 20 23088 CFTR-Intron10-4207 + GUCCAAGAUAGUGGGAAAAGC 21 23089 CFTR-Intron10-4208 + UGUCCAAGAUAGUGGGAAAAGC 22 23090 CFTR-Intron10-4209 + UUGUCCAAGAUAGUGGGAAAAGC 23 23091 CFTR-Intron10-4210 + GUUGUCCAAGAUAGUGGGAAAAGC 24 23092 CFTR-Intron10-4211 + UUACUCAGUCCAGAAAGC 18 23093 CFTR-Intron10-4212 + GUUACUCAGUCCAGAAAGC 19 23094 CFTR-Intron10-4213 + AGUUACUCAGUCCAGAAAGC 20 23095 CFTR-Intron10-4214 + CAGUUACUCAGUCCAGAAAGC 21 23096 CFTR-Intron10-4215 + CCAGUUACUCAGUCCAGAAAGC 22 23097 CFTR-Intron10-4216 + UCCAGUUACUCAGUCCAGAAAGC 23 23098 CFTR-Intron10-4217 + UUCCAGUUACUCAGUCCAGAAAGC 24 23099 CFTR-Intron10-4218 + CCGCCACUGCACUCCAGC 18 23100 CFTR-Intron10-4219 + CCCGCCACUGCACUCCAGC 19 23101 CFTR-Intron10-4220 + UCCCGCCACUGCACUCCAGC 20 23102 CFTR-Intron10-4221 + AUCCCGCCACUGCACUCCAGC 21 23103 CFTR-Intron10-4222 + GAUCCCGCCACUGCACUCCAGC 22 23104 CFTR-Intron10-4223 + AGAUCCCGCCACUGCACUCCAGC 23 23105 CFTR-Intron10-4224 + GAGAUCCCGCCACUGCACUCCAGC 24 23106 CFTR-Intron10-4225 + CAGGAGAAUUGCUUGAGC 18 23107 CFTR-Intron10-4226 + GCAGGAGAAUUGCUUGAGC 19 23108 CFTR-Intron10-4227 + GGCAGGAGAAUUGCUUGAGC 20 23109 CFTR-Intron10-4228 + AGGCAGGAGAAUUGCUUGAGC 21 23110 CFTR-Intron10-4229 + GAGGCAGGAGAAUUGCUUGAGC 22 23111 CFTR-Intron10-4230 + UGAGGCAGGAGAAUUGCUUGAGC 23 23112 CFTR-Intron10-4231 + GUGAGGCAGGAGAAUUGCUUGAGC 24 23113 CFTR-Intron10-1222 + ACCUCAGCCUCCCAAGUAGC 20 20107 CFTR-Intron10-4232 + CACCUCAGCCUCCCAAGUAGC 21 23114 CFTR-Intron10-4233 + CCACCUCAGCCUCCCAAGUAGC 22 23115 CFTR-Intron10-4234 + CCCACCUCAGCCUCCCAAGUAGC 23 23116 CFTR-Intron10-4235 + UCCCACCUCAGCCUCCCAAGUAGC 24 23117 CFTR-Intron10-4236 + CUCAGCCUCCCGAGUAGC 18 23118 CFTR-Intron10-4237 + CCUCAGCCUCCCGAGUAGC 19 23119 CFTR-Intron10-675 + GCCUCAGCCUCCCGAGUAGC 20 19561 CFTR-Intron10-4238 + UGCCUCAGCCUCCCGAGUAGC 21 23120 CFTR-Intron10-4239 + CUGCCUCAGCCUCCCGAGUAGC 22 23121 CFTR-Intron10-4240 + CCUGCCUCAGCCUCCCGAGUAGC 23 23122 CFTR-Intron10-4241 + UCCUGCCUCAGCCUCCCGAGUAGC 24 23123 CFTR-Intron10-4242 + AAACUCAUAAGGGACCGC 18 23124 CFTR-Intron10-4243 + AAAACUCAUAAGGGACCGC 19 23125 CFTR-Intron10-4244 + GAAAACUCAUAAGGGACCGC 20 23126 CFTR-Intron10-4245 + AGAAAACUCAUAAGGGACCGC 21 23127 CFTR-Intron10-4246 + GAGAAAACUCAUAAGGGACCGC 22 23128 CFTR-Intron10-4247 + AGAGAAAACUCAUAAGGGACCGC 23 23129 CFTR-Intron10-4248 + UAGAGAAAACUCAUAAGGGACCGC 24 23130 CFTR-Intron10-4249 + UCUCACAGUUCUGGAGGC 18 23131 CFTR-Intron10-4250 + UUCUCACAGUUCUGGAGGC 19 23132 CFTR-Intron10-1229 + UUUCUCACAGUUCUGGAGGC 20 20114 CFTR-Intron10-4251 + AUUUCUCACAGUUCUGGAGGC 21 23133 CFTR-Intron10-4252 + UAUUUCUCACAGUUCUGGAGGC 22 23134 CFTR-Intron10-4253 + UUAUUUCUCACAGUUCUGGAGGC 23 23135 CFTR-Intron10-4254 + UUUAUUUCUCACAGUUCUGGAGGC 24 23136 CFTR-Intron10-4255 + UACUUGGGAGGCUGAGGC 18 23137 CFTR-Intron10-4256 + CUACUUGGGAGGCUGAGGC 19 23138 CFTR-Intron10-681 + GCUACUUGGGAGGCUGAGGC 20 19567 CFTR-Intron10-4257 + AGCUACUUGGGAGGCUGAGGC 21 23139 CFTR-Intron10-4258 + CAGCUACUUGGGAGGCUGAGGC 22 23140 CFTR-Intron10-4259 + CCAGCUACUUGGGAGGCUGAGGC 23 23141 CFTR-Intron10-4260 + CCCAGCUACUUGGGAGGCUGAGGC 24 23142 CFTR-Intron10-4261 + UACUUGGGAGGGUGAGGC 18 23143 CFTR-Intron10-4262 + CUACUUGGGAGGGUGAGGC 19 23144 CFTR-Intron10-682 + GCUACUUGGGAGGGUGAGGC 20 19568 CFTR-Intron10-4263 + AGCUACUUGGGAGGGUGAGGC 21 23145 CFTR-Intron10-4264 + CAGCUACUUGGGAGGGUGAGGC 22 23146 CFTR-Intron10-4265 + CCAGCUACUUGGGAGGGUGAGGC 23 23147 CFTR-Intron10-4266 + CCCAGCUACUUGGGAGGGUGAGGC 24 23148 CFTR-Intron10-4267 + CUGAGGCAGGAGAAUGGC 18 23149 CFTR-Intron10-4268 + GCUGAGGCAGGAGAAUGGC 19 23150 CFTR-Intron10-4269 + GGCUGAGGCAGGAGAAUGGC 20 23151 CFTR-Intron10-4270 + AGGCUGAGGCAGGAGAAUGGC 21 23152 CFTR-Intron10-4271 + GAGGCUGAGGCAGGAGAAUGGC 22 23153 CFTR-Intron10-4272 + GGAGGCUGAGGCAGGAGAAUGGC 23 23154 CFTR-Intron10-4273 + GGGAGGCUGAGGCAGGAGAAUGGC 24 23155 CFTR-Intron10-4274 + UUUCAACAUAUGAAUGGC 18 23156 CFTR-Intron10-4275 + AUUUCAACAUAUGAAUGGC 19 23157 CFTR-Intron10-683 + GAUUUCAACAUAUGAAUGGC 20 19569 CFTR-Intron10-4276 + GGAUUUCAACAUAUGAAUGGC 21 23158 CFTR-Intron10-4277 + AGGAUUUCAACAUAUGAAUGGC 22 23159 CFTR-Intron10-4278 + UAGGAUUUCAACAUAUGAAUGGC 23 23160 CFTR-Intron10-4279 + UUAGGAUUUCAACAUAUGAAUGGC 24 23161 CFTR-Intron10-4280 + AAUGGCUAUCCACAAUGC 18 23162 CFTR-Intron10-4281 + AAAUGGCUAUCCACAAUGC 19 23163 CFTR-Intron10-4282 + UAAAUGGCUAUCCACAAUGC 20 23164 CFTR-Intron10-4283 + UUAAAUGGCUAUCCACAAUGC 21 23165 CFTR-Intron10-4284 + UUUAAAUGGCUAUCCACAAUGC 22 23166 CFTR-Intron10-4285 + UUUUAAAUGGCUAUCCACAAUGC 23 23167 CFTR-Intron10-4286 + GUUUUAAAUGGCUAUCCACAAUGC 24 23168 CFTR-Intron10-4287 + GGUUGGAUGAGGGAAUGC 18 23169 CFTR-Intron10-4288 + UGGUUGGAUGAGGGAAUGC 19 23170 CFTR-Intron10-431 + UUGGUUGGAUGAGGGAAUGC 20 19317 CFTR-Intron10-4289 + CUUGGUUGGAUGAGGGAAUGC 21 23171 CFTR-Intron10-4290 + CCUUGGUUGGAUGAGGGAAUGC 22 23172 CFTR-Intron10-4291 + ACCUUGGUUGGAUGAGGGAAUGC 23 23173 CFTR-Intron10-4292 + UACCUUGGUUGGAUGAGGGAAUGC 24 23174 CFTR-Intron10-4293 + ACAUGAUGAAAAAUAUGC 18 23175 CFTR-Intron10-4294 + AACAUGAUGAAAAAUAUGC 19 23176 CFTR-Intron10-4295 + AAACAUGAUGAAAAAUAUGC 20 23177 CFTR-Intron10-4296 + UAAACAUGAUGAAAAAUAUGC 21 23178 CFTR-Intron10-4297 + CUAAACAUGAUGAAAAAUAUGC 22 23179 CFTR-Intron10-4298 + ACUAAACAUGAUGAAAAAUAUGC 23 23180 CFTR-Intron10-4299 + CACUAAACAUGAUGAAAAAUAUGC 24 23181 CFTR-Intron10-4300 + CAAUUUUAAUAAAACUGC 18 23182 CFTR-Intron10-4301 + UCAAUUUUAAUAAAACUGC 19 23183 CFTR-Intron10-4302 + AUCAAUUUUAAUAAAACUGC 20 23184 CFTR-Intron10-4303 + CAUCAAUUUUAAUAAAACUGC 21 23185 CFTR-Intron10-4304 + UCAUCAAUUUUAAUAAAACUGC 22 23186 CFTR-Intron10-4305 + CUCAUCAAUUUUAAUAAAACUGC 23 23187 CFTR-Intron10-4306 + GCUCAUCAAUUUUAAUAAAACUGC 24 23188 CFTR-Intron10-4307 + GUGAGGCAGGAGAAUUGC 18 23189 CFTR-Intron10-4308 + GGUGAGGCAGGAGAAUUGC 19 23190 CFTR-Intron10-4309 + GGGUGAGGCAGGAGAAUUGC 20 23191 CFTR-Intron10-4310 + AGGGUGAGGCAGGAGAAUUGC 21 23192 CFTR-Intron10-4311 + GAGGGUGAGGCAGGAGAAUUGC 22 23193 CFTR-Intron10-4312 + GGAGGGUGAGGCAGGAGAAUUGC 23 23194 CFTR-Intron10-4313 + GGGAGGGUGAGGCAGGAGAAUUGC 24 23195 CFTR-Intron10-4314 + GCCACCAUCAUCACUUGC 18 23196 CFTR-Intron10-4315 + AGCCACCAUCAUCACUUGC 19 23197 CFTR-Intron10-4316 + AAGCCACCAUCAUCACUUGC 20 23198 CFTR-Intron10-4317 + CAAGCCACCAUCAUCACUUGC 21 23199 CFTR-Intron10-4318 + UCAAGCCACCAUCAUCACUUGC 22 23200 CFTR-Intron10-4319 + AUCAAGCCACCAUCAUCACUUGC 23 23201 CFTR-Intron10-4320 + GAUCAAGCCACCAUCAUCACUUGC 24 23202 CFTR-Intron10-4321 + ACAAAGUAACAGAAAAUC 18 23203 CFTR-Intron10-4322 + AACAAAGUAACAGAAAAUC 19 23204 CFTR-Intron10-4323 + UAACAAAGUAACAGAAAAUC 20 23205 CFTR-Intron10-4324 + GUAACAAAGUAACAGAAAAUC 21 23206 CFTR-Intron10-4325 + AGUAACAAAGUAACAGAAAAUC 22 23207 CFTR-Intron10-4326 + AAGUAACAAAGUAACAGAAAAUC 23 23208 CFTR-Intron10-4327 + AAAGUAACAAAGUAACAGAAAAUC 24 23209 CFTR-Intron10-4328 + UGCUAUUUAAACAGAAUC 18 23210 CFTR-Intron10-4329 + GUGCUAUUUAAACAGAAUC 19 23211 CFTR-Intron10-433 + AGUGCUAUUUAAACAGAAUC 20 19319 CFTR-Intron10-4330 + CAGUGCUAUUUAAACAGAAUC 21 23212 CFTR-Intron10-4331 + CCAGUGCUAUUUAAACAGAAUC 22 23213 CFTR-Intron10-4332 + UCCAGUGCUAUUUAAACAGAAUC 23 23214 CFTR-Intron10-4333 + CUCCAGUGCUAUUUAAACAGAAUC 24 23215 CFTR-Intron10-4334 + UUUAGUAGAAACCUAAUC 18 23216 CFTR-Intron10-4335 + UUUUAGUAGAAACCUAAUC 19 23217 CFTR-Intron10-91 + GUUUUAGUAGAAACCUAAUC 20 18977 CFTR-Intron10-4336 + GGUUUUAGUAGAAACCUAAUC 21 23218 CFTR-Intron10-4337 + UGGUUUUAGUAGAAACCUAAUC 22 23219 CFTR-Intron10-4338 + UUGGUUUUAGUAGAAACCUAAUC 23 23220 CFTR-Intron10-4339 + UUUGGUUUUAGUAGAAACCUAAUC 24 23221 CFTR-Intron10-4340 + GGCCGAGGCAGGCAGAUC 18 23222 CFTR-Intron10-4341 + AGGCCGAGGCAGGCAGAUC 19 23223 CFTR-Intron10-4342 + GAGGCCGAGGCAGGCAGAUC 20 23224 CFTR-Intron10-4343 + GGAGGCCGAGGCAGGCAGAUC 21 23225 CFTR-Intron10-4344 + GGGAGGCCGAGGCAGGCAGAUC 22 23226 CFTR-Intron10-4345 + UGGGAGGCCGAGGCAGGCAGAUC 23 23227 CFTR-Intron10-4346 + UUGGGAGGCCGAGGCAGGCAGAUC 24 23228 CFTR-Intron10-4347 + GGCCGAGGCGGGCGGAUC 18 23229 CFTR-Intron10-4348 + AGGCCGAGGCGGGCGGAUC 19 23230 CFTR-Intron10-4349 + GAGGCCGAGGCGGGCGGAUC 20 23231 CFTR-Intron10-4350 + GGAGGCCGAGGCGGGCGGAUC 21 23232 CFTR-Intron10-4351 + GGGAGGCCGAGGCGGGCGGAUC 22 23233 CFTR-Intron10-4352 + UGGGAGGCCGAGGCGGGCGGAUC 23 23234 CFTR-Intron10-4353 + UUGGGAGGCCGAGGCGGGCGGAUC 24 23235 CFTR-Intron10-4354 + UCUAUCAUAGAAUUGAUC 18 23236 CFTR-Intron10-4355 + AUCUAUCAUAGAAUUGAUC 19 23237 CFTR-Intron10-4356 + CAUCUAUCAUAGAAUUGAUC 20 23238 CFTR-Intron10-4357 + ACAUCUAUCAUAGAAUUGAUC 21 23239 CFTR-Intron10-4358 + CACAUCUAUCAUAGAAUUGAUC 22 23240 CFTR-Intron10-4359 + GCACAUCUAUCAUAGAAUUGAUC 23 23241 CFTR-Intron10-4360 + UGCACAUCUAUCAUAGAAUUGAUC 24 23242 CFTR-Intron10-4361 + AUACUGGGUUCAUUUAUC 18 23243 CFTR-Intron10-4362 + UAUACUGGGUUCAUUUAUC 19 23244 CFTR-Intron10-4363 + UUAUACUGGGUUCAUUUAUC 20 23245 CFTR-Intron10-4364 + UUUAUACUGGGUUCAUUUAUC 21 23246 CFTR-Intron10-4365 + CUUUAUACUGGGUUCAUUUAUC 22 23247 CFTR-Intron10-4366 + UCUUUAUACUGGGUUCAUUUAUC 23 23248 CFTR-Intron10-4367 + GUCUUUAUACUGGGUUCAUUUAUC 24 23249 CFTR-Intron10-4368 + CACGCUGGUCUCAAACUC 18 23250 CFTR-Intron10-4369 + CCACGCUGGUCUCAAACUC 19 23251 CFTR-Intron10-4370 + CCCACGCUGGUCUCAAACUC 20 23252 CFTR-Intron10-4371 + GCCCACGCUGGUCUCAAACUC 21 23253 CFTR-Intron10-4372 + UGCCCACGCUGGUCUCAAACUC 22 23254 CFTR-Intron10-4373 + UUGCCCACGCUGGUCUCAAACUC 23 23255 CFTR-Intron10-4374 + GUUGCCCACGCUGGUCUCAAACUC 24 23256 CFTR-Intron10-4375 + GUAUUAGCAAGUGGACUC 18 23257 CFTR-Intron10-4376 + UGUAUUAGCAAGUGGACUC 19 23258 CFTR-Intron10-4377 + UUGUAUUAGCAAGUGGACUC 20 23259 CFTR-Intron10-4378 + AUUGUAUUAGCAAGUGGACUC 21 23260 CFTR-Intron10-4379 + AAUUGUAUUAGCAAGUGGACUC 22 23261 CFTR-Intron10-4380 + CAAUUGUAUUAGCAAGUGGACUC 23 23262 CFTR-Intron10-4381 + UCAAUUGUAUUAGCAAGUGGACUC 24 23263 CFTR-Intron10-4382 + ACUAAAGACUUCACCCUC 18 23264 CFTR-Intron10-4383 + UACUAAAGACUUCACCCUC 19 23265 CFTR-Intron10-4384 + UUACUAAAGACUUCACCCUC 20 23266 CFTR-Intron10-4385 + UUUACUAAAGACUUCACCCUC 21 23267 CFTR-Intron10-4386 + AUUUACUAAAGACUUCACCCUC 22 23268 CFTR-Intron10-4387 + CAUUUACUAAAGACUUCACCCUC 23 23269 CFTR-Intron10-4388 + UCAUUUACUAAAGACUUCACCCUC 24 23270 CFTR-Intron10-4389 + CCACCCAAUUUUUGGCUC 18 23271 CFTR-Intron10-4390 + CCCACCCAAUUUUUGGCUC 19 23272 CFTR-Intron10-4391 + CCCCACCCAAUUUUUGGCUC 20 23273 CFTR-Intron10-4392 + CCCCCACCCAAUUUUUGGCUC 21 23274 CFTR-Intron10-4393 + UCCCCCACCCAAUUUUUGGCUC 22 23275 CFTR-Intron10-4394 + CUCCCCCACCCAAUUUUUGGCUC 23 23276 CFTR-Intron10-4395 + GCUCCCCCACCCAAUUUUUGGCUC 24 23277 CFTR-Intron10-4396 + UAUAGAGAGAAACAUCUC 18 23278 CFTR-Intron10-4397 + AUAUAGAGAGAAACAUCUC 19 23279 CFTR-Intron10-1238 + UAUAUAGAGAGAAACAUCUC 20 20123 CFTR-Intron10-4398 + AUAUAUAGAGAGAAACAUCUC 21 23280 CFTR-Intron10-4399 + UAUAUAUAGAGAGAAACAUCUC 22 23281 CFTR-Intron10-4400 + AUAUAUAUAGAGAGAAACAUCUC 23 23282 CFTR-Intron10-4401 + UAUAUAUAUAGAGAGAAACAUCUC 24 23283 CFTR-Intron10-4402 + UUUAAUUGCCAGUAAGUC 18 23284 CFTR-Intron10-4403 + AUUUAAUUGCCAGUAAGUC 19 23285 CFTR-Intron10-4404 + AAUUUAAUUGCCAGUAAGUC 20 23286 CFTR-Intron10-4405 + AAAUUUAAUUGCCAGUAAGUC 21 23287 CFTR-Intron10-4406 + GAAAUUUAAUUGCCAGUAAGUC 22 23288 CFTR-Intron10-4407 + UGAAAUUUAAUUGCCAGUAAGUC 23 23289 CFTR-Intron10-4408 + CUGAAAUUUAAUUGCCAGUAAGUC 24 23290 CFTR-Intron10-4409 + CCUUCCAGUUACUCAGUC 18 23291 CFTR-Intron10-4410 + UCCUUCCAGUUACUCAGUC 19 23292 CFTR-Intron10-4411 + AUCCUUCCAGUUACUCAGUC 20 23293 CFTR-Intron10-4412 + UAUCCUUCCAGUUACUCAGUC 21 23294 CFTR-Intron10-4413 + UUAUCCUUCCAGUUACUCAGUC 22 23295 CFTR-Intron10-4414 + UUUAUCCUUCCAGUUACUCAGUC 23 23296 CFTR-Intron10-4415 + AUUUAUCCUUCCAGUUACUCAGUC 24 23297 CFTR-Intron10-4416 + AUAAGCCAGCUUUCAGUC 18 23298 CFTR-Intron10-4417 + CAUAAGCCAGCUUUCAGUC 19 23299 CFTR-Intron10-4418 + CCAUAAGCCAGCUUUCAGUC 20 23300 CFTR-Intron10-4419 + GCCAUAAGCCAGCUUUCAGUC 21 23301 CFTR-Intron10-4420 + UGCCAUAAGCCAGCUUUCAGUC 22 23302 CFTR-Intron10-4421 + AUGCCAUAAGCCAGCUUUCAGUC 23 23303 CFTR-Intron10-4422 + GAUGCCAUAAGCCAGCUUUCAGUC 24 23304 CFTR-Intron10-4423 + CGGGCGGAUCACGAGGUC 18 23305 CFTR-Intron10-4424 + GCGGGCGGAUCACGAGGUC 19 23306 CFTR-Intron10-688 + GGCGGGCGGAUCACGAGGUC 20 19574 CFTR-Intron10-4425 + AGGCGGGCGGAUCACGAGGUC 21 23307 CFTR-Intron10-4426 + GAGGCGGGCGGAUCACGAGGUC 22 23308 CFTR-Intron10-4427 + CGAGGCGGGCGGAUCACGAGGUC 23 23309 CFTR-Intron10-4428 + CCGAGGCGGGCGGAUCACGAGGUC 24 23310 CFTR-Intron10-4429 + CAGGCAGAUCAUGAGGUC 18 23311 CFTR-Intron10-4430 + GCAGGCAGAUCAUGAGGUC 19 23312 CFTR-Intron10-4431 + GGCAGGCAGAUCAUGAGGUC 20 23313 CFTR-Intron10-4432 + AGGCAGGCAGAUCAUGAGGUC 21 23314 CFTR-Intron10-4433 + GAGGCAGGCAGAUCAUGAGGUC 22 23315 CFTR-Intron10-4434 + CGAGGCAGGCAGAUCAUGAGGUC 23 23316 CFTR-Intron10-4435 + CCGAGGCAGGCAGAUCAUGAGGUC 24 23317 CFTR-Intron10-4436 + GCUUCACUAAAAUAAUUC 18 23318 CFTR-Intron10-4437 + UGCUUCACUAAAAUAAUUC 19 23319 CFTR-Intron10-4438 + UUGCUUCACUAAAAUAAUUC 20 23320 CFTR-Intron10-4439 + AUUGCUUCACUAAAAUAAUUC 21 23321 CFTR-Intron10-4440 + UAUUGCUUCACUAAAAUAAUUC 22 23322 CFTR-Intron10-4441 + AUAUUGCUUCACUAAAAUAAUUC 23 23323 CFTR-Intron10-4442 + AAUAUUGCUUCACUAAAAUAAUUC 24 23324 CFTR-Intron10-4443 + GAUUAUUCGGUAUAAUUC 18 23325 CFTR-Intron10-4444 + AGAUUAUUCGGUAUAAUUC 19 23326 CFTR-Intron10-4445 + UAGAUUAUUCGGUAUAAUUC 20 23327 CFTR-Intron10-4446 + UUAGAUUAUUCGGUAUAAUUC 21 23328 CFTR-Intron10-4447 + CUUAGAUUAUUCGGUAUAAUUC 22 23329 CFTR-Intron10-4448 + UCUUAGAUUAUUCGGUAUAAUUC 23 23330 CFTR-Intron10-4449 + GUCUUAGAUUAUUCGGUAUAAUUC 24 23331 CFTR-Intron10-4450 + AAAUCUAAAAGCUAAUUC 18 23332 CFTR-Intron10-4451 + UAAAUCUAAAAGCUAAUUC 19 23333 CFTR-Intron10-4452 + GUAAAUCUAAAAGCUAAUUC 20 23334 CFTR-Intron10-4453 + AGUAAAUCUAAAAGCUAAUUC 21 23335 CFTR-Intron10-4454 + AAGUAAAUCUAAAAGCUAAUUC 22 23336 CFTR-Intron10-4455 + UAAGUAAAUCUAAAAGCUAAUUC 23 23337 CFTR-Intron10-4456 + AUAAGUAAAUCUAAAAGCUAAUUC 24 23338 CFTR-Intron10-4457 + AUAAUUUGAACAACAUUC 18 23339 CFTR-Intron10-4458 + AAUAAUUUGAACAACAUUC 19 23340 CFTR-Intron10-4459 + AAAUAAUUUGAACAACAUUC 20 23341 CFTR-Intron10-4460 + GAAAUAAUUUGAACAACAUUC 21 23342 CFTR-Intron10-4461 + AGAAAUAAUUUGAACAACAUUC 22 23343 CFTR-Intron10-4462 + UAGAAAUAAUUUGAACAACAUUC 23 23344 CFTR-Intron10-4463 + GUAGAAAUAAUUUGAACAACAUUC 24 23345 CFTR-Intron10-4464 + AUUUAAAAAGCAAUAUUC 18 23346 CFTR-Intron10-4465 + AAUUUAAAAAGCAAUAUUC 19 23347 CFTR-Intron10-4466 + AAAUUUAAAAAGCAAUAUUC 20 23348 CFTR-Intron10-4467 + UAAAUUUAAAAAGCAAUAUUC 21 23349 CFTR-Intron10-4468 + UUAAAUUUAAAAAGCAAUAUUC 22 23350 CFTR-Intron10-4469 + AUUAAAUUUAAAAAGCAAUAUUC 23 23351 CFTR-Intron10-4470 + UAUUAAAUUUAAAAAGCAAUAUUC 24 23352 CFTR-Intron10-4471 + ACACAAUGGGUUAUAUUC 18 23353 CFTR-Intron10-4472 + UACACAAUGGGUUAUAUUC 19 23354 CFTR-Intron10-4473 + CUACACAAUGGGUUAUAUUC 20 23355 CFTR-Intron10-4474 + UCUACACAAUGGGUUAUAUUC 21 23356 CFTR-Intron10-4475 + AUCUACACAAUGGGUUAUAUUC 22 23357 CFTR-Intron10-4476 + UAUCUACACAAUGGGUUAUAUUC 23 23358 CFTR-Intron10-4477 + UUAUCUACACAAUGGGUUAUAUUC 24 23359 CFTR-Intron10-4478 + AGUAUUUUGAAAAGCUUC 18 23360 CFTR-Intron10-4479 + AAGUAUUUUGAAAAGCUUC 19 23361 CFTR-Intron10-4480 + AAAGUAUUUUGAAAAGCUUC 20 23362 CFTR-Intron10-4481 + GAAAGUAUUUUGAAAAGCUUC 21 23363 CFTR-Intron10-4482 + AGAAAGUAUUUUGAAAAGCUUC 22 23364 CFTR-Intron10-4483 + UAGAAAGUAUUUUGAAAAGCUUC 23 23365 CFTR-Intron10-4484 + CUAGAAAGUAUUUUGAAAAGCUUC 24 23366 CFTR-Intron10-4485 + AUUUAUUUCUCACAGUUC 18 23367 CFTR-Intron10-4486 + AAUUUAUUUCUCACAGUUC 19 23368 CFTR-Intron10-689 + GAAUUUAUUUCUCACAGUUC 20 19575 CFTR-Intron10-4487 + GGAAUUUAUUUCUCACAGUUC 21 23369 CFTR-Intron10-4488 + AGGAAUUUAUUUCUCACAGUUC 22 23370 CFTR-Intron10-4489 + CAGGAAUUUAUUUCUCACAGUUC 23 23371 CFTR-Intron10-4490 + ACAGGAAUUUAUUUCUCACAGUUC 24 23372 CFTR-Intron10-4491 + CGAAUUGGUACAAAUUUC 18 23373 CFTR-Intron10-4492 + ACGAAUUGGUACAAAUUUC 19 23374 CFTR-Intron10-443 + UACGAAUUGGUACAAAUUUC 20 19329 CFTR-Intron10-4493 + GUACGAAUUGGUACAAAUUUC 21 23375 CFTR-Intron10-4494 + AGUACGAAUUGGUACAAAUUUC 22 23376 CFTR-Intron10-4495 + GAGUACGAAUUGGUACAAAUUUC 23 23377 CFTR-Intron10-4496 + UGAGUACGAAUUGGUACAAAUUUC 24 23378 CFTR-Intron10-4497 + GAAAAUUUGUUUUCUUUC 18 23379 CFTR-Intron10-4498 + AGAAAAUUUGUUUUCUUUC 19 23380 CFTR-Intron10-1248 + AAGAAAAUUUGUUUUCUUUC 20 20133 CFTR-Intron10-4499 + AAAGAAAAUUUGUUUUCUUUC 21 23381 CFTR-Intron10-4500 + CAAAGAAAAUUUGUUUUCUUUC 22 23382 CFTR-Intron10-4501 + ACAAAGAAAAUUUGUUUUCUUUC 23 23383 CFTR-Intron10-4502 + AACAAAGAAAAUUUGUUUUCUUUC 24 23384 CFTR-Intron10-4503 + UCAAAGCUACAGAUUUUC 18 23385 CFTR-Intron10-4504 + AUCAAAGCUACAGAUUUUC 19 23386 CFTR-Intron10-4505 + AAUCAAAGCUACAGAUUUUC 20 23387 CFTR-Intron10-4506 + AAAUCAAAGCUACAGAUUUUC 21 23388 CFTR-Intron10-4507 + UAAAUCAAAGCUACAGAUUUUC 22 23389 CFTR-Intron10-4508 + AUAAAUCAAAGCUACAGAUUUUC 23 23390 CFTR-Intron10-4509 + UAUAAAUCAAAGCUACAGAUUUUC 24 23391 CFTR-Intron10-4510 + UUGCUUUAUUAAGAAAAG 18 23392 CFTR-Intron10-4511 + AUUGCUUUAUUAAGAAAAG 19 23393 CFTR-Intron10-4512 + GAUUGCUUUAUUAAGAAAAG 20 23394 CFTR-Intron10-4513 + UGAUUGCUUUAUUAAGAAAAG 21 23395 CFTR-Intron10-4514 + CUGAUUGCUUUAUUAAGAAAAG 22 23396 CFTR-Intron10-4515 + GCUGAUUGCUUUAUUAAGAAAAG 23 23397 CFTR-Intron10-4516 + UGCUGAUUGCUUUAUUAAGAAAAG 24 23398 CFTR-Intron10-4517 + GGAUAUCUUAGGUCAAAG 18 23399 CFTR-Intron10-4518 + AGGAUAUCUUAGGUCAAAG 19 23400 CFTR-Intron10-447 + UAGGAUAUCUUAGGUCAAAG 20 19333 CFTR-Intron10-4519 + UUAGGAUAUCUUAGGUCAAAG 21 23401 CFTR-Intron10-4520 + CUUAGGAUAUCUUAGGUCAAAG 22 23402 CFTR-Intron10-4521 + CCUUAGGAUAUCUUAGGUCAAAG 23 23403 CFTR-Intron10-4522 + CCCUUAGGAUAUCUUAGGUCAAAG 24 23404 CFTR-Intron10-4523 + UGUUAAUGGCAAAGCAAG 18 23405 CFTR-Intron10-4524 + CUGUUAAUGGCAAAGCAAG 19 23406 CFTR-Intron10-4525 + UCUGUUAAUGGCAAAGCAAG 20 23407 CFTR-Intron10-4526 + AUCUGUUAAUGGCAAAGCAAG 21 23408 CFTR-Intron10-4527 + UAUCUGUUAAUGGCAAAGCAAG 22 23409 CFTR-Intron10-4528 + UUAUCUGUUAAUGGCAAAGCAAG 23 23410 CFTR-Intron10-4529 + UUUAUCUGUUAAUGGCAAAGCAAG 24 23411 CFTR-Intron10-4530 + UUGGGUAAGUUAUAGAAG 18 23412 CFTR-Intron10-4531 + UUUGGGUAAGUUAUAGAAG 19 23413 CFTR-Intron10-4532 + AUUUGGGUAAGUUAUAGAAG 20 23414 CFTR-Intron10-4533 + UAUUUGGGUAAGUUAUAGAAG 21 23415 CFTR-Intron10-4534 + AUAUUUGGGUAAGUUAUAGAAG 22 23416 CFTR-Intron10-4535 + CAUAUUUGGGUAAGUUAUAGAAG 23 23417 CFTR-Intron10-4536 + ACAUAUUUGGGUAAGUUAUAGAAG 24 23418 CFTR-Intron10-4537 + CACUUUGGGAGGCUGAAG 18 23419 CFTR-Intron10-4538 + GCACUUUGGGAGGCUGAAG 19 23420 CFTR-Intron10-1252 + AGCACUUUGGGAGGCUGAAG 20 20137 CFTR-Intron10-4539 + CAGCACUUUGGGAGGCUGAAG 21 23421 CFTR-Intron10-4540 + CCAGCACUUUGGGAGGCUGAAG 22 23422 CFTR-Intron10-4541 + CCCAGCACUUUGGGAGGCUGAAG 23 23423 CFTR-Intron10-4542 + ACCCAGCACUUUGGGAGGCUGAAG 24 23424 CFTR-Intron10-4543 + UACUAUUUUCCCUAUAAG 18 23425 CFTR-Intron10-4544 + AUACUAUUUUCCCUAUAAG 19 23426 CFTR-Intron10-4545 + CAUACUAUUUUCCCUAUAAG 20 23427 CFTR-Intron10-4546 + ACAUACUAUUUUCCCUAUAAG 21 23428 CFTR-Intron10-4547 + GACAUACUAUUUUCCCUAUAAG 22 23429 CFTR-Intron10-4548 + UGACAUACUAUUUUCCCUAUAAG 23 23430 CFTR-Intron10-4549 + UUGACAUACUAUUUUCCCUAUAAG 24 23431 CFTR-Intron10-4550 + AUUCCUCCUGUGUAUAAG 18 23432 CFTR-Intron10-4551 + AAUUCCUCCUGUGUAUAAG 19 23433 CFTR-Intron10-4552 + AAAUUCCUCCUGUGUAUAAG 20 23434 CFTR-Intron10-4553 + GAAAUUCCUCCUGUGUAUAAG 21 23435 CFTR-Intron10-4554 + AGAAAUUCCUCCUGUGUAUAAG 22 23436 CFTR-Intron10-4555 + GAGAAAUUCCUCCUGUGUAUAAG 23 23437 CFTR-Intron10-4556 + AGAGAAAUUCCUCCUGUGUAUAAG 24 23438 CFTR-Intron10-4557 + CUUAACCCAUCUAUUAAG 18 23439 CFTR-Intron10-4558 + GCUUAACCCAUCUAUUAAG 19 23440 CFTR-Intron10-97 + GGCUUAACCCAUCUAUUAAG 20 18983 CFTR-Intron10-4559 + UGGCUUAACCCAUCUAUUAAG 21 23441 CFTR-Intron10-4560 + UUGGCUUAACCCAUCUAUUAAG 22 23442 CFTR-Intron10-4561 + GUUGGCUUAACCCAUCUAUUAAG 23 23443 CFTR-Intron10-4562 + AGUUGGCUUAACCCAUCUAUUAAG 24 23444 CFTR-Intron10-4563 + CUGUGAUGCAGACAACAG 18 23445 CFTR-Intron10-4564 + GCUGUGAUGCAGACAACAG 19 23446 CFTR-Intron10-4565 + AGCUGUGAUGCAGACAACAG 20 23447 CFTR-Intron10-4566 + CAGCUGUGAUGCAGACAACAG 21 23448 CFTR-Intron10-4567 + UCAGCUGUGAUGCAGACAACAG 22 23449 CFTR-Intron10-4568 + UUCAGCUGUGAUGCAGACAACAG 23 23450 CFTR-Intron10-4569 + CUUCAGCUGUGAUGCAGACAACAG 24 23451 CFTR-Intron10-4570 + AGAAUGGAAAAUGGACAG 18 23452 CFTR-Intron10-4571 + GAGAAUGGAAAAUGGACAG 19 23453 CFTR-Intron10-4572 + GGAGAAUGGAAAAUGGACAG 20 23454 CFTR-Intron10-4573 + AGGAGAAUGGAAAAUGGACAG 21 23455 CFTR-Intron10-4574 + CAGGAGAAUGGAAAAUGGACAG 22 23456 CFTR-Intron10-4575 + GCAGGAGAAUGGAAAAUGGACAG 23 23457 CFTR-Intron10-4576 + UGCAGGAGAAUGGAAAAUGGACAG 24 23458 CFTR-Intron10-4577 + AGCUAAAGUAUUACCCAG 18 23459 CFTR-Intron10-4578 + CAGCUAAAGUAUUACCCAG 19 23460 CFTR-Intron10-451 + ACAGCUAAAGUAUUACCCAG 20 19337 CFTR-Intron10-4579 + UACAGCUAAAGUAUUACCCAG 21 23461 CFTR-Intron10-4580 + AUACAGCUAAAGUAUUACCCAG 22 23462 CFTR-Intron10-4581 + UAUACAGCUAAAGUAUUACCCAG 23 23463 CFTR-Intron10-4582 + AUAUACAGCUAAAGUAUUACCCAG 24 23464 CFTR-Intron10-4583 + GAUAAAAAUUCCAAGCAG 18 23465 CFTR-Intron10-4584 + UGAUAAAAAUUCCAAGCAG 19 23466 CFTR-Intron10-4585 + AUGAUAAAAAUUCCAAGCAG 20 23467 CFTR-Intron10-4586 + AAUGAUAAAAAUUCCAAGCAG 21 23468 CFTR-Intron10-4587 + AAAUGAUAAAAAUUCCAAGCAG 22 23469 CFTR-Intron10-4588 + AAAAUGAUAAAAAUUCCAAGCAG 23 23470 CFTR-Intron10-4589 + AAAAAUGAUAAAAAUUCCAAGCAG 24 23471 CFTR-Intron10-4590 + AAGGAAAGGAGGUAGCAG 18 23472 CFTR-Intron10-4591 + GAAGGAAAGGAGGUAGCAG 19 23473 CFTR-Intron10-1260 + AGAAGGAAAGGAGGUAGCAG 20 20145 CFTR-Intron10-4592 + UAGAAGGAAAGGAGGUAGCAG 21 23474 CFTR-Intron10-4593 + GUAGAAGGAAAGGAGGUAGCAG 22 23475 CFTR-Intron10-4594 + AGUAGAAGGAAAGGAGGUAGCAG 23 23476 CFTR-Intron10-4595 + GAGUAGAAGGAAAGGAGGUAGCAG 24 23477 CFTR-Intron10-4596 + UCAACAUAUGAAUGGCAG 18 23478 CFTR-Intron10-4597 + UUCAACAUAUGAAUGGCAG 19 23479 CFTR-Intron10-1263 + UUUCAACAUAUGAAUGGCAG 20 20148 CFTR-Intron10-4598 + AUUUCAACAUAUGAAUGGCAG 21 23480 CFTR-Intron10-4599 + GAUUUCAACAUAUGAAUGGCAG 22 23481 CFTR-Intron10-4600 + GGAUUUCAACAUAUGAAUGGCAG 23 23482 CFTR-Intron10-4601 + AGGAUUUCAACAUAUGAAUGGCAG 24 23483 CFTR-Intron10-4602 + CUAUUUAAACAGAAUCAG 18 23484 CFTR-Intron10-4603 + GCUAUUUAAACAGAAUCAG 19 23485 CFTR-Intron10-453 + UGCUAUUUAAACAGAAUCAG 20 19339 CFTR-Intron10-4604 + GUGCUAUUUAAACAGAAUCAG 21 23486 CFTR-Intron10-4605 + AGUGCUAUUUAAACAGAAUCAG 22 23487 CFTR-Intron10-4606 + CAGUGCUAUUUAAACAGAAUCAG 23 23488 CFTR-Intron10-4607 + CCAGUGCUAUUUAAACAGAAUCAG 24 23489 CFTR-Intron10-4608 + CAUAAUAAGACAGCUCAG 18 23490 CFTR-Intron10-4609 + ACAUAAUAAGACAGCUCAG 19 23491 CFTR-Intron10-4610 + AACAUAAUAAGACAGCUCAG 20 23492 CFTR-Intron10-4611 + AAACAUAAUAAGACAGCUCAG 21 23493 CFTR-Intron10-4612 + AAAACAUAAUAAGACAGCUCAG 22 23494 CFTR-Intron10-4613 + CAAAACAUAAUAAGACAGCUCAG 23 23495 CFTR-Intron10-4614 + ACAAAACAUAAUAAGACAGCUCAG 24 23496 CFTR-Intron10-4615 + AAGAGGAAAAGACUUCAG 18 23497 CFTR-Intron10-4616 + UAAGAGGAAAAGACUUCAG 19 23498 CFTR-Intron10-4617 + UUAAGAGGAAAAGACUUCAG 20 23499 CFTR-Intron10-4618 + AUUAAGAGGAAAAGACUUCAG 21 23500 CFTR-Intron10-4619 + UAUUAAGAGGAAAAGACUUCAG 22 23501 CFTR-Intron10-4620 + CUAUUAAGAGGAAAAGACUUCAG 23 23502 CFTR-Intron10-4621 + UCUAUUAAGAGGAAAAGACUUCAG 24 23503 CFTR-Intron10-4622 + UGUUACAUAAAAAGAGAG 18 23504 CFTR-Intron10-4623 + UUGUUACAUAAAAAGAGAG 19 23505 CFTR-Intron10-4624 + AUUGUUACAUAAAAAGAGAG 20 23506 CFTR-Intron10-4625 + UAUUGUUACAUAAAAAGAGAG 21 23507 CFTR-Intron10-4626 + AUAUUGUUACAUAAAAAGAGAG 22 23508 CFTR-Intron10-4627 + CAUAUUGUUACAUAAAAAGAGAG 23 23509 CFTR-Intron10-4628 + GCAUAUUGUUACAUAAAAAGAGAG 24 23510 CFTR-Intron10-4629 + UUUGUAUUUUUAGUAGAG 18 23511 CFTR-Intron10-4630 + UUUUGUAUUUUUAGUAGAG 19 23512 CFTR-Intron10-4631 + UUUUUGUAUUUUUAGUAGAG 20 23513 CFTR-Intron10-4632 + UUUUUUGUAUUUUUAGUAGAG 21 23514 CFTR-Intron10-4633 + AUUUUUUGUAUUUUUAGUAGAG 22 23515 CFTR-Intron10-4634 + AAUUUUUUGUAUUUUUAGUAGAG 23 23516 CFTR-Intron10-4635 + UAAUUUUUUGUAUUUUUAGUAGAG 24 23517 CFTR-Intron10-4636 + UUUGUGUUUUUUGUAGAG 18 23518 CFTR-Intron10-4637 + GUUUGUGUUUUUUGUAGAG 19 23519 CFTR-Intron10-4638 + UGUUUGUGUUUUUUGUAGAG 20 23520 CFTR-Intron10-4639 + UUGUUUGUGUUUUUUGUAGAG 21 23521 CFTR-Intron10-4640 + UUUGUUUGUGUUUUUUGUAGAG 22 23522 CFTR-Intron10-4641 + UUUUGUUUGUGUUUUUUGUAGAG 23 23523 CFTR-Intron10-4642 + CUUUUGUUUGUGUUUUUUGUAGAG 24 23524 CFTR-Intron10-4643 + GCACUUUGGGAGGCCGAG 18 23525 CFTR-Intron10-4644 + AGCACUUUGGGAGGCCGAG 19 23526 CFTR-Intron10-4645 + CAGCACUUUGGGAGGCCGAG 20 23527 CFTR-Intron10-4646 + CCAGCACUUUGGGAGGCCGAG 21 23528 CFTR-Intron10-4647 + CCCAGCACUUUGGGAGGCCGAG 22 23529 CFTR-Intron10-4648 + UCCCAGCACUUUGGGAGGCCGAG 23 23530 CFTR-Intron10-4649 + AUCCCAGCACUUUGGGAGGCCGAG 24 23531 CFTR-Intron10-4650 + CUAAUGGCAGAAUUCGAG 18 23532 CFTR-Intron10-4651 + ACUAAUGGCAGAAUUCGAG 19 23533 CFTR-Intron10-4652 + AACUAAUGGCAGAAUUCGAG 20 23534 CFTR-Intron10-4653 + AAACUAAUGGCAGAAUUCGAG 21 23535 CFTR-Intron10-4654 + AAAACUAAUGGCAGAAUUCGAG 22 23536 CFTR-Intron10-4655 + UAAAACUAAUGGCAGAAUUCGAG 23 23537 CFTR-Intron10-4656 + UUAAAACUAAUGGCAGAAUUCGAG 24 23538 CFTR-Intron10-4657 + AUGGCGUGAACCCGGGAG 18 23539 CFTR-Intron10-4658 + AAUGGCGUGAACCCGGGAG 19 23540 CFTR-Intron10-4659 + GAAUGGCGUGAACCCGGGAG 20 23541 CFTR-Intron10-4660 + AGAAUGGCGUGAACCCGGGAG 21 23542 CFTR-Intron10-4661 + GAGAAUGGCGUGAACCCGGGAG 22 23543 CFTR-Intron10-4662 + GGAGAAUGGCGUGAACCCGGGAG 23 23544 CFTR-Intron10-4663 + AGGAGAAUGGCGUGAACCCGGGAG 24 23545 CFTR-Intron10-4664 + UUAGGGUGGGAUAUGGAG 18 23546 CFTR-Intron10-4665 + CUUAGGGUGGGAUAUGGAG 19 23547 CFTR-Intron10-4666 + UCUUAGGGUGGGAUAUGGAG 20 23548 CFTR-Intron10-4667 + UUCUUAGGGUGGGAUAUGGAG 21 23549 CFTR-Intron10-4668 + GUUCUUAGGGUGGGAUAUGGAG 22 23550 CFTR-Intron10-4669 + UGUUCUUAGGGUGGGAUAUGGAG 23 23551 CFTR-Intron10-4670 + UUGUUCUUAGGGUGGGAUAUGGAG 24 23552 CFTR-Intron10-4671 + CUACUGACUAAAACUGAG 18 23553 CFTR-Intron10-4672 + ACUACUGACUAAAACUGAG 19 23554 CFTR-Intron10-4673 + UACUACUGACUAAAACUGAG 20 23555 CFTR-Intron10-4674 + AUACUACUGACUAAAACUGAG 21 23556 CFTR-Intron10-4675 + AAUACUACUGACUAAAACUGAG 22 23557 CFTR-Intron10-4676 + UAAUACUACUGACUAAAACUGAG 23 23558 CFTR-Intron10-4677 + AUAAUACUACUGACUAAAACUGAG 24 23559 CFTR-Intron10-4678 + GGCGGAGCUUGCAGUGAG 18 23560 CFTR-Intron10-4679 + AGGCGGAGCUUGCAGUGAG 19 23561 CFTR-Intron10-4680 + GAGGCGGAGCUUGCAGUGAG 20 23562 CFTR-Intron10-4681 + GGAGGCGGAGCUUGCAGUGAG 21 23563 CFTR-Intron10-4682 + GGGAGGCGGAGCUUGCAGUGAG 22 23564 CFTR-Intron10-4683 + CGGGAGGCGGAGCUUGCAGUGAG 23 23565 CFTR-Intron10-4684 + CCGGGAGGCGGAGCUUGCAGUGAG 24 23566 CFTR-Intron10-4685 + GGCAGAGGUUGCAGUGAG 18 23567 CFTR-Intron10-4686 + AGGCAGAGGUUGCAGUGAG 19 23568 CFTR-Intron10-4687 + GAGGCAGAGGUUGCAGUGAG 20 23569 CFTR-Intron10-4688 + GGAGGCAGAGGUUGCAGUGAG 21 23570 CFTR-Intron10-4689 + GGGAGGCAGAGGUUGCAGUGAG 22 23571 CFTR-Intron10-4690 + CGGGAGGCAGAGGUUGCAGUGAG 23 23572 CFTR-Intron10-4691 + CCGGGAGGCAGAGGUUGCAGUGAG 24 23573 CFTR-Intron10-4692 + GACACCAAAUUUAUUGAG 18 23574 CFTR-Intron10-4693 + UGACACCAAAUUUAUUGAG 19 23575 CFTR-Intron10-457 + CUGACACCAAAUUUAUUGAG 20 19343 CFTR-Intron10-4694 + CCUGACACCAAAUUUAUUGAG 21 23576 CFTR-Intron10-4695 + GCCUGACACCAAAUUUAUUGAG 22 23577 CFTR-Intron10-4696 + AGCCUGACACCAAAUUUAUUGAG 23 23578 CFTR-Intron10-4697 + CAGCCUGACACCAAAUUUAUUGAG 24 23579 CFTR-Intron10-4698 + UAAUAGCCUAUUGUUGAG 18 23580 CFTR-Intron10-4699 + CUAAUAGCCUAUUGUUGAG 19 23581 CFTR-Intron10-1271 + ACUAAUAGCCUAUUGUUGAG 20 20156 CFTR-Intron10-4700 + UACUAAUAGCCUAUUGUUGAG 21 23582 CFTR-Intron10-4701 + CUACUAAUAGCCUAUUGUUGAG 22 23583 CFTR-Intron10-4702 + ACUACUAAUAGCCUAUUGUUGAG 23 23584 CFTR-Intron10-4703 + AACUACUAAUAGCCUAUUGUUGAG 24 23585 CFTR-Intron10-4704 + CUAGAUGAUUAUUAAUAG 18 23586 CFTR-Intron10-4705 + CCUAGAUGAUUAUUAAUAG 19 23587 CFTR-Intron10-100 + GCCUAGAUGAUUAUUAAUAG 20 18986 CFTR-Intron10-4706 + AGCCUAGAUGAUUAUUAAUAG 21 23588 CFTR-Intron10-4707 + CAGCCUAGAUGAUUAUUAAUAG 22 23589 CFTR-Intron10-4708 + GCAGCCUAGAUGAUUAUUAAUAG 23 23590 CFTR-Intron10-4709 + UGCAGCCUAGAUGAUUAUUAAUAG 24 23591 CFTR-Intron10-4710 + GAAAGUUGUCCAAGAUAG 18 23592 CFTR-Intron10-4711 + GGAAAGUUGUCCAAGAUAG 19 23593 CFTR-Intron10-459 + UGGAAAGUUGUCCAAGAUAG 20 19345 CFTR-Intron10-4712 + AUGGAAAGUUGUCCAAGAUAG 21 23594 CFTR-Intron10-4713 + UAUGGAAAGUUGUCCAAGAUAG 22 23595 CFTR-Intron10-4714 + AUAUGGAAAGUUGUCCAAGAUAG 23 23596 CFTR-Intron10-4715 + AAUAUGGAAAGUUGUCCAAGAUAG 24 23597 CFTR-Intron10-4716 + CCUCAGCCUCCCAAGUAG 18 23598 CFTR-Intron10-4717 + ACCUCAGCCUCCCAAGUAG 19 23599 CFTR-Intron10-4718 + CACCUCAGCCUCCCAAGUAG 20 23600 CFTR-Intron10-4719 + CCACCUCAGCCUCCCAAGUAG 21 23601 CFTR-Intron10-4720 + CCCACCUCAGCCUCCCAAGUAG 22 23602 CFTR-Intron10-4721 + UCCCACCUCAGCCUCCCAAGUAG 23 23603 CFTR-Intron10-4722 + CUCCCACCUCAGCCUCCCAAGUAG 24 23604 CFTR-Intron10-4723 + GGUAAGUUAUAGAAGUAG 18 23605 CFTR-Intron10-4724 + GGGUAAGUUAUAGAAGUAG 19 23606 CFTR-Intron10-4725 + UGGGUAAGUUAUAGAAGUAG 20 23607 CFTR-Intron10-4726 + UUGGGUAAGUUAUAGAAGUAG 21 23608 CFTR-Intron10-4727 + UUUGGGUAAGUUAUAGAAGUAG 22 23609 CFTR-Intron10-4728 + AUUUGGGUAAGUUAUAGAAGUAG 23 23610 CFTR-Intron10-4729 + UAUUUGGGUAAGUUAUAGAAGUAG 24 23611 CFTR-Intron10-4730 + CCUCAGCCUCCCGAGUAG 18 23612 CFTR-Intron10-4731 + GCCUCAGCCUCCCGAGUAG 19 23613 CFTR-Intron10-4732 + UGCCUCAGCCUCCCGAGUAG 20 23614 CFTR-Intron10-4733 + CUGCCUCAGCCUCCCGAGUAG 21 23615 CFTR-Intron10-4734 + CCUGCCUCAGCCUCCCGAGUAG 22 23616 CFTR-Intron10-4735 + UCCUGCCUCAGCCUCCCGAGUAG 23 23617 CFTR-Intron10-4736 + CUCCUGCCUCAGCCUCCCGAGUAG 24 23618 CFTR-Intron10-4737 + CUGACUAAAACUGAGUAG 18 23619 CFTR-Intron10-4738 + ACUGACUAAAACUGAGUAG 19 23620 CFTR-Intron10-4739 + UACUGACUAAAACUGAGUAG 20 23621 CFTR-Intron10-4740 + CUACUGACUAAAACUGAGUAG 21 23622 CFTR-Intron10-4741 + ACUACUGACUAAAACUGAGUAG 22 23623 CFTR-Intron10-4742 + UACUACUGACUAAAACUGAGUAG 23 23624 CFTR-Intron10-4743 + AUACUACUGACUAAAACUGAGUAG 24 23625 CFTR-Intron10-4744 + UAGAAGGAAAGGAGGUAG 18 23626 CFTR-Intron10-4745 + GUAGAAGGAAAGGAGGUAG 19 23627 CFTR-Intron10-4746 + AGUAGAAGGAAAGGAGGUAG 20 23628 CFTR-Intron10-4747 + GAGUAGAAGGAAAGGAGGUAG 21 23629 CFTR-Intron10-4748 + UGAGUAGAAGGAAAGGAGGUAG 22 23630 CFTR-Intron10-4749 + CUGAGUAGAAGGAAAGGAGGUAG 23 23631 CFTR-Intron10-4750 + ACUGAGUAGAAGGAAAGGAGGUAG 24 23632 CFTR-Intron10-4751 + AGGGAGAAAUGUAUGUAG 18 23633 CFTR-Intron10-4752 + CAGGGAGAAAUGUAUGUAG 19 23634 CFTR-Intron10-4753 + ACAGGGAGAAAUGUAUGUAG 20 23635 CFTR-Intron10-4754 + AACAGGGAGAAAUGUAUGUAG 21 23636 CFTR-Intron10-4755 + UAACAGGGAGAAAUGUAUGUAG 22 23637 CFTR-Intron10-4756 + AUAACAGGGAGAAAUGUAUGUAG 23 23638 CFTR-Intron10-4757 + AAUAACAGGGAGAAAUGUAUGUAG 24 23639 CFTR-Intron10-4758 + AAAAAUACAAAAAAUUAG 18 23640 CFTR-Intron10-4759 + UAAAAAUACAAAAAAUUAG 19 23641 CFTR-Intron10-4760 + CUAAAAAUACAAAAAAUUAG 20 23642 CFTR-Intron10-4761 + ACUAAAAAUACAAAAAAUUAG 21 23643 CFTR-Intron10-4762 + UACUAAAAAUACAAAAAAUUAG 22 23644 CFTR-Intron10-4763 + CUACUAAAAAUACAAAAAAUUAG 23 23645 CFTR-Intron10-4764 + UCUACUAAAAAUACAAAAAAUUAG 24 23646 CFTR-Intron10-4765 + AAGCUUGUUUGGUUUUAG 18 23647 CFTR-Intron10-4766 + AAAGCUUGUUUGGUUUUAG 19 23648 CFTR-Intron10-4767 + GAAAGCUUGUUUGGUUUUAG 20 23649 CFTR-Intron10-4768 + GGAAAGCUUGUUUGGUUUUAG 21 23650 CFTR-Intron10-4769 + UGGAAAGCUUGUUUGGUUUUAG 22 23651 CFTR-Intron10-4770 + AUGGAAAGCUUGUUUGGUUUUAG 23 23652 CFTR-Intron10-4771 + CAUGGAAAGCUUGUUUGGUUUUAG 24 23653 CFTR-Intron10-4772 + AAUUUUUUGUAUUUUUAG 18 23654 CFTR-Intron10-4773 + UAAUUUUUUGUAUUUUUAG 19 23655 CFTR-Intron10-4774 + CUAAUUUUUUGUAUUUUUAG 20 23656 CFTR-Intron10-4775 + GCUAAUUUUUUGUAUUUUUAG 21 23657 CFTR-Intron10-4776 + GGCUAAUUUUUUGUAUUUUUAG 22 23658 CFTR-Intron10-4777 + UGGCUAAUUUUUUGUAUUUUUAG 23 23659 CFTR-Intron10-4778 + CUGGCUAAUUUUUUGUAUUUUUAG 24 23660 CFTR-Intron10-4779 + ACCAUCCCGGCUAAAACG 18 23661 CFTR-Intron10-4780 + GACCAUCCCGGCUAAAACG 19 23662 CFTR-Intron10-4781 + AGACCAUCCCGGCUAAAACG 20 23663 CFTR-Intron10-4782 + GAGACCAUCCCGGCUAAAACG 21 23664 CFTR-Intron10-4783 + CGAGACCAUCCCGGCUAAAACG 22 23665 CFTR-Intron10-4784 + UCGAGACCAUCCCGGCUAAAACG 23 23666 CFTR-Intron10-4785 + AUCGAGACCAUCCCGGCUAAAACG 24 23667 CFTR-Intron10-4786 + AAAAACAACAAAAAAGCG 18 23668 CFTR-Intron10-4787 + GAAAAACAACAAAAAAGCG 19 23669 CFTR-Intron10-4788 + AGAAAAACAACAAAAAAGCG 20 23670 CFTR-Intron10-4789 + UAGAAAAACAACAAAAAAGCG 21 23671 CFTR-Intron10-4790 + CUAGAAAAACAACAAAAAAGCG 22 23672 CFTR-Intron10-4791 + ACUAGAAAAACAACAAAAAAGCG 23 23673 CFTR-Intron10-4792 + AACUAGAAAAACAACAAAAAAGCG 24 23674 CFTR-Intron10-4793 + GCAAAGAGUGCAUAAAGG 18 23675 CFTR-Intron10-4794 + AGCAAAGAGUGCAUAAAGG 19 23676 CFTR-Intron10-4795 + AAGCAAAGAGUGCAUAAAGG 20 23677 CFTR-Intron10-4796 + AAAGCAAAGAGUGCAUAAAGG 21 23678 CFTR-Intron10-4797 + UAAAGCAAAGAGUGCAUAAAGG 22 23679 CFTR-Intron10-4798 + CUAAAGCAAAGAGUGCAUAAAGG 23 23680 CFTR-Intron10-4799 + CCUAAAGCAAAGAGUGCAUAAAGG 24 23681 CFTR-Intron10-4800 + UAUAAGAAAUGAAACAGG 18 23682 CFTR-Intron10-4801 + AUAUAAGAAAUGAAACAGG 19 23683 CFTR-Intron10-4802 + GAUAUAAGAAAUGAAACAGG 20 23684 CFTR-Intron10-4803 + CGAUAUAAGAAAUGAAACAGG 21 23685 CFTR-Intron10-4804 + ACGAUAUAAGAAAUGAAACAGG 22 23686 CFTR-Intron10-4805 + UACGAUAUAAGAAAUGAAACAGG 23 23687 CFTR-Intron10-4806 + AUACGAUAUAAGAAAUGAAACAGG 24 23688 CFTR-Intron10-4807 + CCUAUAAGGAAUAACAGG 18 23689 CFTR-Intron10-4808 + ACCUAUAAGGAAUAACAGG 19 23690 CFTR-Intron10-4809 + AACCUAUAAGGAAUAACAGG 20 23691 CFTR-Intron10-4810 + GAACCUAUAAGGAAUAACAGG 21 23692 CFTR-Intron10-4811 + AGAACCUAUAAGGAAUAACAGG 22 23693 CFTR-Intron10-4812 + CAGAACCUAUAAGGAAUAACAGG 23 23694 CFTR-Intron10-4813 + ACAGAACCUAUAAGGAAUAACAGG 24 23695 CFTR-Intron10-4814 + AGUAGAAACCUAAUCAGG 18 23696 CFTR-Intron10-4815 + UAGUAGAAACCUAAUCAGG 19 23697 CFTR-Intron10-4816 + UUAGUAGAAACCUAAUCAGG 20 23698 CFTR-Intron10-4817 + UUUAGUAGAAACCUAAUCAGG 21 23699 CFTR-Intron10-4818 + UUUUAGUAGAAACCUAAUCAGG 22 23700 CFTR-Intron10-4819 + GUUUUAGUAGAAACCUAAUCAGG 23 23701 CFTR-Intron10-4820 + GGUUUUAGUAGAAACCUAAUCAGG 24 23702 CFTR-Intron10-4821 + GAAAGGAGGUAGCAGAGG 18 23703 CFTR-Intron10-4822 + GGAAAGGAGGUAGCAGAGG 19 23704 CFTR-Intron10-4823 + AGGAAAGGAGGUAGCAGAGG 20 23705 CFTR-Intron10-4824 + AAGGAAAGGAGGUAGCAGAGG 21 23706 CFTR-Intron10-4825 + GAAGGAAAGGAGGUAGCAGAGG 22 23707 CFTR-Intron10-4826 + AGAAGGAAAGGAGGUAGCAGAGG 23 23708 CFTR-Intron10-4827 + UAGAAGGAAAGGAGGUAGCAGAGG 24 23709 CFTR-Intron10-4828 + GUUACAUAAAAAGAGAGG 18 23710 CFTR-Intron10-4829 + UGUUACAUAAAAAGAGAGG 19 23711 CFTR-Intron10-469 + UUGUUACAUAAAAAGAGAGG 20 19355 CFTR-Intron10-4830 + AUUGUUACAUAAAAAGAGAGG 21 23712 CFTR-Intron10-4831 + UAUUGUUACAUAAAAAGAGAGG 22 23713 CFTR-Intron10-4832 + AUAUUGUUACAUAAAAAGAGAGG 23 23714 CFTR-Intron10-4833 + CAUAUUGUUACAUAAAAAGAGAGG 24 23715 CFTR-Intron10-4834 + UGGCGUGAACCCGGGAGG 18 23716 CFTR-Intron10-4835 + AUGGCGUGAACCCGGGAGG 19 23717 CFTR-Intron10-1287 + AAUGGCGUGAACCCGGGAGG 20 20172 CFTR-Intron10-4836 + GAAUGGCGUGAACCCGGGAGG 21 23718 CFTR-Intron10-4837 + AGAAUGGCGUGAACCCGGGAGG 22 23719 CFTR-Intron10-4838 + GAGAAUGGCGUGAACCCGGGAGG 23 23720 CFTR-Intron10-4839 + GGAGAAUGGCGUGAACCCGGGAGG 24 23721 CFTR-Intron10-4840 + UUGCUUGAGCCCGGGAGG 18 23722 CFTR-Intron10-4841 + AUUGCUUGAGCCCGGGAGG 19 23723 CFTR-Intron10-4842 + AAUUGCUUGAGCCCGGGAGG 20 23724 CFTR-Intron10-4843 + GAAUUGCUUGAGCCCGGGAGG 21 23725 CFTR-Intron10-4844 + AGAAUUGCUUGAGCCCGGGAGG 22 23726 CFTR-Intron10-4845 + GAGAAUUGCUUGAGCCCGGGAGG 23 23727 CFTR-Intron10-4846 + GGAGAAUUGCUUGAGCCCGGGAGG 24 23728 CFTR-Intron10-4847 + UCCCAGCUACUUGGGAGG 18 23729 CFTR-Intron10-4848 + GUCCCAGCUACUUGGGAGG 19 23730 CFTR-Intron10-4849 + AGUCCCAGCUACUUGGGAGG 20 23731 CFTR-Intron10-4850 + UAGUCCCAGCUACUUGGGAGG 21 23732 CFTR-Intron10-4851 + GUAGUCCCAGCUACUUGGGAGG 22 23733 CFTR-Intron10-4852 + UGUAGUCCCAGCUACUUGGGAGG 23 23734 CFTR-Intron10-4853 + CUGUAGUCCCAGCUACUUGGGAGG 24 23735 CFTR-Intron10-4854 + UCCCAACACUUUGGGAGG 18 23736 CFTR-Intron10-4855 + AUCCCAACACUUUGGGAGG 19 23737 CFTR-Intron10-4856 + AAUCCCAACACUUUGGGAGG 20 23738 CFTR-Intron10-4857 + UAAUCCCAACACUUUGGGAGG 21 23739 CFTR-Intron10-4858 + GUAAUCCCAACACUUUGGGAGG 22 23740 CFTR-Intron10-4859 + UGUAAUCCCAACACUUUGGGAGG 23 23741 CFTR-Intron10-4860 + CUGUAAUCCCAACACUUUGGGAGG 24 23742 CFTR-Intron10-4861 + ACCCAGCACUUUGGGAGG 18 23743 CFTR-Intron10-4862 + AACCCAGCACUUUGGGAGG 19 23744 CFTR-Intron10-4863 + AAACCCAGCACUUUGGGAGG 20 23745 CFTR-Intron10-4864 + UAAACCCAGCACUUUGGGAGG 21 23746 CFTR-Intron10-4865 + AUAAACCCAGCACUUUGGGAGG 22 23747 CFTR-Intron10-4866 + UAUAAACCCAGCACUUUGGGAGG 23 23748 CFTR-Intron10-4867 + CUAUAAACCCAGCACUUUGGGAGG 24 23749 CFTR-Intron10-4868 + UCCCAGCACUUUGGGAGG 18 23750 CFTR-Intron10-4869 + AUCCCAGCACUUUGGGAGG 19 23751 CFTR-Intron10-4870 + AAUCCCAGCACUUUGGGAGG 20 23752 CFTR-Intron10-4871 + UAAUCCCAGCACUUUGGGAGG 21 23753 CFTR-Intron10-4872 + GUAAUCCCAGCACUUUGGGAGG 22 23754 CFTR-Intron10-4873 + UGUAAUCCCAGCACUUUGGGAGG 23 23755 CFTR-Intron10-4874 + CUGUAAUCCCAGCACUUUGGGAGG 24 23756 CFTR-Intron10-4875 + UUCUCACAGUUCUGGAGG 18 23757 CFTR-Intron10-4876 + UUUCUCACAGUUCUGGAGG 19 23758 CFTR-Intron10-4877 + AUUUCUCACAGUUCUGGAGG 20 23759 CFTR-Intron10-4878 + UAUUUCUCACAGUUCUGGAGG 21 23760 CFTR-Intron10-4879 + UUAUUUCUCACAGUUCUGGAGG 22 23761 CFTR-Intron10-4880 + UUUAUUUCUCACAGUUCUGGAGG 23 23762 CFTR-Intron10-4881 + AUUUAUUUCUCACAGUUCUGGAGG 24 23763 CFTR-Intron10-4882 + CAGCUACUUGGGAGGCUGAGG 21 23764 CFTR-Intron10-4883 + CCAGCUACUUGGGAGGCUGAGG 22 23765 CFTR-Intron10-4884 + CCCAGCUACUUGGGAGGCUGAGG 23 23766 CFTR-Intron10-4885 + UCCCAGCUACUUGGGAGGCUGAGG 24 23767 CFTR-Intron10-4886 + CUACUUGGGAGGGUGAGG 18 23768 CFTR-Intron10-4887 + GCUACUUGGGAGGGUGAGG 19 23769 CFTR-Intron10-4888 + AGCUACUUGGGAGGGUGAGG 20 23770 CFTR-Intron10-4889 + CAGCUACUUGGGAGGGUGAGG 21 23771 CFTR-Intron10-4890 + CCAGCUACUUGGGAGGGUGAGG 22 23772 CFTR-Intron10-4891 + CCCAGCUACUUGGGAGGGUGAGG 23 23773 CFTR-Intron10-4892 + UCCCAGCUACUUGGGAGGGUGAGG 24 23774 CFTR-Intron10-4893 + GGUUAAGUUGUUCUUAGG 18 23775 CFTR-Intron10-4894 + AGGUUAAGUUGUUCUUAGG 19 23776 CFTR-Intron10-4895 + CAGGUUAAGUUGUUCUUAGG 20 23777 CFTR-Intron10-4896 + CCAGGUUAAGUUGUUCUUAGG 21 23778 CFTR-Intron10-4897 + GCCAGGUUAAGUUGUUCUUAGG 22 23779 CFTR-Intron10-4898 + UGCCAGGUUAAGUUGUUCUUAGG 23 23780 CFTR-Intron10-4899 + AUGCCAGGUUAAGUUGUUCUUAGG 24 23781 CFTR-Intron10-4900 + CUCACAUGGCAGAAAGGG 18 23782 CFTR-Intron10-4901 + UCUCACAUGGCAGAAAGGG 19 23783 CFTR-Intron10-4902 + UUCUCACAUGGCAGAAAGGG 20 23784 CFTR-Intron10-4903 + GUUCUCACAUGGCAGAAAGGG 21 23785 CFTR-Intron10-4904 + UGUUCUCACAUGGCAGAAAGGG 22 23786 CFTR-Intron10-4905 + GUGUUCUCACAUGGCAGAAAGGG 23 23787 CFTR-Intron10-4906 + UGUGUUCUCACAUGGCAGAAAGGG 24 23788 CFTR-Intron10-4907 + AACAUAUGAAUGGCAGGG 18 23789 CFTR-Intron10-4908 + CAACAUAUGAAUGGCAGGG 19 23790 CFTR-Intron10-4909 + UCAACAUAUGAAUGGCAGGG 20 23791 CFTR-Intron10-4910 + UUCAACAUAUGAAUGGCAGGG 21 23792 CFTR-Intron10-4911 + UUUCAACAUAUGAAUGGCAGGG 22 23793 CFTR-Intron10-4912 + AUUUCAACAUAUGAAUGGCAGGG 23 23794 CFTR-Intron10-4913 + GAUUUCAACAUAUGAAUGGCAGGG 24 23795 CFTR-Intron10-4914 + UUGGUACAAAUUUCAGGG 18 23796 CFTR-Intron10-4915 + AUUGGUACAAAUUUCAGGG 19 23797 CFTR-Intron10-4916 + AAUUGGUACAAAUUUCAGGG 20 23798 CFTR-Intron10-4917 + GAAUUGGUACAAAUUUCAGGG 21 23799 CFTR-Intron10-4918 + CGAAUUGGUACAAAUUUCAGGG 22 23800 CFTR-Intron10-4919 + ACGAAUUGGUACAAAUUUCAGGG 23 23801 CFTR-Intron10-4920 + UACGAAUUGGUACAAAUUUCAGGG 24 23802 CFTR-Intron10-4921 + AUUUCAACAUAUGAAUGG 18 23803 CFTR-Intron10-4922 + GAUUUCAACAUAUGAAUGG 19 23804 CFTR-Intron10-4923 + GGAUUUCAACAUAUGAAUGG 20 23805 CFTR-Intron10-4924 + AGGAUUUCAACAUAUGAAUGG 21 23806 CFTR-Intron10-4925 + UAGGAUUUCAACAUAUGAAUGG 22 23807 CFTR-Intron10-4926 + UUAGGAUUUCAACAUAUGAAUGG 23 23808 CFTR-Intron10-4927 + AUUAGGAUUUCAACAUAUGAAUGG 24 23809 CFTR-Intron10-4928 + UGCUGUGUUCUCACAUGG 18 23810 CFTR-Intron10-4929 + CUGCUGUGUUCUCACAUGG 19 23811 CFTR-Intron10-4930 + CCUGCUGUGUUCUCACAUGG 20 23812 CFTR-Intron10-4931 + UCCUGCUGUGUUCUCACAUGG 21 23813 CFTR-Intron10-4932 + UUCCUGCUGUGUUCUCACAUGG 22 23814 CFTR-Intron10-4933 + CUUCCUGCUGUGUUCUCACAUGG 23 23815 CFTR-Intron10-4934 + UCUUCCUGCUGUGUUCUCACAUGG 24 23816 CFTR-Intron10-4935 + AUUGGCUACCUUGGUUGG 18 23817 CFTR-Intron10-4936 + GAUUGGCUACCUUGGUUGG 19 23818 CFTR-Intron10-4937 + GGAUUGGCUACCUUGGUUGG 20 23819 CFTR-Intron10-4938 + UGGAUUGGCUACCUUGGUUGG 21 23820 CFTR-Intron10-4939 + CUGGAUUGGCUACCUUGGUUGG 22 23821 CFTR-Intron10-4940 + CCUGGAUUGGCUACCUUGGUUGG 23 23822 CFTR-Intron10-4941 + ACCUGGAUUGGCUACCUUGGUUGG 24 23823 CFTR-Intron10-4942 + UGGUUGGAUGAGGGAAUG 18 23824 CFTR-Intron10-4943 + UUGGUUGGAUGAGGGAAUG 19 23825 CFTR-Intron10-4944 + CUUGGUUGGAUGAGGGAAUG 20 23826 CFTR-Intron10-4945 + CCUUGGUUGGAUGAGGGAAUG 21 23827 CFTR-Intron10-4946 + ACCUUGGUUGGAUGAGGGAAUG 22 23828 CFTR-Intron10-4947 + UACCUUGGUUGGAUGAGGGAAUG 23 23829 CFTR-Intron10-4948 + CUACCUUGGUUGGAUGAGGGAAUG 24 23830 CFTR-Intron10-4949 + GAAAGCAGUGUUAUAAUG 18 23831 CFTR-Intron10-4950 + UGAAAGCAGUGUUAUAAUG 19 23832 CFTR-Intron10-4951 + CUGAAAGCAGUGUUAUAAUG 20 23833 CFTR-Intron10-4952 + CCUGAAAGCAGUGUUAUAAUG 21 23834 CFTR-Intron10-4953 + UCCUGAAAGCAGUGUUAUAAUG 22 23835 CFTR-Intron10-4954 + CUCCUGAAAGCAGUGUUAUAAUG 23 23836 CFTR-Intron10-4955 + GCUCCUGAAAGCAGUGUUAUAAUG 24 23837 CFTR-Intron10-4956 + GGCAUUGCACUAAACAUG 18 23838 CFTR-Intron10-4957 + UGGCAUUGCACUAAACAUG 19 23839 CFTR-Intron10-4958 + AUGGCAUUGCACUAAACAUG 20 23840 CFTR-Intron10-4959 + UAUGGCAUUGCACUAAACAUG 21 23841 CFTR-Intron10-4960 + UUAUGGCAUUGCACUAAACAUG 22 23842 CFTR-Intron10-4961 + UUUAUGGCAUUGCACUAAACAUG 23 23843 CFTR-Intron10-4962 + GUUUAUGGCAUUGCACUAAACAUG 24 23844 CFTR-Intron10-4963 + ACCAUCCUGGCCAACAUG 18 23845 CFTR-Intron10-4964 + UACCAUCCUGGCCAACAUG 19 23846 CFTR-Intron10-4965 + AUACCAUCCUGGCCAACAUG 20 23847 CFTR-Intron10-4966 + AAUACCAUCCUGGCCAACAUG 21 23848 CFTR-Intron10-4967 + CAAUACCAUCCUGGCCAACAUG 22 23849 CFTR-Intron10-4968 + UCAAUACCAUCCUGGCCAACAUG 23 23850 CFTR-Intron10-4969 + AUCAAUACCAUCCUGGCCAACAUG 24 23851 CFTR-Intron10-4970 + AAAAGAUAAGUGAAGAUG 18 23852 CFTR-Intron10-4971 + AAAAAGAUAAGUGAAGAUG 19 23853 CFTR-Intron10-4972 + AAAAAAGAUAAGUGAAGAUG 20 23854 CFTR-Intron10-4973 + GAAAAAAGAUAAGUGAAGAUG 21 23855 CFTR-Intron10-4974 + AGAAAAAAGAUAAGUGAAGAUG 22 23856 CFTR-Intron10-4975 + UAGAAAAAAGAUAAGUGAAGAUG 23 23857 CFTR-Intron10-4976 + GUAGAAAAAAGAUAAGUGAAGAUG 24 23858 CFTR-Intron10-4977 + GGCUACCUUGGUUGGAUG 18 23859 CFTR-Intron10-4978 + UGGCUACCUUGGUUGGAUG 19 23860 CFTR-Intron10-481 + UUGGCUACCUUGGUUGGAUG 20 19367 CFTR-Intron10-4979 + AUUGGCUACCUUGGUUGGAUG 21 23861 CFTR-Intron10-4980 + GAUUGGCUACCUUGGUUGGAUG 22 23862 CFTR-Intron10-4981 + GGAUUGGCUACCUUGGUUGGAUG 23 23863 CFTR-Intron10-4982 + UGGAUUGGCUACCUUGGUUGGAUG 24 23864 CFTR-Intron10-4983 + UUCUUAGGGUGGGAUAUG 18 23865 CFTR-Intron10-4984 + GUUCUUAGGGUGGGAUAUG 19 23866 CFTR-Intron10-4985 + UGUUCUUAGGGUGGGAUAUG 20 23867 CFTR-Intron10-4986 + UUGUUCUUAGGGUGGGAUAUG 21 23868 CFTR-Intron10-4987 + GUUGUUCUUAGGGUGGGAUAUG 22 23869 CFTR-Intron10-4988 + AGUUGUUCUUAGGGUGGGAUAUG 23 23870 CFTR-Intron10-4989 + AAGUUGUUCUUAGGGUGGGAUAUG 24 23871 CFTR-Intron10-4990 + UAAAAGCUGUUUCGUAUG 18 23872 CFTR-Intron10-4991 + UUAAAAGCUGUUUCGUAUG 19 23873 CFTR-Intron10-4992 + UUUAAAAGCUGUUUCGUAUG 20 23874 CFTR-Intron10-4993 + UUUUAAAAGCUGUUUCGUAUG 21 23875 CFTR-Intron10-4994 + GUUUUAAAAGCUGUUUCGUAUG 22 23876 CFTR-Intron10-4995 + UGUUUUAAAAGCUGUUUCGUAUG 23 23877 CFTR-Intron10-4996 + UUGUUUUAAAAGCUGUUUCGUAUG 24 23878 CFTR-Intron10-4997 + UAUGUAGGAAAACAACUG 18 23879 CFTR-Intron10-4998 + GUAUGUAGGAAAACAACUG 19 23880 CFTR-Intron10-4999 + CGUAUGUAGGAAAACAACUG 20 23881 CFTR-Intron10-5000 + UCGUAUGUAGGAAAACAACUG 21 23882 CFTR-Intron10-5001 + UUCGUAUGUAGGAAAACAACUG 22 23883 CFTR-Intron10-5002 + UUUCGUAUGUAGGAAAACAACUG 23 23884 CFTR-Intron10-5003 + GUUUCGUAUGUAGGAAAACAACUG 24 23885 CFTR-Intron10-5004 + GAAACUCCCCACACACUG 18 23886 CFTR-Intron10-5005 + UGAAACUCCCCACACACUG 19 23887 CFTR-Intron10-5006 + CUGAAACUCCCCACACACUG 20 23888 CFTR-Intron10-5007 + ACUGAAACUCCCCACACACUG 21 23889 CFTR-Intron10-5008 + GACUGAAACUCCCCACACACUG 22 23890 CFTR-Intron10-5009 + GGACUGAAACUCCCCACACACUG 23 23891 CFTR-Intron10-5010 + AGGACUGAAACUCCCCACACACUG 24 23892 CFTR-Intron10-5011 + GCAAUAUGCAAUUUACUG 18 23893 CFTR-Intron10-5012 + UGCAAUAUGCAAUUUACUG 19 23894 CFTR-Intron10-5013 + CUGCAAUAUGCAAUUUACUG 20 23895 CFTR-Intron10-5014 + ACUGCAAUAUGCAAUUUACUG 21 23896 CFTR-Intron10-5015 + UACUGCAAUAUGCAAUUUACUG 22 23897 CFTR-Intron10-5016 + UUACUGCAAUAUGCAAUUUACUG 23 23898 CFTR-Intron10-5017 + UUUACUGCAAUAUGCAAUUUACUG 24 23899 CFTR-Intron10-5018 + CAUCUGUUAGUAAUGCUG 18 23900 CFTR-Intron10-5019 + UCAUCUGUUAGUAAUGCUG 19 23901 CFTR-Intron10-485 + AUCAUCUGUUAGUAAUGCUG 20 19371 CFTR-Intron10-5020 + UAUCAUCUGUUAGUAAUGCUG 21 23902 CFTR-Intron10-5021 + AUAUCAUCUGUUAGUAAUGCUG 22 23903 CFTR-Intron10-5022 + AAUAUCAUCUGUUAGUAAUGCUG 23 23904 CFTR-Intron10-5023 + UAAUAUCAUCUGUUAGUAAUGCUG 24 23905 CFTR-Intron10-5024 + AAUUAGCCGGGCGUAGUG 18 23906 CFTR-Intron10-5025 + AAAUUAGCCGGGCGUAGUG 19 23907 CFTR-Intron10-5026 + AAAAUUAGCCGGGCGUAGUG 20 23908 CFTR-Intron10-5027 + AAAAAUUAGCCGGGCGUAGUG 21 23909 CFTR-Intron10-5028 + AAAAAAUUAGCCGGGCGUAGUG 22 23910 CFTR-Intron10-5029 + CAAAAAAUUAGCCGGGCGUAGUG 23 23911 CFTR-Intron10-5030 + ACAAAAAAUUAGCCGGGCGUAGUG 24 23912 CFTR-Intron10-5031 + UCUGUUAGUAAUGCUGUG 18 23913 CFTR-Intron10-5032 + AUCUGUUAGUAAUGCUGUG 19 23914 CFTR-Intron10-490 + CAUCUGUUAGUAAUGCUGUG 20 19376 CFTR-Intron10-5033 + UCAUCUGUUAGUAAUGCUGUG 21 23915 CFTR-Intron10-5034 + AUCAUCUGUUAGUAAUGCUGUG 22 23916 CFTR-Intron10-5035 + UAUCAUCUGUUAGUAAUGCUGUG 23 23917 CFTR-Intron10-5036 + AUAUCAUCUGUUAGUAAUGCUGUG 24 23918 CFTR-Intron10-5037 + AUUCAAAAAAUAUUUGUG 18 23919 CFTR-Intron10-5038 + UAUUCAAAAAAUAUUUGUG 19 23920 CFTR-Intron10-5039 + CUAUUCAAAAAAUAUUUGUG 20 23921 CFTR-Intron10-5040 + UCUAUUCAAAAAAUAUUUGUG 21 23922 CFTR-Intron10-5041 + AUCUAUUCAAAAAAUAUUUGUG 22 23923 CFTR-Intron10-5042 + AAUCUAUUCAAAAAAUAUUUGUG 23 23924 CFTR-Intron10-5043 + UAAUCUAUUCAAAAAAUAUUUGUG 24 23925 CFTR-Intron10-5044 + CUAUUCAAAAAAUAUUUG 18 23926 CFTR-Intron10-5045 + UCUAUUCAAAAAAUAUUUG 19 23927 CFTR-Intron10-1323 + AUCUAUUCAAAAAAUAUUUG 20 20208 CFTR-Intron10-5046 + AAUCUAUUCAAAAAAUAUUUG 21 23928 CFTR-Intron10-5047 + UAAUCUAUUCAAAAAAUAUUUG 22 23929 CFTR-Intron10-5048 + CUAAUCUAUUCAAAAAAUAUUUG 23 23930 CFTR-Intron10-5049 + GCUAAUCUAUUCAAAAAAUAUUUG 24 23931 CFTR-Intron10-5050 + CUUAUAUUUUUAUUUUUG 18 23932 CFTR-Intron10-5051 + ACUUAUAUUUUUAUUUUUG 19 23933 CFTR-Intron10-5052 + CACUUAUAUUUUUAUUUUUG 20 23934 CFTR-Intron10-5053 + CCACUUAUAUUUUUAUUUUUG 21 23935 CFTR-Intron10-5054 + GCCACUUAUAUUUUUAUUUUUG 22 23936 CFTR-Intron10-5055 + GGCCACUUAUAUUUUUAUUUUUG 23 23937 CFTR-Intron10-5056 + AGGCCACUUAUAUUUUUAUUUUUG 24 23938 CFTR-Intron10-5057 + UUUUGUUUGUGUUUUUUG 18 23939 CFTR-Intron10-5058 + CUUUUGUUUGUGUUUUUUG 19 23940 CFTR-Intron10-5059 + UCUUUUGUUUGUGUUUUUUG 20 23941 CFTR-Intron10-5060 + UUCUUUUGUUUGUGUUUUUUG 21 23942 CFTR-Intron10-5061 + UUUCUUUUGUUUGUGUUUUUUG 22 23943 CFTR-Intron10-5062 + UUUUCUUUUGUUUGUGUUUUUUG 23 23944 CFTR-Intron10-5063 + AUUUUCUUUUGUUUGUGUUUUUUG 24 23945 CFTR-Intron10-5064 + CUAAAAUGACAAUCAAAU 18 23946 CFTR-Intron10-5065 + GCUAAAAUGACAAUCAAAU 19 23947 CFTR-Intron10-498 + AGCUAAAAUGACAAUCAAAU 20 19384 CFTR-Intron10-5066 + CAGCUAAAAUGACAAUCAAAU 21 23948 CFTR-Intron10-5067 + ACAGCUAAAAUGACAAUCAAAU 22 23949 CFTR-Intron10-5068 + CACAGCUAAAAUGACAAUCAAAU 23 23950 CFTR-Intron10-5069 + CCACAGCUAAAAUGACAAUCAAAU 24 23951 CFTR-Intron10-5070 + AACAAUACAAAGAUAAAU 18 23952 CFTR-Intron10-5071 + UAACAAUACAAAGAUAAAU 19 23953 CFTR-Intron10-5072 + UUAACAAUACAAAGAUAAAU 20 23954 CFTR-Intron10-5073 + UUUAACAAUACAAAGAUAAAU 21 23955 CFTR-Intron10-5074 + AUUUAACAAUACAAAGAUAAAU 22 23956 CFTR-Intron10-5075 + GAUUUAACAAUACAAAGAUAAAU 23 23957 CFTR-Intron10-5076 + AGAUUUAACAAUACAAAGAUAAAU 24 23958 CFTR-Intron10-5077 + GUUAUAUGUCCUGACAAU 18 23959 CFTR-Intron10-5078 + UGUUAUAUGUCCUGACAAU 19 23960 CFTR-Intron10-5079 + AUGUUAUAUGUCCUGACAAU 20 23961 CFTR-Intron10-5080 + UAUGUUAUAUGUCCUGACAAU 21 23962 CFTR-Intron10-5081 + AUAUGUUAUAUGUCCUGACAAU 22 23963 CFTR-Intron10-5082 + AAUAUGUUAUAUGUCCUGACAAU 23 23964 CFTR-Intron10-5083 + AAAUAUGUUAUAUGUCCUGACAAU 24 23965 CFTR-Intron10-5084 + GUGCUAUUUAAACAGAAU 18 23966 CFTR-Intron10-5085 + AGUGCUAUUUAAACAGAAU 19 23967 CFTR-Intron10-5086 + CAGUGCUAUUUAAACAGAAU 20 23968 CFTR-Intron10-5087 + CCAGUGCUAUUUAAACAGAAU 21 23969 CFTR-Intron10-5088 + UCCAGUGCUAUUUAAACAGAAU 22 23970 CFTR-Intron10-5089 + CUCCAGUGCUAUUUAAACAGAAU 23 23971 CFTR-Intron10-5090 + ACUCCAGUGCUAUUUAAACAGAAU 24 23972 CFTR-Intron10-5091 + GUCCUCUGUGCUUUGAAU 18 23973 CFTR-Intron10-5092 + AGUCCUCUGUGCUUUGAAU 19 23974 CFTR-Intron10-5093 + AAGUCCUCUGUGCUUUGAAU 20 23975 CFTR-Intron10-5094 + CAAGUCCUCUGUGCUUUGAAU 21 23976 CFTR-Intron10-5095 + GCAAGUCCUCUGUGCUUUGAAU 22 23977 CFTR-Intron10-5096 + UGCAAGUCCUCUGUGCUUUGAAU 23 23978 CFTR-Intron10-5097 + GUGCAAGUCCUCUGUGCUUUGAAU 24 23979 CFTR-Intron10-5098 + CCAAGCAGUAGAAAUAAU 18 23980 CFTR-Intron10-5099 + UCCAAGCAGUAGAAAUAAU 19 23981 CFTR-Intron10-5100 + UUCCAAGCAGUAGAAAUAAU 20 23982 CFTR-Intron10-5101 + AUUCCAAGCAGUAGAAAUAAU 21 23983 CFTR-Intron10-5102 + AAUUCCAAGCAGUAGAAAUAAU 22 23984 CFTR-Intron10-5103 + AAAUUCCAAGCAGUAGAAAUAAU 23 23985 CFTR-Intron10-5104 + AAAAUUCCAAGCAGUAGAAAUAAU 24 23986 CFTR-Intron10-5105 + UUUUAGUAGAAACCUAAU 18 23987 CFTR-Intron10-5106 + GUUUUAGUAGAAACCUAAU 19 23988 CFTR-Intron10-5107 + GGUUUUAGUAGAAACCUAAU 20 23989 CFTR-Intron10-5108 + UGGUUUUAGUAGAAACCUAAU 21 23990 CFTR-Intron10-5109 + UUGGUUUUAGUAGAAACCUAAU 22 23991 CFTR-Intron10-5110 + UUUGGUUUUAGUAGAAACCUAAU 23 23992 CFTR-Intron10-5111 + GUUUGGUUUUAGUAGAAACCUAAU 24 23993 CFTR-Intron10-5112 + GCCUAGAUGAUUAUUAAU 18 23994 CFTR-Intron10-5113 + AGCCUAGAUGAUUAUUAAU 19 23995 CFTR-Intron10-503 + CAGCCUAGAUGAUUAUUAAU 20 19389 CFTR-Intron10-5114 + GCAGCCUAGAUGAUUAUUAAU 21 23996 CFTR-Intron10-5115 + UGCAGCCUAGAUGAUUAUUAAU 22 23997 CFTR-Intron10-5116 + UUGCAGCCUAGAUGAUUAUUAAU 23 23998 CFTR-Intron10-5117 + UUUGCAGCCUAGAUGAUUAUUAAU 24 23999 CFTR-Intron10-5118 + UUACAAUUCUUAUUACAU 18 24000 CFTR-Intron10-5119 + UUUACAAUUCUUAUUACAU 19 24001 CFTR-Intron10-1333 + UUUUACAAUUCUUAUUACAU 20 20218 CFTR-Intron10-5120 + AUUUUACAAUUCUUAUUACAU 21 24002 CFTR-Intron10-5121 + AAUUUUACAAUUCUUAUUACAU 22 24003 CFTR-Intron10-5122 + AAAUUUUACAAUUCUUAUUACAU 23 24004 CFTR-Intron10-5123 + UAAAUUUUACAAUUCUUAUUACAU 24 24005 CFTR-Intron10-5124 + AGGUAUAGUCAGUCCCAU 18 24006 CFTR-Intron10-5125 + CAGGUAUAGUCAGUCCCAU 19 24007 CFTR-Intron10-5126 + ACAGGUAUAGUCAGUCCCAU 20 24008 CFTR-Intron10-5127 + GACAGGUAUAGUCAGUCCCAU 21 24009 CFTR-Intron10-5128 + AGACAGGUAUAGUCAGUCCCAU 22 24010 CFTR-Intron10-5129 + CAGACAGGUAUAGUCAGUCCCAU 23 24011 CFTR-Intron10-5130 + CCAGACAGGUAUAGUCAGUCCCAU 24 24012 CFTR-Intron10-5131 + AACAUAGAGAAAACUCAU 18 24013 CFTR-Intron10-5132 + AAACAUAGAGAAAACUCAU 19 24014 CFTR-Intron10-5133 + AAAACAUAGAGAAAACUCAU 20 24015 CFTR-Intron10-5134 + UAAAACAUAGAGAAAACUCAU 21 24016 CFTR-Intron10-5135 + AUAAAACAUAGAGAAAACUCAU 22 24017 CFTR-Intron10-5136 + AAUAAAACAUAGAGAAAACUCAU 23 24018 CFTR-Intron10-5137 + AAAUAAAACAUAGAGAAAACUCAU 24 24019 CFTR-Intron10-5138 + CUAUUUUCCCUAUAAGAU 18 24020 CFTR-Intron10-5139 + ACUAUUUUCCCUAUAAGAU 19 24021 CFTR-Intron10-5140 + UACUAUUUUCCCUAUAAGAU 20 24022 CFTR-Intron10-5141 + AUACUAUUUUCCCUAUAAGAU 21 24023 CFTR-Intron10-5142 + CAUACUAUUUUCCCUAUAAGAU 22 24024 CFTR-Intron10-5143 + ACAUACUAUUUUCCCUAUAAGAU 23 24025 CFTR-Intron10-5144 + GACAUACUAUUUUCCCUAUAAGAU 24 24026 CFTR-Intron10-5145 + AAUGGAAAAUGGACAGAU 18 24027 CFTR-Intron10-5146 + GAAUGGAAAAUGGACAGAU 19 24028 CFTR-Intron10-5147 + AGAAUGGAAAAUGGACAGAU 20 24029 CFTR-Intron10-5148 + GAGAAUGGAAAAUGGACAGAU 21 24030 CFTR-Intron10-5149 + GGAGAAUGGAAAAUGGACAGAU 22 24031 CFTR-Intron10-5150 + AGGAGAAUGGAAAAUGGACAGAU 23 24032 CFTR-Intron10-5151 + CAGGAGAAUGGAAAAUGGACAGAU 24 24033 CFTR-Intron10-5152 + UUGUUCUUAGGGUGGGAU 18 24034 CFTR-Intron10-5153 + GUUGUUCUUAGGGUGGGAU 19 24035 CFTR-Intron10-5154 + AGUUGUUCUUAGGGUGGGAU 20 24036 CFTR-Intron10-5155 + AAGUUGUUCUUAGGGUGGGAU 21 24037 CFTR-Intron10-5156 + UAAGUUGUUCUUAGGGUGGGAU 22 24038 CFTR-Intron10-5157 + UUAAGUUGUUCUUAGGGUGGGAU 23 24039 CFTR-Intron10-5158 + GUUAAGUUGUUCUUAGGGUGGGAU 24 24040 CFTR-Intron10-5159 + UGGCUACCUUGGUUGGAU 18 24041 CFTR-Intron10-5160 + UUGGCUACCUUGGUUGGAU 19 24042 CFTR-Intron10-5161 + AUUGGCUACCUUGGUUGGAU 20 24043 CFTR-Intron10-5162 + GAUUGGCUACCUUGGUUGGAU 21 24044 CFTR-Intron10-5163 + GGAUUGGCUACCUUGGUUGGAU 22 24045 CFTR-Intron10-5164 + UGGAUUGGCUACCUUGGUUGGAU 23 24046 CFTR-Intron10-5165 + CUGGAUUGGCUACCUUGGUUGGAU 24 24047 CFTR-Intron10-5166 + AAACAUGAUGAAAAAUAU 18 24048 CFTR-Intron10-5167 + UAAACAUGAUGAAAAAUAU 19 24049 CFTR-Intron10-5168 + CUAAACAUGAUGAAAAAUAU 20 24050 CFTR-Intron10-5169 + ACUAAACAUGAUGAAAAAUAU 21 24051 CFTR-Intron10-5170 + CACUAAACAUGAUGAAAAAUAU 22 24052 CFTR-Intron10-5171 + GCACUAAACAUGAUGAAAAAUAU 23 24053 CFTR-Intron10-5172 + UGCACUAAACAUGAUGAAAAAUAU 24 24054 CFTR-Intron10-5173 + UUUGUGUUAACAAAAUAU 18 24055 CFTR-Intron10-5174 + CUUUGUGUUAACAAAAUAU 19 24056 CFTR-Intron10-506 + UCUUUGUGUUAACAAAAUAU 20 19392 CFTR-Intron10-5175 + UUCUUUGUGUUAACAAAAUAU 21 24057 CFTR-Intron10-5176 + GUUCUUUGUGUUAACAAAAUAU 22 24058 CFTR-Intron10-5177 + UGUUCUUUGUGUUAACAAAAUAU 23 24059 CFTR-Intron10-5178 + UUGUUCUUUGUGUUAACAAAAUAU 24 24060 CFTR-Intron10-5179 + GUUGCAAAAAUACGAUAU 18 24061 CFTR-Intron10-5180 + AGUUGCAAAAAUACGAUAU 19 24062 CFTR-Intron10-5181 + GAGUUGCAAAAAUACGAUAU 20 24063 CFTR-Intron10-5182 + GGAGUUGCAAAAAUACGAUAU 21 24064 CFTR-Intron10-5183 + AGGAGUUGCAAAAAUACGAUAU 22 24065 CFTR-Intron10-5184 + AAGGAGUUGCAAAAAUACGAUAU 23 24066 CFTR-Intron10-5185 + AAAGGAGUUGCAAAAAUACGAUAU 24 24067 CFTR-Intron10-5186 + AAAAAUUACAGAACCUAU 18 24068 CFTR-Intron10-5187 + CAAAAAUUACAGAACCUAU 19 24069 CFTR-Intron10-5188 + GCAAAAAUUACAGAACCUAU 20 24070 CFTR-Intron10-5189 + AGCAAAAAUUACAGAACCUAU 21 24071 CFTR-Intron10-5190 + AAGCAAAAAUUACAGAACCUAU 22 24072 CFTR-Intron10-5191 + GAAGCAAAAAUUACAGAACCUAU 23 24073 CFTR-Intron10-5192 + UGAAGCAAAAAUUACAGAACCUAU 24 24074 CFTR-Intron10-5193 + AAAUGCUUGACCACUUAU 18 24075 CFTR-Intron10-5194 + CAAAUGCUUGACCACUUAU 19 24076 CFTR-Intron10-508 + ACAAAUGCUUGACCACUUAU 20 19394 CFTR-Intron10-5195 + CACAAAUGCUUGACCACUUAU 21 24077 CFTR-Intron10-5196 + ACACAAAUGCUUGACCACUUAU 22 24078 CFTR-Intron10-5197 + UACACAAAUGCUUGACCACUUAU 23 24079 CFTR-Intron10-5198 + GUACACAAAUGCUUGACCACUUAU 24 24080 CFTR-Intron10-5199 + AAAAAGCACUGAUUUUAU 18 24081 CFTR-Intron10-5200 + GAAAAAGCACUGAUUUUAU 19 24082 CFTR-Intron10-5201 + CGAAAAAGCACUGAUUUUAU 20 24083 CFTR-Intron10-5202 + UCGAAAAAGCACUGAUUUUAU 21 24084 CFTR-Intron10-5203 + CUCGAAAAAGCACUGAUUUUAU 22 24085 CFTR-Intron10-5204 + CCUCGAAAAAGCACUGAUUUUAU 23 24086 CFTR-Intron10-5205 + ACCUCGAAAAAGCACUGAUUUUAU 24 24087 CFTR-Intron10-5206 + ACAAAGAUUUAUAUAACU 18 24088 CFTR-Intron10-5207 + AACAAAGAUUUAUAUAACU 19 24089 CFTR-Intron10-5208 + GAACAAAGAUUUAUAUAACU 20 24090 CFTR-Intron10-5209 + UGAACAAAGAUUUAUAUAACU 21 24091 CFTR-Intron10-5210 + GUGAACAAAGAUUUAUAUAACU 22 24092 CFTR-Intron10-5211 + AGUGAACAAAGAUUUAUAUAACU 23 24093 CFTR-Intron10-5212 + CAGUGAACAAAGAUUUAUAUAACU 24 24094 CFTR-Intron10-5213 + GCCUGUAAUCCCAACACU 18 24095 CFTR-Intron10-5214 + UGCCUGUAAUCCCAACACU 19 24096 CFTR-Intron10-5215 + AUGCCUGUAAUCCCAACACU 20 24097 CFTR-Intron10-5216 + CAUGCCUGUAAUCCCAACACU 21 24098 CFTR-Intron10-5217 + UCAUGCCUGUAAUCCCAACACU 22 24099 CFTR-Intron10-5218 + CUCAUGCCUGUAAUCCCAACACU 23 24100 CFTR-Intron10-5219 + GCUCAUGCCUGUAAUCCCAACACU 24 24101 CFTR-Intron10-5220 + GCCUAUAAACCCAGCACU 18 24102 CFTR-Intron10-5221 + UGCCUAUAAACCCAGCACU 19 24103 CFTR-Intron10-5222 + AUGCCUAUAAACCCAGCACU 20 24104 CFTR-Intron10-5223 + CAUGCCUAUAAACCCAGCACU 21 24105 CFTR-Intron10-5224 + UCAUGCCUAUAAACCCAGCACU 22 24106 CFTR-Intron10-5225 + CUCAUGCCUAUAAACCCAGCACU 23 24107 CFTR-Intron10-5226 + GCUCAUGCCUAUAAACCCAGCACU 24 24108 CFTR-Intron10-5227 + GCCUGUAAUCCCAGCACU 18 24109 CFTR-Intron10-5228 + CGCCUGUAAUCCCAGCACU 19 24110 CFTR-Intron10-5229 + ACGCCUGUAAUCCCAGCACU 20 24111 CFTR-Intron10-5230 + CACGCCUGUAAUCCCAGCACU 21 24112 CFTR-Intron10-5231 + UCACGCCUGUAAUCCCAGCACU 22 24113 CFTR-Intron10-5232 + CUCACGCCUGUAAUCCCAGCACU 23 24114 CFTR-Intron10-5233 + GCUCACGCCUGUAAUCCCAGCACU 24 24115 CFTR-Intron10-5234 + UCCCGAGUAGCUGGGACU 18 24116 CFTR-Intron10-5235 + CUCCCGAGUAGCUGGGACU 19 24117 CFTR-Intron10-5236 + CCUCCCGAGUAGCUGGGACU 20 24118 CFTR-Intron10-5237 + GCCUCCCGAGUAGCUGGGACU 21 24119 CFTR-Intron10-5238 + AGCCUCCCGAGUAGCUGGGACU 22 24120 CFTR-Intron10-5239 + CAGCCUCCCGAGUAGCUGGGACU 23 24121 CFTR-Intron10-5240 + UCAGCCUCCCGAGUAGCUGGGACU 24 24122 CFTR-Intron10-5241 + CCUGUAGUCCCAGCUACU 18 17604 CFTR-Intron10-5242 + GCCUGUAGUCCCAGCUACU 19 17605 CFTR-Intron10-1344 + CGCCUGUAGUCCCAGCUACU 20 20229 CFTR-Intron10-5243 + GCGCCUGUAGUCCCAGCUACU 21 24123 CFTR-Intron10-5244 + GGCGCCUGUAGUCCCAGCUACU 22 24124 CFTR-Intron10-5245 + GGGCGCCUGUAGUCCCAGCUACU 23 24125 CFTR-Intron10-5246 + CGGGCGCCUGUAGUCCCAGCUACU 24 24126 CFTR-Intron10-1345 + UGCCUGUAGUCCCAGCUACU 20 17606 CFTR-Intron10-5247 + CGUGCCUGUAGUCCCAGCUACU 22 24127 CFTR-Intron10-5248 + GCGUGCCUGUAGUCCCAGCUACU 23 24128 CFTR-Intron10-5249 + UGCGUGCCUGUAGUCCCAGCUACU 24 24129 CFTR-Intron10-5250 + CUUGCUUCACCUGCUACU 18 24130 CFTR-Intron10-5251 + ACUUGCUUCACCUGCUACU 19 24131 CFTR-Intron10-512 + CACUUGCUUCACCUGCUACU 20 19398 CFTR-Intron10-5252 + GCACUUGCUUCACCUGCUACU 21 24132 CFTR-Intron10-5253 + UGCACUUGCUUCACCUGCUACU 22 24133 CFTR-Intron10-5254 + UUGCACUUGCUUCACCUGCUACU 23 24134 CFTR-Intron10-5255 + UUUGCACUUGCUUCACCUGCUACU 24 24135 CFTR-Intron10-5256 + AAUCUUAUAGAGAUUACU 18 24136 CFTR-Intron10-5257 + AAAUCUUAUAGAGAUUACU 19 24137 CFTR-Intron10-513 + AAAAUCUUAUAGAGAUUACU 20 19399 CFTR-Intron10-5258 + CAAAAUCUUAUAGAGAUUACU 21 24138 CFTR-Intron10-5259 + ACAAAAUCUUAUAGAGAUUACU 22 24139 CFTR-Intron10-5260 + AACAAAAUCUUAUAGAGAUUACU 23 24140 CFTR-Intron10-5261 + UAACAAAAUCUUAUAGAGAUUACU 24 24141 CFTR-Intron10-5262 + CCUGCAAUACCAUCACCU 18 24142 CFTR-Intron10-5263 + CCCUGCAAUACCAUCACCU 19 24143 CFTR-Intron10-1346 + ACCCUGCAAUACCAUCACCU 20 20230 CFTR-Intron10-5264 + CACCCUGCAAUACCAUCACCU 21 24144 CFTR-Intron10-5265 + CCACCCUGCAAUACCAUCACCU 22 24145 CFTR-Intron10-5266 + CCCACCCUGCAAUACCAUCACCU 23 24146 CFTR-Intron10-5267 + CCCCACCCUGCAAUACCAUCACCU 24 24147 CFTR-Intron10-5268 + AACUCAUAAGGGACCGCU 18 24148 CFTR-Intron10-5269 + AAACUCAUAAGGGACCGCU 19 24149 CFTR-Intron10-518 + AAAACUCAUAAGGGACCGCU 20 19404 CFTR-Intron10-5270 + GAAAACUCAUAAGGGACCGCU 21 24150 CFTR-Intron10-5271 + AGAAAACUCAUAAGGGACCGCU 22 24151 CFTR-Intron10-5272 + GAGAAAACUCAUAAGGGACCGCU 23 24152 CFTR-Intron10-5273 + AGAGAAAACUCAUAAGGGACCGCU 24 24153 CFTR-Intron10-5274 + CUCACAGUUCUGGAGGCU 18 24154 CFTR-Intron10-5275 + UCUCACAGUUCUGGAGGCU 19 24155 CFTR-Intron10-1357 + UUCUCACAGUUCUGGAGGCU 20 20241 CFTR-Intron10-5276 + UUUCUCACAGUUCUGGAGGCU 21 24156 CFTR-Intron10-5277 + AUUUCUCACAGUUCUGGAGGCU 22 24157 CFTR-Intron10-5278 + UAUUUCUCACAGUUCUGGAGGCU 23 24158 CFTR-Intron10-5279 + UUAUUUCUCACAGUUCUGGAGGCU 24 24159 CFTR-Intron10-5280 + UCAUCUGUUAGUAAUGCU 18 24160 CFTR-Intron10-5281 + AUCAUCUGUUAGUAAUGCU 19 24161 CFTR-Intron10-5282 + UAUCAUCUGUUAGUAAUGCU 20 24162 CFTR-Intron10-5283 + AUAUCAUCUGUUAGUAAUGCU 21 24163 CFTR-Intron10-5284 + AAUAUCAUCUGUUAGUAAUGCU 22 24164 CFTR-Intron10-5285 + UAAUAUCAUCUGUUAGUAAUGCU 23 24165 CFTR-Intron10-5286 + AUAAUAUCAUCUGUUAGUAAUGCU 24 24166 CFTR-Intron10-5287 + AGCAGAUUUGGGUCUGCU 18 24167 CFTR-Intron10-5288 + CAGCAGAUUUGGGUCUGCU 19 24168 CFTR-Intron10-5289 + CCAGCAGAUUUGGGUCUGCU 20 24169 CFTR-Intron10-5290 + GCCAGCAGAUUUGGGUCUGCU 21 24170 CFTR-Intron10-5291 + UGCCAGCAGAUUUGGGUCUGCU 22 24171 CFTR-Intron10-5292 + GUGCCAGCAGAUUUGGGUCUGCU 23 24172 CFTR-Intron10-5293 + GGUGCCAGCAGAUUUGGGUCUGCU 24 24173 CFTR-Intron10-5294 + AUAUAGAGAGAAACAUCU 18 24174 CFTR-Intron10-5295 + UAUAUAGAGAGAAACAUCU 19 24175 CFTR-Intron10-5296 + AUAUAUAGAGAGAAACAUCU 20 24176 CFTR-Intron10-5297 + UAUAUAUAGAGAGAAACAUCU 21 24177 CFTR-Intron10-5298 + AUAUAUAUAGAGAGAAACAUCU 22 24178 CFTR-Intron10-5299 + UAUAUAUAUAGAGAGAAACAUCU 23 24179 CFTR-Intron10-5300 + UUAUAUAUAUAGAGAGAAACAUCU 24 24180 CFTR-Intron10-5301 + AUAGAGAGAAACAUCUCU 18 24181 CFTR-Intron10-5302 + UAUAGAGAGAAACAUCUCU 19 24182 CFTR-Intron10-1365 + AUAUAGAGAGAAACAUCUCU 20 20249 CFTR-Intron10-5303 + UAUAUAGAGAGAAACAUCUCU 21 24183 CFTR-Intron10-5304 + AUAUAUAGAGAGAAACAUCUCU 22 24184 CFTR-Intron10-5305 + UAUAUAUAGAGAGAAACAUCUCU 23 24185 CFTR-Intron10-5306 + AUAUAUAUAGAGAGAAACAUCUCU 24 24186 CFTR-Intron10-5307 + AUUAAUUUUAAAAAUUCU 18 24187 CFTR-Intron10-5308 + AAUUAAUUUUAAAAAUUCU 19 24188 CFTR-Intron10-5309 + GAAUUAAUUUUAAAAAUUCU 20 24189 CFTR-Intron10-5310 + AGAAUUAAUUUUAAAAAUUCU 21 24190 CFTR-Intron10-5311 + CAGAAUUAAUUUUAAAAAUUCU 22 24191 CFTR-Intron10-5312 + GCAGAAUUAAUUUUAAAAAUUCU 23 24192 CFTR-Intron10-5313 + CGCAGAAUUAAUUUUAAAAAUUCU 24 24193 CFTR-Intron10-5314 + UAAUUUGAACAACAUUCU 18 24194 CFTR-Intron10-5315 + AUAAUUUGAACAACAUUCU 19 24195 CFTR-Intron10-527 + AAUAAUUUGAACAACAUUCU 20 19413 CFTR-Intron10-5316 + AAAUAAUUUGAACAACAUUCU 21 24196 CFTR-Intron10-5317 + GAAAUAAUUUGAACAACAUUCU 22 24197 CFTR-Intron10-5318 + AGAAAUAAUUUGAACAACAUUCU 23 24198 CFTR-Intron10-5319 + UAGAAAUAAUUUGAACAACAUUCU 24 24199 CFTR-Intron10-5320 + UUAGUAAACUCCGUUUCU 18 24200 CFTR-Intron10-5321 + GUUAGUAAACUCCGUUUCU 19 24201 CFTR-Intron10-5322 + AGUUAGUAAACUCCGUUUCU 20 24202 CFTR-Intron10-5323 + GAGUUAGUAAACUCCGUUUCU 21 24203 CFTR-Intron10-5324 + UGAGUUAGUAAACUCCGUUUCU 22 24204 CFTR-Intron10-5325 + UUGAGUUAGUAAACUCCGUUUCU 23 24205 CFTR-Intron10-5326 + AUUGAGUUAGUAAACUCCGUUUCU 24 24206 CFTR-Intron10-5327 + CCUGACAAUAAGAAAAGU 18 24207 CFTR-Intron10-5328 + UCCUGACAAUAAGAAAAGU 19 24208 CFTR-Intron10-5329 + GUCCUGACAAUAAGAAAAGU 20 24209 CFTR-Intron10-5330 + UGUCCUGACAAUAAGAAAAGU 21 24210 CFTR-Intron10-5331 + AUGUCCUGACAAUAAGAAAAGU 22 24211 CFTR-Intron10-5332 + UAUGUCCUGACAAUAAGAAAAGU 23 24212 CFTR-Intron10-5333 + AUAUGUCCUGACAAUAAGAAAAGU 24 24213 CFTR-Intron10-5334 + AGUGCUAGGAUUACAAGU 18 24214 CFTR-Intron10-5335 + AAGUGCUAGGAUUACAAGU 19 24215 CFTR-Intron10-5336 + AAAGUGCUAGGAUUACAAGU 20 24216 CFTR-Intron10-5337 + AAAAGUGCUAGGAUUACAAGU 21 24217 CFTR-Intron10-5338 + CAAAAGUGCUAGGAUUACAAGU 22 24218 CFTR-Intron10-5339 + CCAAAAGUGCUAGGAUUACAAGU 23 24219 CFTR-Intron10-5340 + UCCAAAAGUGCUAGGAUUACAAGU 24 24220 CFTR-Intron10-5341 + AGGAAAUGGGGUAUAAGU 18 24221 CFTR-Intron10-5342 + AAGGAAAUGGGGUAUAAGU 19 24222 CFTR-Intron10-5343 + AAAGGAAAUGGGGUAUAAGU 20 24223 CFTR-Intron10-5344 + CAAAGGAAAUGGGGUAUAAGU 21 24224 CFTR-Intron10-5345 + ACAAAGGAAAUGGGGUAUAAGU 22 24225 CFTR-Intron10-5346 + AACAAAGGAAAUGGGGUAUAAGU 23 24226 CFTR-Intron10-5347 + AAACAAAGGAAAUGGGGUAUAAGU 24 24227 CFTR-Intron10-5348 + ACAGAAAUAUUCAGCAGU 18 24228 CFTR-Intron10-5349 + GACAGAAAUAUUCAGCAGU 19 24229 CFTR-Intron10-5350 + AGACAGAAAUAUUCAGCAGU 20 24230 CFTR-Intron10-5351 + GAGACAGAAAUAUUCAGCAGU 21 24231 CFTR-Intron10-5352 + AGAGACAGAAAUAUUCAGCAGU 22 24232 CFTR-Intron10-5353 + GAGAGACAGAAAUAUUCAGCAGU 23 24233 CFTR-Intron10-5354 + GGAGAGACAGAAAUAUUCAGCAGU 24 24234 CFTR-Intron10-5355 + AAAGUUGUCCAAGAUAGU 18 24235 CFTR-Intron10-5356 + GAAAGUUGUCCAAGAUAGU 19 24236 CFTR-Intron10-120 + GGAAAGUUGUCCAAGAUAGU 20 19006 CFTR-Intron10-5357 + UGGAAAGUUGUCCAAGAUAGU 21 24237 CFTR-Intron10-5358 + AUGGAAAGUUGUCCAAGAUAGU 22 24238 CFTR-Intron10-5359 + UAUGGAAAGUUGUCCAAGAUAGU 23 24239 CFTR-Intron10-5360 + AUAUGGAAAGUUGUCCAAGAUAGU 24 24240 CFTR-Intron10-5361 + CUUUAUCAACAUGAAGGU 18 24241 CFTR-Intron10-5362 + CCUUUAUCAACAUGAAGGU 19 24242 CFTR-Intron10-5363 + CCCUUUAUCAACAUGAAGGU 20 24243 CFTR-Intron10-5364 + ACCCUUUAUCAACAUGAAGGU 21 24244 CFTR-Intron10-5365 + GACCCUUUAUCAACAUGAAGGU 22 24245 CFTR-Intron10-5366 + UGACCCUUUAUCAACAUGAAGGU 23 24246 CFTR-Intron10-5367 + UUGACCCUUUAUCAACAUGAAGGU 24 24247 CFTR-Intron10-5368 + UGAGGGUCUCUCUAAGGU 18 24248 CFTR-Intron10-5369 + GUGAGGGUCUCUCUAAGGU 19 24249 CFTR-Intron10-5370 + GGUGAGGGUCUCUCUAAGGU 20 24250 CFTR-Intron10-5371 + GGGUGAGGGUCUCUCUAAGGU 21 24251 CFTR-Intron10-5372 + GGGGUGAGGGUCUCUCUAAGGU 22 24252 CFTR-Intron10-5373 + AGGGGUGAGGGUCUCUCUAAGGU 23 24253 CFTR-Intron10-5374 + AAGGGGUGAGGGUCUCUCUAAGGU 24 24254 CFTR-Intron10-5375 + UUACAUAAAAAGAGAGGU 18 24255 CFTR-Intron10-5376 + GUUACAUAAAAAGAGAGGU 19 24256 CFTR-Intron10-535 + UGUUACAUAAAAAGAGAGGU 20 19421 CFTR-Intron10-5377 + UUGUUACAUAAAAAGAGAGGU 21 24257 CFTR-Intron10-5378 + AUUGUUACAUAAAAAGAGAGGU 22 24258 CFTR-Intron10-5379 + UAUUGUUACAUAAAAAGAGAGGU 23 24259 CFTR-Intron10-5380 + AUAUUGUUACAUAAAAAGAGAGGU 24 24260 CFTR-Intron10-5381 + GCGGGCGGAUCACGAGGU 18 24261 CFTR-Intron10-5382 + GGCGGGCGGAUCACGAGGU 19 24262 CFTR-Intron10-5383 + AGGCGGGCGGAUCACGAGGU 20 24263 CFTR-Intron10-5384 + GAGGCGGGCGGAUCACGAGGU 21 24264 CFTR-Intron10-5385 + CGAGGCGGGCGGAUCACGAGGU 22 24265 CFTR-Intron10-5386 + CCGAGGCGGGCGGAUCACGAGGU 23 24266 CFTR-Intron10-5387 + GCCGAGGCGGGCGGAUCACGAGGU 24 24267 CFTR-Intron10-5388 + UAUAUUCUUUUAUGUGGU 18 24268 CFTR-Intron10-5389 + AUAUAUUCUUUUAUGUGGU 19 24269 CFTR-Intron10-5390 + AAUAUAUUCUUUUAUGUGGU 20 24270 CFTR-Intron10-5391 + GAAUAUAUUCUUUUAUGUGGU 21 24271 CFTR-Intron10-5392 + CGAAUAUAUUCUUUUAUGUGGU 22 24272 CFTR-Intron10-5393 + ACGAAUAUAUUCUUUUAUGUGGU 23 24273 CFTR-Intron10-5394 + CACGAAUAUAUUCUUUUAUGUGGU 24 24274 CFTR-Intron10-5395 + AAAAGCUGUUUCGUAUGU 18 24275 CFTR-Intron10-5396 + UAAAAGCUGUUUCGUAUGU 19 24276 CFTR-Intron10-539 + UUAAAAGCUGUUUCGUAUGU 20 19425 CFTR-Intron10-5397 + UUUAAAAGCUGUUUCGUAUGU 21 24277 CFTR-Intron10-5398 + UUUUAAAAGCUGUUUCGUAUGU 22 24278 CFTR-Intron10-5399 + GUUUUAAAAGCUGUUUCGUAUGU 23 24279 CFTR-Intron10-5400 + UGUUUUAAAAGCUGUUUCGUAUGU 24 24280 CFTR-Intron10-5401 + AUCUGUUAGUAAUGCUGU 18 24281 CFTR-Intron10-5402 + CAUCUGUUAGUAAUGCUGU 19 24282 CFTR-Intron10-540 + UCAUCUGUUAGUAAUGCUGU 20 19426 CFTR-Intron10-5403 + AUCAUCUGUUAGUAAUGCUGU 21 24283 CFTR-Intron10-5404 + UAUCAUCUGUUAGUAAUGCUGU 22 24284 CFTR-Intron10-5405 + AUAUCAUCUGUUAGUAAUGCUGU 23 24285 CFTR-Intron10-5406 + AAUAUCAUCUGUUAGUAAUGCUGU 24 24286 CFTR-Intron10-5407 + AUAGAGACAAGGUGGUGU 18 24287 CFTR-Intron10-5408 + AAUAGAGACAAGGUGGUGU 19 24288 CFTR-Intron10-5409 + UAAUAGAGACAAGGUGGUGU 20 24289 CFTR-Intron10-5410 + AUAAUAGAGACAAGGUGGUGU 21 24290 CFTR-Intron10-5411 + AAUAAUAGAGACAAGGUGGUGU 22 24291 CFTR-Intron10-5412 + CAAUAAUAGAGACAAGGUGGUGU 23 24292 CFTR-Intron10-5413 + UCAAUAAUAGAGACAAGGUGGUGU 24 24293 CFTR-Intron10-5414 + GAAAGAAAAUGUUUUUGU 18 24294 CFTR-Intron10-5415 + AGAAAGAAAAUGUUUUUGU 19 24295 CFTR-Intron10-5416 + AAGAAAGAAAAUGUUUUUGU 20 24296 CFTR-Intron10-5417 + UAAGAAAGAAAAUGUUUUUGU 21 24297 CFTR-Intron10-5418 + UUAAGAAAGAAAAUGUUUUUGU 22 24298 CFTR-Intron10-5419 + UUUAAGAAAGAAAAUGUUUUUGU 23 24299 CFTR-Intron10-5420 + UUUUAAGAAAGAAAAUGUUUUUGU 24 24300 CFTR-Intron10-5421 + UGGCUUAACCCAUCUAUU 18 24301 CFTR-Intron10-5422 + UUGGCUUAACCCAUCUAUU 19 24302 CFTR-Intron10-5423 + GUUGGCUUAACCCAUCUAUU 20 24303 CFTR-Intron10-5424 + AGUUGGCUUAACCCAUCUAUU 21 24304 CFTR-Intron10-5425 + CAGUUGGCUUAACCCAUCUAUU 22 24305 CFTR-Intron10-5426 + UCAGUUGGCUUAACCCAUCUAUU 23 24306 CFTR-Intron10-5427 + UUCAGUUGGCUUAACCCAUCUAUU 24 24307 CFTR-Intron10-5428 + AUAAUUCUAGAAAGUAUU 18 24308 CFTR-Intron10-5429 + UAUAAUUCUAGAAAGUAUU 19 24309 CFTR-Intron10-5430 + GUAUAAUUCUAGAAAGUAUU 20 24310 CFTR-Intron10-5431 + GGUAUAAUUCUAGAAAGUAUU 21 24311 CFTR-Intron10-5432 + CGGUAUAAUUCUAGAAAGUAUU 22 24312 CFTR-Intron10-5433 + UCGGUAUAAUUCUAGAAAGUAUU 23 24313 CFTR-Intron10-5434 + UUCGGUAUAAUUCUAGAAAGUAUU 24 24314 CFTR-Intron10-5435 + UUUAUUUAUUUAUUUAUU 18 24315 CFTR-Intron10-5436 + AUUUAUUUAUUUAUUUAUU 19 24316 CFTR-Intron10-5437 + UAUUUAUUUAUUUAUUUAUU 20 24317 CFTR-Intron10-5438 + UUAUUUAUUUAUUUAUUUAUU 21 24318 CFTR-Intron10-5439 + UUUAUUUAUUUAUUUAUUUAUU 22 24319 CFTR-Intron10-5440 + AUUUAUUUAUUUAUUUAUUUAUU 23 24320 CFTR-Intron10-5441 + UAUUUAUUUAUUUAUUUAUUUAUU 24 24321 CFTR-Intron10-5442 + UUUGCUGAUUGCUUUAUU 18 24322 CFTR-Intron10-5443 + AUUUGCUGAUUGCUUUAUU 19 24323 CFTR-Intron10-5444 + AAUUUGCUGAUUGCUUUAUU 20 24324 CFTR-Intron10-5445 + AAAUUUGCUGAUUGCUUUAUU 21 24325 CFTR-Intron10-5446 + GAAAUUUGCUGAUUGCUUUAUU 22 24326 CFTR-Intron10-5447 + GGAAAUUUGCUGAUUGCUUUAUU 23 24327 CFTR-Intron10-5448 + AGGAAAUUUGCUGAUUGCUUUAUU 24 24328 CFTR-Intron10-5449 + CCUGUAAUCCCAACACUU 18 24329 CFTR-Intron10-5450 + GCCUGUAAUCCCAACACUU 19 24330 CFTR-Intron10-1391 + UGCCUGUAAUCCCAACACUU 20 20275 CFTR-Intron10-5451 + AUGCCUGUAAUCCCAACACUU 21 24331 CFTR-Intron10-5452 + CAUGCCUGUAAUCCCAACACUU 22 24332 CFTR-Intron10-5453 + UCAUGCCUGUAAUCCCAACACUU 23 24333 CFTR-Intron10-5454 + CUCAUGCCUGUAAUCCCAACACUU 24 24334 CFTR-Intron10-5455 + CCUAUAAACCCAGCACUU 18 24335 CFTR-Intron10-5456 + GCCUAUAAACCCAGCACUU 19 24336 CFTR-Intron10-1392 + UGCCUAUAAACCCAGCACUU 20 20276 CFTR-Intron10-5457 + AUGCCUAUAAACCCAGCACUU 21 24337 CFTR-Intron10-5458 + CAUGCCUAUAAACCCAGCACUU 22 24338 CFTR-Intron10-5459 + UCAUGCCUAUAAACCCAGCACUU 23 24339 CFTR-Intron10-5460 + CUCAUGCCUAUAAACCCAGCACUU 24 24340 CFTR-Intron10-5461 + CCUGUAAUCCCAGCACUU 18 24341 CFTR-Intron10-5462 + GCCUGUAAUCCCAGCACUU 19 24342 CFTR-Intron10-1393 + CGCCUGUAAUCCCAGCACUU 20 20277 CFTR-Intron10-5463 + ACGCCUGUAAUCCCAGCACUU 21 24343 CFTR-Intron10-5464 + CACGCCUGUAAUCCCAGCACUU 22 24344 CFTR-Intron10-5465 + UCACGCCUGUAAUCCCAGCACUU 23 24345 CFTR-Intron10-5466 + CUCACGCCUGUAAUCCCAGCACUU 24 24346 CFTR-Intron10-5467 + GAACCAUUUUAUAGACUU 18 24347 CFTR-Intron10-5468 + GGAACCAUUUUAUAGACUU 19 24348 CFTR-Intron10-5469 + AGGAACCAUUUUAUAGACUU 20 24349 CFTR-Intron10-5470 + AAGGAACCAUUUUAUAGACUU 21 24350 CFTR-Intron10-5471 + CAAGGAACCAUUUUAUAGACUU 22 24351 CFTR-Intron10-5472 + ACAAGGAACCAUUUUAUAGACUU 23 24352 CFTR-Intron10-5473 + AACAAGGAACCAUUUUAUAGACUU 24 24353 CFTR-Intron10-5474 + CUGUAGUCCCAGCUACUU 18 24354 CFTR-Intron10-5475 + CCUGUAGUCCCAGCUACUU 19 24355 CFTR-Intron10-720 + GCCUGUAGUCCCAGCUACUU 20 19606 CFTR-Intron10-5476 + CGCCUGUAGUCCCAGCUACUU 21 24356 CFTR-Intron10-5477 + GCGCCUGUAGUCCCAGCUACUU 22 24357 CFTR-Intron10-5478 + GGCGCCUGUAGUCCCAGCUACUU 23 24358 CFTR-Intron10-5479 + GGGCGCCUGUAGUCCCAGCUACUU 24 24359 CFTR-Intron10-5480 + UGCCUGUAGUCCCAGCUACUU 21 24360 CFTR-Intron10-5481 + GUGCCUGUAGUCCCAGCUACUU 22 24361 CFTR-Intron10-5482 + CGUGCCUGUAGUCCCAGCUACUU 23 24362 CFTR-Intron10-5483 + GCGUGCCUGUAGUCCCAGCUACUU 24 24363 CFTR-Intron10-5484 + AAUUUAUUUCUCACAGUU 18 24364 CFTR-Intron10-5485 + GAAUUUAUUUCUCACAGUU 19 24365 CFTR-Intron10-5486 + GGAAUUUAUUUCUCACAGUU 20 24366 CFTR-Intron10-5487 + AGGAAUUUAUUUCUCACAGUU 21 24367 CFTR-Intron10-5488 + CAGGAAUUUAUUUCUCACAGUU 22 24368 CFTR-Intron10-5489 + ACAGGAAUUUAUUUCUCACAGUU 23 24369 CFTR-Intron10-5490 + AACAGGAAUUUAUUUCUCACAGUU 24 24370 CFTR-Intron10-5491 + CUUGACAUCAGUUGGGUU 18 24371 CFTR-Intron10-5492 + GCUUGACAUCAGUUGGGUU 19 24372 CFTR-Intron10-5493 + UGCUUGACAUCAGUUGGGUU 20 24373 CFTR-Intron10-5494 + CUGCUUGACAUCAGUUGGGUU 21 24374 CFTR-Intron10-5495 + UCUGCUUGACAUCAGUUGGGUU 22 24375 CFTR-Intron10-5496 + UUCUGCUUGACAUCAGUUGGGUU 23 24376 CFTR-Intron10-5497 + CUUCUGCUUGACAUCAGUUGGGUU 24 24377 CFTR-Intron10-5498 + AAAAUAUACCCAAAAUUU 18 24378 CFTR-Intron10-5499 + UAAAAUAUACCCAAAAUUU 19 24379 CFTR-Intron10-5500 + AUAAAAUAUACCCAAAAUUU 20 24380 CFTR-Intron10-5501 + UAUAAAAUAUACCCAAAAUUU 21 24381 CFTR-Intron10-5502 + AUAUAAAAUAUACCCAAAAUUU 22 24382 CFTR-Intron10-5503 + AAUAUAAAAUAUACCCAAAAUUU 23 24383 CFTR-Intron10-5504 + AAAUAUAAAAUAUACCCAAAAUUU 24 24384 CFTR-Intron10-5505 + ACGAAUUGGUACAAAUUU 18 24385 CFTR-Intron10-5506 + UACGAAUUGGUACAAAUUU 19 24386 CFTR-Intron10-5507 + GUACGAAUUGGUACAAAUUU 20 24387 CFTR-Intron10-5508 + AGUACGAAUUGGUACAAAUUU 21 24388 CFTR-Intron10-5509 + GAGUACGAAUUGGUACAAAUUU 22 24389 CFTR-Intron10-5510 + UGAGUACGAAUUGGUACAAAUUU 23 24390 CFTR-Intron10-5511 + AUGAGUACGAAUUGGUACAAAUUU 24 24391 CFTR-Intron10-5512 + CCCUAUUAUUCAACAUUU 18 24392 CFTR-Intron10-5513 + CCCCUAUUAUUCAACAUUU 19 24393 CFTR-Intron10-5514 + ACCCCUAUUAUUCAACAUUU 20 24394 CFTR-Intron10-5515 + AACCCCUAUUAUUCAACAUUU 21 24395 CFTR-Intron10-5516 + AAACCCCUAUUAUUCAACAUUU 22 24396 CFTR-Intron10-5517 + CAAACCCCUAUUAUUCAACAUUU 23 24397 CFTR-Intron10-5518 + UCAAACCCCUAUUAUUCAACAUUU 24 24398 CFTR-Intron10-5519 + UCUAUUCAAAAAAUAUUU 18 24399 CFTR-Intron10-5520 + AUCUAUUCAAAAAAUAUUU 19 24400 CFTR-Intron10-5521 + AAUCUAUUCAAAAAAUAUUU 20 24401 CFTR-Intron10-5522 + UAAUCUAUUCAAAAAAUAUUU 21 24402 CFTR-Intron10-5523 + CUAAUCUAUUCAAAAAAUAUUU 22 24403 CFTR-Intron10-5524 + GCUAAUCUAUUCAAAAAAUAUUU 23 24404 CFTR-Intron10-5525 + AGCUAAUCUAUUCAAAAAAUAUUU 24 24405 CFTR-Intron10-5526 + CGAGUUAUCUCCGUAUUU 18 24406 CFTR-Intron10-5527 + ACGAGUUAUCUCCGUAUUU 19 24407 CFTR-Intron10-5528 + CACGAGUUAUCUCCGUAUUU 20 24408 CFTR-Intron10-5529 + UCACGAGUUAUCUCCGUAUUU 21 24409 CFTR-Intron10-5530 + GUCACGAGUUAUCUCCGUAUUU 22 24410 CFTR-Intron10-5531 + AGUCACGAGUUAUCUCCGUAUUU 23 24411 CFTR-Intron10-5532 + AAGUCACGAGUUAUCUCCGUAUUU 24 24412 CFTR-Intron10-5533 + CUGUAAUCCCAACACUUU 18 24413 CFTR-Intron10-5534 + CCUGUAAUCCCAACACUUU 19 24414 CFTR-Intron10-722 + GCCUGUAAUCCCAACACUUU 20 19608 CFTR-Intron10-5535 + UGCCUGUAAUCCCAACACUUU 21 24415 CFTR-Intron10-5536 + AUGCCUGUAAUCCCAACACUUU 22 24416 CFTR-Intron10-5537 + CAUGCCUGUAAUCCCAACACUUU 23 24417 CFTR-Intron10-5538 + UCAUGCCUGUAAUCCCAACACUUU 24 24418 CFTR-Intron10-5539 + CUAUAAACCCAGCACUUU 18 24419 CFTR-Intron10-5540 + CCUAUAAACCCAGCACUUU 19 24420 CFTR-Intron10-723 + GCCUAUAAACCCAGCACUUU 20 19609 CFTR-Intron10-5541 + UGCCUAUAAACCCAGCACUUU 21 24421 CFTR-Intron10-5542 + AUGCCUAUAAACCCAGCACUUU 22 24422 CFTR-Intron10-5543 + CAUGCCUAUAAACCCAGCACUUU 23 24423 CFTR-Intron10-5544 + UCAUGCCUAUAAACCCAGCACUUU 24 24424 CFTR-Intron10-5545 + CUGUAAUCCCAGCACUUU 18 24425 CFTR-Intron10-5546 + CCUGUAAUCCCAGCACUUU 19 24426 CFTR-Intron10-724 + GCCUGUAAUCCCAGCACUUU 20 19610 CFTR-Intron10-5547 + CGCCUGUAAUCCCAGCACUUU 21 24427 CFTR-Intron10-5548 + ACGCCUGUAAUCCCAGCACUUU 22 24428 CFTR-Intron10-5549 + CACGCCUGUAAUCCCAGCACUUU 23 24429 CFTR-Intron10-5550 + UCACGCCUGUAAUCCCAGCACUUU 24 24430 CFTR-Intron10-5551 + UGAUAAAUAAUUGCCUUU 18 24431 CFTR-Intron10-5552 + UUGAUAAAUAAUUGCCUUU 19 24432 CFTR-Intron10-5553 + AUUGAUAAAUAAUUGCCUUU 20 24433 CFTR-Intron10-5554 + UAUUGAUAAAUAAUUGCCUUU 21 24434 CFTR-Intron10-5555 + AUAUUGAUAAAUAAUUGCCUUU 22 24435 CFTR-Intron10-5556 + GAUAUUGAUAAAUAAUUGCCUUU 23 24436 CFTR-Intron10-5557 + AGAUAUUGAUAAAUAAUUGCCUUU 24 24437 CFTR-Intron10-5558 + AAAUAAGCCUUAGUCUUU 18 24438 CFTR-Intron10-5559 + GAAAUAAGCCUUAGUCUUU 19 24439 CFTR-Intron10-5560 + AGAAAUAAGCCUUAGUCUUU 20 24440 CFTR-Intron10-5561 + GAGAAAUAAGCCUUAGUCUUU 21 24441 CFTR-Intron10-5562 + AGAGAAAUAAGCCUUAGUCUUU 22 24442 CFTR-Intron10-5563 + CAGAGAAAUAAGCCUUAGUCUUU 23 24443 CFTR-Intron10-5564 + CCAGAGAAAUAAGCCUUAGUCUUU 24 24444 CFTR-Intron10-5565 + AGAAAAUUUGUUUUCUUU 18 24445 CFTR-Intron10-5566 + AAGAAAAUUUGUUUUCUUU 19 24446 CFTR-Intron10-5567 + AAAGAAAAUUUGUUUUCUUU 20 24447 CFTR-Intron10-5568 + CAAAGAAAAUUUGUUUUCUUU 21 24448 CFTR-Intron10-5569 + ACAAAGAAAAUUUGUUUUCUUU 22 24449 CFTR-Intron10-5570 + AACAAAGAAAAUUUGUUUUCUUU 23 24450 CFTR-Intron10-5571 + AAACAAAGAAAAUUUGUUUUCUUU 24 24451 CFTR-Intron10-5572 + GAAAAAUAAUAACAUUUU 18 24452 CFTR-Intron10-5573 + AGAAAAAUAAUAACAUUUU 19 24453 CFTR-Intron10-5574 + AAGAAAAAUAAUAACAUUUU 20 24454 CFTR-Intron10-5575 + AAAGAAAAAUAAUAACAUUUU 21 24455 CFTR-Intron10-5576 + AAAAGAAAAAUAAUAACAUUUU 22 24456 CFTR-Intron10-5577 + UAAAAGAAAAAUAAUAACAUUUU 23 24457 CFTR-Intron10-5578 + AUAAAAGAAAAAUAAUAACAUUUU 24 24458 CFTR-Intron10-5579 + AUACAUACAUAUGAUUUU 18 24459 CFTR-Intron10-5580 + UAUACAUACAUAUGAUUUU 19 24460 CFTR-Intron10-5581 + AUAUACAUACAUAUGAUUUU 20 24461 CFTR-Intron10-5582 + UAUAUACAUACAUAUGAUUUU 21 24462 CFTR-Intron10-5583 + AUAUAUACAUACAUAUGAUUUU 22 24463 CFTR-Intron10-5584 + CAUAUAUACAUACAUAUGAUUUU 23 24464 CFTR-Intron10-5585 + ACAUAUAUACAUACAUAUGAUUUU 24 24465 CFTR-Intron10-5586 + CACCAAUUUUUUUUUUUU 18 24466 CFTR-Intron10-5587 + ACACCAAUUUUUUUUUUUU 19 24467 CFTR-Intron10-5588 + AACACCAAUUUUUUUUUUUU 20 24468 CFTR-Intron10-5589 + AAACACCAAUUUUUUUUUUUU 21 24469 CFTR-Intron10-5590 + CAAACACCAAUUUUUUUUUUUU 22 24470 CFTR-Intron10-5591 + GCAAACACCAAUUUUUUUUUUUU 23 24471 CFTR-Intron10-5592 + UGCAAACACCAAUUUUUUUUUUUU 24 24472 CFTR-Intron10-5593 UAAAAAUGUUAAUGAAAA 18 24473 CFTR-Intron10-5594 GUAAAAAUGUUAAUGAAAA 19 24474 CFTR-Intron10-5595 GGUAAAAAUGUUAAUGAAAA 20 24475 CFTR-Intron10-5596 AGGUAAAAAUGUUAAUGAAAA 21 24476 CFTR-Intron10-5597 UAGGUAAAAAUGUUAAUGAAAA 22 24477 CFTR-Intron10-5598 GUAGGUAAAAAUGUUAAUGAAAA 23 24478 CFTR-Intron10-5599 UGUAGGUAAAAAUGUUAAUGAAAA 24 24479 CFTR-Intron10-5600 AUUUAUUAAAAUUUAAAA 18 24480 CFTR-Intron10-5601 UAUUUAUUAAAAUUUAAAA 19 24481 CFTR-Intron10-5602 UUAUUUAUUAAAAUUUAAAA 20 24482 CFTR-Intron10-5603 AUUAUUUAUUAAAAUUUAAAA 21 24483 CFTR-Intron10-5604 UAUUAUUUAUUAAAAUUUAAAA 22 24484 CFTR-Intron10-5605 AUAUUAUUUAUUAAAAUUUAAAA 23 24485 CFTR-Intron10-5606 GAUAUUAUUUAUUAAAAUUUAAAA 24 24486 CFTR-Intron10-5607 CGAAUAAUCUAAGACAAA 18 24487 CFTR-Intron10-5608 CCGAAUAAUCUAAGACAAA 19 24488 CFTR-Intron10-5609 ACCGAAUAAUCUAAGACAAA 20 24489 CFTR-Intron10-5610 UACCGAAUAAUCUAAGACAAA 21 24490 CFTR-Intron10-5611 AUACCGAAUAAUCUAAGACAAA 22 24491 CFTR-Intron10-5612 UAUACCGAAUAAUCUAAGACAAA 23 24492 CFTR-Intron10-5613 UUAUACCGAAUAAUCUAAGACAAA 24 24493 CFTR-Intron10-5614 GCCUAUUUGACAUCCAAA 18 24494 CFTR-Intron10-5615 UGCCUAUUUGACAUCCAAA 19 24495 CFTR-Intron10-5616 AUGCCUAUUUGACAUCCAAA 20 24496 CFTR-Intron10-5617 AAUGCCUAUUUGACAUCCAAA 21 24497 CFTR-Intron10-5618 AAAUGCCUAUUUGACAUCCAAA 22 24498 CFTR-Intron10-5619 GAAAUGCCUAUUUGACAUCCAAA 23 24499 CFTR-Intron10-5620 UGAAAUGCCUAUUUGACAUCCAAA 24 24500 CFTR-Intron10-5621 GACAAACAGAAAAAGAAA 18 24501 CFTR-Intron10-5622 AGACAAACAGAAAAAGAAA 19 24502 CFTR-Intron10-5623 AAGACAAACAGAAAAAGAAA 20 24503 CFTR-Intron10-5624 UAAGACAAACAGAAAAAGAAA 21 24504 CFTR-Intron10-5625 CUAAGACAAACAGAAAAAGAAA 22 24505 CFTR-Intron10-5626 UCUAAGACAAACAGAAAAAGAAA 23 24506 CFTR-Intron10-5627 AUCUAAGACAAACAGAAAAAGAAA 24 24507 CFTR-Intron10-5628 AUCUAAGACAAACAGAAA 18 24508 CFTR-Intron10-5629 AAUCUAAGACAAACAGAAA 19 24509 CFTR-Intron10-5630 UAAUCUAAGACAAACAGAAA 20 24510 CFTR-Intron10-5631 AUAAUCUAAGACAAACAGAAA 21 24511 CFTR-Intron10-5632 AAUAAUCUAAGACAAACAGAAA 22 24512 CFTR-Intron10-5633 GAAUAAUCUAAGACAAACAGAAA 23 24513 CFTR-Intron10-5634 CGAAUAAUCUAAGACAAACAGAAA 24 24514 CFTR-Intron10-5635 GGCACCAUUCACAGUAAA 18 24515 CFTR-Intron10-5636 UGGCACCAUUCACAGUAAA 19 24516 CFTR-Intron10-5637 CUGGCACCAUUCACAGUAAA 20 24517 CFTR-Intron10-5638 CCUGGCACCAUUCACAGUAAA 21 24518 CFTR-Intron10-5639 ACCUGGCACCAUUCACAGUAAA 22 24519 CFTR-Intron10-5640 UACCUGGCACCAUUCACAGUAAA 23 24520 CFTR-Intron10-5641 CUACCUGGCACCAUUCACAGUAAA 24 24521 CFTR-Intron10-5642 CCACUGGAGAGUUUUAAA 18 24522 CFTR-Intron10-5643 GCCACUGGAGAGUUUUAAA 19 24523 CFTR-Intron10-5644 GGCCACUGGAGAGUUUUAAA 20 24524 CFTR-Intron10-5645 AGGCCACUGGAGAGUUUUAAA 21 24525 CFTR-Intron10-5646 GAGGCCACUGGAGAGUUUUAAA 22 24526 CFTR-Intron10-5647 AGAGGCCACUGGAGAGUUUUAAA 23 24527 CFTR-Intron10-5648 UAGAGGCCACUGGAGAGUUUUAAA 24 24528 CFTR-Intron10-5649 UACAAAAAACACAAACAA 18 24529 CFTR-Intron10-5650 CUACAAAAAACACAAACAA 19 24530 CFTR-Intron10-5651 UCUACAAAAAACACAAACAA 20 24531 CFTR-Intron10-5652 CUCUACAAAAAACACAAACAA 21 24532 CFTR-Intron10-5653 CCUCUACAAAAAACACAAACAA 22 24533 CFTR-Intron10-5654 ACCUCUACAAAAAACACAAACAA 23 24534 CFTR-Intron10-5655 CACCUCUACAAAAAACACAAACAA 24 24535 CFTR-Intron10-5656 UAAAGACUGUUGUAACAA 18 24536 CFTR-Intron10-5657 AUAAAGACUGUUGUAACAA 19 24537 CFTR-Intron10-5658 UAUAAAGACUGUUGUAACAA 20 24538 CFTR-Intron10-5659 GUAUAAAGACUGUUGUAACAA 21 24539 CFTR-Intron10-5660 AGUAUAAAGACUGUUGUAACAA 22 24540 CFTR-Intron10-5661 CAGUAUAAAGACUGUUGUAACAA 23 24541 CFTR-Intron10-5662 CCAGUAUAAAGACUGUUGUAACAA 24 24542 CFTR-Intron10-5663 UAUUCUGUAGGGAGACAA 18 24543 CFTR-Intron10-5664 CUAUUCUGUAGGGAGACAA 19 24544 CFTR-Intron10-66 GCUAUUCUGUAGGGAGACAA 20 18952 CFTR-Intron10-5665 GGCUAUUCUGUAGGGAGACAA 21 24545 CFTR-Intron10-5666 AGGCUAUUCUGUAGGGAGACAA 22 24546 CFTR-Intron10-5667 UAGGCUAUUCUGUAGGGAGACAA 23 24547 CFTR-Intron10-5668 UUAGGCUAUUCUGUAGGGAGACAA 24 24548 CFTR-Intron10-5669 AUAGAUGGGUUAAGCCAA 18 24549 CFTR-Intron10-5670 AAUAGAUGGGUUAAGCCAA 19 24550 CFTR-Intron10-5671 UAAUAGAUGGGUUAAGCCAA 20 24551 CFTR-Intron10-5672 UUAAUAGAUGGGUUAAGCCAA 21 24552 CFTR-Intron10-5673 CUUAAUAGAUGGGUUAAGCCAA 22 24553 CFTR-Intron10-5674 UCUUAAUAGAUGGGUUAAGCCAA 23 24554 CFTR-Intron10-5675 CUCUUAAUAGAUGGGUUAAGCCAA 24 24555 CFTR-Intron10-5676 AGAAAGAAAAAACAGCAA 18 24556 CFTR-Intron10-5677 UAGAAAGAAAAAACAGCAA 19 24557 CFTR-Intron10-5678 UUAGAAAGAAAAAACAGCAA 20 24558 CFTR-Intron10-5679 AUUAGAAAGAAAAAACAGCAA 21 24559 CFTR-Intron10-5680 GAUUAGAAAGAAAAAACAGCAA 22 24560 CFTR-Intron10-5681 AGAUUAGAAAGAAAAAACAGCAA 23 24561 CFTR-Intron10-5682 UAGAUUAGAAAGAAAAAACAGCAA 24 24562 CFTR-Intron10-5683 ACUGUUGUAACAAAAGAA 18 24563 CFTR-Intron10-5684 GACUGUUGUAACAAAAGAA 19 24564 CFTR-Intron10-5685 AGACUGUUGUAACAAAAGAA 20 24565 CFTR-Intron10-5686 AAGACUGUUGUAACAAAAGAA 21 24566 CFTR-Intron10-5687 AAAGACUGUUGUAACAAAAGAA 22 24567 CFTR-Intron10-5688 UAAAGACUGUUGUAACAAAAGAA 23 24568 CFTR-Intron10-5689 AUAAAGACUGUUGUAACAAAAGAA 24 24569 CFTR-Intron10-5690 GAAGGAAAUGAGGAAGAA 18 24570 CFTR-Intron10-5691 AGAAGGAAAUGAGGAAGAA 19 24571 CFTR-Intron10-1105 AAGAAGGAAAUGAGGAAGAA 20 19990 CFTR-Intron10-5692 AAAGAAGGAAAUGAGGAAGAA 21 24572 CFTR-Intron10-5693 GAAAGAAGGAAAUGAGGAAGAA 22 24573 CFTR-Intron10-5694 AGAAAGAAGGAAAUGAGGAAGAA 23 24574 CFTR-Intron10-5695 AAGAAAGAAGGAAAUGAGGAAGAA 24 24575 CFTR-Intron10-5696 AAAGAGGGUUGAUAAGAA 18 24576 CFTR-Intron10-5697 GAAAGAGGGUUGAUAAGAA 19 24577 CFTR-Intron10-5698 GGAAAGAGGGUUGAUAAGAA 20 24578 CFTR-Intron10-5699 AGGAAAGAGGGUUGAUAAGAA 21 24579 CFTR-Intron10-5700 AAGGAAAGAGGGUUGAUAAGAA 22 24580 CFTR-Intron10-5701 AAAGGAAAGAGGGUUGAUAAGAA 23 24581 CFTR-Intron10-5702 UAAAGGAAAGAGGGUUGAUAAGAA 24 24582 CFTR-Intron10-5703 AUCACCUGAGCCUGAGAA 18 24583 CFTR-Intron10-5704 GAUCACCUGAGCCUGAGAA 19 24584 CFTR-Intron10-5705 GGAUCACCUGAGCCUGAGAA 20 24585 CFTR-Intron10-5706 AGGAUCACCUGAGCCUGAGAA 21 24586 CFTR-Intron10-5707 GAGGAUCACCUGAGCCUGAGAA 22 24587 CFTR-Intron10-5708 GGAGGAUCACCUGAGCCUGAGAA 23 24588 CFTR-Intron10-5709 GGGAGGAUCACCUGAGCCUGAGAA 24 24589 CFTR-Intron10-5710 UUUAAACACUUCUGAGAA 18 24590 CFTR-Intron10-5711 AUUUAAACACUUCUGAGAA 19 24591 CFTR-Intron10-5712 UAUUUAAACACUUCUGAGAA 20 24592 CFTR-Intron10-5713 AUAUUUAAACACUUCUGAGAA 21 24593 CFTR-Intron10-5714 AAUAUUUAAACACUUCUGAGAA 22 24594 CFTR-Intron10-5715 GAAUAUUUAAACACUUCUGAGAA 23 24595 CFTR-Intron10-5716 GGAAUAUUUAAACACUUCUGAGAA 24 24596 CFTR-Intron10-5717 AAGGAAUUUUAUAUAGAA 18 24597 CFTR-Intron10-5718 AAAGGAAUUUUAUAUAGAA 19 24598 CFTR-Intron10-5719 CAAAGGAAUUUUAUAUAGAA 20 24599 CFTR-Intron10-5720 ACAAAGGAAUUUUAUAUAGAA 21 24600 CFTR-Intron10-5721 UACAAAGGAAUUUUAUAUAGAA 22 24601 CFTR-Intron10-5722 GUACAAAGGAAUUUUAUAUAGAA 23 24602 CFTR-Intron10-5723 UGUACAAAGGAAUUUUAUAUAGAA 24 24603 CFTR-Intron10-5724 AAGUCUAGUUUCAAGGAA 18 24604 CFTR-Intron10-5725 CAAGUCUAGUUUCAAGGAA 19 24605 CFTR-Intron10-5726 ACAAGUCUAGUUUCAAGGAA 20 24606 CFTR-Intron10-5727 UACAAGUCUAGUUUCAAGGAA 21 24607 CFTR-Intron10-5728 GUACAAGUCUAGUUUCAAGGAA 22 24608 CFTR-Intron10-5729 UGUACAAGUCUAGUUUCAAGGAA 23 24609 CFTR-Intron10-5730 AUGUACAAGUCUAGUUUCAAGGAA 24 24610 CFTR-Intron10-5731 GAAGGAAGAAAGAAGGAA 18 24611 CFTR-Intron10-5732 GGAAGGAAGAAAGAAGGAA 19 24612 CFTR-Intron10-5733 AGGAAGGAAGAAAGAAGGAA 20 24613 CFTR-Intron10-5734 GAGGAAGGAAGAAAGAAGGAA 21 24614 CFTR-Intron10-5735 AGAGGAAGGAAGAAAGAAGGAA 22 24615 CFTR-Intron10-5736 GAGAGGAAGGAAGAAAGAAGGAA 23 24616 CFTR-Intron10-5737 AGAGAGGAAGGAAGAAAGAAGGAA 24 24617 CFTR-Intron10-5738 UUUUAGUAGUAUUAGGAA 18 24618 CFTR-Intron10-5739 CUUUUAGUAGUAUUAGGAA 19 24619 CFTR-Intron10-350 CCUUUUAGUAGUAUUAGGAA 20 19236 CFTR-Intron10-5740 GCCUUUUAGUAGUAUUAGGAA 21 24620 CFTR-Intron10-5741 UGCCUUUUAGUAGUAUUAGGAA 22 24621 CFTR-Intron10-5742 CUGCCUUUUAGUAGUAUUAGGAA 23 24622 CFTR-Intron10-5743 GCUGCCUUUUAGUAGUAUUAGGAA 24 24623 CFTR-Intron10-5744 UGAAAUUAGAAAGAAUAA 18 24624 CFTR-Intron10-5745 AUGAAAUUAGAAAGAAUAA 19 24625 CFTR-Intron10-5746 AAUGAAAUUAGAAAGAAUAA 20 24626 CFTR-Intron10-5747 GAAUGAAAUUAGAAAGAAUAA 21 24627 CFTR-Intron10-5748 AGAAUGAAAUUAGAAAGAAUAA 22 24628 CFTR-Intron10-5749 CAGAAUGAAAUUAGAAAGAAUAA 23 24629 CFTR-Intron10-5750 CCAGAAUGAAAUUAGAAAGAAUAA 24 24630 CFTR-Intron10-5751 AAAUAUAAGAUUGAAUAA 18 24631 CFTR-Intron10-5752 AAAAUAUAAGAUUGAAUAA 19 24632 CFTR-Intron10-5753 UAAAAUAUAAGAUUGAAUAA 20 24633 CFTR-Intron10-5754 CUAAAAUAUAAGAUUGAAUAA 21 24634 CFTR-Intron10-5755 GCUAAAAUAUAAGAUUGAAUAA 22 24635 CFTR-Intron10-5756 AGCUAAAAUAUAAGAUUGAAUAA 23 24636 CFTR-Intron10-5757 UAGCUAAAAUAUAAGAUUGAAUAA 24 24637 CFTR-Intron10-5758 CCCAUAAAUGUUGAAUAA 18 24638 CFTR-Intron10-5759 CCCCAUAAAUGUUGAAUAA 19 24639 CFTR-Intron10-5760 GCCCCAUAAAUGUUGAAUAA 20 24640 CFTR-Intron10-5761 AGCCCCAUAAAUGUUGAAUAA 21 24641 CFTR-Intron10-5762 GAGCCCCAUAAAUGUUGAAUAA 22 24642 CFTR-Intron10-5763 GGAGCCCCAUAAAUGUUGAAUAA 23 24643 CFTR-Intron10-5764 GGGAGCCCCAUAAAUGUUGAAUAA 24 24644 CFTR-Intron10-5765 AGCUUAUUCUUGUAAUAA 18 24645 CFTR-Intron10-5766 UAGCUUAUUCUUGUAAUAA 19 24646 CFTR-Intron10-5767 UUAGCUUAUUCUUGUAAUAA 20 24647 CFTR-Intron10-5768 UUUAGCUUAUUCUUGUAAUAA 21 24648 CFTR-Intron10-5769 UUUUAGCUUAUUCUUGUAAUAA 22 24649 CFTR-Intron10-5770 GUUUUAGCUUAUUCUUGUAAUAA 23 24650 CFTR-Intron10-5771 AGUUUUAGCUUAUUCUUGUAAUAA 24 24651 CFTR-Intron10-5772 CGUUUACUAGAAAGAUAA 18 24652 CFTR-Intron10-5773 CCGUUUACUAGAAAGAUAA 19 24653 CFTR-Intron10-69 GCCGUUUACUAGAAAGAUAA 20 18955 CFTR-Intron10-5774 UGCCGUUUACUAGAAAGAUAA 21 24654 CFTR-Intron10-5775 GUGCCGUUUACUAGAAAGAUAA 22 24655 CFTR-Intron10-5776 UGUGCCGUUUACUAGAAAGAUAA 23 24656 CFTR-Intron10-5777 AUGUGCCGUUUACUAGAAAGAUAA 24 24657 CFTR-Intron10-5778 CCUGCAAUUUCGAGAUAA 18 24658 CFTR-Intron10-5779 GCCUGCAAUUUCGAGAUAA 19 24659 CFTR-Intron10-5780 UGCCUGCAAUUUCGAGAUAA 20 24660 CFTR-Intron10-5781 UUGCCUGCAAUUUCGAGAUAA 21 24661 CFTR-Intron10-5782 GUUGCCUGCAAUUUCGAGAUAA 22 24662 CFTR-Intron10-5783 AGUUGCCUGCAAUUUCGAGAUAA 23 24663 CFTR-Intron10-5784 CAGUUGCCUGCAAUUUCGAGAUAA 24 24664 CFTR-Intron10-5785 AGAUUAGUGUCUUUAUAA 18 24665 CFTR-Intron10-5786 GAGAUUAGUGUCUUUAUAA 19 24666 CFTR-Intron10-5787 UGAGAUUAGUGUCUUUAUAA 20 24667 CFTR-Intron10-5788 AUGAGAUUAGUGUCUUUAUAA 21 24668 CFTR-Intron10-5789 AAUGAGAUUAGUGUCUUUAUAA 22 24669 CFTR-Intron10-5790 AAAUGAGAUUAGUGUCUUUAUAA 23 24670 CFTR-Intron10-5791 UAAAUGAGAUUAGUGUCUUUAUAA 24 24671 CFTR-Intron10-5792 UGACCUAAGAUAUCCUAA 18 24672 CFTR-Intron10-5793 UUGACCUAAGAUAUCCUAA 19 24673 CFTR-Intron10-358 UUUGACCUAAGAUAUCCUAA 20 19244 CFTR-Intron10-5794 CUUUGACCUAAGAUAUCCUAA 21 24674 CFTR-Intron10-5795 UCUUUGACCUAAGAUAUCCUAA 22 24675 CFTR-Intron10-5796 CUCUUUGACCUAAGAUAUCCUAA 23 24676 CFTR-Intron10-5797 CCUCUUUGACCUAAGAUAUCCUAA 24 24677 CFTR-Intron10-5798 GGCUGGAUAAGAUUCUAA 18 24678 CFTR-Intron10-5799 GGGCUGGAUAAGAUUCUAA 19 24679 CFTR-Intron10-71 GGGGCUGGAUAAGAUUCUAA 20 18957 CFTR-Intron10-5800 UGGGGCUGGAUAAGAUUCUAA 21 24680 CFTR-Intron10-5801 AUGGGGCUGGAUAAGAUUCUAA 22 24681 CFTR-Intron10-5802 GAUGGGGCUGGAUAAGAUUCUAA 23 24682 CFTR-Intron10-5803 AGAUGGGGCUGGAUAAGAUUCUAA 24 24683 CFTR-Intron10-5804 AGUUUUAAACAGAAGUAA 18 24684 CFTR-Intron10-5805 GAGUUUUAAACAGAAGUAA 19 24685 CFTR-Intron10-5806 AGAGUUUUAAACAGAAGUAA 20 24686 CFTR-Intron10-5807 GAGAGUUUUAAACAGAAGUAA 21 24687 CFTR-Intron10-5808 GGAGAGUUUUAAACAGAAGUAA 22 24688 CFTR-Intron10-5809 UGGAGAGUUUUAAACAGAAGUAA 23 24689 CFTR-Intron10-5810 CUGGAGAGUUUUAAACAGAAGUAA 24 24690 CFTR-Intron10-5811 AAAGAAGGAAGGAAGUAA 18 24691 CFTR-Intron10-5812 GAAAGAAGGAAGGAAGUAA 19 24692 CFTR-Intron10-5813 GGAAAGAAGGAAGGAAGUAA 20 24693 CFTR-Intron10-5814 AGGAAAGAAGGAAGGAAGUAA 21 24694 CFTR-Intron10-5815 AAGGAAAGAAGGAAGGAAGUAA 22 24695 CFTR-Intron10-5816 GAAGGAAAGAAGGAAGGAAGUAA 23 24696 CFTR-Intron10-5817 GGAAGGAAAGAAGGAAGGAAGUAA 24 24697 CFTR-Intron10-5818 GCUUUCUGGACUGAGUAA 18 24698 CFTR-Intron10-5819 AGCUUUCUGGACUGAGUAA 19 24699 CFTR-Intron10-5820 AAGCUUUCUGGACUGAGUAA 20 24700 CFTR-Intron10-5821 CAAGCUUUCUGGACUGAGUAA 21 24701 CFTR-Intron10-5822 CCAAGCUUUCUGGACUGAGUAA 22 24702 CFTR-Intron10-5823 UCCAAGCUUUCUGGACUGAGUAA 23 24703 CFTR-Intron10-5824 UUCCAAGCUUUCUGGACUGAGUAA 24 24704 CFTR-Intron10-5825 GGGUGAAGUCUUUAGUAA 18 24705 CFTR-Intron10-5826 AGGGUGAAGUCUUUAGUAA 19 24706 CFTR-Intron10-5827 GAGGGUGAAGUCUUUAGUAA 20 24707 CFTR-Intron10-5828 UGAGGGUGAAGUCUUUAGUAA 21 24708 CFTR-Intron10-5829 AUGAGGGUGAAGUCUUUAGUAA 22 24709 CFTR-Intron10-5830 CAUGAGGGUGAAGUCUUUAGUAA 23 24710 CFTR-Intron10-5831 CCAUGAGGGUGAAGUCUUUAGUAA 24 24711 CFTR-Intron10-5832 AUAAGUGGCCUUUAAACA 18 24712 CFTR-Intron10-5833 UAUAAGUGGCCUUUAAACA 19 24713 CFTR-Intron10-5834 AUAUAAGUGGCCUUUAAACA 20 24714 CFTR-Intron10-5835 AAUAUAAGUGGCCUUUAAACA 21 24715 CFTR-Intron10-5836 AAAUAUAAGUGGCCUUUAAACA 22 24716 CFTR-Intron10-5837 AAAAUAUAAGUGGCCUUUAAACA 23 24717 CFTR-Intron10-5838 AAAAAUAUAAGUGGCCUUUAAACA 24 24718 CFTR-Intron10-5839 ACCAUCCUGGCUAACACA 18 24719 CFTR-Intron10-5840 GACCAUCCUGGCUAACACA 19 24720 CFTR-Intron10-5841 AGACCAUCCUGGCUAACACA 20 24721 CFTR-Intron10-5842 AAGACCAUCCUGGCUAACACA 21 24722 CFTR-Intron10-5843 CAAGACCAUCCUGGCUAACACA 22 24723 CFTR-Intron10-5844 UCAAGACCAUCCUGGCUAACACA 23 24724 CFTR-Intron10-5845 AUCAAGACCAUCCUGGCUAACACA 24 24725 CFTR-Intron10-5846 CAAUAUUUUGUUAACACA 18 24726 CFTR-Intron10-5847 CCAAUAUUUUGUUAACACA 19 24727 CFTR-Intron10-5848 UCCAAUAUUUUGUUAACACA 20 24728 CFTR-Intron10-5849 UUCCAAUAUUUUGUUAACACA 21 24729 CFTR-Intron10-5850 UUUCCAAUAUUUUGUUAACACA 22 24730 CFTR-Intron10-5851 GUUUCCAAUAUUUUGUUAACACA 23 24731 CFTR-Intron10-5852 UGUUUCCAAUAUUUUGUUAACACA 24 24732 CFTR-Intron10-5853 UUCCAUAUUCAAAGCACA 18 24733 CFTR-Intron10-5854 UUUCCAUAUUCAAAGCACA 19 24734 CFTR-Intron10-5855 CUUUCCAUAUUCAAAGCACA 20 24735 CFTR-Intron10-5856 ACUUUCCAUAUUCAAAGCACA 21 24736 CFTR-Intron10-5857 AACUUUCCAUAUUCAAAGCACA 22 24737 CFTR-Intron10-5858 CAACUUUCCAUAUUCAAAGCACA 23 24738 CFTR-Intron10-5859 ACAACUUUCCAUAUUCAAAGCACA 24 24739 CFTR-Intron10-5860 CAUAUGAGAAAAGUCACA 18 24740 CFTR-Intron10-5861 GCAUAUGAGAAAAGUCACA 19 24741 CFTR-Intron10-5862 GGCAUAUGAGAAAAGUCACA 20 24742 CFTR-Intron10-5863 UGGCAUAUGAGAAAAGUCACA 21 24743 CFTR-Intron10-5864 AUGGCAUAUGAGAAAAGUCACA 22 24744 CFTR-Intron10-5865 AAUGGCAUAUGAGAAAAGUCACA 23 24745 CFTR-Intron10-5866 CAAUGGCAUAUGAGAAAAGUCACA 24 24746 CFTR-Intron10-5867 CUGGCAUAGAGUAAGACA 18 24747 CFTR-Intron10-5868 GCUGGCAUAGAGUAAGACA 19 24748 CFTR-Intron10-74 GGCUGGCAUAGAGUAAGACA 20 18960 CFTR-Intron10-5869 AGGCUGGCAUAGAGUAAGACA 21 24749 CFTR-Intron10-5870 GAGGCUGGCAUAGAGUAAGACA 22 24750 CFTR-Intron10-5871 UGAGGCUGGCAUAGAGUAAGACA 23 24751 CFTR-Intron10-5872 CUGAGGCUGGCAUAGAGUAAGACA 24 24752 CFTR-Intron10-5873 CUAUUCUGUAGGGAGACA 18 24753 CFTR-Intron10-5874 GCUAUUCUGUAGGGAGACA 19 24754 CFTR-Intron10-75 GGCUAUUCUGUAGGGAGACA 20 18961 CFTR-Intron10-5875 AGGCUAUUCUGUAGGGAGACA 21 24755 CFTR-Intron10-5876 UAGGCUAUUCUGUAGGGAGACA 22 24756 CFTR-Intron10-5877 UUAGGCUAUUCUGUAGGGAGACA 23 24757 CFTR-Intron10-5878 UUUAGGCUAUUCUGUAGGGAGACA 24 24758 CFTR-Intron10-5879 UUUUUUUCAGUUAAUACA 18 24759 CFTR-Intron10-5880 UUUUUUUUCAGUUAAUACA 19 24760 CFTR-Intron10-5881 AUUUUUUUUCAGUUAAUACA 20 24761 CFTR-Intron10-5882 AAUUUUUUUUCAGUUAAUACA 21 24762 CFTR-Intron10-5883 GAAUUUUUUUUCAGUUAAUACA 22 24763 CFTR-Intron10-5884 UGAAUUUUUUUUCAGUUAAUACA 23 24764 CFTR-Intron10-5885 GUGAAUUUUUUUUCAGUUAAUACA 24 24765 CFTR-Intron10-5886 AUCAUUUCAACUUAUACA 18 24766 CFTR-Intron10-5887 UAUCAUUUCAACUUAUACA 19 24767 CFTR-Intron10-5888 AUAUCAUUUCAACUUAUACA 20 24768 CFTR-Intron10-5889 AAUAUCAUUUCAACUUAUACA 21 24769 CFTR-Intron10-5890 AAAUAUCAUUUCAACUUAUACA 22 24770 CFTR-Intron10-5891 AAAAUAUCAUUUCAACUUAUACA 23 24771 CFTR-Intron10-5892 UAAAAUAUCAUUUCAACUUAUACA 24 24772 CFTR-Intron10-5893 UAGGUUUAAUUUUGUACA 18 24773 CFTR-Intron10-5894 CUAGGUUUAAUUUUGUACA 19 24774 CFTR-Intron10-5895 UCUAGGUUUAAUUUUGUACA 20 24775 CFTR-Intron10-5896 UUCUAGGUUUAAUUUUGUACA 21 24776 CFTR-Intron10-5897 CUUCUAGGUUUAAUUUUGUACA 22 24777 CFTR-Intron10-5898 ACUUCUAGGUUUAAUUUUGUACA 23 24778 CFTR-Intron10-5899 CACUUCUAGGUUUAAUUUUGUACA 24 24779 CFTR-Intron10-5900 GGGUGAGAUUAGAGGCCA 18 24780 CFTR-Intron10-5901 UGGGUGAGAUUAGAGGCCA 19 24781 CFTR-Intron10-5902 CUGGGUGAGAUUAGAGGCCA 20 24782 CFTR-Intron10-5903 UCUGGGUGAGAUUAGAGGCCA 21 24783 CFTR-Intron10-5904 CUCUGGGUGAGAUUAGAGGCCA 22 24784 CFTR-Intron10-5905 UCUCUGGGUGAGAUUAGAGGCCA 23 24785 CFTR-Intron10-5906 UUCUCUGGGUGAGAUUAGAGGCCA 24 24786 CFTR-Intron10-5907 CUUUCCAUAUUCAAAGCA 18 24787 CFTR-Intron10-5908 ACUUUCCAUAUUCAAAGCA 19 24788 CFTR-Intron10-5909 AACUUUCCAUAUUCAAAGCA 20 24789 CFTR-Intron10-5910 CAACUUUCCAUAUUCAAAGCA 21 24790 CFTR-Intron10-5911 ACAACUUUCCAUAUUCAAAGCA 22 24791 CFTR-Intron10-5912 GACAACUUUCCAUAUUCAAAGCA 23 24792 CFTR-Intron10-5913 GGACAACUUUCCAUAUUCAAAGCA 24 24793 CFTR-Intron10-5914 GAGACAAGGGAGGAAGCA 18 24794 CFTR-Intron10-5915 GGAGACAAGGGAGGAAGCA 19 24795 CFTR-Intron10-650 GGGAGACAAGGGAGGAAGCA 20 19536 CFTR-Intron10-5916 AGGGAGACAAGGGAGGAAGCA 21 24796 CFTR-Intron10-5917 UAGGGAGACAAGGGAGGAAGCA 22 24797 CFTR-Intron10-5918 GUAGGGAGACAAGGGAGGAAGCA 23 24798 CFTR-Intron10-5919 UGUAGGGAGACAAGGGAGGAAGCA 24 24799 CFTR-Intron10-5920 GAUUCUGUUUAAAUAGCA 18 24800 CFTR-Intron10-5921 UGAUUCUGUUUAAAUAGCA 19 24801 CFTR-Intron10-5922 CUGAUUCUGUUUAAAUAGCA 20 24802 CFTR-Intron10-5923 CCUGAUUCUGUUUAAAUAGCA 21 24803 CFTR-Intron10-5924 CCCUGAUUCUGUUUAAAUAGCA 22 24804 CFTR-Intron10-5925 CCCCUGAUUCUGUUUAAAUAGCA 23 24805 CFTR-Intron10-5926 UCCCCUGAUUCUGUUUAAAUAGCA 24 24806 CFTR-Intron10-5927 AGUGCCACUAGUGAUGCA 18 24807 CFTR-Intron10-5928 AAGUGCCACUAGUGAUGCA 19 24808 CFTR-Intron10-1129 AAAGUGCCACUAGUGAUGCA 20 20014 CFTR-Intron10-5929 CAAAGUGCCACUAGUGAUGCA 21 24809 CFTR-Intron10-5930 ACAAAGUGCCACUAGUGAUGCA 22 24810 CFTR-Intron10-5931 UACAAAGUGCCACUAGUGAUGCA 23 24811 CFTR-Intron10-5932 AUACAAAGUGCCACUAGUGAUGCA 24 24812 CFTR-Intron10-5933 UGAGAAGUGGAGGCUGCA 18 24813 CFTR-Intron10-5934 CUGAGAAGUGGAGGCUGCA 19 24814 CFTR-Intron10-5935 CCUGAGAAGUGGAGGCUGCA 20 24815 CFTR-Intron10-5936 GCCUGAGAAGUGGAGGCUGCA 21 24816 CFTR-Intron10-5937 AGCCUGAGAAGUGGAGGCUGCA 22 24817 CFTR-Intron10-5938 GAGCCUGAGAAGUGGAGGCUGCA 23 24818 CFTR-Intron10-5939 UGAGCCUGAGAAGUGGAGGCUGCA 24 24819 CFTR-Intron10-5940 CAGGAGGCAGAACUUGCA 18 24820 CFTR-Intron10-5941 CCAGGAGGCAGAACUUGCA 19 24821 CFTR-Intron10-5942 CCCAGGAGGCAGAACUUGCA 20 24822 CFTR-Intron10-5943 ACCCAGGAGGCAGAACUUGCA 21 24823 CFTR-Intron10-5944 AACCCAGGAGGCAGAACUUGCA 22 24824 CFTR-Intron10-5945 GAACCCAGGAGGCAGAACUUGCA 23 24825 CFTR-Intron10-5946 UGAACCCAGGAGGCAGAACUUGCA 24 24826 CFTR-Intron10-5947 GGCAUAUGAGAAAAGUCA 18 24827 CFTR-Intron10-5948 UGGCAUAUGAGAAAAGUCA 19 24828 CFTR-Intron10-5949 AUGGCAUAUGAGAAAAGUCA 20 24829 CFTR-Intron10-5950 AAUGGCAUAUGAGAAAAGUCA 21 24830 CFTR-Intron10-5951 CAAUGGCAUAUGAGAAAAGUCA 22 24831 CFTR-Intron10-5952 ACAAUGGCAUAUGAGAAAAGUCA 23 24832 CFTR-Intron10-5953 AACAAUGGCAUAUGAGAAAAGUCA 24 24833 CFTR-Intron10-5954 AGAACAGUAAGGAGGUCA 18 24834 CFTR-Intron10-5955 AAGAACAGUAAGGAGGUCA 19 24835 CFTR-Intron10-5956 GAAGAACAGUAAGGAGGUCA 20 24836 CFTR-Intron10-5957 UGAAGAACAGUAAGGAGGUCA 21 24837 CFTR-Intron10-5958 UUGAAGAACAGUAAGGAGGUCA 22 24838 CFTR-Intron10-5959 UUUGAAGAACAGUAAGGAGGUCA 23 24839 CFTR-Intron10-5960 GUUUGAAGAACAGUAAGGAGGUCA 24 24840 CFTR-Intron10-5961 GAGGGUAGAAUACUGUCA 18 24841 CFTR-Intron10-5962 GGAGGGUAGAAUACUGUCA 19 24842 CFTR-Intron10-5963 GGGAGGGUAGAAUACUGUCA 20 24843 CFTR-Intron10-5964 AGGGAGGGUAGAAUACUGUCA 21 24844 CFTR-Intron10-5965 CAGGGAGGGUAGAAUACUGUCA 22 24845 CFTR-Intron10-5966 ACAGGGAGGGUAGAAUACUGUCA 23 24846 CFTR-Intron10-5967 GACAGGGAGGGUAGAAUACUGUCA 24 24847 CFTR-Intron10-5968 UGUACAAGUCUAGUUUCA 18 24848 CFTR-Intron10-5969 AUGUACAAGUCUAGUUUCA 19 24849 CFTR-Intron10-79 GAUGUACAAGUCUAGUUUCA 20 18965 CFTR-Intron10-5970 GGAUGUACAAGUCUAGUUUCA 21 24850 CFTR-Intron10-5971 UGGAUGUACAAGUCUAGUUUCA 22 24851 CFTR-Intron10-5972 UUGGAUGUACAAGUCUAGUUUCA 23 24852 CFTR-Intron10-5973 GUUGGAUGUACAAGUCUAGUUUCA 24 24853 CFTR-Intron10-5974 AAGACAAACAGAAAAAGA 18 24854 CFTR-Intron10-5975 UAAGACAAACAGAAAAAGA 19 24855 CFTR-Intron10-5976 CUAAGACAAACAGAAAAAGA 20 24856 CFTR-Intron10-5977 UCUAAGACAAACAGAAAAAGA 21 24857 CFTR-Intron10-5978 AUCUAAGACAAACAGAAAAAGA 22 24858 CFTR-Intron10-5979 AAUCUAAGACAAACAGAAAAAGA 23 24859 CFTR-Intron10-5980 UAAUCUAAGACAAACAGAAAAAGA 24 24860 CFTR-Intron10-5981 CAAACAGAAAAAGAAAGA 18 24861 CFTR-Intron10-5982 ACAAACAGAAAAAGAAAGA 19 24862 CFTR-Intron10-5983 GACAAACAGAAAAAGAAAGA 20 24863 CFTR-Intron10-5984 AGACAAACAGAAAAAGAAAGA 21 24864 CFTR-Intron10-5985 AAGACAAACAGAAAAAGAAAGA 22 24865 CFTR-Intron10-5986 UAAGACAAACAGAAAAAGAAAGA 23 24866 CFTR-Intron10-5987 CUAAGACAAACAGAAAAAGAAAGA 24 24867 CFTR-Intron10-5988 GAGAGGAAGGAAGAAAGA 18 24868 CFTR-Intron10-5989 AGAGAGGAAGGAAGAAAGA 19 24869 CFTR-Intron10-1137 AAGAGAGGAAGGAAGAAAGA 20 20022 CFTR-Intron10-5990 AAAGAGAGGAAGGAAGAAAGA 21 24870 CFTR-Intron10-5991 GAAAGAGAGGAAGGAAGAAAGA 22 24871 CFTR-Intron10-5992 AGAAAGAGAGGAAGGAAGAAAGA 23 24872 CFTR-Intron10-5993 AAGAAAGAGAGGAAGGAAGAAAGA 24 24873 CFTR-Intron10-5994 GAAGGAAGGAAGGAAAGA 18 24874 CFTR-Intron10-5995 GGAAGGAAGGAAGGAAAGA 19 24875 CFTR-Intron10-1138 AGGAAGGAAGGAAGGAAAGA 20 20023 CFTR-Intron10-5996 GAGGAAGGAAGGAAGGAAAGA 21 24876 CFTR-Intron10-5997 GGAGGAAGGAAGGAAGGAAAGA 22 24877 CFTR-Intron10-5998 AGGAGGAAGGAAGGAAGGAAAGA 23 24878 CFTR-Intron10-5999 UAGGAGGAAGGAAGGAAGGAAAGA 24 24879 CFTR-Intron10-6000 GUCUAGUUUCAAGGAAGA 18 24880 CFTR-Intron10-6001 AGUCUAGUUUCAAGGAAGA 19 24881 CFTR-Intron10-372 AAGUCUAGUUUCAAGGAAGA 20 19258 CFTR-Intron10-6002 CAAGUCUAGUUUCAAGGAAGA 21 24882 CFTR-Intron10-6003 ACAAGUCUAGUUUCAAGGAAGA 22 24883 CFTR-Intron10-6004 UACAAGUCUAGUUUCAAGGAAGA 23 24884 CFTR-Intron10-6005 GUACAAGUCUAGUUUCAAGGAAGA 24 24885 CFTR-Intron10-6006 GAAAGAGAGGAAGGAAGA 18 24886 CFTR-Intron10-6007 AGAAAGAGAGGAAGGAAGA 19 24887 CFTR-Intron10-6008 AAGAAAGAGAGGAAGGAAGA 20 24888 CFTR-Intron10-6009 AAAGAAAGAGAGGAAGGAAGA 21 24889 CFTR-Intron10-6010 AAAAGAAAGAGAGGAAGGAAGA 22 24890 CFTR-Intron10-6011 AAAAAGAAAGAGAGGAAGGAAGA 23 24891 CFTR-Intron10-6012 GAAAAAGAAAGAGAGGAAGGAAGA 24 24892 CFTR-Intron10-6013 AGAAGGAAAUGAGGAAGA 18 24893 CFTR-Intron10-6014 AAGAAGGAAAUGAGGAAGA 19 24894 CFTR-Intron10-6015 AAAGAAGGAAAUGAGGAAGA 20 24895 CFTR-Intron10-6016 GAAAGAAGGAAAUGAGGAAGA 21 24896 CFTR-Intron10-6017 AGAAAGAAGGAAAUGAGGAAGA 22 24897 CFTR-Intron10-6018 AAGAAAGAAGGAAAUGAGGAAGA 23 24898 CFTR-Intron10-6019 GAAGAAAGAAGGAAAUGAGGAAGA 24 24899 CFTR-Intron10-6020 GGGCUGGUAGUGUGAAGA 18 24900 CFTR-Intron10-6021 GGGGCUGGUAGUGUGAAGA 19 24901 CFTR-Intron10-80 GGGGGCUGGUAGUGUGAAGA 20 18966 CFTR-Intron10-6022 AGGGGGCUGGUAGUGUGAAGA 21 24902 CFTR-Intron10-6023 GAGGGGGCUGGUAGUGUGAAGA 22 24903 CFTR-Intron10-6024 AGAGGGGGCUGGUAGUGUGAAGA 23 24904 CFTR-Intron10-6025 AAGAGGGGGCUGGUAGUGUGAAGA 24 24905 CFTR-Intron10-6026 AGAAGGAAGGAAGUAAGA 18 24906 CFTR-Intron10-6027 AAGAAGGAAGGAAGUAAGA 19 24907 CFTR-Intron10-1139 AAAGAAGGAAGGAAGUAAGA 20 20024 CFTR-Intron10-6028 GAAAGAAGGAAGGAAGUAAGA 21 24908 CFTR-Intron10-6029 GGAAAGAAGGAAGGAAGUAAGA 22 24909 CFTR-Intron10-6030 AGGAAAGAAGGAAGGAAGUAAGA 23 24910 CFTR-Intron10-6031 AAGGAAAGAAGGAAGGAAGUAAGA 24 24911 CFTR-Intron10-6032 GGCUGGCAUAGAGUAAGA 18 24912 CFTR-Intron10-6033 AGGCUGGCAUAGAGUAAGA 19 24913 CFTR-Intron10-6034 GAGGCUGGCAUAGAGUAAGA 20 24914 CFTR-Intron10-6035 UGAGGCUGGCAUAGAGUAAGA 21 24915 CFTR-Intron10-6036 CUGAGGCUGGCAUAGAGUAAGA 22 24916 CFTR-Intron10-6037 ACUGAGGCUGGCAUAGAGUAAGA 23 24917 CFTR-Intron10-6038 CACUGAGGCUGGCAUAGAGUAAGA 24 24918 CFTR-Intron10-6039 UCUAGCCUGGGUGACAGA 18 24919 CFTR-Intron10-6040 CUCUAGCCUGGGUGACAGA 19 24920 CFTR-Intron10-6041 ACUCUAGCCUGGGUGACAGA 20 24921 CFTR-Intron10-6042 CACUCUAGCCUGGGUGACAGA 21 24922 CFTR-Intron10-6043 GCACUCUAGCCUGGGUGACAGA 22 24923 CFTR-Intron10-6044 UGCACUCUAGCCUGGGUGACAGA 23 24924 CFTR-Intron10-6045 CUGCACUCUAGCCUGGGUGACAGA 24 24925 CFTR-Intron10-6046 AGGUCAAACUUGACCAGA 18 24926 CFTR-Intron10-6047 AAGGUCAAACUUGACCAGA 19 24927 CFTR-Intron10-6048 GAAGGUCAAACUUGACCAGA 20 24928 CFTR-Intron10-6049 AGAAGGUCAAACUUGACCAGA 21 24929 CFTR-Intron10-6050 GAGAAGGUCAAACUUGACCAGA 22 24930 CFTR-Intron10-6051 AGAGAAGGUCAAACUUGACCAGA 23 24931 CFTR-Intron10-6052 UAGAGAAGGUCAAACUUGACCAGA 24 24932 CFTR-Intron10-6053 AAUUUAACAUUUUCCAGA 18 24933 CFTR-Intron10-6054 AAAUUUAACAUUUUCCAGA 19 24934 CFTR-Intron10-6055 AAAAUUUAACAUUUUCCAGA 20 24935 CFTR-Intron10-6056 GAAAAUUUAACAUUUUCCAGA 21 24936 CFTR-Intron10-6057 GGAAAAUUUAACAUUUUCCAGA 22 24937 CFTR-Intron10-6058 GGGAAAAUUUAACAUUUUCCAGA 23 24938 CFTR-Intron10-6059 AGGGAAAAUUUAACAUUUUCCAGA 24 24939 CFTR-Intron10-6060 AAGUGCAAAGCUUUCAGA 18 24940 CFTR-Intron10-6061 CAAGUGCAAAGCUUUCAGA 19 24941 CFTR-Intron10-82 GCAAGUGCAAAGCUUUCAGA 20 18968 CFTR-Intron10-6062 AGCAAGUGCAAAGCUUUCAGA 21 24942 CFTR-Intron10-6063 AAGCAAGUGCAAAGCUUUCAGA 22 24943 CFTR-Intron10-6064 GAAGCAAGUGCAAAGCUUUCAGA 23 24944 CFTR-Intron10-6065 UGAAGCAAGUGCAAAGCUUUCAGA 24 24945 CFTR-Intron10-6066 AGGGUUGAUAAGAAGAGA 18 24946 CFTR-Intron10-6067 GAGGGUUGAUAAGAAGAGA 19 24947 CFTR-Intron10-6068 AGAGGGUUGAUAAGAAGAGA 20 24948 CFTR-Intron10-6069 AAGAGGGUUGAUAAGAAGAGA 21 24949 CFTR-Intron10-6070 AAAGAGGGUUGAUAAGAAGAGA 22 24950 CFTR-Intron10-6071 GAAAGAGGGUUGAUAAGAAGAGA 23 24951 CFTR-Intron10-6072 GGAAAGAGGGUUGAUAAGAAGAGA 24 24952 CFTR-Intron10-6073 AUCAAAUUAGAGAUGAGA 18 24953 CFTR-Intron10-6074 AAUCAAAUUAGAGAUGAGA 19 24954 CFTR-Intron10-6075 GAAUCAAAUUAGAGAUGAGA 20 24955 CFTR-Intron10-6076 AGAAUCAAAUUAGAGAUGAGA 21 24956 CFTR-Intron10-6077 AAGAAUCAAAUUAGAGAUGAGA 22 24957 CFTR-Intron10-6078 AAAGAAUCAAAUUAGAGAUGAGA 23 24958 CFTR-Intron10-6079 GAAAGAAUCAAAUUAGAGAUGAGA 24 24959 CFTR-Intron10-6080 AAAAAAUAGUAGAUUAGA 18 24960 CFTR-Intron10-6081 GAAAAAAUAGUAGAUUAGA 19 24961 CFTR-Intron10-6082 UGAAAAAAUAGUAGAUUAGA 20 24962 CFTR-Intron10-6083 CUGAAAAAAUAGUAGAUUAGA 21 24963 CFTR-Intron10-6084 UCUGAAAAAAUAGUAGAUUAGA 22 24964 CFTR-Intron10-6085 AUCUGAAAAAAUAGUAGAUUAGA 23 24965 CFTR-Intron10-6086 CAUCUGAAAAAAUAGUAGAUUAGA 24 24966 CFTR-Intron10-6087 GAGCUUUCUAGUAUUAGA 18 24967 CFTR-Intron10-6088 AGAGCUUUCUAGUAUUAGA 19 24968 CFTR-Intron10-6089 AAGAGCUUUCUAGUAUUAGA 20 24969 CFTR-Intron10-6090 AAAGAGCUUUCUAGUAUUAGA 21 24970 CFTR-Intron10-6091 GAAAGAGCUUUCUAGUAUUAGA 22 24971 CFTR-Intron10-6092 AGAAAGAGCUUUCUAGUAUUAGA 23 24972 CFTR-Intron10-6093 GAGAAAGAGCUUUCUAGUAUUAGA 24 24973 CFTR-Intron10-6094 GGAUAAGAUUCUAAAGGA 18 24974 CFTR-Intron10-6095 UGGAUAAGAUUCUAAAGGA 19 24975 CFTR-Intron10-6096 CUGGAUAAGAUUCUAAAGGA 20 24976 CFTR-Intron10-6097 GCUGGAUAAGAUUCUAAAGGA 21 24977 CFTR-Intron10-6098 GGCUGGAUAAGAUUCUAAAGGA 22 24978 CFTR-Intron10-6099 GGGCUGGAUAAGAUUCUAAAGGA 23 24979 CFTR-Intron10-6100 GGGGCUGGAUAAGAUUCUAAAGGA 24 24980 CFTR-Intron10-6101 GAAGGAAGGAAAGAAGGA 18 24981 CFTR-Intron10-6102 GGAAGGAAGGAAAGAAGGA 19 24982 CFTR-Intron10-1145 AGGAAGGAAGGAAAGAAGGA 20 20030 CFTR-Intron10-6103 AAGGAAGGAAGGAAAGAAGGA 21 24983 CFTR-Intron10-6104 GAAGGAAGGAAGGAAAGAAGGA 22 24984 CFTR-Intron10-6105 GGAAGGAAGGAAGGAAAGAAGGA 23 24985 CFTR-Intron10-6106 AGGAAGGAAGGAAGGAAAGAAGGA 24 24986 CFTR-Intron10-6107 GGAGGAAGGAAGGAAGGA 18 24987 CFTR-Intron10-6108 AGGAGGAAGGAAGGAAGGA 19 24988 CFTR-Intron10-6109 UAGGAGGAAGGAAGGAAGGA 20 24989 CFTR-Intron10-6110 GUAGGAGGAAGGAAGGAAGGA 21 24990 CFTR-Intron10-6111 AGUAGGAGGAAGGAAGGAAGGA 22 24991 CFTR-Intron10-6112 AAGUAGGAGGAAGGAAGGAAGGA 23 24992 CFTR-Intron10-6113 GAAGUAGGAGGAAGGAAGGAAGGA 24 24993 CFTR-Intron10-6114 AGUAGGAGGAAGGAAGGA 18 24994 CFTR-Intron10-6115 AAGUAGGAGGAAGGAAGGA 19 24995 CFTR-Intron10-652 GAAGUAGGAGGAAGGAAGGA 20 19538 CFTR-Intron10-6116 GGAAGUAGGAGGAAGGAAGGA 21 24996 CFTR-Intron10-6117 AGGAAGUAGGAGGAAGGAAGGA 22 24997 CFTR-Intron10-6118 AAGGAAGUAGGAGGAAGGAAGGA 23 24998 CFTR-Intron10-6119 AAAGGAAGUAGGAGGAAGGAAGGA 24 24999 CFTR-Intron10-6120 AGGAAGUAGGAGGAAGGA 18 25000 CFTR-Intron10-6121 AAGGAAGUAGGAGGAAGGA 19 25001 CFTR-Intron10-1146 AAAGGAAGUAGGAGGAAGGA 20 20031 CFTR-Intron10-6122 GAAAGGAAGUAGGAGGAAGGA 21 25002 CFTR-Intron10-6123 AGAAAGGAAGUAGGAGGAAGGA 22 25003 CFTR-Intron10-6124 AAGAAAGGAAGUAGGAGGAAGGA 23 25004 CFTR-Intron10-6125 GAAGAAAGGAAGUAGGAGGAAGGA 24 25005 CFTR-Intron10-6126 UUAGAAAGAAUAAGAGGA 18 25006 CFTR-Intron10-6127 AUUAGAAAGAAUAAGAGGA 19 25007 CFTR-Intron10-6128 AAUUAGAAAGAAUAAGAGGA 20 25008 CFTR-Intron10-6129 AAAUUAGAAAGAAUAAGAGGA 21 25009 CFTR-Intron10-6130 GAAAUUAGAAAGAAUAAGAGGA 22 25010 CFTR-Intron10-6131 UGAAAUUAGAAAGAAUAAGAGGA 23 25011 CFTR-Intron10-6132 AUGAAAUUAGAAAGAAUAAGAGGA 24 25012 CFTR-Intron10-6133 AGAAAAAGAAAGAGAGGA 18 25013 CFTR-Intron10-6134 CAGAAAAAGAAAGAGAGGA 19 25014 CFTR-Intron10-1149 ACAGAAAAAGAAAGAGAGGA 20 20034 CFTR-Intron10-6135 AACAGAAAAAGAAAGAGAGGA 21 25015 CFTR-Intron10-6136 AAACAGAAAAAGAAAGAGAGGA 22 25016 CFTR-Intron10-6137 CAAACAGAAAAAGAAAGAGAGGA 23 25017 CFTR-Intron10-6138 ACAAACAGAAAAAGAAAGAGAGGA 24 25018 CFTR-Intron10-6139 AGAAAGGAAGUAGGAGGA 18 25019 CFTR-Intron10-6140 AAGAAAGGAAGUAGGAGGA 19 25020 CFTR-Intron10-653 GAAGAAAGGAAGUAGGAGGA 20 19539 CFTR-Intron10-6141 GGAAGAAAGGAAGUAGGAGGA 21 25021 CFTR-Intron10-6142 AGGAAGAAAGGAAGUAGGAGGA 22 25022 CFTR-Intron10-6143 GAGGAAGAAAGGAAGUAGGAGGA 23 25023 CFTR-Intron10-6144 UGAGGAAGAAAGGAAGUAGGAGGA 24 25024 CFTR-Intron10-6145 CUUUUAGUAGUAUUAGGA 18 25025 CFTR-Intron10-6146 CCUUUUAGUAGUAUUAGGA 19 25026 CFTR-Intron10-6147 GCCUUUUAGUAGUAUUAGGA 20 25027 CFTR-Intron10-6148 UGCCUUUUAGUAGUAUUAGGA 21 25028 CFTR-Intron10-6149 CUGCCUUUUAGUAGUAUUAGGA 22 25029 CFTR-Intron10-6150 GCUGCCUUUUAGUAGUAUUAGGA 23 25030 CFTR-Intron10-6151 GGCUGCCUUUUAGUAGUAUUAGGA 24 25031 CFTR-Intron10-6152 GGAGAAACAGGUUUUGGA 18 25032 CFTR-Intron10-6153 GGGAGAAACAGGUUUUGGA 19 25033 CFTR-Intron10-1157 UGGGAGAAACAGGUUUUGGA 20 20042 CFTR-Intron10-6154 AUGGGAGAAACAGGUUUUGGA 21 25034 CFTR-Intron10-6155 AAUGGGAGAAACAGGUUUUGGA 22 25035 CFTR-Intron10-6156 UAAUGGGAGAAACAGGUUUUGGA 23 25036 CFTR-Intron10-6157 AUAAUGGGAGAAACAGGUUUUGGA 24 25037 CFTR-Intron10-6158 AUCACUGGAUGCCCUUGA 18 25038 CFTR-Intron10-6159 CAUCACUGGAUGCCCUUGA 19 25039 CFTR-Intron10-6160 GCAUCACUGGAUGCCCUUGA 20 25040 CFTR-Intron10-6161 UGCAUCACUGGAUGCCCUUGA 21 25041 CFTR-Intron10-6162 UUGCAUCACUGGAUGCCCUUGA 22 25042 CFTR-Intron10-6163 UUUGCAUCACUGGAUGCCCUUGA 23 25043 CFTR-Intron10-6164 UUUUGCAUCACUGGAUGCCCUUGA 24 25044 CFTR-Intron10-6165 AUUCAGGACAUGCUUUGA 18 25045 CFTR-Intron10-6166 GAUUCAGGACAUGCUUUGA 19 25046 CFTR-Intron10-1164 AGAUUCAGGACAUGCUUUGA 20 20049 CFTR-Intron10-6167 CAGAUUCAGGACAUGCUUUGA 21 25047 CFTR-Intron10-6168 UCAGAUUCAGGACAUGCUUUGA 22 25048 CFTR-Intron10-6169 AUCAGAUUCAGGACAUGCUUUGA 23 25049 CFTR-Intron10-6170 GAUCAGAUUCAGGACAUGCUUUGA 24 25050 CFTR-Intron10-6171 CUGUCUAGCCUAGAAAUA 18 25051 CFTR-Intron10-6172 ACUGUCUAGCCUAGAAAUA 19 25052 CFTR-Intron10-6173 AACUGUCUAGCCUAGAAAUA 20 25053 CFTR-Intron10-6174 AAACUGUCUAGCCUAGAAAUA 21 25054 CFTR-Intron10-6175 CAAACUGUCUAGCCUAGAAAUA 22 25055 CFTR-Intron10-6176 ACAAACUGUCUAGCCUAGAAAUA 23 25056 CFTR-Intron10-6177 CACAAACUGUCUAGCCUAGAAAUA 24 25057 CFTR-Intron10-6178 CCGGUGUCUUCUGAAAUA 18 25058 CFTR-Intron10-6179 ACCGGUGUCUUCUGAAAUA 19 25059 CFTR-Intron10-380 AACCGGUGUCUUCUGAAAUA 20 19266 CFTR-Intron10-6180 UAACCGGUGUCUUCUGAAAUA 21 25060 CFTR-Intron10-6181 UUAACCGGUGUCUUCUGAAAUA 22 25061 CFTR-Intron10-6182 AUUAACCGGUGUCUUCUGAAAUA 23 25062 CFTR-Intron10-6183 AAUUAACCGGUGUCUUCUGAAAUA 24 25063 CFTR-Intron10-6184 AGUGAUCCUAGAAUCAUA 18 25064 CFTR-Intron10-6185 AAGUGAUCCUAGAAUCAUA 19 25065 CFTR-Intron10-6186 AAAGUGAUCCUAGAAUCAUA 20 25066 CFTR-Intron10-6187 UAAAGUGAUCCUAGAAUCAUA 21 25067 CFTR-Intron10-6188 AUAAAGUGAUCCUAGAAUCAUA 22 25068 CFTR-Intron10-6189 UAUAAAGUGAUCCUAGAAUCAUA 23 25069 CFTR-Intron10-6190 AUAUAAAGUGAUCCUAGAAUCAUA 24 25070 CFTR-Intron10-6191 CCGUUUACUAGAAAGAUA 18 25071 CFTR-Intron10-6192 GCCGUUUACUAGAAAGAUA 19 25072 CFTR-Intron10-6193 UGCCGUUUACUAGAAAGAUA 20 25073 CFTR-Intron10-6194 GUGCCGUUUACUAGAAAGAUA 21 25074 CFTR-Intron10-6195 UGUGCCGUUUACUAGAAAGAUA 22 25075 CFTR-Intron10-6196 AUGUGCCGUUUACUAGAAAGAUA 23 25076 CFTR-Intron10-6197 AAUGUGCCGUUUACUAGAAAGAUA 24 25077 CFTR-Intron10-6198 CUUGGUAUUUACCAUAUA 18 25078 CFTR-Intron10-6199 GCUUGGUAUUUACCAUAUA 19 25079 CFTR-Intron10-6200 UGCUUGGUAUUUACCAUAUA 20 25080 CFTR-Intron10-6201 UUGCUUGGUAUUUACCAUAUA 21 25081 CFTR-Intron10-6202 GUUGCUUGGUAUUUACCAUAUA 22 25082 CFTR-Intron10-6203 AGUUGCUUGGUAUUUACCAUAUA 23 25083 CFTR-Intron10-6204 GAGUUGCUUGGUAUUUACCAUAUA 24 25084 CFTR-Intron10-6205 UUACACUCUAGCAUUAUA 18 25085 CFTR-Intron10-6206 AUUACACUCUAGCAUUAUA 19 25086 CFTR-Intron10-6207 AAUUACACUCUAGCAUUAUA 20 25087 CFTR-Intron10-6208 UAAUUACACUCUAGCAUUAUA 21 25088 CFTR-Intron10-6209 AUAAUUACACUCUAGCAUUAUA 22 25089 CFTR-Intron10-6210 UAUAAUUACACUCUAGCAUUAUA 23 25090 CFTR-Intron10-6211 UUAUAAUUACACUCUAGCAUUAUA 24 25091 CFTR-Intron10-6212 AAAGUUUCUCAUCUUAUA 18 25092 CFTR-Intron10-6213 AAAAGUUUCUCAUCUUAUA 19 25093 CFTR-Intron10-1171 AAAAAGUUUCUCAUCUUAUA 20 20056 CFTR-Intron10-6214 UAAAAAGUUUCUCAUCUUAUA 21 25094 CFTR-Intron10-6215 UUAAAAAGUUUCUCAUCUUAUA 22 25095 CFTR-Intron10-6216 UUUAAAAAGUUUCUCAUCUUAUA 23 25096 CFTR-Intron10-6217 AUUUAAAAAGUUUCUCAUCUUAUA 24 25097 CFTR-Intron10-6218 GUACAAAGGAAUUUUAUA 18 25098 CFTR-Intron10-6219 UGUACAAAGGAAUUUUAUA 19 25099 CFTR-Intron10-6220 UUGUACAAAGGAAUUUUAUA 20 25100 CFTR-Intron10-6221 UUUGUACAAAGGAAUUUUAUA 21 25101 CFTR-Intron10-6222 UUUUGUACAAAGGAAUUUUAUA 22 25102 CFTR-Intron10-6223 AUUUUGUACAAAGGAAUUUUAUA 23 25103 CFTR-Intron10-6224 AAUUUUGUACAAAGGAAUUUUAUA 24 25104 CFTR-Intron10-6225 CUUGCUCUCUUUUAACUA 18 25105 CFTR-Intron10-6226 ACUUGCUCUCUUUUAACUA 19 25106 CFTR-Intron10-6227 AACUUGCUCUCUUUUAACUA 20 25107 CFTR-Intron10-6228 AAACUUGCUCUCUUUUAACUA 21 25108 CFTR-Intron10-6229 AAAACUUGCUCUCUUUUAACUA 22 25109 CFTR-Intron10-6230 AAAAACUUGCUCUCUUUUAACUA 23 25110 CFTR-Intron10-6231 UAAAAACUUGCUCUCUUUUAACUA 24 25111 CFTR-Intron10-6232 UAUUAAAAAAUUAUACUA 18 25112 CFTR-Intron10-6233 CUAUUAAAAAAUUAUACUA 19 25113 CFTR-Intron10-6234 ACUAUUAAAAAAUUAUACUA 20 25114 CFTR-Intron10-6235 CACUAUUAAAAAAUUAUACUA 21 25115 CFTR-Intron10-6236 UCACUAUUAAAAAAUUAUACUA 22 25116 CFTR-Intron10-6237 UUCACUAUUAAAAAAUUAUACUA 23 25117 CFTR-Intron10-6238 GUUCACUAUUAAAAAAUUAUACUA 24 25118 CFTR-Intron10-6239 UUGACCUAAGAUAUCCUA 18 25119 CFTR-Intron10-6240 UUUGACCUAAGAUAUCCUA 19 25120 CFTR-Intron10-387 CUUUGACCUAAGAUAUCCUA 20 19273 CFTR-Intron10-6241 UCUUUGACCUAAGAUAUCCUA 21 25121 CFTR-Intron10-6242 CUCUUUGACCUAAGAUAUCCUA 22 25122 CFTR-Intron10-6243 CCUCUUUGACCUAAGAUAUCCUA 23 25123 CFTR-Intron10-6244 UCCUCUUUGACCUAAGAUAUCCUA 24 25124 CFTR-Intron10-6245 UAGUAUUAGAAUGGGCUA 18 25125 CFTR-Intron10-6246 CUAGUAUUAGAAUGGGCUA 19 25126 CFTR-Intron10-6247 UCUAGUAUUAGAAUGGGCUA 20 25127 CFTR-Intron10-6248 UUCUAGUAUUAGAAUGGGCUA 21 25128 CFTR-Intron10-6249 UUUCUAGUAUUAGAAUGGGCUA 22 25129 CFTR-Intron10-6250 CUUUCUAGUAUUAGAAUGGGCUA 23 25130 CFTR-Intron10-6251 GCUUUCUAGUAUUAGAAUGGGCUA 24 25131 CFTR-Intron10-6252 GGGCUGGAUAAGAUUCUA 18 25132 CFTR-Intron10-6253 GGGGCUGGAUAAGAUUCUA 19 25133 CFTR-Intron10-6254 UGGGGCUGGAUAAGAUUCUA 20 25134 CFTR-Intron10-6255 AUGGGGCUGGAUAAGAUUCUA 21 25135 CFTR-Intron10-6256 GAUGGGGCUGGAUAAGAUUCUA 22 25136 CFTR-Intron10-6257 AGAUGGGGCUGGAUAAGAUUCUA 23 25137 CFTR-Intron10-6258 AAGAUGGGGCUGGAUAAGAUUCUA 24 25138 CFTR-Intron10-6259 CUGGUUUGAAGAACAGUA 18 25139 CFTR-Intron10-6260 UCUGGUUUGAAGAACAGUA 19 25140 CFTR-Intron10-86 GUCUGGUUUGAAGAACAGUA 20 18972 CFTR-Intron10-6261 UGUCUGGUUUGAAGAACAGUA 21 25141 CFTR-Intron10-6262 CUGUCUGGUUUGAAGAACAGUA 22 25142 CFTR-Intron10-6263 CCUGUCUGGUUUGAAGAACAGUA 23 25143 CFTR-Intron10-6264 ACCUGUCUGGUUUGAAGAACAGUA 24 25144 CFTR-Intron10-6265 CUGGCACCAUUCACAGUA 18 25145 CFTR-Intron10-6266 CCUGGCACCAUUCACAGUA 19 25146 CFTR-Intron10-6267 ACCUGGCACCAUUCACAGUA 20 25147 CFTR-Intron10-6268 UACCUGGCACCAUUCACAGUA 21 25148 CFTR-Intron10-6269 CUACCUGGCACCAUUCACAGUA 22 25149 CFTR-Intron10-6270 CCUACCUGGCACCAUUCACAGUA 23 25150 CFTR-Intron10-6271 CCCUACCUGGCACCAUUCACAGUA 24 25151 CFTR-Intron10-6272 UUAAUGAAAGCAAUAGUA 18 25152 CFTR-Intron10-6273 CUUAAUGAAAGCAAUAGUA 19 25153 CFTR-Intron10-6274 ACUUAAUGAAAGCAAUAGUA 20 25154 CFTR-Intron10-6275 GACUUAAUGAAAGCAAUAGUA 21 25155 CFTR-Intron10-6276 UGACUUAAUGAAAGCAAUAGUA 22 25156 CFTR-Intron10-6277 GUGACUUAAUGAAAGCAAUAGUA 23 25157 CFTR-Intron10-6278 CGUGACUUAAUGAAAGCAAUAGUA 24 25158 CFTR-Intron10-6279 GGCUUGAUCCAGGUAGUA 18 25159 CFTR-Intron10-6280 UGGCUUGAUCCAGGUAGUA 19 25160 CFTR-Intron10-6281 GUGGCUUGAUCCAGGUAGUA 20 25161 CFTR-Intron10-6282 GGUGGCUUGAUCCAGGUAGUA 21 25162 CFTR-Intron10-6283 UGGUGGCUUGAUCCAGGUAGUA 22 25163 CFTR-Intron10-6284 AUGGUGGCUUGAUCCAGGUAGUA 23 25164 CFTR-Intron10-6285 GAUGGUGGCUUGAUCCAGGUAGUA 24 25165 CFTR-Intron10-6286 UUUUUAGGCUAUUCUGUA 18 25166 CFTR-Intron10-6287 GUUUUUAGGCUAUUCUGUA 19 25167 CFTR-Intron10-390 UGUUUUUAGGCUAUUCUGUA 20 19276 CFTR-Intron10-6288 AUGUUUUUAGGCUAUUCUGUA 21 25168 CFTR-Intron10-6289 AAUGUUUUUAGGCUAUUCUGUA 22 25169 CFTR-Intron10-6290 UAAUGUUUUUAGGCUAUUCUGUA 23 25170 CFTR-Intron10-6291 CUAAUGUUUUUAGGCUAUUCUGUA 24 25171 CFTR-Intron10-6292 CACUUGACAGGUAUAUUA 18 25172 CFTR-Intron10-6293 GCACUUGACAGGUAUAUUA 19 25173 CFTR-Intron10-6294 AGCACUUGACAGGUAUAUUA 20 25174 CFTR-Intron10-6295 UAGCACUUGACAGGUAUAUUA 21 25175 CFTR-Intron10-6296 CUAGCACUUGACAGGUAUAUUA 22 25176 CFTR-Intron10-6297 CCUAGCACUUGACAGGUAUAUUA 23 25177 CFTR-Intron10-6298 GCCUAGCACUUGACAGGUAUAUUA 24 25178 CFTR-Intron10-6299 GAGAUAACUCGUGACUUA 18 25179 CFTR-Intron10-6300 GGAGAUAACUCGUGACUUA 19 25180 CFTR-Intron10-6301 CGGAGAUAACUCGUGACUUA 20 25181 CFTR-Intron10-6302 ACGGAGAUAACUCGUGACUUA 21 25182 CFTR-Intron10-6303 UACGGAGAUAACUCGUGACUUA 22 25183 CFTR-Intron10-6304 AUACGGAGAUAACUCGUGACUUA 23 25184 CFTR-Intron10-6305 AAUACGGAGAUAACUCGUGACUUA 24 25185 CFTR-Intron10-6306 UUUAUAAAAGAAACCUUA 18 25186 CFTR-Intron10-6307 CUUUAUAAAAGAAACCUUA 19 25187 CFTR-Intron10-6308 UCUUUAUAAAAGAAACCUUA 20 25188 CFTR-Intron10-6309 GUCUUUAUAAAAGAAACCUUA 21 25189 CFTR-Intron10-6310 UGUCUUUAUAAAAGAAACCUUA 22 25190 CFTR-Intron10-6311 GUGUCUUUAUAAAAGAAACCUUA 23 25191 CFTR-Intron10-6312 AGUGUCUUUAUAAAAGAAACCUUA 24 25192 CFTR-Intron10-6313 AGAGACCCUCACACCUUA 18 25193 CFTR-Intron10-6314 GAGAGACCCUCACACCUUA 19 25194 CFTR-Intron10-6315 AGAGAGACCCUCACACCUUA 20 25195 CFTR-Intron10-6316 UAGAGAGACCCUCACACCUUA 21 25196 CFTR-Intron10-6317 UUAGAGAGACCCUCACACCUUA 22 25197 CFTR-Intron10-6318 CUUAGAGAGACCCUCACACCUUA 23 25198 CFTR-Intron10-6319 CCUUAGAGAGACCCUCACACCUUA 24 25199 CFTR-Intron10-6320 AAAAAGUUUCUCAUCUUA 18 25200 CFTR-Intron10-6321 UAAAAAGUUUCUCAUCUUA 19 25201 CFTR-Intron10-6322 UUAAAAAGUUUCUCAUCUUA 20 25202 CFTR-Intron10-6323 UUUAAAAAGUUUCUCAUCUUA 21 25203 CFTR-Intron10-6324 AUUUAAAAAGUUUCUCAUCUUA 22 25204 CFTR-Intron10-6325 AAUUUAAAAAGUUUCUCAUCUUA 23 25205 CFTR-Intron10-6326 UAAUUUAAAAAGUUUCUCAUCUUA 24 25206 CFTR-Intron10-6327 GCUAUGAAGGCAGAGUUA 18 25207 CFTR-Intron10-6328 AGCUAUGAAGGCAGAGUUA 19 25208 CFTR-Intron10-6329 CAGCUAUGAAGGCAGAGUUA 20 25209 CFTR-Intron10-6330 GCAGCUAUGAAGGCAGAGUUA 21 25210 CFTR-Intron10-6331 AGCAGCUAUGAAGGCAGAGUUA 22 25211 CFTR-Intron10-6332 AAGCAGCUAUGAAGGCAGAGUUA 23 25212 CFTR-Intron10-6333 AAAGCAGCUAUGAAGGCAGAGUUA 24 25213 CFTR-Intron10-6334 UCUAAGUAUUAGAGGUUA 18 25214 CFTR-Intron10-6335 UUCUAAGUAUUAGAGGUUA 19 25215 CFTR-Intron10-397 AUUCUAAGUAUUAGAGGUUA 20 19283 CFTR-Intron10-6336 CAUUCUAAGUAUUAGAGGUUA 21 25216 CFTR-Intron10-6337 GCAUUCUAAGUAUUAGAGGUUA 22 25217 CFTR-Intron10-6338 GGCAUUCUAAGUAUUAGAGGUUA 23 25218 CFTR-Intron10-6339 GGGCAUUCUAAGUAUUAGAGGUUA 24 25219 CFTR-Intron10-6340 CUGUAGGUAAAAAUGUUA 18 25220 CFTR-Intron10-6341 GCUGUAGGUAAAAAUGUUA 19 25221 CFTR-Intron10-6342 UGCUGUAGGUAAAAAUGUUA 20 25222 CFTR-Intron10-6343 CUGCUGUAGGUAAAAAUGUUA 21 25223 CFTR-Intron10-6344 GCUGCUGUAGGUAAAAAUGUUA 22 25224 CFTR-Intron10-6345 UGCUGCUGUAGGUAAAAAUGUUA 23 25225 CFTR-Intron10-6346 CUGCUGCUGUAGGUAAAAAUGUUA 24 25226 CFTR-Intron10-6347 UAAGAAUUGUAAAAUUUA 18 25227 CFTR-Intron10-6348 AUAAGAAUUGUAAAAUUUA 19 25228 CFTR-Intron10-6349 AAUAAGAAUUGUAAAAUUUA 20 25229 CFTR-Intron10-6350 UAAUAAGAAUUGUAAAAUUUA 21 25230 CFTR-Intron10-6351 GUAAUAAGAAUUGUAAAAUUUA 22 25231 CFTR-Intron10-6352 UGUAAUAAGAAUUGUAAAAUUUA 23 25232 CFTR-Intron10-6353 AUGUAAUAAGAAUUGUAAAAUUUA 24 25233 CFTR-Intron10-6354 CUUCCUUGAAUUAUUUUA 18 25234 CFTR-Intron10-6355 ACUUCCUUGAAUUAUUUUA 19 25235 CFTR-Intron10-6356 AACUUCCUUGAAUUAUUUUA 20 25236 CFTR-Intron10-6357 AAACUUCCUUGAAUUAUUUUA 21 25237 CFTR-Intron10-6358 GAAACUUCCUUGAAUUAUUUUA 22 25238 CFTR-Intron10-6359 UGAAACUUCCUUGAAUUAUUUUA 23 25239 CFTR-Intron10-6360 AUGAAACUUCCUUGAAUUAUUUUA 24 25240 CFTR-Intron10-6361 UGUUAUAGCAGCCUGAAC 18 25241 CFTR-Intron10-6362 UUGUUAUAGCAGCCUGAAC 19 25242 CFTR-Intron10-6363 UUUGUUAUAGCAGCCUGAAC 20 25243 CFTR-Intron10-6364 UUUUGUUAUAGCAGCCUGAAC 21 25244 CFTR-Intron10-6365 AUUUUGUUAUAGCAGCCUGAAC 22 25245 CFTR-Intron10-6366 UAUUUUGUUAUAGCAGCCUGAAC 23 25246 CFTR-Intron10-6367 GUAUUUUGUUAUAGCAGCCUGAAC 24 25247 CFTR-Intron10-6368 GCUUAUUCUUGUAAUAAC 18 25248 CFTR-Intron10-6369 AGCUUAUUCUUGUAAUAAC 19 25249 CFTR-Intron10-404 UAGCUUAUUCUUGUAAUAAC 20 19290 CFTR-Intron10-6370 UUAGCUUAUUCUUGUAAUAAC 21 25250 CFTR-Intron10-6371 UUUAGCUUAUUCUUGUAAUAAC 22 25251 CFTR-Intron10-6372 UUUUAGCUUAUUCUUGUAAUAAC 23 25252 CFTR-Intron10-6373 GUUUUAGCUUAUUCUUGUAAUAAC 24 25253 CFTR-Intron10-6374 GGCCUGCAUAUGUCUAAC 18 25254 CFTR-Intron10-6375 GGGCCUGCAUAUGUCUAAC 19 25255 CFTR-Intron10-6376 UGGGCCUGCAUAUGUCUAAC 20 25256 CFTR-Intron10-6377 UUGGGCCUGCAUAUGUCUAAC 21 25257 CFTR-Intron10-6378 UUUGGGCCUGCAUAUGUCUAAC 22 25258 CFTR-Intron10-6379 AUUUGGGCCUGCAUAUGUCUAAC 23 25259 CFTR-Intron10-6380 UAUUUGGGCCUGCAUAUGUCUAAC 24 25260 CFTR-Intron10-6381 CUUUCUGGACUGAGUAAC 18 25261 CFTR-Intron10-6382 GCUUUCUGGACUGAGUAAC 19 25262 CFTR-Intron10-1182 AGCUUUCUGGACUGAGUAAC 20 20067 CFTR-Intron10-6383 AAGCUUUCUGGACUGAGUAAC 21 25263 CFTR-Intron10-6384 CAAGCUUUCUGGACUGAGUAAC 22 25264 CFTR-Intron10-6385 CCAAGCUUUCUGGACUGAGUAAC 23 25265 CFTR-Intron10-6386 UCCAAGCUUUCUGGACUGAGUAAC 24 25266 CFTR-Intron10-6387 UCAUUUCAACUUAUACAC 18 25267 CFTR-Intron10-6388 AUCAUUUCAACUUAUACAC 19 25268 CFTR-Intron10-407 UAUCAUUUCAACUUAUACAC 20 19293 CFTR-Intron10-6389 AUAUCAUUUCAACUUAUACAC 21 25269 CFTR-Intron10-6390 AAUAUCAUUUCAACUUAUACAC 22 25270 CFTR-Intron10-6391 AAAUAUCAUUUCAACUUAUACAC 23 25271 CFTR-Intron10-6392 AAAAUAUCAUUUCAACUUAUACAC 24 25272 CFTR-Intron10-6393 GGUGAGAUUAGAGGCCAC 18 25273 CFTR-Intron10-6394 GGGUGAGAUUAGAGGCCAC 19 25274 CFTR-Intron10-409 UGGGUGAGAUUAGAGGCCAC 20 19295 CFTR-Intron10-6395 CUGGGUGAGAUUAGAGGCCAC 21 25275 CFTR-Intron10-6396 UCUGGGUGAGAUUAGAGGCCAC 22 25276 CFTR-Intron10-6397 CUCUGGGUGAGAUUAGAGGCCAC 23 25277 CFTR-Intron10-6398 UCUCUGGGUGAGAUUAGAGGCCAC 24 25278 CFTR-Intron10-6399 CUGAGGUGGGAGGAUCAC 18 25279 CFTR-Intron10-6400 GCUGAGGUGGGAGGAUCAC 19 25280 CFTR-Intron10-6401 GGCUGAGGUGGGAGGAUCAC 20 25281 CFTR-Intron10-6402 AGGCUGAGGUGGGAGGAUCAC 21 25282 CFTR-Intron10-6403 GAGGCUGAGGUGGGAGGAUCAC 22 25283 CFTR-Intron10-6404 GGAGGCUGAGGUGGGAGGAUCAC 23 25284 CFTR-Intron10-6405 GGGAGGCUGAGGUGGGAGGAUCAC 24 25285 CFTR-Intron10-6406 GUUUGUCUUUAAUUUCAC 18 25286 CFTR-Intron10-6407 GGUUUGUCUUUAAUUUCAC 19 25287 CFTR-Intron10-6408 AGGUUUGUCUUUAAUUUCAC 20 25288 CFTR-Intron10-6409 UAGGUUUGUCUUUAAUUUCAC 21 25289 CFTR-Intron10-6410 UUAGGUUUGUCUUUAAUUUCAC 22 25290 CFTR-Intron10-6411 GUUAGGUUUGUCUUUAAUUUCAC 23 25291 CFTR-Intron10-6412 AGUUAGGUUUGUCUUUAAUUUCAC 24 25292 CFTR-Intron10-6413 GGAAAUAAAUUUAAAGAC 18 25293 CFTR-Intron10-6414 AGGAAAUAAAUUUAAAGAC 19 25294 CFTR-Intron10-6415 GAGGAAAUAAAUUUAAAGAC 20 25295 CFTR-Intron10-6416 UGAGGAAAUAAAUUUAAAGAC 21 25296 CFTR-Intron10-6417 UUGAGGAAAUAAAUUUAAAGAC 22 25297 CFTR-Intron10-6418 AUUGAGGAAAUAAAUUUAAAGAC 23 25298 CFTR-Intron10-6419 UAUUGAGGAAAUAAAUUUAAAGAC 24 25299 CFTR-Intron10-6420 GCUGGCAUAGAGUAAGAC 18 25300 CFTR-Intron10-6421 GGCUGGCAUAGAGUAAGAC 19 25301 CFTR-Intron10-412 AGGCUGGCAUAGAGUAAGAC 20 19298 CFTR-Intron10-6422 GAGGCUGGCAUAGAGUAAGAC 21 25302 CFTR-Intron10-6423 UGAGGCUGGCAUAGAGUAAGAC 22 25303 CFTR-Intron10-6424 CUGAGGCUGGCAUAGAGUAAGAC 23 25304 CFTR-Intron10-6425 ACUGAGGCUGGCAUAGAGUAAGAC 24 25305 CFTR-Intron10-6426 GCUAUUCUGUAGGGAGAC 18 25306 CFTR-Intron10-6427 GGCUAUUCUGUAGGGAGAC 19 25307 CFTR-Intron10-6428 AGGCUAUUCUGUAGGGAGAC 20 25308 CFTR-Intron10-6429 UAGGCUAUUCUGUAGGGAGAC 21 25309 CFTR-Intron10-6430 UUAGGCUAUUCUGUAGGGAGAC 22 25310 CFTR-Intron10-6431 UUUAGGCUAUUCUGUAGGGAGAC 23 25311 CFTR-Intron10-6432 UUUUAGGCUAUUCUGUAGGGAGAC 24 25312 CFTR-Intron10-6433 AAGAAUUGAAUAUGAGAC 18 25313 CFTR-Intron10-6434 GAAGAAUUGAAUAUGAGAC 19 25314 CFTR-Intron10-6435 UGAAGAAUUGAAUAUGAGAC 20 25315 CFTR-Intron10-6436 UUGAAGAAUUGAAUAUGAGAC 21 25316 CFTR-Intron10-6437 UUUGAAGAAUUGAAUAUGAGAC 22 25317 CFTR-Intron10-6438 UUUUGAAGAAUUGAAUAUGAGAC 23 25318 CFTR-Intron10-6439 AUUUUGAAGAAUUGAAUAUGAGAC 24 25319 CFTR-Intron10-6440 GCCCGUAGUCCCAGCUAC 18 25320 CFTR-Intron10-6441 UGCCCGUAGUCCCAGCUAC 19 25321 CFTR-Intron10-6442 GUGCCCGUAGUCCCAGCUAC 20 25322 CFTR-Intron10-6443 GGUGCCCGUAGUCCCAGCUAC 21 25323 CFTR-Intron10-6444 GGGUGCCCGUAGUCCCAGCUAC 22 25324 CFTR-Intron10-6445 CGGGUGCCCGUAGUCCCAGCUAC 23 25325 CFTR-Intron10-6446 GCGGGUGCCCGUAGUCCCAGCUAC 24 25326 CFTR-Intron10-6447 UGUGCCUGUAGUCCCAGCUAC 21 25327 CFTR-Intron10-6448 GUGUGCCUGUAGUCCCAGCUAC 22 25328 CFTR-Intron10-6449 UGUGUGCCUGUAGUCCCAGCUAC 23 25329 CFTR-Intron10-6450 GUGUGUGCCUGUAGUCCCAGCUAC 24 25330 CFTR-Intron10-6451 GAAAAGUUGUAACAGUAC 18 25331 CFTR-Intron10-6452 GGAAAAGUUGUAACAGUAC 19 25332 CFTR-Intron10-6453 CGGAAAAGUUGUAACAGUAC 20 25333 CFTR-Intron10-6454 ACGGAAAAGUUGUAACAGUAC 21 25334 CFTR-Intron10-6455 CACGGAAAAGUUGUAACAGUAC 22 25335 CFTR-Intron10-6456 GCACGGAAAAGUUGUAACAGUAC 23 25336 CFTR-Intron10-6457 UGCACGGAAAAGUUGUAACAGUAC 24 25337 CFTR-Intron10-6458 GAUAAAUGUGCCGUUUAC 18 25338 CFTR-Intron10-6459 GGAUAAAUGUGCCGUUUAC 19 25339 CFTR-Intron10-6460 AGGAUAAAUGUGCCGUUUAC 20 25340 CFTR-Intron10-6461 AAGGAUAAAUGUGCCGUUUAC 21 25341 CFTR-Intron10-6462 GAAGGAUAAAUGUGCCGUUUAC 22 25342 CFTR-Intron10-6463 GGAAGGAUAAAUGUGCCGUUUAC 23 25343 CFTR-Intron10-6464 UGGAAGGAUAAAUGUGCCGUUUAC 24 25344 CFTR-Intron10-6465 UCAUAGCUCACUGUAACC 18 25345 CFTR-Intron10-6466 AUCAUAGCUCACUGUAACC 19 25346 CFTR-Intron10-6467 GAUCAUAGCUCACUGUAACC 20 25347 CFTR-Intron10-6468 UGAUCAUAGCUCACUGUAACC 21 25348 CFTR-Intron10-6469 GUGAUCAUAGCUCACUGUAACC 22 25349 CFTR-Intron10-6470 UGUGAUCAUAGCUCACUGUAACC 23 25350 CFTR-Intron10-6471 GUGUGAUCAUAGCUCACUGUAACC 24 25351 CFTR-Intron10-6472 GUCUAGCCUAGAAAUACC 18 25352 CFTR-Intron10-6473 UGUCUAGCCUAGAAAUACC 19 25353 CFTR-Intron10-6474 CUGUCUAGCCUAGAAAUACC 20 25354 CFTR-Intron10-6475 ACUGUCUAGCCUAGAAAUACC 21 25355 CFTR-Intron10-6476 AACUGUCUAGCCUAGAAAUACC 22 25356 CFTR-Intron10-6477 AAACUGUCUAGCCUAGAAAUACC 23 25357 CFTR-Intron10-6478 CAAACUGUCUAGCCUAGAAAUACC 24 25358 CFTR-Intron10-6479 GAGGAAGGCAGUGGUCCC 18 25359 CFTR-Intron10-6480 AGAGGAAGGCAGUGGUCCC 19 25360 CFTR-Intron10-6481 UAGAGGAAGGCAGUGGUCCC 20 25361 CFTR-Intron10-6482 UUAGAGGAAGGCAGUGGUCCC 21 25362 CFTR-Intron10-6483 GUUAGAGGAAGGCAGUGGUCCC 22 25363 CFTR-Intron10-6484 AGUUAGAGGAAGGCAGUGGUCCC 23 25364 CFTR-Intron10-6485 GAGUUAGAGGAAGGCAGUGGUCCC 24 25365 CFTR-Intron10-6486 CUCACAAACUGUCUAGCC 18 25366 CFTR-Intron10-6487 ACUCACAAACUGUCUAGCC 19 25367 CFTR-Intron10-6488 AACUCACAAACUGUCUAGCC 20 25368 CFTR-Intron10-6489 AAACUCACAAACUGUCUAGCC 21 25369 CFTR-Intron10-6490 AAAACUCACAAACUGUCUAGCC 22 25370 CFTR-Intron10-6491 AAAAACUCACAAACUGUCUAGCC 23 25371 CFTR-Intron10-6492 AAAAAACUCACAAACUGUCUAGCC 24 25372 CFTR-Intron10-6493 UGAAUGAAUGUGGUAUCC 18 25373 CFTR-Intron10-6494 GUGAAUGAAUGUGGUAUCC 19 25374 CFTR-Intron10-425 AGUGAAUGAAUGUGGUAUCC 20 19311 CFTR-Intron10-6495 UAGUGAAUGAAUGUGGUAUCC 21 25375 CFTR-Intron10-6496 CUAGUGAAUGAAUGUGGUAUCC 22 25376 CFTR-Intron10-6497 GCUAGUGAAUGAAUGUGGUAUCC 23 25377 CFTR-Intron10-6498 AGCUAGUGAAUGAAUGUGGUAUCC 24 25378 CFTR-Intron10-6499 UUGGGAGGUGAUUAGUCC 18 25379 CFTR-Intron10-6500 UUUGGGAGGUGAUUAGUCC 19 25380 CFTR-Intron10-6501 CUUUGGGAGGUGAUUAGUCC 20 25381 CFTR-Intron10-6502 CCUUUGGGAGGUGAUUAGUCC 21 25382 CFTR-Intron10-6503 GCCUUUGGGAGGUGAUUAGUCC 22 25383 CFTR-Intron10-6504 GGCCUUUGGGAGGUGAUUAGUCC 23 25384 CFTR-Intron10-6505 GGGCCUUUGGGAGGUGAUUAGUCC 24 25385 CFTR-Intron10-6506 UCUUUAUUUUUAUAUUCC 18 25386 CFTR-Intron10-6507 UUCUUUAUUUUUAUAUUCC 19 25387 CFTR-Intron10-6508 CUUCUUUAUUUUUAUAUUCC 20 25388 CFTR-Intron10-6509 UCUUCUUUAUUUUUAUAUUCC 21 25389 CFTR-Intron10-6510 GUCUUCUUUAUUUUUAUAUUCC 22 25390 CFTR-Intron10-6511 UGUCUUCUUUAUUUUUAUAUUCC 23 25391 CFTR-Intron10-6512 AUGUCUUCUUUAUUUUUAUAUUCC 24 25392 CFTR-Intron10-6513 GUUGUCAAAUGUCCUUCC 18 25393 CFTR-Intron10-6514 UGUUGUCAAAUGUCCUUCC 19 25394 CFTR-Intron10-6515 AUGUUGUCAAAUGUCCUUCC 20 25395 CFTR-Intron10-6516 GAUGUUGUCAAAUGUCCUUCC 21 25396 CFTR-Intron10-6517 AGAUGUUGUCAAAUGUCCUUCC 22 25397 CFTR-Intron10-6518 UAGAUGUUGUCAAAUGUCCUUCC 23 25398 CFTR-Intron10-6519 GUAGAUGUUGUCAAAUGUCCUUCC 24 25399 CFTR-Intron10-6520 CUUUUUUUAGUAUCUUCC 18 25400 CFTR-Intron10-6521 ACUUUUUUUAGUAUCUUCC 19 25401 CFTR-Intron10-6522 AACUUUUUUUAGUAUCUUCC 20 25402 CFTR-Intron10-6523 UAACUUUUUUUAGUAUCUUCC 21 25403 CFTR-Intron10-6524 GUAACUUUUUUUAGUAUCUUCC 22 25404 CFTR-Intron10-6525 GGUAACUUUUUUUAGUAUCUUCC 23 25405 CFTR-Intron10-6526 AGGUAACUUUUUUUAGUAUCUUCC 24 25406 CFTR-Intron10-6527 GGAGACAAGGGAGGAAGC 18 25407 CFTR-Intron10-6528 GGGAGACAAGGGAGGAAGC 19 25408 CFTR-Intron10-6529 AGGGAGACAAGGGAGGAAGC 20 25409 CFTR-Intron10-6530 UAGGGAGACAAGGGAGGAAGC 21 25410 CFTR-Intron10-6531 GUAGGGAGACAAGGGAGGAAGC 22 25411 CFTR-Intron10-6532 UGUAGGGAGACAAGGGAGGAAGC 23 25412 CFTR-Intron10-6533 CUGUAGGGAGACAAGGGAGGAAGC 24 25413 CFTR-Intron10-6534 GCCAUGUGAGAACACAGC 18 25414 CFTR-Intron10-6535 UGCCAUGUGAGAACACAGC 19 25415 CFTR-Intron10-1218 CUGCCAUGUGAGAACACAGC 20 20103 CFTR-Intron10-6536 UCUGCCAUGUGAGAACACAGC 21 25416 CFTR-Intron10-6537 UUCUGCCAUGUGAGAACACAGC 22 25417 CFTR-Intron10-6538 UUUCUGCCAUGUGAGAACACAGC 23 25418 CFTR-Intron10-6539 CUUUCUGCCAUGUGAGAACACAGC 24 25419 CFTR-Intron10-6540 CAGGAGUUUGAGACCAGC 18 25420 CFTR-Intron10-6541 CCAGGAGUUUGAGACCAGC 19 25421 CFTR-Intron10-6542 UCCAGGAGUUUGAGACCAGC 20 25422 CFTR-Intron10-6543 GUCCAGGAGUUUGAGACCAGC 21 25423 CFTR-Intron10-6544 AGUCCAGGAGUUUGAGACCAGC 22 25424 CFTR-Intron10-6545 GAGUCCAGGAGUUUGAGACCAGC 23 25425 CFTR-Intron10-6546 UGAGUCCAGGAGUUUGAGACCAGC 24 25426 CFTR-Intron10-6547 GUAUUUUGUUAUAGCAGC 18 25427 CFTR-Intron10-6548 GGUAUUUUGUUAUAGCAGC 19 25428 CFTR-Intron10-6549 UGGUAUUUUGUUAUAGCAGC 20 25429 CFTR-Intron10-6550 AUGGUAUUUUGUUAUAGCAGC 21 25430 CFTR-Intron10-6551 CAUGGUAUUUUGUUAUAGCAGC 22 25431 CFTR-Intron10-6552 UCAUGGUAUUUUGUUAUAGCAGC 23 25432 CFTR-Intron10-6553 UUCAUGGUAUUUUGUUAUAGCAGC 24 25433 CFTR-Intron10-6554 UGGGAGGAUCACCUGAGC 18 25434 CFTR-Intron10-6555 GUGGGAGGAUCACCUGAGC 19 25435 CFTR-Intron10-6556 GGUGGGAGGAUCACCUGAGC 20 25436 CFTR-Intron10-6557 AGGUGGGAGGAUCACCUGAGC 21 25437 CFTR-Intron10-6558 GAGGUGGGAGGAUCACCUGAGC 22 25438 CFTR-Intron10-6559 UGAGGUGGGAGGAUCACCUGAGC 23 25439 CFTR-Intron10-6560 CUGAGGUGGGAGGAUCACCUGAGC 24 25440 CFTR-Intron10-6561 CUCACCCUCCCAAGUAGC 18 25441 CFTR-Intron10-6562 CCUCACCCUCCCAAGUAGC 19 25442 CFTR-Intron10-672 GCCUCACCCUCCCAAGUAGC 20 19558 CFTR-Intron10-6563 UGCCUCACCCUCCCAAGUAGC 21 25443 CFTR-Intron10-6564 CUGCCUCACCCUCCCAAGUAGC 22 25444 CFTR-Intron10-6565 CCUGCCUCACCCUCCCAAGUAGC 23 25445 CFTR-Intron10-6566 UCCUGCCUCACCCUCCCAAGUAGC 24 25446 CFTR-Intron10-6567 CUCAGCCUCCCAAGUAGC 18 25447 CFTR-Intron10-6568 CCUCAGCCUCCCAAGUAGC 19 25448 CFTR-Intron10-673 GCCUCAGCCUCCCAAGUAGC 20 19559 CFTR-Intron10-6569 UGCCUCAGCCUCCCAAGUAGC 21 25449 CFTR-Intron10-6570 CUGCCUCAGCCUCCCAAGUAGC 22 25450 CFTR-Intron10-6571 CCUGCCUCAGCCUCCCAAGUAGC 23 25451 CFTR-Intron10-6572 UCCUGCCUCAGCCUCCCAAGUAGC 24 25452 CFTR-Intron10-6573 CCCUUAAACAAUACAGGC 18 25453 CFTR-Intron10-6574 ACCCUUAAACAAUACAGGC 19 25454 CFTR-Intron10-6575 GACCCUUAAACAAUACAGGC 20 25455 CFTR-Intron10-6576 UGACCCUUAAACAAUACAGGC 21 25456 CFTR-Intron10-6577 UUGACCCUUAAACAAUACAGGC 22 25457 CFTR-Intron10-6578 AUUGACCCUUAAACAAUACAGGC 23 25458 CFTR-Intron10-6579 AAUUGACCCUUAAACAAUACAGGC 24 25459 CFTR-Intron10-6580 AGUGCUGGGAUUACAGGC 18 25460 CFTR-Intron10-6581 AAGUGCUGGGAUUACAGGC 19 25461 CFTR-Intron10-6582 AAAGUGCUGGGAUUACAGGC 20 25462 CFTR-Intron10-6583 CAAAGUGCUGGGAUUACAGGC 21 25463 CFTR-Intron10-6584 CCAAAGUGCUGGGAUUACAGGC 22 25464 CFTR-Intron10-6585 CCCAAAGUGCUGGGAUUACAGGC 23 25465 CFTR-Intron10-6586 UCCCAAAGUGCUGGGAUUACAGGC 24 25466 CFTR-Intron10-6587 AGUGUUGGGAUUACAGGC 18 25467 CFTR-Intron10-6588 AAGUGUUGGGAUUACAGGC 19 25468 CFTR-Intron10-6589 AAAGUGUUGGGAUUACAGGC 20 25469 CFTR-Intron10-6590 CAAAGUGUUGGGAUUACAGGC 21 25470 CFTR-Intron10-6591 CCAAAGUGUUGGGAUUACAGGC 22 25471 CFTR-Intron10-6592 CCCAAAGUGUUGGGAUUACAGGC 23 25472 CFTR-Intron10-6593 UCCCAAAGUGUUGGGAUUACAGGC 24 25473 CFTR-Intron10-6594 GUCUUACUGUCACCAGGC 18 25474 CFTR-Intron10-6595 AGUCUUACUGUCACCAGGC 19 25475 CFTR-Intron10-677 GAGUCUUACUGUCACCAGGC 20 19563 CFTR-Intron10-6596 AGAGUCUUACUGUCACCAGGC 21 25476 CFTR-Intron10-6597 CAGAGUCUUACUGUCACCAGGC 22 25477 CFTR-Intron10-6598 ACAGAGUCUUACUGUCACCAGGC 23 25478 CFTR-Intron10-6599 GACAGAGUCUUACUGUCACCAGGC 24 25479 CFTR-Intron10-6600 UACUCGGGAGGCUGAGGC 18 25480 CFTR-Intron10-6601 CUACUCGGGAGGCUGAGGC 19 25481 CFTR-Intron10-680 GCUACUCGGGAGGCUGAGGC 20 19566 CFTR-Intron10-6602 AGCUACUCGGGAGGCUGAGGC 21 25482 CFTR-Intron10-6603 CAGCUACUCGGGAGGCUGAGGC 22 25483 CFTR-Intron10-6604 CCAGCUACUCGGGAGGCUGAGGC 23 25484 CFTR-Intron10-6605 CCCAGCUACUCGGGAGGCUGAGGC 24 25485 CFTR-Intron10-6606 AGUGCUGGGUUUAUAGGC 18 25486 CFTR-Intron10-6607 AAGUGCUGGGUUUAUAGGC 19 25487 CFTR-Intron10-6608 AAAGUGCUGGGUUUAUAGGC 20 25488 CFTR-Intron10-6609 CAAAGUGCUGGGUUUAUAGGC 21 25489 CFTR-Intron10-6610 CCAAAGUGCUGGGUUUAUAGGC 22 25490 CFTR-Intron10-6611 CCCAAAGUGCUGGGUUUAUAGGC 23 25491 CFTR-Intron10-6612 UCCCAAAGUGCUGGGUUUAUAGGC 24 25492 CFTR-Intron10-6613 AAGUGCCACUAGUGAUGC 18 25493 CFTR-Intron10-6614 AAAGUGCCACUAGUGAUGC 19 25494 CFTR-Intron10-6615 CAAAGUGCCACUAGUGAUGC 20 25495 CFTR-Intron10-6616 ACAAAGUGCCACUAGUGAUGC 21 25496 CFTR-Intron10-6617 UACAAAGUGCCACUAGUGAUGC 22 25497 CFTR-Intron10-6618 AUACAAAGUGCCACUAGUGAUGC 23 25498 CFTR-Intron10-6619 CAUACAAAGUGCCACUAGUGAUGC 24 25499 CFTR-Intron10-6620 UCAAAUUAUUUCUACUGC 18 25500 CFTR-Intron10-6621 UUCAAAUUAUUUCUACUGC 19 25501 CFTR-Intron10-6622 GUUCAAAUUAUUUCUACUGC 20 25502 CFTR-Intron10-6623 UGUUCAAAUUAUUUCUACUGC 21 25503 CFTR-Intron10-6624 UUGUUCAAAUUAUUUCUACUGC 22 25504 CFTR-Intron10-6625 GUUGUUCAAAUUAUUUCUACUGC 23 25505 CFTR-Intron10-6626 UGUUGUUCAAAUUAUUUCUACUGC 24 25506 CFTR-Intron10-6627 AUUUGAACAAAGACUUGC 18 25507 CFTR-Intron10-6628 CAUUUGAACAAAGACUUGC 19 25508 CFTR-Intron10-1236 ACAUUUGAACAAAGACUUGC 20 20121 CFTR-Intron10-6629 AACAUUUGAACAAAGACUUGC 21 25509 CFTR-Intron10-6630 UAACAUUUGAACAAAGACUUGC 22 25510 CFTR-Intron10-6631 GUAACAUUUGAACAAAGACUUGC 23 25511 CFTR-Intron10-6632 GGUAACAUUUGAACAAAGACUUGC 24 25512 CFTR-Intron10-6633 GAGUUUACUAACUCAAUC 18 25513 CFTR-Intron10-6634 GGAGUUUACUAACUCAAUC 19 25514 CFTR-Intron10-6635 CGGAGUUUACUAACUCAAUC 20 25515 CFTR-Intron10-6636 ACGGAGUUUACUAACUCAAUC 21 25516 CFTR-Intron10-6637 AACGGAGUUUACUAACUCAAUC 22 25517 CFTR-Intron10-6638 AAACGGAGUUUACUAACUCAAUC 23 25518 CFTR-Intron10-6639 GAAACGGAGUUUACUAACUCAAUC 24 25519 CFTR-Intron10-6640 UCUGCUGGCACCUUGAUC 18 25520 CFTR-Intron10-6641 AUCUGCUGGCACCUUGAUC 19 25521 CFTR-Intron10-6642 AAUCUGCUGGCACCUUGAUC 20 25522 CFTR-Intron10-6643 AAAUCUGCUGGCACCUUGAUC 21 25523 CFTR-Intron10-6644 CAAAUCUGCUGGCACCUUGAUC 22 25524 CFTR-Intron10-6645 CCAAAUCUGCUGGCACCUUGAUC 23 25525 CFTR-Intron10-6646 CCCAAAUCUGCUGGCACCUUGAUC 24 25526 CFTR-Intron10-6647 CUUGCUUUUCCCACUAUC 18 25527 CFTR-Intron10-6648 UCUUGCUUUUCCCACUAUC 19 25528 CFTR-Intron10-6649 UUCUUGCUUUUCCCACUAUC 20 25529 CFTR-Intron10-6650 CUUCUUGCUUUUCCCACUAUC 21 25530 CFTR-Intron10-6651 GCUUCUUGCUUUUCCCACUAUC 22 25531 CFTR-Intron10-6652 UGCUUCUUGCUUUUCCCACUAUC 23 25532 CFTR-Intron10-6653 UUGCUUCUUGCUUUUCCCACUAUC 24 25533 CFTR-Intron10-6654 GUGAAUGAAUGUGGUAUC 18 25534 CFTR-Intron10-6655 AGUGAAUGAAUGUGGUAUC 19 25535 CFTR-Intron10-6656 UAGUGAAUGAAUGUGGUAUC 20 25536 CFTR-Intron10-6657 CUAGUGAAUGAAUGUGGUAUC 21 25537 CFTR-Intron10-6658 GCUAGUGAAUGAAUGUGGUAUC 22 25538 CFTR-Intron10-6659 AGCUAGUGAAUGAAUGUGGUAUC 23 25539 CFTR-Intron10-6660 AAGCUAGUGAAUGAAUGUGGUAUC 24 25540 CFTR-Intron10-6661 CACUGUAACCUUGAACUC 18 25541 CFTR-Intron10-6662 UCACUGUAACCUUGAACUC 19 25542 CFTR-Intron10-6663 CUCACUGUAACCUUGAACUC 20 25543 CFTR-Intron10-6664 GCUCACUGUAACCUUGAACUC 21 25544 CFTR-Intron10-6665 AGCUCACUGUAACCUUGAACUC 22 25545 CFTR-Intron10-6666 UAGCUCACUGUAACCUUGAACUC 23 25546 CFTR-Intron10-6667 AUAGCUCACUGUAACCUUGAACUC 24 25547 CFTR-Intron10-6668 AGAAAUUAAGAAAGACUC 18 25548 CFTR-Intron10-6669 UAGAAAUUAAGAAAGACUC 19 25549 CFTR-Intron10-6670 AUAGAAAUUAAGAAAGACUC 20 25550 CFTR-Intron10-6671 AAUAGAAAUUAAGAAAGACUC 21 25551 CFTR-Intron10-6672 AAAUAGAAAUUAAGAAAGACUC 22 25552 CFTR-Intron10-6673 AAAAUAGAAAUUAAGAAAGACUC 23 25553 CFTR-Intron10-6674 GAAAAUAGAAAUUAAGAAAGACUC 24 25554 CFTR-Intron10-6675 AUUAGGGAAUGCAGACUC 18 25555 CFTR-Intron10-6676 GAUUAGGGAAUGCAGACUC 19 25556 CFTR-Intron10-92 GGAUUAGGGAAUGCAGACUC 20 18978 CFTR-Intron10-6677 GGGAUUAGGGAAUGCAGACUC 21 25557 CFTR-Intron10-6678 AGGGAUUAGGGAAUGCAGACUC 22 25558 CFTR-Intron10-6679 GAGGGAUUAGGGAAUGCAGACUC 23 25559 CFTR-Intron10-6680 UGAGGGAUUAGGGAAUGCAGACUC 24 25560 CFTR-Intron10-6681 UAUUCUUUUGAUAUACUC 18 25561 CFTR-Intron10-6682 UUAUUCUUUUGAUAUACUC 19 25562 CFTR-Intron10-6683 CUUAUUCUUUUGAUAUACUC 20 25563 CFTR-Intron10-6684 CCUUAUUCUUUUGAUAUACUC 21 25564 CFTR-Intron10-6685 GCCUUAUUCUUUUGAUAUACUC 22 25565 CFTR-Intron10-6686 UGCCUUAUUCUUUUGAUAUACUC 23 25566 CFTR-Intron10-6687 AUGCCUUAUUCUUUUGAUAUACUC 24 25567 CFTR-Intron10-6688 CCGUAGUCCCAGCUACUC 18 25568 CFTR-Intron10-6689 CCCGUAGUCCCAGCUACUC 19 25569 CFTR-Intron10-687 GCCCGUAGUCCCAGCUACUC 20 19573 CFTR-Intron10-6690 UGCCCGUAGUCCCAGCUACUC 21 25570 CFTR-Intron10-6691 GUGCCCGUAGUCCCAGCUACUC 22 25571 CFTR-Intron10-6692 GGUGCCCGUAGUCCCAGCUACUC 23 25572 CFTR-Intron10-6693 GGGUGCCCGUAGUCCCAGCUACUC 24 25573 CFTR-Intron10-6694 CUUGGACUUCCCAGCCUC 18 25574 CFTR-Intron10-6695 UCUUGGACUUCCCAGCCUC 19 25575 CFTR-Intron10-6696 AUCUUGGACUUCCCAGCCUC 20 25576 CFTR-Intron10-6697 GAUCUUGGACUUCCCAGCCUC 21 25577 CFTR-Intron10-6698 UGAUCUUGGACUUCCCAGCCUC 22 25578 CFTR-Intron10-6699 UUGAUCUUGGACUUCCCAGCCUC 23 25579 CFTR-Intron10-6700 CUUGAUCUUGGACUUCCCAGCCUC 24 25580 CFTR-Intron10-6701 CACUGCAACCUCUGCCUC 18 25581 CFTR-Intron10-6702 UCACUGCAACCUCUGCCUC 19 25582 CFTR-Intron10-6703 CUCACUGCAACCUCUGCCUC 20 25583 CFTR-Intron10-6704 GCUCACUGCAACCUCUGCCUC 21 25584 CFTR-Intron10-6705 GGCUCACUGCAACCUCUGCCUC 22 25585 CFTR-Intron10-6706 CGGCUCACUGCAACCUCUGCCUC 23 25586 CFTR-Intron10-6707 UCGGCUCACUGCAACCUCUGCCUC 24 25587 CFTR-Intron10-6708 AAAAAGUUUAGUGGUCUC 18 25588 CFTR-Intron10-6709 GAAAAAGUUUAGUGGUCUC 19 25589 CFTR-Intron10-6710 AGAAAAAGUUUAGUGGUCUC 20 25590 CFTR-Intron10-6711 GAGAAAAAGUUUAGUGGUCUC 21 25591 CFTR-Intron10-6712 UGAGAAAAAGUUUAGUGGUCUC 22 25592 CFTR-Intron10-6713 GUGAGAAAAAGUUUAGUGGUCUC 23 25593 CFTR-Intron10-6714 UGUGAGAAAAAGUUUAGUGGUCUC 24 25594 CFTR-Intron10-6715 AGGUGAAUUGCUUGAGUC 18 25595 CFTR-Intron10-6716 CAGGUGAAUUGCUUGAGUC 19 25596 CFTR-Intron10-6717 GCAGGUGAAUUGCUUGAGUC 20 25597 CFTR-Intron10-6718 GGCAGGUGAAUUGCUUGAGUC 21 25598 CFTR-Intron10-6719 AGGCAGGUGAAUUGCUUGAGUC 22 25599 CFTR-Intron10-6720 GAGGCAGGUGAAUUGCUUGAGUC 23 25600 CFTR-Intron10-6721 AGAGGCAGGUGAAUUGCUUGAGUC 24 25601 CFTR-Intron10-6722 UAUGUAUAUAUGUGUGUC 18 25602 CFTR-Intron10-6723 GUAUGUAUAUAUGUGUGUC 19 25603 CFTR-Intron10-1242 UGUAUGUAUAUAUGUGUGUC 20 20127 CFTR-Intron10-6724 AUGUAUGUAUAUAUGUGUGUC 21 25604 CFTR-Intron10-6725 UAUGUAUGUAUAUAUGUGUGUC 22 25605 CFTR-Intron10-6726 AUAUGUAUGUAUAUAUGUGUGUC 23 25606 CFTR-Intron10-6727 CAUAUGUAUGUAUAUAUGUGUGUC 24 25607 CFTR-Intron10-6728 GACCAAAACUUUAUUGUC 18 25608 CFTR-Intron10-6729 GGACCAAAACUUUAUUGUC 19 25609 CFTR-Intron10-440 AGGACCAAAACUUUAUUGUC 20 19326 CFTR-Intron10-6730 AAGGACCAAAACUUUAUUGUC 21 25610 CFTR-Intron10-6731 AAAGGACCAAAACUUUAUUGUC 22 25611 CFTR-Intron10-6732 AAAAGGACCAAAACUUUAUUGUC 23 25612 CFTR-Intron10-6733 CAAAAGGACCAAAACUUUAUUGUC 24 25613 CFTR-Intron10-6734 CAUUAUAACACUGCUUUC 18 25614 CFTR-Intron10-6735 UCAUUAUAACACUGCUUUC 19 25615 CFTR-Intron10-1247 UUCAUUAUAACACUGCUUUC 20 20132 CFTR-Intron10-6736 CUUCAUUAUAACACUGCUUUC 21 25616 CFTR-Intron10-6737 UCUUCAUUAUAACACUGCUUUC 22 25617 CFTR-Intron10-6738 CUCUUCAUUAUAACACUGCUUUC 23 25618 CFTR-Intron10-6739 GCUCUUCAUUAUAACACUGCUUUC 24 25619 CFTR-Intron10-6740 AUGUACAAGUCUAGUUUC 18 25620 CFTR-Intron10-6741 GAUGUACAAGUCUAGUUUC 19 25621 CFTR-Intron10-6742 GGAUGUACAAGUCUAGUUUC 20 25622 CFTR-Intron10-6743 UGGAUGUACAAGUCUAGUUUC 21 25623 CFTR-Intron10-6744 UUGGAUGUACAAGUCUAGUUUC 22 25624 CFTR-Intron10-6745 GUUGGAUGUACAAGUCUAGUUUC 23 25625 CFTR-Intron10-6746 AGUUGGAUGUACAAGUCUAGUUUC 24 25626 CFTR-Intron10-6747 GGAAAAUUUAACAUUUUC 18 25627 CFTR-Intron10-6748 GGGAAAAUUUAACAUUUUC 19 25628 CFTR-Intron10-6749 AGGGAAAAUUUAACAUUUUC 20 25629 CFTR-Intron10-6750 AAGGGAAAAUUUAACAUUUUC 21 25630 CFTR-Intron10-6751 UAAGGGAAAAUUUAACAUUUUC 22 25631 CFTR-Intron10-6752 CUAAGGGAAAAUUUAACAUUUUC 23 25632 CFTR-Intron10-6753 CCUAAGGGAAAAUUUAACAUUUUC 24 25633 CFTR-Intron10-6754 UUCCAUUACAUUGUUUUC 18 25634 CFTR-Intron10-6755 UUUCCAUUACAUUGUUUUC 19 25635 CFTR-Intron10-6756 GUUUCCAUUACAUUGUUUUC 20 25636 CFTR-Intron10-6757 UGUUUCCAUUACAUUGUUUUC 21 25637 CFTR-Intron10-6758 GUGUUUCCAUUACAUUGUUUUC 22 25638 CFTR-Intron10-6759 AGUGUUUCCAUUACAUUGUUUUC 23 25639 CFTR-Intron10-6760 UAGUGUUUCCAUUACAUUGUUUUC 24 25640 CFTR-Intron10-6761 AUUAAAAUAUAUAAAAAG 18 25641 CFTR-Intron10-6762 AAUUAAAAUAUAUAAAAAG 19 25642 CFTR-Intron10-6763 AAAUUAAAAUAUAUAAAAAG 20 25643 CFTR-Intron10-6764 AAAAUUAAAAUAUAUAAAAAG 21 25644 CFTR-Intron10-6765 GAAAAUUAAAAUAUAUAAAAAG 22 25645 CFTR-Intron10-6766 UGAAAAUUAAAAUAUAUAAAAAG 23 25646 CFTR-Intron10-6767 AUGAAAAUUAAAAUAUAUAAAAAG 24 25647 CFTR-Intron10-6768 AGAGAGGAAGGAAGAAAG 18 25648 CFTR-Intron10-6769 AAGAGAGGAAGGAAGAAAG 19 25649 CFTR-Intron10-6770 AAAGAGAGGAAGGAAGAAAG 20 25650 CFTR-Intron10-6771 GAAAGAGAGGAAGGAAGAAAG 21 25651 CFTR-Intron10-6772 AGAAAGAGAGGAAGGAAGAAAG 22 25652 CFTR-Intron10-6773 AAGAAAGAGAGGAAGGAAGAAAG 23 25653 CFTR-Intron10-6774 AAAGAAAGAGAGGAAGGAAGAAAG 24 25654 CFTR-Intron10-6775 GGAAGGAAGGAAGGAAAG 18 25655 CFTR-Intron10-6776 AGGAAGGAAGGAAGGAAAG 19 25656 CFTR-Intron10-6777 GAGGAAGGAAGGAAGGAAAG 20 25657 CFTR-Intron10-6778 GGAGGAAGGAAGGAAGGAAAG 21 25658 CFTR-Intron10-6779 AGGAGGAAGGAAGGAAGGAAAG 22 25659 CFTR-Intron10-6780 UAGGAGGAAGGAAGGAAGGAAAG 23 25660 CFTR-Intron10-6781 GUAGGAGGAAGGAAGGAAGGAAAG 24 25661 CFTR-Intron10-6782 AACCCAACUGAUGUCAAG 18 25662 CFTR-Intron10-6783 GAACCCAACUGAUGUCAAG 19 25663 CFTR-Intron10-6784 GGAACCCAACUGAUGUCAAG 20 25664 CFTR-Intron10-6785 CGGAACCCAACUGAUGUCAAG 21 25665 CFTR-Intron10-6786 CCGGAACCCAACUGAUGUCAAG 22 25666 CFTR-Intron10-6787 CCCGGAACCCAACUGAUGUCAAG 23 25667 CFTR-Intron10-6788 UCCCGGAACCCAACUGAUGUCAAG 24 25668 CFTR-Intron10-6789 UCACCUGAGCCUGAGAAG 18 25669 CFTR-Intron10-6790 AUCACCUGAGCCUGAGAAG 19 25670 CFTR-Intron10-692 GAUCACCUGAGCCUGAGAAG 20 19578 CFTR-Intron10-6791 GGAUCACCUGAGCCUGAGAAG 21 25671 CFTR-Intron10-6792 AGGAUCACCUGAGCCUGAGAAG 22 25672 CFTR-Intron10-6793 GAGGAUCACCUGAGCCUGAGAAG 23 25673 CFTR-Intron10-6794 GGAGGAUCACCUGAGCCUGAGAAG 24 25674 CFTR-Intron10-6795 AAUGAGGAAGAAAGGAAG 18 25675 CFTR-Intron10-6796 AAAUGAGGAAGAAAGGAAG 19 25676 CFTR-Intron10-6797 GAAAUGAGGAAGAAAGGAAG 20 25677 CFTR-Intron10-6798 GGAAAUGAGGAAGAAAGGAAG 21 25678 CFTR-Intron10-6799 AGGAAAUGAGGAAGAAAGGAAG 22 25679 CFTR-Intron10-6800 AAGGAAAUGAGGAAGAAAGGAAG 23 25680 CFTR-Intron10-6801 GAAGGAAAUGAGGAAGAAAGGAAG 24 25681 CFTR-Intron10-6802 AGUCUAGUUUCAAGGAAG 18 25682 CFTR-Intron10-6803 AAGUCUAGUUUCAAGGAAG 19 25683 CFTR-Intron10-449 CAAGUCUAGUUUCAAGGAAG 20 19335 CFTR-Intron10-6804 ACAAGUCUAGUUUCAAGGAAG 21 25684 CFTR-Intron10-6805 UACAAGUCUAGUUUCAAGGAAG 22 25685 CFTR-Intron10-6806 GUACAAGUCUAGUUUCAAGGAAG 23 25686 CFTR-Intron10-6807 UGUACAAGUCUAGUUUCAAGGAAG 24 25687 CFTR-Intron10-6808 GGGGCUGGUAGUGUGAAG 18 25688 CFTR-Intron10-6809 GGGGGCUGGUAGUGUGAAG 19 25689 CFTR-Intron10-6810 AGGGGGCUGGUAGUGUGAAG 20 25690 CFTR-Intron10-6811 GAGGGGGCUGGUAGUGUGAAG 21 25691 CFTR-Intron10-6812 AGAGGGGGCUGGUAGUGUGAAG 22 25692 CFTR-Intron10-6813 AAGAGGGGGCUGGUAGUGUGAAG 23 25693 CFTR-Intron10-6814 GAAGAGGGGGCUGGUAGUGUGAAG 24 25694 CFTR-Intron10-6815 GAAAUUAGAAAGAAUAAG 18 25695 CFTR-Intron10-6816 UGAAAUUAGAAAGAAUAAG 19 25696 CFTR-Intron10-1254 AUGAAAUUAGAAAGAAUAAG 20 20139 CFTR-Intron10-6817 AAUGAAAUUAGAAAGAAUAAG 21 25697 CFTR-Intron10-6818 GAAUGAAAUUAGAAAGAAUAAG 22 25698 CFTR-Intron10-6819 AGAAUGAAAUUAGAAAGAAUAAG 23 25699 CFTR-Intron10-6820 CAGAAUGAAAUUAGAAAGAAUAAG 24 25700 CFTR-Intron10-6821 AUAGGAUUAAUGGAUAAG 18 25701 CFTR-Intron10-6822 AAUAGGAUUAAUGGAUAAG 19 25702 CFTR-Intron10-6823 CAAUAGGAUUAAUGGAUAAG 20 25703 CFTR-Intron10-6824 CCAAUAGGAUUAAUGGAUAAG 21 25704 CFTR-Intron10-6825 UCCAAUAGGAUUAAUGGAUAAG 22 25705 CFTR-Intron10-6826 AUCCAAUAGGAUUAAUGGAUAAG 23 25706 CFTR-Intron10-6827 GAUCCAAUAGGAUUAAUGGAUAAG 24 25707 CFTR-Intron10-6828 GGAAAGAGGGUUGAUAAG 18 25708 CFTR-Intron10-6829 AGGAAAGAGGGUUGAUAAG 19 25709 CFTR-Intron10-6830 AAGGAAAGAGGGUUGAUAAG 20 25710 CFTR-Intron10-6831 AAAGGAAAGAGGGUUGAUAAG 21 25711 CFTR-Intron10-6832 UAAAGGAAAGAGGGUUGAUAAG 22 25712 CFTR-Intron10-6833 CUAAAGGAAAGAGGGUUGAUAAG 23 25713 CFTR-Intron10-6834 UCUAAAGGAAAGAGGGUUGAUAAG 24 25714 CFTR-Intron10-6835 UAUUUAUCAAUAUCUAAG 18 25715 CFTR-Intron10-6836 UUAUUUAUCAAUAUCUAAG 19 25716 CFTR-Intron10-6837 AUUAUUUAUCAAUAUCUAAG 20 25717 CFTR-Intron10-6838 AAUUAUUUAUCAAUAUCUAAG 21 25718 CFTR-Intron10-6839 CAAUUAUUUAUCAAUAUCUAAG 22 25719 CFTR-Intron10-6840 GCAAUUAUUUAUCAAUAUCUAAG 23 25720 CFTR-Intron10-6841 GGCAAUUAUUUAUCAAUAUCUAAG 24 25721 CFTR-Intron10-6842 GCUCAUUCAUCAAGUAAG 18 25722 CFTR-Intron10-6843 UGCUCAUUCAUCAAGUAAG 19 25723 CFTR-Intron10-6844 AUGCUCAUUCAUCAAGUAAG 20 25724 CFTR-Intron10-6845 AAUGCUCAUUCAUCAAGUAAG 21 25725 CFTR-Intron10-6846 AAAUGCUCAUUCAUCAAGUAAG 22 25726 CFTR-Intron10-6847 CAAAUGCUCAUUCAUCAAGUAAG 23 25727 CFTR-Intron10-6848 UCAAAUGCUCAUUCAUCAAGUAAG 24 25728 CFTR-Intron10-6849 AAGAAGGAAGGAAGUAAG 18 25729 CFTR-Intron10-6850 AAAGAAGGAAGGAAGUAAG 19 25730 CFTR-Intron10-693 GAAAGAAGGAAGGAAGUAAG 20 19579 CFTR-Intron10-6851 GGAAAGAAGGAAGGAAGUAAG 21 25731 CFTR-Intron10-6852 AGGAAAGAAGGAAGGAAGUAAG 22 25732 CFTR-Intron10-6853 AAGGAAAGAAGGAAGGAAGUAAG 23 25733 CFTR-Intron10-6854 GAAGGAAAGAAGGAAGGAAGUAAG 24 25734 CFTR-Intron10-6855 UGCCAUGUGAGAACACAG 18 25735 CFTR-Intron10-6856 CUGCCAUGUGAGAACACAG 19 25736 CFTR-Intron10-6857 UCUGCCAUGUGAGAACACAG 20 25737 CFTR-Intron10-6858 UUCUGCCAUGUGAGAACACAG 21 25738 CFTR-Intron10-6859 UUUCUGCCAUGUGAGAACACAG 22 25739 CFTR-Intron10-6860 CUUUCUGCCAUGUGAGAACACAG 23 25740 CFTR-Intron10-6861 CCUUUCUGCCAUGUGAGAACACAG 24 25741 CFTR-Intron10-6862 AUUUCAACUUAUACACAG 18 25742 CFTR-Intron10-6863 CAUUUCAACUUAUACACAG 19 25743 CFTR-Intron10-6864 UCAUUUCAACUUAUACACAG 20 25744 CFTR-Intron10-6865 AUCAUUUCAACUUAUACACAG 21 25745 CFTR-Intron10-6866 UAUCAUUUCAACUUAUACACAG 22 25746 CFTR-Intron10-6867 AUAUCAUUUCAACUUAUACACAG 23 25747 CFTR-Intron10-6868 AAUAUCAUUUCAACUUAUACACAG 24 25748 CFTR-Intron10-6869 CUGUUGUCUGCAUCACAG 18 25749 CFTR-Intron10-6870 UCUGUUGUCUGCAUCACAG 19 25750 CFTR-Intron10-6871 UUCUGUUGUCUGCAUCACAG 20 25751 CFTR-Intron10-6872 CUUCUGUUGUCUGCAUCACAG 21 25752 CFTR-Intron10-6873 CCUUCUGUUGUCUGCAUCACAG 22 25753 CFTR-Intron10-6874 UCCUUCUGUUGUCUGCAUCACAG 23 25754 CFTR-Intron10-6875 GUCCUUCUGUUGUCUGCAUCACAG 24 25755 CFTR-Intron10-6876 GAGUCUUCCAAGUAGCAG 18 25756 CFTR-Intron10-6877 AGAGUCUUCCAAGUAGCAG 19 25757 CFTR-Intron10-6878 AAGAGUCUUCCAAGUAGCAG 20 25758 CFTR-Intron10-6879 GAAGAGUCUUCCAAGUAGCAG 21 25759 CFTR-Intron10-6880 GGAAGAGUCUUCCAAGUAGCAG 22 25760 CFTR-Intron10-6881 GGGAAGAGUCUUCCAAGUAGCAG 23 25761 CFTR-Intron10-6882 UGGGAAGAGUCUUCCAAGUAGCAG 24 25762 CFTR-Intron10-6883 CCAAAACUUUAUUGUCAG 18 25763 CFTR-Intron10-6884 ACCAAAACUUUAUUGUCAG 19 25764 CFTR-Intron10-6885 GACCAAAACUUUAUUGUCAG 20 25765 CFTR-Intron10-6886 GGACCAAAACUUUAUUGUCAG 21 25766 CFTR-Intron10-6887 AGGACCAAAACUUUAUUGUCAG 22 25767 CFTR-Intron10-6888 AAGGACCAAAACUUUAUUGUCAG 23 25768 CFTR-Intron10-6889 AAAGGACCAAAACUUUAUUGUCAG 24 25769 CFTR-Intron10-6890 CAAGUGCAAAGCUUUCAG 18 25770 CFTR-Intron10-6891 GCAAGUGCAAAGCUUUCAG 19 25771 CFTR-Intron10-6892 AGCAAGUGCAAAGCUUUCAG 20 25772 CFTR-Intron10-6893 AAGCAAGUGCAAAGCUUUCAG 21 25773 CFTR-Intron10-6894 GAAGCAAGUGCAAAGCUUUCAG 22 25774 CFTR-Intron10-6895 UGAAGCAAGUGCAAAGCUUUCAG 23 25775 CFTR-Intron10-6896 GUGAAGCAAGUGCAAAGCUUUCAG 24 25776 CFTR-Intron10-6897 AAACAGAAAAAGAAAGAG 18 25777 CFTR-Intron10-6898 CAAACAGAAAAAGAAAGAG 19 25778 CFTR-Intron10-1269 ACAAACAGAAAAAGAAAGAG 20 20154 CFTR-Intron10-6899 GACAAACAGAAAAAGAAAGAG 21 25779 CFTR-Intron10-6900 AGACAAACAGAAAAAGAAAGAG 22 25780 CFTR-Intron10-6901 AAGACAAACAGAAAAAGAAAGAG 23 25781 CFTR-Intron10-6902 UAAGACAAACAGAAAAAGAAAGAG 24 25782 CFTR-Intron10-6903 AUUUUUGUAUUUUUAGUAGAG 21 25783 CFTR-Intron10-6904 AAUUUUUGUAUUUUUAGUAGAG 22 25784 CFTR-Intron10-6905 UAAUUUUUGUAUUUUUAGUAGAG 23 25785 CFTR-Intron10-6906 CUAAUUUUUGUAUUUUUAGUAGAG 24 25786 CFTR-Intron10-6907 GAAAGAAUCAAAUUAGAG 18 25787 CFTR-Intron10-6908 UGAAAGAAUCAAAUUAGAG 19 25788 CFTR-Intron10-6909 AUGAAAGAAUCAAAUUAGAG 20 25789 CFTR-Intron10-6910 CAUGAAAGAAUCAAAUUAGAG 21 25790 CFTR-Intron10-6911 ACAUGAAAGAAUCAAAUUAGAG 22 25791 CFTR-Intron10-6912 GACAUGAAAGAAUCAAAUUAGAG 23 25792 CFTR-Intron10-6913 AGACAUGAAAGAAUCAAAUUAGAG 24 25793 CFTR-Intron10-6914 AACAAAGACUUGCAGGAG 18 25794 CFTR-Intron10-6915 GAACAAAGACUUGCAGGAG 19 25795 CFTR-Intron10-6916 UGAACAAAGACUUGCAGGAG 20 25796 CFTR-Intron10-6917 UUGAACAAAGACUUGCAGGAG 21 25797 CFTR-Intron10-6918 UUUGAACAAAGACUUGCAGGAG 22 25798 CFTR-Intron10-6919 AUUUGAACAAAGACUUGCAGGAG 23 25799 CFTR-Intron10-6920 CAUUUGAACAAAGACUUGCAGGAG 24 25800 CFTR-Intron10-6921 AUCAAUAUCUAAGAUGAG 18 25801 CFTR-Intron10-6922 UAUCAAUAUCUAAGAUGAG 19 25802 CFTR-Intron10-6923 UUAUCAAUAUCUAAGAUGAG 20 25803 CFTR-Intron10-6924 UUUAUCAAUAUCUAAGAUGAG 21 25804 CFTR-Intron10-6925 AUUUAUCAAUAUCUAAGAUGAG 22 25805 CFTR-Intron10-6926 UAUUUAUCAAUAUCUAAGAUGAG 23 25806 CFTR-Intron10-6927 UUAUUUAUCAAUAUCUAAGAUGAG 24 25807 CFTR-Intron10-6928 GCUACUUGGGAGGCUGAG 18 25808 CFTR-Intron10-6929 AGCUACUUGGGAGGCUGAG 19 25809 CFTR-Intron10-6930 CAGCUACUUGGGAGGCUGAG 20 25810 CFTR-Intron10-6931 CCAGCUACUUGGGAGGCUGAG 21 25811 CFTR-Intron10-6932 CCCAGCUACUUGGGAGGCUGAG 22 25812 CFTR-Intron10-6933 UCCCAGCUACUUGGGAGGCUGAG 23 25813 CFTR-Intron10-6934 GUCCCAGCUACUUGGGAGGCUGAG 24 25814 CFTR-Intron10-6935 GGCAGAACUUGCAGUGAG 18 25815 CFTR-Intron10-6936 AGGCAGAACUUGCAGUGAG 19 25816 CFTR-Intron10-6937 GAGGCAGAACUUGCAGUGAG 20 25817 CFTR-Intron10-6938 GGAGGCAGAACUUGCAGUGAG 21 25818 CFTR-Intron10-6939 AGGAGGCAGAACUUGCAGUGAG 22 25819 CFTR-Intron10-6940 CAGGAGGCAGAACUUGCAGUGAG 23 25820 CFTR-Intron10-6941 CCAGGAGGCAGAACUUGCAGUGAG 24 25821 CFTR-Intron10-6942 UUUUUUUUUUUUUUUGAG 18 25822 CFTR-Intron10-6943 UUUUUUUUUUUUUUUUGAG 19 25823 CFTR-Intron10-6944 UUUUUUUUUUUUUUUUUGAG 20 25824 CFTR-Intron10-6945 UUUUUUUUUUUUUUUUUUGAG 21 25825 CFTR-Intron10-6946 UUUUUUUUUUUUUUUUUUUGAG 22 25826 CFTR-Intron10-6947 UUUUUUUUUUUUUUUUUUUUGAG 23 25827 CFTR-Intron10-6948 UUUUUUUUUUUUUUUUUUUUUGAG 24 25828 CFTR-Intron10-6949 GCUUUUAAAACAAAAUAG 18 25829 CFTR-Intron10-6950 AGCUUUUAAAACAAAAUAG 19 25830 CFTR-Intron10-6951 CAGCUUUUAAAACAAAAUAG 20 25831 CFTR-Intron10-6952 ACAGCUUUUAAAACAAAAUAG 21 25832 CFTR-Intron10-6953 AACAGCUUUUAAAACAAAAUAG 22 25833 CFTR-Intron10-6954 AAACAGCUUUUAAAACAAAAUAG 23 25834 CFTR-Intron10-6955 GAAACAGCUUUUAAAACAAAAUAG 24 25835 CFTR-Intron10-6956 ACUUAAUGAAAGCAAUAG 18 25836 CFTR-Intron10-6957 GACUUAAUGAAAGCAAUAG 19 25837 CFTR-Intron10-6958 UGACUUAAUGAAAGCAAUAG 20 25838 CFTR-Intron10-6959 GUGACUUAAUGAAAGCAAUAG 21 25839 CFTR-Intron10-6960 CGUGACUUAAUGAAAGCAAUAG 22 25840 CFTR-Intron10-6961 UCGUGACUUAAUGAAAGCAAUAG 23 25841 CFTR-Intron10-6962 CUCGUGACUUAAUGAAAGCAAUAG 24 25842 CFTR-Intron10-6963 UAAAAAAUUAUACUAUAG 18 25843 CFTR-Intron10-6964 UUAAAAAAUUAUACUAUAG 19 25844 CFTR-Intron10-6965 AUUAAAAAAUUAUACUAUAG 20 25845 CFTR-Intron10-6966 UAUUAAAAAAUUAUACUAUAG 21 25846 CFTR-Intron10-6967 CUAUUAAAAAAUUAUACUAUAG 22 25847 CFTR-Intron10-6968 ACUAUUAAAAAAUUAUACUAUAG 23 25848 CFTR-Intron10-6969 CACUAUUAAAAAAUUAUACUAUAG 24 25849 CFTR-Intron10-6970 GUAGUGGAAGUAGUAUAG 18 25850 CFTR-Intron10-6971 AGUAGUGGAAGUAGUAUAG 19 25851 CFTR-Intron10-6972 UAGUAGUGGAAGUAGUAUAG 20 25852 CFTR-Intron10-6973 GUAGUAGUGGAAGUAGUAUAG 21 25853 CFTR-Intron10-6974 GGUAGUAGUGGAAGUAGUAUAG 22 25854 CFTR-Intron10-6975 AGGUAGUAGUGGAAGUAGUAUAG 23 25855 CFTR-Intron10-6976 CAGGUAGUAGUGGAAGUAGUAUAG 24 25856 CFTR-Intron10-6977 CCUCACCCUCCCAAGUAG 18 25857 CFTR-Intron10-6978 GCCUCACCCUCCCAAGUAG 19 25858 CFTR-Intron10-6979 UGCCUCACCCUCCCAAGUAG 20 25859 CFTR-Intron10-6980 CUGCCUCACCCUCCCAAGUAG 21 25860 CFTR-Intron10-6981 CCUGCCUCACCCUCCCAAGUAG 22 25861 CFTR-Intron10-6982 UCCUGCCUCACCCUCCCAAGUAG 23 25862 CFTR-Intron10-6983 CUCCUGCCUCACCCUCCCAAGUAG 24 25863 CFTR-Intron10-6984 GCCUCAGCCUCCCAAGUAG 19 25864 CFTR-Intron10-6985 UGCCUCAGCCUCCCAAGUAG 20 25865 CFTR-Intron10-6986 CUGCCUCAGCCUCCCAAGUAG 21 25866 CFTR-Intron10-6987 CCUGCCUCAGCCUCCCAAGUAG 22 25867 CFTR-Intron10-6988 UCCUGCCUCAGCCUCCCAAGUAG 23 25868 CFTR-Intron10-6989 CUCCUGCCUCAGCCUCCCAAGUAG 24 25869 CFTR-Intron10-6990 GAGGAAGAAAGGAAGUAG 18 25870 CFTR-Intron10-6991 UGAGGAAGAAAGGAAGUAG 19 25871 CFTR-Intron10-6992 AUGAGGAAGAAAGGAAGUAG 20 25872 CFTR-Intron10-6993 AAUGAGGAAGAAAGGAAGUAG 21 25873 CFTR-Intron10-6994 AAAUGAGGAAGAAAGGAAGUAG 22 25874 CFTR-Intron10-6995 GAAAUGAGGAAGAAAGGAAGUAG 23 25875 CFTR-Intron10-6996 GGAAAUGAGGAAGAAAGGAAGUAG 24 25876 CFTR-Intron10-6997 GCUUGAUCCAGGUAGUAG 18 25877 CFTR-Intron10-6998 GGCUUGAUCCAGGUAGUAG 19 25878 CFTR-Intron10-461 UGGCUUGAUCCAGGUAGUAG 20 19347 CFTR-Intron10-6999 GUGGCUUGAUCCAGGUAGUAG 21 25879 CFTR-Intron10-7000 GGUGGCUUGAUCCAGGUAGUAG 22 25880 CFTR-Intron10-7001 UGGUGGCUUGAUCCAGGUAGUAG 23 25881 CFTR-Intron10-7002 AUGGUGGCUUGAUCCAGGUAGUAG 24 25882 CFTR-Intron10-7003 CUAUGAAGGCAGAGUUAG 18 25883 CFTR-Intron10-7004 GCUAUGAAGGCAGAGUUAG 19 25884 CFTR-Intron10-464 AGCUAUGAAGGCAGAGUUAG 20 19350 CFTR-Intron10-7005 CAGCUAUGAAGGCAGAGUUAG 21 25885 CFTR-Intron10-7006 GCAGCUAUGAAGGCAGAGUUAG 22 25886 CFTR-Intron10-7007 AGCAGCUAUGAAGGCAGAGUUAG 23 25887 CFTR-Intron10-7008 AAGCAGCUAUGAAGGCAGAGUUAG 24 25888 CFTR-Intron10-7009 GGGGUUUCACCGUUUUAG 18 25889 CFTR-Intron10-7010 CGGGGUUUCACCGUUUUAG 19 25890 CFTR-Intron10-7011 ACGGGGUUUCACCGUUUUAG 20 25891 CFTR-Intron10-7012 GACGGGGUUUCACCGUUUUAG 21 25892 CFTR-Intron10-7013 AGACGGGGUUUCACCGUUUUAG 22 25893 CFTR-Intron10-7014 GAGACGGGGUUUCACCGUUUUAG 23 25894 CFTR-Intron10-7015 AGAGACGGGGUUUCACCGUUUUAG 24 25895 CFTR-Intron10-7016 UAAUUUUUGUAUUUUUAG 18 25896 CFTR-Intron10-7017 CUAAUUUUUGUAUUUUUAG 19 25897 CFTR-Intron10-7018 GCUAAUUUUUGUAUUUUUAG 20 25898 CFTR-Intron10-7019 AGCUAAUUUUUGUAUUUUUAG 21 25899 CFTR-Intron10-7020 CAGCUAAUUUUUGUAUUUUUAG 22 25900 CFTR-Intron10-7021 UCAGCUAAUUUUUGUAUUUUUAG 23 25901 CFTR-Intron10-7022 CUCAGCUAAUUUUUGUAUUUUUAG 24 25902 CFTR-Intron10-7023 CGGCUAAUUUUUUGUAUUUUUAG 23 25903 CFTR-Intron10-7024 CCGGCUAAUUUUUUGUAUUUUUAG 24 25904 CFTR-Intron10-7025 UCAGAGAAGUAAUCGGCG 18 25905 CFTR-Intron10-7026 GUCAGAGAAGUAAUCGGCG 19 25906 CFTR-Intron10-7027 UGUCAGAGAAGUAAUCGGCG 20 25907 CFTR-Intron10-7028 CUGUCAGAGAAGUAAUCGGCG 21 25908 CFTR-Intron10-7029 ACUGUCAGAGAAGUAAUCGGCG 22 25909 CFTR-Intron10-7030 UACUGUCAGAGAAGUAAUCGGCG 23 25910 CFTR-Intron10-7031 AUACUGUCAGAGAAGUAAUCGGCG 24 25911 CFTR-Intron10-7032 UUCUGUAGGGAGACAAGG 18 25912 CFTR-Intron10-7033 AUUCUGUAGGGAGACAAGG 19 25913 CFTR-Intron10-7034 UAUUCUGUAGGGAGACAAGG 20 25914 CFTR-Intron10-7035 CUAUUCUGUAGGGAGACAAGG 21 25915 CFTR-Intron10-7036 GCUAUUCUGUAGGGAGACAAGG 22 25916 CFTR-Intron10-7037 GGCUAUUCUGUAGGGAGACAAGG 23 25917 CFTR-Intron10-7038 AGGCUAUUCUGUAGGGAGACAAGG 24 25918 CFTR-Intron10-7039 ACAAGUCUAGUUUCAAGG 18 25919 CFTR-Intron10-7040 UACAAGUCUAGUUUCAAGG 19 25920 CFTR-Intron10-7041 GUACAAGUCUAGUUUCAAGG 20 25921 CFTR-Intron10-7042 UGUACAAGUCUAGUUUCAAGG 21 25922 CFTR-Intron10-7043 AUGUACAAGUCUAGUUUCAAGG 22 25923 CFTR-Intron10-7044 GAUGUACAAGUCUAGUUUCAAGG 23 25924 CFTR-Intron10-7045 GGAUGUACAAGUCUAGUUUCAAGG 24 25925 CFTR-Intron10-7046 GGAAGGAAGGAAAGAAGG 18 25926 CFTR-Intron10-7047 AGGAAGGAAGGAAAGAAGG 19 25927 CFTR-Intron10-7048 AAGGAAGGAAGGAAAGAAGG 20 25928 CFTR-Intron10-7049 GAAGGAAGGAAGGAAAGAAGG 21 25929 CFTR-Intron10-7050 GGAAGGAAGGAAGGAAAGAAGG 22 25930 CFTR-Intron10-7051 AGGAAGGAAGGAAGGAAAGAAGG 23 25931 CFTR-Intron10-7052 GAGGAAGGAAGGAAGGAAAGAAGG 24 25932 CFTR-Intron10-7053 AAGUAGGAGGAAGGAAGG 18 25933 CFTR-Intron10-7054 GAAGUAGGAGGAAGGAAGG 19 25934 CFTR-Intron10-7055 GGAAGUAGGAGGAAGGAAGG 20 25935 CFTR-Intron10-7056 AGGAAGUAGGAGGAAGGAAGG 21 25936 CFTR-Intron10-7057 AAGGAAGUAGGAGGAAGGAAGG 22 25937 CFTR-Intron10-7058 AAAGGAAGUAGGAGGAAGGAAGG 23 25938 CFTR-Intron10-7059 GAAAGGAAGUAGGAGGAAGGAAGG 24 25939 CFTR-Intron10-7060 AAAAGAAAGAGAGGAAGG 18 25940 CFTR-Intron10-7061 AAAAAGAAAGAGAGGAAGG 19 25941 CFTR-Intron10-7062 GAAAAAGAAAGAGAGGAAGG 20 25942 CFTR-Intron10-7063 AGAAAAAGAAAGAGAGGAAGG 21 25943 CFTR-Intron10-7064 CAGAAAAAGAAAGAGAGGAAGG 22 25944 CFTR-Intron10-7065 ACAGAAAAAGAAAGAGAGGAAGG 23 25945 CFTR-Intron10-7066 AACAGAAAAAGAAAGAGAGGAAGG 24 25946 CFTR-Intron10-7067 AAGGAAGUAGGAGGAAGG 18 25947 CFTR-Intron10-7068 AAAGGAAGUAGGAGGAAGG 19 25948 CFTR-Intron10-7069 GAAAGGAAGUAGGAGGAAGG 20 25949 CFTR-Intron10-7070 AGAAAGGAAGUAGGAGGAAGG 21 25950 CFTR-Intron10-7071 AAGAAAGGAAGUAGGAGGAAGG 22 25951 CFTR-Intron10-7072 GAAGAAAGGAAGUAGGAGGAAGG 23 25952 CFTR-Intron10-7073 GGAAGAAAGGAAGUAGGAGGAAGG 24 25953 CFTR-Intron10-7074 AGUCUUACUGUCACCAGG 18 25954 CFTR-Intron10-7075 GAGUCUUACUGUCACCAGG 19 25955 CFTR-Intron10-7076 AGAGUCUUACUGUCACCAGG 20 25956 CFTR-Intron10-7077 CAGAGUCUUACUGUCACCAGG 21 25957 CFTR-Intron10-7078 ACAGAGUCUUACUGUCACCAGG 22 25958 CFTR-Intron10-7079 GACAGAGUCUUACUGUCACCAGG 23 25959 CFTR-Intron10-7080 AGACAGAGUCUUACUGUCACCAGG 24 25960 CFTR-Intron10-7081 CUUACUCUGUCACCCAGG 18 25961 CFTR-Intron10-7082 UCUUACUCUGUCACCCAGG 19 25962 CFTR-Intron10-7083 GUCUUACUCUGUCACCCAGG 20 25963 CFTR-Intron10-7084 GGUCUUACUCUGUCACCCAGG 21 25964 CFTR-Intron10-7085 AGGUCUUACUCUGUCACCCAGG 22 25965 CFTR-Intron10-7086 UAGGUCUUACUCUGUCACCCAGG 23 25966 CFTR-Intron10-7087 UUAGGUCUUACUCUGUCACCCAGG 24 25967 CFTR-Intron10-7088 CUCGCUCUGUCGCCCAGG 18 25968 CFTR-Intron10-7089 UCUCGCUCUGUCGCCCAGG 19 25969 CFTR-Intron10-7090 GUCUCGCUCUGUCGCCCAGG 20 25970 CFTR-Intron10-7091 AGUCUCGCUCUGUCGCCCAGG 21 25971 CFTR-Intron10-7092 GAGUCUCGCUCUGUCGCCCAGG 22 25972 CFTR-Intron10-7093 GGAGUCUCGCUCUGUCGCCCAGG 23 25973 CFTR-Intron10-7094 CGGAGUCUCGCUCUGUCGCCCAGG 24 25974 CFTR-Intron10-7095 AGGUGAUGGUAUUGCAGG 18 25975 CFTR-Intron10-7096 AAGGUGAUGGUAUUGCAGG 19 25976 CFTR-Intron10-7097 CAAGGUGAUGGUAUUGCAGG 20 25977 CFTR-Intron10-7098 CCAAGGUGAUGGUAUUGCAGG 21 25978 CFTR-Intron10-7099 CCCAAGGUGAUGGUAUUGCAGG 22 25979 CFTR-Intron10-7100 UCCCAAGGUGAUGGUAUUGCAGG 23 25980 CFTR-Intron10-7101 UUCCCAAGGUGAUGGUAUUGCAGG 24 25981 CFTR-Intron10-7102 CAGAAAAAGAAAGAGAGG 18 25982 CFTR-Intron10-7103 ACAGAAAAAGAAAGAGAGG 19 25983 CFTR-Intron10-7104 AACAGAAAAAGAAAGAGAGG 20 25984 CFTR-Intron10-7105 AAACAGAAAAAGAAAGAGAGG 21 25985 CFTR-Intron10-7106 CAAACAGAAAAAGAAAGAGAGG 22 25986 CFTR-Intron10-7107 ACAAACAGAAAAAGAAAGAGAGG 23 25987 CFTR-Intron10-7108 GACAAACAGAAAAAGAAAGAGAGG 24 25988 CFTR-Intron10-7109 UGGCGUGAACCCAGGAGG 18 25989 CFTR-Intron10-7110 AUGGCGUGAACCCAGGAGG 19 25990 CFTR-Intron10-7111 AAUGGCGUGAACCCAGGAGG 20 25991 CFTR-Intron10-7112 GAAUGGCGUGAACCCAGGAGG 21 25992 CFTR-Intron10-7113 AGAAUGGCGUGAACCCAGGAGG 22 25993 CFTR-Intron10-7114 GAGAAUGGCGUGAACCCAGGAGG 23 25994 CFTR-Intron10-7115 GGAGAAUGGCGUGAACCCAGGAGG 24 25995 CFTR-Intron10-7116 AAGAAAGGAAGUAGGAGG 18 25996 CFTR-Intron10-7117 GAAGAAAGGAAGUAGGAGG 19 25997 CFTR-Intron10-7118 GGAAGAAAGGAAGUAGGAGG 20 25998 CFTR-Intron10-7119 AGGAAGAAAGGAAGUAGGAGG 21 25999 CFTR-Intron10-7120 GAGGAAGAAAGGAAGUAGGAGG 22 26000 CFTR-Intron10-7121 UGAGGAAGAAAGGAAGUAGGAGG 23 26001 CFTR-Intron10-7122 AUGAGGAAGAAAGGAAGUAGGAGG 24 26002 CFTR-Intron10-7123 UCCCAGCUACUCGGGAGG 18 26003 CFTR-Intron10-7124 GUCCCAGCUACUCGGGAGG 19 26004 CFTR-Intron10-7125 AGUCCCAGCUACUCGGGAGG 20 26005 CFTR-Intron10-7126 UAGUCCCAGCUACUCGGGAGG 21 26006 CFTR-Intron10-7127 GUAGUCCCAGCUACUCGGGAGG 22 26007 CFTR-Intron10-7128 CGUAGUCCCAGCUACUCGGGAGG 23 26008 CFTR-Intron10-7129 CCGUAGUCCCAGCUACUCGGGAGG 24 26009 CFTR-Intron10-7130 AGUAAUCGGCGGUGGAGG 18 26010 CFTR-Intron10-7131 AAGUAAUCGGCGGUGGAGG 19 26011 CFTR-Intron10-7132 GAAGUAAUCGGCGGUGGAGG 20 26012 CFTR-Intron10-7133 AGAAGUAAUCGGCGGUGGAGG 21 26013 CFTR-Intron10-7134 GAGAAGUAAUCGGCGGUGGAGG 22 26014 CFTR-Intron10-7135 AGAGAAGUAAUCGGCGGUGGAGG 23 26015 CFTR-Intron10-7136 CAGAGAAGUAAUCGGCGGUGGAGG 24 26016 CFTR-Intron10-7137 UCCUAGCACUUUUGGAGG 18 26017 CFTR-Intron10-7138 AUCCUAGCACUUUUGGAGG 19 26018 CFTR-Intron10-7139 AAUCCUAGCACUUUUGGAGG 20 26019 CFTR-Intron10-7140 UAAUCCUAGCACUUUUGGAGG 21 26020 CFTR-Intron10-7141 GUAAUCCUAGCACUUUUGGAGG 22 26021 CFTR-Intron10-7142 UGUAAUCCUAGCACUUUUGGAGG 23 26022 CFTR-Intron10-7143 UUGUAAUCCUAGCACUUUUGGAGG 24 26023 CFTR-Intron10-7144 AGAAAGAAGGAAAUGAGG 18 26024 CFTR-Intron10-7145 AAGAAAGAAGGAAAUGAGG 19 26025 CFTR-Intron10-7146 GAAGAAAGAAGGAAAUGAGG 20 26026 CFTR-Intron10-7147 GGAAGAAAGAAGGAAAUGAGG 21 26027 CFTR-Intron10-7148 AGGAAGAAAGAAGGAAAUGAGG 22 26028 CFTR-Intron10-7149 AAGGAAGAAAGAAGGAAAUGAGG 23 26029 CFTR-Intron10-7150 GAAGGAAGAAAGAAGGAAAUGAGG 24 26030 CFTR-Intron10-7151 GGUGAUUAGUCCAUGAGG 18 26031 CFTR-Intron10-7152 AGGUGAUUAGUCCAUGAGG 19 26032 CFTR-Intron10-7153 GAGGUGAUUAGUCCAUGAGG 20 26033 CFTR-Intron10-7154 GGAGGUGAUUAGUCCAUGAGG 21 26034 CFTR-Intron10-7155 GGGAGGUGAUUAGUCCAUGAGG 22 26035 CFTR-Intron10-7156 UGGGAGGUGAUUAGUCCAUGAGG 23 26036 CFTR-Intron10-7157 UUGGGAGGUGAUUAGUCCAUGAGG 24 26037 CFTR-Intron10-7158 CUACUCGGGAGGCUGAGG 18 26038 CFTR-Intron10-7159 GCUACUCGGGAGGCUGAGG 19 26039 CFTR-Intron10-7160 AGCUACUCGGGAGGCUGAGG 20 26040 CFTR-Intron10-7161 CAGCUACUCGGGAGGCUGAGG 21 26041 CFTR-Intron10-7162 CCAGCUACUCGGGAGGCUGAGG 22 26042 CFTR-Intron10-7163 CCCAGCUACUCGGGAGGCUGAGG 23 26043 CFTR-Intron10-7164 UCCCAGCUACUCGGGAGGCUGAGG 24 26044 CFTR-Intron10-7165 CUACUUGGGAGGCUGAGG 18 26045 CFTR-Intron10-7166 GCUACUUGGGAGGCUGAGG 19 26046 CFTR-Intron10-1288 AGCUACUUGGGAGGCUGAGG 20 20173 CFTR-Intron10-7167 AAAAAAUUAUACUAUAGG 18 26047 CFTR-Intron10-7168 UAAAAAAUUAUACUAUAGG 19 26048 CFTR-Intron10-1289 UUAAAAAAUUAUACUAUAGG 20 20174 CFTR-Intron10-7169 AUUAAAAAAUUAUACUAUAGG 21 26049 CFTR-Intron10-7170 UAUUAAAAAAUUAUACUAUAGG 22 26050 CFTR-Intron10-7171 CUAUUAAAAAAUUAUACUAUAGG 23 26051 CFTR-Intron10-7172 ACUAUUAAAAAAUUAUACUAUAGG 24 26052 CFTR-Intron10-7173 AGGAAGAAAGGAAGUAGG 18 26053 CFTR-Intron10-7174 GAGGAAGAAAGGAAGUAGG 19 26054 CFTR-Intron10-1290 UGAGGAAGAAAGGAAGUAGG 20 20175 CFTR-Intron10-7175 AUGAGGAAGAAAGGAAGUAGG 21 26055 CFTR-Intron10-7176 AAUGAGGAAGAAAGGAAGUAGG 22 26056 CFTR-Intron10-7177 AAAUGAGGAAGAAAGGAAGUAGG 23 26057 CFTR-Intron10-7178 GAAAUGAGGAAGAAAGGAAGUAGG 24 26058 CFTR-Intron10-7179 CAGAGAAGUAAUCGGCGG 18 26059 CFTR-Intron10-7180 UCAGAGAAGUAAUCGGCGG 19 26060 CFTR-Intron10-105 GUCAGAGAAGUAAUCGGCGG 20 18991 CFTR-Intron10-7181 UGUCAGAGAAGUAAUCGGCGG 21 26061 CFTR-Intron10-7182 CUGUCAGAGAAGUAAUCGGCGG 22 26062 CFTR-Intron10-7183 ACUGUCAGAGAAGUAAUCGGCGG 23 26063 CFTR-Intron10-7184 UACUGUCAGAGAAGUAAUCGGCGG 24 26064 CFTR-Intron10-7185 UCUGUAGGGAGACAAGGG 18 26065 CFTR-Intron10-7186 UUCUGUAGGGAGACAAGGG 19 26066 CFTR-Intron10-473 AUUCUGUAGGGAGACAAGGG 20 19359 CFTR-Intron10-7187 UAUUCUGUAGGGAGACAAGGG 21 26067 CFTR-Intron10-7188 CUAUUCUGUAGGGAGACAAGGG 22 26068 CFTR-Intron10-7189 GCUAUUCUGUAGGGAGACAAGGG 23 26069 CFTR-Intron10-7190 GGCUAUUCUGUAGGGAGACAAGGG 24 26070 CFTR-Intron10-7191 GGUGAUGGUAUUGCAGGG 18 26071 CFTR-Intron10-7192 AGGUGAUGGUAUUGCAGGG 19 26072 CFTR-Intron10-1292 AAGGUGAUGGUAUUGCAGGG 20 20177 CFTR-Intron10-7193 CAAGGUGAUGGUAUUGCAGGG 21 26073 CFTR-Intron10-7194 CCAAGGUGAUGGUAUUGCAGGG 22 26074 CFTR-Intron10-7195 CCCAAGGUGAUGGUAUUGCAGGG 23 26075 CFTR-Intron10-7196 UCCCAAGGUGAUGGUAUUGCAGGG 24 26076 CFTR-Intron10-7197 CAGGAGCCAAAAAUUGGG 18 26077 CFTR-Intron10-7198 UCAGGAGCCAAAAAUUGGG 19 26078 CFTR-Intron10-476 UUCAGGAGCCAAAAAUUGGG 20 19362 CFTR-Intron10-7199 UUUCAGGAGCCAAAAAUUGGG 21 26079 CFTR-Intron10-7200 CUUUCAGGAGCCAAAAAUUGGG 22 26080 CFTR-Intron10-7201 GCUUUCAGGAGCCAAAAAUUGGG 23 26081 CFTR-Intron10-7202 UGCUUUCAGGAGCCAAAAAUUGGG 24 26082 CFTR-Intron10-7203 UUACUAGAAAGAUAAUGG 18 26083 CFTR-Intron10-7204 UUUACUAGAAAGAUAAUGG 19 26084 CFTR-Intron10-7205 GUUUACUAGAAAGAUAAUGG 20 26085 CFTR-Intron10-7206 CGUUUACUAGAAAGAUAAUGG 21 26086 CFTR-Intron10-7207 CCGUUUACUAGAAAGAUAAUGG 22 26087 CFTR-Intron10-7208 GCCGUUUACUAGAAAGAUAAUGG 23 26088 CFTR-Intron10-7209 UGCCGUUUACUAGAAAGAUAAUGG 24 26089 CFTR-Intron10-7210 UAAGGCUUAUUUCUCUGG 18 26090 CFTR-Intron10-7211 CUAAGGCUUAUUUCUCUGG 19 26091 CFTR-Intron10-7212 ACUAAGGCUUAUUUCUCUGG 20 26092 CFTR-Intron10-7213 GACUAAGGCUUAUUUCUCUGG 21 26093 CFTR-Intron10-7214 AGACUAAGGCUUAUUUCUCUGG 22 26094 CFTR-Intron10-7215 AAGACUAAGGCUUAUUUCUCUGG 23 26095 CFTR-Intron10-7216 AAAGACUAAGGCUUAUUUCUCUGG 24 26096 CFTR-Intron10-7217 UAGAGGUUAAGGAGGUGG 18 26097 CFTR-Intron10-7218 UUAGAGGUUAAGGAGGUGG 19 26098 CFTR-Intron10-7219 AUUAGAGGUUAAGGAGGUGG 20 26099 CFTR-Intron10-7220 UAUUAGAGGUUAAGGAGGUGG 21 26100 CFTR-Intron10-7221 GUAUUAGAGGUUAAGGAGGUGG 22 26101 CFTR-Intron10-7222 AGUAUUAGAGGUUAAGGAGGUGG 23 26102 CFTR-Intron10-7223 AAGUAUUAGAGGUUAAGGAGGUGG 24 26103 CFTR-Intron10-7224 GAGCCAAAAAUUGGGUGG 18 26104 CFTR-Intron10-7225 GGAGCCAAAAAUUGGGUGG 19 26105 CFTR-Intron10-478 AGGAGCCAAAAAUUGGGUGG 20 19364 CFTR-Intron10-7226 CAGGAGCCAAAAAUUGGGUGG 21 26106 CFTR-Intron10-7227 UCAGGAGCCAAAAAUUGGGUGG 22 26107 CFTR-Intron10-7228 UUCAGGAGCCAAAAAUUGGGUGG 23 26108 CFTR-Intron10-7229 UUUCAGGAGCCAAAAAUUGGGUGG 24 26109 CFTR-Intron10-7230 UCAGGAGCCAAAAAUUGG 18 26110 CFTR-Intron10-7231 UUCAGGAGCCAAAAAUUGG 19 26111 CFTR-Intron10-7232 UUUCAGGAGCCAAAAAUUGG 20 26112 CFTR-Intron10-7233 CUUUCAGGAGCCAAAAAUUGG 21 26113 CFTR-Intron10-7234 GCUUUCAGGAGCCAAAAAUUGG 22 26114 CFTR-Intron10-7235 UGCUUUCAGGAGCCAAAAAUUGG 23 26115 CFTR-Intron10-7236 CUGCUUUCAGGAGCCAAAAAUUGG 24 26116 CFTR-Intron10-7237 GGGAGAAACAGGUUUUGG 18 26117 CFTR-Intron10-7238 UGGGAGAAACAGGUUUUGG 19 26118 CFTR-Intron10-7239 AUGGGAGAAACAGGUUUUGG 20 26119 CFTR-Intron10-7240 AAUGGGAGAAACAGGUUUUGG 21 26120 CFTR-Intron10-7241 UAAUGGGAGAAACAGGUUUUGG 22 26121 CFTR-Intron10-7242 AUAAUGGGAGAAACAGGUUUUGG 23 26122 CFTR-Intron10-7243 GAUAAUGGGAGAAACAGGUUUUGG 24 26123 CFTR-Intron10-7244 GGAAGAAAGAAGGAAAUG 18 26124 CFTR-Intron10-7245 AGGAAGAAAGAAGGAAAUG 19 26125 CFTR-Intron10-1311 AAGGAAGAAAGAAGGAAAUG 20 20196 CFTR-Intron10-7246 GAAGGAAGAAAGAAGGAAAUG 21 26126 CFTR-Intron10-7247 GGAAGGAAGAAAGAAGGAAAUG 22 26127 CFTR-Intron10-7248 AGGAAGGAAGAAAGAAGGAAAUG 23 26128 CFTR-Intron10-7249 GAGGAAGGAAGAAAGAAGGAAAUG 24 26129 CFTR-Intron10-7250 UUAUCAAUAUCUAAGAUG 18 26130 CFTR-Intron10-7251 UUUAUCAAUAUCUAAGAUG 19 26131 CFTR-Intron10-480 AUUUAUCAAUAUCUAAGAUG 20 19366 CFTR-Intron10-7252 UAUUUAUCAAUAUCUAAGAUG 21 26132 CFTR-Intron10-7253 UUAUUUAUCAAUAUCUAAGAUG 22 26133 CFTR-Intron10-7254 AUUAUUUAUCAAUAUCUAAGAUG 23 26134 CFTR-Intron10-7255 AAUUAUUUAUCAAUAUCUAAGAUG 24 26135 CFTR-Intron10-7256 UCCCCUGCCAUUCAUAUG 18 26136 CFTR-Intron10-7257 CUCCCCUGCCAUUCAUAUG 19 26137 CFTR-Intron10-7258 UCUCCCCUGCCAUUCAUAUG 20 26138 CFTR-Intron10-7259 CUCUCCCCUGCCAUUCAUAUG 21 26139 CFTR-Intron10-7260 UCUCUCCCCUGCCAUUCAUAUG 22 26140 CFTR-Intron10-7261 GUCUCUCCCCUGCCAUUCAUAUG 23 26141 CFTR-Intron10-7262 UGUCUCUCCCCUGCCAUUCAUAUG 24 26142 CFTR-Intron10-7263 UGUUUUUAGGCUAUUCUG 18 26143 CFTR-Intron10-7264 AUGUUUUUAGGCUAUUCUG 19 26144 CFTR-Intron10-7265 AAUGUUUUUAGGCUAUUCUG 20 26145 CFTR-Intron10-7266 UAAUGUUUUUAGGCUAUUCUG 21 26146 CFTR-Intron10-7267 CUAAUGUUUUUAGGCUAUUCUG 22 26147 CFTR-Intron10-7268 GCUAAUGUUUUUAGGCUAUUCUG 23 26148 CFTR-Intron10-7269 GGCUAAUGUUUUUAGGCUAUUCUG 24 26149 CFTR-Intron10-7270 CCUCGGCCUCCCAAAGUG 18 26150 CFTR-Intron10-7271 GCCUCGGCCUCCCAAAGUG 19 26151 CFTR-Intron10-7272 CGCCUCGGCCUCCCAAAGUG 20 26152 CFTR-Intron10-7273 CCGCCUCGGCCUCCCAAAGUG 21 26153 CFTR-Intron10-7274 CCCGCCUCGGCCUCCCAAAGUG 22 26154 CFTR-Intron10-7275 GCCCGCCUCGGCCUCCCAAAGUG 23 26155 CFTR-Intron10-7276 CGCCCGCCUCGGCCUCCCAAAGUG 24 26156 CFTR-Intron10-7277 UGCCUCGGCCUCCCAAAGUG 20 26157 CFTR-Intron10-7278 CUGCCUCGGCCUCCCAAAGUG 21 26158 CFTR-Intron10-7279 CCUGCCUCGGCCUCCCAAAGUG 22 26159 CFTR-Intron10-7280 GCCUGCCUCGGCCUCCCAAAGUG 23 26160 CFTR-Intron10-7281 UGCCUGCCUCGGCCUCCCAAAGUG 24 26161 CFTR-Intron10-7282 CCAGGCUGGAGUGCAGUG 18 26162 CFTR-Intron10-7283 CCCAGGCUGGAGUGCAGUG 19 26163 CFTR-Intron10-7284 GCCCAGGCUGGAGUGCAGUG 20 26164 CFTR-Intron10-7285 CGCCCAGGCUGGAGUGCAGUG 21 26165 CFTR-Intron10-7286 UCGCCCAGGCUGGAGUGCAGUG 22 26166 CFTR-Intron10-7287 GUCGCCCAGGCUGGAGUGCAGUG 23 26167 CFTR-Intron10-7288 UGUCGCCCAGGCUGGAGUGCAGUG 24 26168 CFTR-Intron10-7289 UAAGAAGAGAAAGGGGUG 18 26169 CFTR-Intron10-7290 AUAAGAAGAGAAAGGGGUG 19 26170 CFTR-Intron10-7291 GAUAAGAAGAGAAAGGGGUG 20 26171 CFTR-Intron10-7292 UGAUAAGAAGAGAAAGGGGUG 21 26172 CFTR-Intron10-7293 UUGAUAAGAAGAGAAAGGGGUG 22 26173 CFTR-Intron10-7294 GUUGAUAAGAAGAGAAAGGGGUG 23 26174 CFTR-Intron10-7295 GGUUGAUAAGAAGAGAAAGGGGUG 24 26175 CFTR-Intron10-7296 AGGUUAAGGAGGUGGGUG 18 26176 CFTR-Intron10-7297 GAGGUUAAGGAGGUGGGUG 19 26177 CFTR-Intron10-7298 AGAGGUUAAGGAGGUGGGUG 20 26178 CFTR-Intron10-7299 UAGAGGUUAAGGAGGUGGGUG 21 26179 CFTR-Intron10-7300 UUAGAGGUUAAGGAGGUGGGUG 22 26180 CFTR-Intron10-7301 AUUAGAGGUUAAGGAGGUGGGUG 23 26181 CFTR-Intron10-7302 UAUUAGAGGUUAAGGAGGUGGGUG 24 26182 CFTR-Intron10-7303 GGAGCCAAAAAUUGGGUG 18 26183 CFTR-Intron10-7304 AGGAGCCAAAAAUUGGGUG 19 26184 CFTR-Intron10-489 CAGGAGCCAAAAAUUGGGUG 20 19375 CFTR-Intron10-7305 UCAGGAGCCAAAAAUUGGGUG 21 26185 CFTR-Intron10-7306 UUCAGGAGCCAAAAAUUGGGUG 22 26186 CFTR-Intron10-7307 UUUCAGGAGCCAAAAAUUGGGUG 23 26187 CFTR-Intron10-7308 CUUUCAGGAGCCAAAAAUUGGGUG 24 26188 CFTR-Intron10-7309 UGGCAUCUCACCAGUGUG 18 26189 CFTR-Intron10-7310 AUGGCAUCUCACCAGUGUG 19 26190 CFTR-Intron10-491 UAUGGCAUCUCACCAGUGUG 20 19377 CFTR-Intron10-7311 UUAUGGCAUCUCACCAGUGUG 21 26191 CFTR-Intron10-7312 CUUAUGGCAUCUCACCAGUGUG 22 26192 CFTR-Intron10-7313 GCUUAUGGCAUCUCACCAGUGUG 23 26193 CFTR-Intron10-7314 GGCUUAUGGCAUCUCACCAGUGUG 24 26194 CFTR-Intron10-7315 UUAUAAAAAAUAAUUGUG 18 26195 CFTR-Intron10-7316 UUUAUAAAAAAUAAUUGUG 19 26196 CFTR-Intron10-7317 UUUUAUAAAAAAUAAUUGUG 20 26197 CFTR-Intron10-7318 UUUUUAUAAAAAAUAAUUGUG 21 26198 CFTR-Intron10-7319 AUUUUUAUAAAAAAUAAUUGUG 22 26199 CFTR-Intron10-7320 GAUUUUUAUAAAAAAUAAUUGUG 23 26200 CFTR-Intron10-7321 AGAUUUUUAUAAAAAAUAAUUGUG 24 26201 CFTR-Intron10-7322 GCAGUUUUAUUAAAAUUG 18 26202 CFTR-Intron10-7323 GGCAGUUUUAUUAAAAUUG 19 26203 CFTR-Intron10-7324 AGGCAGUUUUAUUAAAAUUG 20 26204 CFTR-Intron10-7325 CAGGCAGUUUUAUUAAAAUUG 21 26205 CFTR-Intron10-7326 UCAGGCAGUUUUAUUAAAAUUG 22 26206 CFTR-Intron10-7327 UUCAGGCAGUUUUAUUAAAAUUG 23 26207 CFTR-Intron10-7328 UUUCAGGCAGUUUUAUUAAAAUUG 24 26208 CFTR-Intron10-7329 GCUCUCUUUUAACUAUUG 18 26209 CFTR-Intron10-7330 UGCUCUCUUUUAACUAUUG 19 26210 CFTR-Intron10-495 UUGCUCUCUUUUAACUAUUG 20 19381 CFTR-Intron10-7331 CUUGCUCUCUUUUAACUAUUG 21 26211 CFTR-Intron10-7332 ACUUGCUCUCUUUUAACUAUUG 22 26212 CFTR-Intron10-7333 AACUUGCUCUCUUUUAACUAUUG 23 26213 CFTR-Intron10-7334 AAACUUGCUCUCUUUUAACUAUUG 24 26214 CFTR-Intron10-7335 CAUUUGAACAAAGACUUG 18 26215 CFTR-Intron10-7336 ACAUUUGAACAAAGACUUG 19 26216 CFTR-Intron10-7337 AACAUUUGAACAAAGACUUG 20 26217 CFTR-Intron10-7338 UAACAUUUGAACAAAGACUUG 21 26218 CFTR-Intron10-7339 GUAACAUUUGAACAAAGACUUG 22 26219 CFTR-Intron10-7340 GGUAACAUUUGAACAAAGACUUG 23 26220 CFTR-Intron10-7341 AGGUAACAUUUGAACAAAGACUUG 24 26221 CFTR-Intron10-7342 UUUAGCUGUGGUACUUUG 18 26222 CFTR-Intron10-7343 UUUUAGCUGUGGUACUUUG 19 26223 CFTR-Intron10-7344 AUUUUAGCUGUGGUACUUUG 20 26224 CFTR-Intron10-7345 CAUUUUAGCUGUGGUACUUUG 21 26225 CFTR-Intron10-7346 UCAUUUUAGCUGUGGUACUUUG 22 26226 CFTR-Intron10-7347 GUCAUUUUAGCUGUGGUACUUUG 23 26227 CFTR-Intron10-7348 UGUCAUUUUAGCUGUGGUACUUUG 24 26228 CFTR-Intron10-7349 GAUUCAGGACAUGCUUUG 18 26229 CFTR-Intron10-7350 AGAUUCAGGACAUGCUUUG 19 26230 CFTR-Intron10-7351 CAGAUUCAGGACAUGCUUUG 20 26231 CFTR-Intron10-7352 UCAGAUUCAGGACAUGCUUUG 21 26232 CFTR-Intron10-7353 AUCAGAUUCAGGACAUGCUUUG 22 26233 CFTR-Intron10-7354 GAUCAGAUUCAGGACAUGCUUUG 23 26234 CFTR-Intron10-7355 UGAUCAGAUUCAGGACAUGCUUUG 24 26235 CFTR-Intron10-7356 CUAUACCUGUCUGGUUUG 18 26236 CFTR-Intron10-7357 ACUAUACCUGUCUGGUUUG 19 26237 CFTR-Intron10-7358 GACUAUACCUGUCUGGUUUG 20 26238 CFTR-Intron10-7359 UGACUAUACCUGUCUGGUUUG 21 26239 CFTR-Intron10-7360 CUGACUAUACCUGUCUGGUUUG 22 26240 CFTR-Intron10-7361 ACUGACUAUACCUGUCUGGUUUG 23 26241 CFTR-Intron10-7362 GACUGACUAUACCUGUCUGGUUUG 24 26242 CFTR-Intron10-7363 CUUACCCAAAUAUGUUUG 18 26243 CFTR-Intron10-7364 ACUUACCCAAAUAUGUUUG 19 26244 CFTR-Intron10-7365 AACUUACCCAAAUAUGUUUG 20 26245 CFTR-Intron10-7366 UAACUUACCCAAAUAUGUUUG 21 26246 CFTR-Intron10-7367 AUAACUUACCCAAAUAUGUUUG 22 26247 CFTR-Intron10-7368 UAUAACUUACCCAAAUAUGUUUG 23 26248 CFTR-Intron10-7369 CUAUAACUUACCCAAAUAUGUUUG 24 26249 CFTR-Intron10-7370 UUACCCAAUAAAAAAAAU 18 26250 CFTR-Intron10-7371 GUUACCCAAUAAAAAAAAU 19 26251 CFTR-Intron10-7372 UGUUACCCAAUAAAAAAAAU 20 26252 CFTR-Intron10-7373 UUGUUACCCAAUAAAAAAAAU 21 26253 CFTR-Intron10-7374 AUUGUUACCCAAUAAAAAAAAU 22 26254 CFTR-Intron10-7375 UAUUGUUACCCAAUAAAAAAAAU 23 26255 CFTR-Intron10-7376 UUAUUGUUACCCAAUAAAAAAAAU 24 26256 CFTR-Intron10-7377 UUUUGCAAAAUACAAAAU 18 26257 CFTR-Intron10-7378 UUUUUGCAAAAUACAAAAU 19 26258 CFTR-Intron10-7379 CUUUUUGCAAAAUACAAAAU 20 26259 CFTR-Intron10-7380 ACUUUUUGCAAAAUACAAAAU 21 26260 CFTR-Intron10-7381 CACUUUUUGCAAAAUACAAAAU 22 26261 CFTR-Intron10-7382 GCACUUUUUGCAAAAUACAAAAU 23 26262 CFTR-Intron10-7383 UGCACUUUUUGCAAAAUACAAAAU 24 26263 CFTR-Intron10-7384 AACAAAAGAAAAGAAAAU 18 26264 CFTR-Intron10-7385 UAACAAAAGAAAAGAAAAU 19 26265 CFTR-Intron10-7386 GUAACAAAAGAAAAGAAAAU 20 26266 CFTR-Intron10-7387 UGUAACAAAAGAAAAGAAAAU 21 26267 CFTR-Intron10-7388 UUGUAACAAAAGAAAAGAAAAU 22 26268 CFTR-Intron10-7389 GUUGUAACAAAAGAAAAGAAAAU 23 26269 CFTR-Intron10-7390 UGUUGUAACAAAAGAAAAGAAAAU 24 26270 CFTR-Intron10-7391 GACAUGAAAGAAUCAAAU 18 26271 CFTR-Intron10-7392 AGACAUGAAAGAAUCAAAU 19 26272 CFTR-Intron10-7393 AAGACAUGAAAGAAUCAAAU 20 26273 CFTR-Intron10-7394 AAAGACAUGAAAGAAUCAAAU 21 26274 CFTR-Intron10-7395 UAAAGACAUGAAAGAAUCAAAU 22 26275 CFTR-Intron10-7396 UUAAAGACAUGAAAGAAUCAAAU 23 26276 CFTR-Intron10-7397 UUUAAAGACAUGAAAGAAUCAAAU 24 26277 CFTR-Intron10-7398 GUGGUACUUUGUAGAAAU 18 26278 CFTR-Intron10-7399 UGUGGUACUUUGUAGAAAU 19 26279 CFTR-Intron10-7400 CUGUGGUACUUUGUAGAAAU 20 26280 CFTR-Intron10-7401 GCUGUGGUACUUUGUAGAAAU 21 26281 CFTR-Intron10-7402 AGCUGUGGUACUUUGUAGAAAU 22 26282 CFTR-Intron10-7403 UAGCUGUGGUACUUUGUAGAAAU 23 26283 CFTR-Intron10-7404 UUAGCUGUGGUACUUUGUAGAAAU 24 26284 CFTR-Intron10-7405 AGGAAGAAAGAAGGAAAU 18 26285 CFTR-Intron10-7406 AAGGAAGAAAGAAGGAAAU 19 26286 CFTR-Intron10-7407 GAAGGAAGAAAGAAGGAAAU 20 26287 CFTR-Intron10-7408 GGAAGGAAGAAAGAAGGAAAU 21 26288 CFTR-Intron10-7409 AGGAAGGAAGAAAGAAGGAAAU 22 26289 CFTR-Intron10-7410 GAGGAAGGAAGAAAGAAGGAAAU 23 26290 CFTR-Intron10-7411 AGAGGAAGGAAGAAAGAAGGAAAU 24 26291 CFTR-Intron10-7412 ACUUGACCAGAAUGAAAU 18 26292 CFTR-Intron10-7413 AACUUGACCAGAAUGAAAU 19 26293 CFTR-Intron10-7414 AAACUUGACCAGAAUGAAAU 20 26294 CFTR-Intron10-7415 CAAACUUGACCAGAAUGAAAU 21 26295 CFTR-Intron10-7416 UCAAACUUGACCAGAAUGAAAU 22 26296 CFTR-Intron10-7417 GUCAAACUUGACCAGAAUGAAAU 23 26297 CFTR-Intron10-7418 GGUCAAACUUGACCAGAAUGAAAU 24 26298 CFTR-Intron10-7419 ACCGGUGUCUUCUGAAAU 18 26299 CFTR-Intron10-7420 AACCGGUGUCUUCUGAAAU 19 26300 CFTR-Intron10-7421 UAACCGGUGUCUUCUGAAAU 20 26301 CFTR-Intron10-7422 UUAACCGGUGUCUUCUGAAAU 21 26302 CFTR-Intron10-7423 AUUAACCGGUGUCUUCUGAAAU 22 26303 CFTR-Intron10-7424 AAUUAACCGGUGUCUUCUGAAAU 23 26304 CFTR-Intron10-7425 UAAUUAACCGGUGUCUUCUGAAAU 24 26305 CFTR-Intron10-7426 UUGGGGUUUUUUGACAAU 18 26306 CFTR-Intron10-7427 UUUGGGGUUUUUUGACAAU 19 26307 CFTR-Intron10-7428 UUUUGGGGUUUUUUGACAAU 20 26308 CFTR-Intron10-7429 UUUUUGGGGUUUUUUGACAAU 21 26309 CFTR-Intron10-7430 AUUUUUGGGGUUUUUUGACAAU 22 26310 CFTR-Intron10-7431 AAUUUUUGGGGUUUUUUGACAAU 23 26311 CFTR-Intron10-7432 AAAUUUUUGGGGUUUUUUGACAAU 24 26312 CFTR-Intron10-7433 AAUGAAAUUAGAAAGAAU 18 26313 CFTR-Intron10-7434 GAAUGAAAUUAGAAAGAAU 19 26314 CFTR-Intron10-7435 AGAAUGAAAUUAGAAAGAAU 20 26315 CFTR-Intron10-7436 CAGAAUGAAAUUAGAAAGAAU 21 26316 CFTR-Intron10-7437 CCAGAAUGAAAUUAGAAAGAAU 22 26317 CFTR-Intron10-7438 ACCAGAAUGAAAUUAGAAAGAAU 23 26318 CFTR-Intron10-7439 GACCAGAAUGAAAUUAGAAAGAAU 24 26319 CFTR-Intron10-7440 UAUUUUGAAGAAUUGAAU 18 26320 CFTR-Intron10-7441 AUAUUUUGAAGAAUUGAAU 19 26321 CFTR-Intron10-7442 CAUAUUUUGAAGAAUUGAAU 20 26322 CFTR-Intron10-7443 CCAUAUUUUGAAGAAUUGAAU 21 26323 CFTR-Intron10-7444 ACCAUAUUUUGAAGAAUUGAAU 22 26324 CFTR-Intron10-7445 AACCAUAUUUUGAAGAAUUGAAU 23 26325 CFTR-Intron10-7446 GAACCAUAUUUUGAAGAAUUGAAU 24 26326 CFTR-Intron10-7447 UGGUACUACUGUAAUAAU 18 26327 CFTR-Intron10-7448 AUGGUACUACUGUAAUAAU 19 26328 CFTR-Intron10-7449 UAUGGUACUACUGUAAUAAU 20 26329 CFTR-Intron10-7450 AUAUGGUACUACUGUAAUAAU 21 26330 CFTR-Intron10-7451 CAUAUGGUACUACUGUAAUAAU 22 26331 CFTR-Intron10-7452 ACAUAUGGUACUACUGUAAUAAU 23 26332 CFTR-Intron10-7453 UACAUAUGGUACUACUGUAAUAAU 24 26333 CFTR-Intron10-7454 GUUUACUAGAAAGAUAAU 18 26334 CFTR-Intron10-7455 CGUUUACUAGAAAGAUAAU 19 26335 CFTR-Intron10-501 CCGUUUACUAGAAAGAUAAU 20 19387 CFTR-Intron10-7456 GCCGUUUACUAGAAAGAUAAU 21 26336 CFTR-Intron10-7457 UGCCGUUUACUAGAAAGAUAAU 22 26337 CFTR-Intron10-7458 GUGCCGUUUACUAGAAAGAUAAU 23 26338 CFTR-Intron10-7459 UGUGCCGUUUACUAGAAAGAUAAU 24 26339 CFTR-Intron10-7460 UGACUCUAGUUCACUAAU 18 26340 CFTR-Intron10-7461 GUGACUCUAGUUCACUAAU 19 26341 CFTR-Intron10-7462 UGUGACUCUAGUUCACUAAU 20 26342 CFTR-Intron10-7463 AUGUGACUCUAGUUCACUAAU 21 26343 CFTR-Intron10-7464 UAUGUGACUCUAGUUCACUAAU 22 26344 CFTR-Intron10-7465 CUAUGUGACUCUAGUUCACUAAU 23 26345 CFTR-Intron10-7466 UCUAUGUGACUCUAGUUCACUAAU 24 26346 CFTR-Intron10-7467 AACAUUGAAAGGUAACAU 18 26347 CFTR-Intron10-7468 AAACAUUGAAAGGUAACAU 19 26348 CFTR-Intron10-7469 UAAACAUUGAAAGGUAACAU 20 26349 CFTR-Intron10-7470 UUAAACAUUGAAAGGUAACAU 21 26350 CFTR-Intron10-7471 UUUAAACAUUGAAAGGUAACAU 22 26351 CFTR-Intron10-7472 CUUUAAACAUUGAAAGGUAACAU 23 26352 CFTR-Intron10-7473 CCUUUAAACAUUGAAAGGUAACAU 24 26353 CFTR-Intron10-7474 UUUUUUCAGUUAAUACAU 18 26354 CFTR-Intron10-7475 UUUUUUUCAGUUAAUACAU 19 26355 CFTR-Intron10-1332 UUUUUUUUCAGUUAAUACAU 20 20217 CFTR-Intron10-7476 AUUUUUUUUCAGUUAAUACAU 21 26356 CFTR-Intron10-7477 AAUUUUUUUUCAGUUAAUACAU 22 26357 CFTR-Intron10-7478 GAAUUUUUUUUCAGUUAAUACAU 23 26358 CFTR-Intron10-7479 UGAAUUUUUUUUCAGUUAAUACAU 24 26359 CFTR-Intron10-7480 GCAUAUUUGGAGAUACAU 18 26360 CFTR-Intron10-7481 GGCAUAUUUGGAGAUACAU 19 26361 CFTR-Intron10-7482 UGGCAUAUUUGGAGAUACAU 20 26362 CFTR-Intron10-7483 CUGGCAUAUUUGGAGAUACAU 21 26363 CFTR-Intron10-7484 CCUGGCAUAUUUGGAGAUACAU 22 26364 CFTR-Intron10-7485 ACCUGGCAUAUUUGGAGAUACAU 23 26365 CFTR-Intron10-7486 AACCUGGCAUAUUUGGAGAUACAU 24 26366 CFTR-Intron10-7487 CCAGUUGUUUUCCUACAU 18 26367 CFTR-Intron10-7488 UCCAGUUGUUUUCCUACAU 19 26368 CFTR-Intron10-7489 CUCCAGUUGUUUUCCUACAU 20 26369 CFTR-Intron10-7490 UCUCCAGUUGUUUUCCUACAU 21 26370 CFTR-Intron10-7491 CUCUCCAGUUGUUUUCCUACAU 22 26371 CFTR-Intron10-7492 UCUCUCCAGUUGUUUUCCUACAU 23 26372 CFTR-Intron10-7493 CUCUCUCCAGUUGUUUUCCUACAU 24 26373 CFTR-Intron10-7494 CUCACCCCUUUCUGCCAU 18 26374 CFTR-Intron10-7495 CCUCACCCCUUUCUGCCAU 19 26375 CFTR-Intron10-7496 CCCUCACCCCUUUCUGCCAU 20 26376 CFTR-Intron10-7497 ACCCUCACCCCUUUCUGCCAU 21 26377 CFTR-Intron10-7498 GACCCUCACCCCUUUCUGCCAU 22 26378 CFTR-Intron10-7499 AGACCCUCACCCCUUUCUGCCAU 23 26379 CFTR-Intron10-7500 GAGACCCUCACCCCUUUCUGCCAU 24 26380 CFTR-Intron10-7501 UAAGUUGAACAAUGGCAU 18 26381 CFTR-Intron10-7502 AUAAGUUGAACAAUGGCAU 19 26382 CFTR-Intron10-7503 GAUAAGUUGAACAAUGGCAU 20 26383 CFTR-Intron10-7504 GGAUAAGUUGAACAAUGGCAU 21 26384 CFTR-Intron10-7505 UGGAUAAGUUGAACAAUGGCAU 22 26385 CFTR-Intron10-7506 AUGGAUAAGUUGAACAAUGGCAU 23 26386 CFTR-Intron10-7507 AAUGGAUAAGUUGAACAAUGGCAU 24 26387 CFTR-Intron10-7508 AAAAUAUCACCAACUCAU 18 26388 CFTR-Intron10-7509 AAAAAUAUCACCAACUCAU 19 26389 CFTR-Intron10-7510 GAAAAAUAUCACCAACUCAU 20 26390 CFTR-Intron10-7511 UGAAAAAUAUCACCAACUCAU 21 26391 CFTR-Intron10-7512 AUGAAAAAUAUCACCAACUCAU 22 26392 CFTR-Intron10-7513 AAUGAAAAAUAUCACCAACUCAU 23 26393 CFTR-Intron10-7514 UAAUGAAAAAUAUCACCAACUCAU 24 26394 CFTR-Intron10-7515 UUUGUAAAUUUGUUUCAU 18 26395 CFTR-Intron10-7516 UUUUGUAAAUUUGUUUCAU 19 26396 CFTR-Intron10-7517 AUUUUGUAAAUUUGUUUCAU 20 26397 CFTR-Intron10-7518 AAUUUUGUAAAUUUGUUUCAU 21 26398 CFTR-Intron10-7519 UAAUUUUGUAAAUUUGUUUCAU 22 26399 CFTR-Intron10-7520 CUAAUUUUGUAAAUUUGUUUCAU 23 26400 CFTR-Intron10-7521 ACUAAUUUUGUAAAUUUGUUUCAU 24 26401 CFTR-Intron10-7522 UUUAUCAAUAUCUAAGAU 18 26402 CFTR-Intron10-7523 AUUUAUCAAUAUCUAAGAU 19 26403 CFTR-Intron10-7524 UAUUUAUCAAUAUCUAAGAU 20 26404 CFTR-Intron10-7525 UUAUUUAUCAAUAUCUAAGAU 21 26405 CFTR-Intron10-7526 AUUAUUUAUCAAUAUCUAAGAU 22 26406 CFTR-Intron10-7527 AAUUAUUUAUCAAUAUCUAAGAU 23 26407 CFTR-Intron10-7528 CAAUUAUUUAUCAAUAUCUAAGAU 24 26408 CFTR-Intron10-7529 AAGAAUCAAAUUAGAGAU 18 26409 CFTR-Intron10-7530 AAAGAAUCAAAUUAGAGAU 19 26410 CFTR-Intron10-7531 GAAAGAAUCAAAUUAGAGAU 20 26411 CFTR-Intron10-7532 UGAAAGAAUCAAAUUAGAGAU 21 26412 CFTR-Intron10-7533 AUGAAAGAAUCAAAUUAGAGAU 22 26413 CFTR-Intron10-7534 CAUGAAAGAAUCAAAUUAGAGAU 23 26414 CFTR-Intron10-7535 ACAUGAAAGAAUCAAAUUAGAGAU 24 26415 CFTR-Intron10-7536 UUUGGAAUUUUGGGAGAU 18 26416 CFTR-Intron10-7537 UUUUGGAAUUUUGGGAGAU 19 26417 CFTR-Intron10-7538 AUUUUGGAAUUUUGGGAGAU 20 26418 CFTR-Intron10-7539 UAUUUUGGAAUUUUGGGAGAU 21 26419 CFTR-Intron10-7540 AUAUUUUGGAAUUUUGGGAGAU 22 26420 CFTR-Intron10-7541 AAUAUUUUGGAAUUUUGGGAGAU 23 26421 CFTR-Intron10-7542 CAAUAUUUUGGAAUUUUGGGAGAU 24 26422 CFTR-Intron10-7543 UAUUUCUCUGGGUGAGAU 18 26423 CFTR-Intron10-7544 UUAUUUCUCUGGGUGAGAU 19 26424 CFTR-Intron10-7545 CUUAUUUCUCUGGGUGAGAU 20 26425 CFTR-Intron10-7546 GCUUAUUUCUCUGGGUGAGAU 21 26426 CFTR-Intron10-7547 GGCUUAUUUCUCUGGGUGAGAU 22 26427 CFTR-Intron10-7548 AGGCUUAUUUCUCUGGGUGAGAU 23 26428 CFTR-Intron10-7549 AAGGCUUAUUUCUCUGGGUGAGAU 24 26429 CFTR-Intron10-7550 UCUGAAAAAAUAGUAGAU 18 26430 CFTR-Intron10-7551 AUCUGAAAAAAUAGUAGAU 19 26431 CFTR-Intron10-7552 CAUCUGAAAAAAUAGUAGAU 20 26432 CFTR-Intron10-7553 ACAUCUGAAAAAAUAGUAGAU 21 26433 CFTR-Intron10-7554 UACAUCUGAAAAAAUAGUAGAU 22 26434 CFTR-Intron10-7555 AUACAUCUGAAAAAAUAGUAGAU 23 26435 CFTR-Intron10-7556 GAUACAUCUGAAAAAAUAGUAGAU 24 26436 CFTR-Intron10-7557 UUGCAGGAGGUGAGGGAU 18 26437 CFTR-Intron10-7558 CUUGCAGGAGGUGAGGGAU 19 26438 CFTR-Intron10-7559 ACUUGCAGGAGGUGAGGGAU 20 26439 CFTR-Intron10-7560 GACUUGCAGGAGGUGAGGGAU 21 26440 CFTR-Intron10-7561 AGACUUGCAGGAGGUGAGGGAU 22 26441 CFTR-Intron10-7562 AAGACUUGCAGGAGGUGAGGGAU 23 26442 CFTR-Intron10-7563 AAAGACUUGCAGGAGGUGAGGGAU 24 26443 CFTR-Intron10-7564 AAAGGAAAGAGGGUUGAU 18 26444 CFTR-Intron10-7565 UAAAGGAAAGAGGGUUGAU 19 26445 CFTR-Intron10-7566 CUAAAGGAAAGAGGGUUGAU 20 26446 CFTR-Intron10-7567 UCUAAAGGAAAGAGGGUUGAU 21 26447 CFTR-Intron10-7568 UUCUAAAGGAAAGAGGGUUGAU 22 26448 CFTR-Intron10-7569 AUUCUAAAGGAAAGAGGGUUGAU 23 26449 CFTR-Intron10-7570 GAUUCUAAAGGAAAGAGGGUUGAU 24 26450 CFTR-Intron10-7571 AGUUGAACAAUGGCAUAU 18 26451 CFTR-Intron10-7572 AAGUUGAACAAUGGCAUAU 19 26452 CFTR-Intron10-7573 UAAGUUGAACAAUGGCAUAU 20 26453 CFTR-Intron10-7574 AUAAGUUGAACAAUGGCAUAU 21 26454 CFTR-Intron10-7575 GAUAAGUUGAACAAUGGCAUAU 22 26455 CFTR-Intron10-7576 GGAUAAGUUGAACAAUGGCAUAU 23 26456 CFTR-Intron10-7577 UGGAUAAGUUGAACAAUGGCAUAU 24 26457 CFTR-Intron10-7578 CAACUUAACCUGGCAUAU 18 26458 CFTR-Intron10-7579 ACAACUUAACCUGGCAUAU 19 26459 CFTR-Intron10-7580 AACAACUUAACCUGGCAUAU 20 26460 CFTR-Intron10-7581 GAACAACUUAACCUGGCAUAU 21 26461 CFTR-Intron10-7582 AGAACAACUUAACCUGGCAUAU 22 26462 CFTR-Intron10-7583 AAGAACAACUUAACCUGGCAUAU 23 26463 CFTR-Intron10-7584 UAAGAACAACUUAACCUGGCAUAU 24 26464 CFTR-Intron10-7585 AUUAAAAAAUUAUACUAU 18 26465 CFTR-Intron10-7586 UAUUAAAAAAUUAUACUAU 19 26466 CFTR-Intron10-1337 CUAUUAAAAAAUUAUACUAU 20 20222 CFTR-Intron10-7587 ACUAUUAAAAAAUUAUACUAU 21 26467 CFTR-Intron10-7588 CACUAUUAAAAAAUUAUACUAU 22 26468 CFTR-Intron10-7589 UCACUAUUAAAAAAUUAUACUAU 23 26469 CFTR-Intron10-7590 UUCACUAUUAAAAAAUUAUACUAU 24 26470 CFTR-Intron10-7591 UUUAUAAAGCUGUACUAU 18 26471 CFTR-Intron10-7592 GUUUAUAAAGCUGUACUAU 19 26472 CFTR-Intron10-7593 GGUUUAUAAAGCUGUACUAU 20 26473 CFTR-Intron10-7594 AGGUUUAUAAAGCUGUACUAU 21 26474 CFTR-Intron10-7595 UAGGUUUAUAAAGCUGUACUAU 22 26475 CFTR-Intron10-7596 UUAGGUUUAUAAAGCUGUACUAU 23 26476 CFTR-Intron10-7597 UUUAGGUUUAUAAAGCUGUACUAU 24 26477 CFTR-Intron10-7598 UAAGGGCAUUCUAAGUAU 18 26478 CFTR-Intron10-7599 CUAAGGGCAUUCUAAGUAU 19 26479 CFTR-Intron10-7600 CCUAAGGGCAUUCUAAGUAU 20 26480 CFTR-Intron10-7601 GCCUAAGGGCAUUCUAAGUAU 21 26481 CFTR-Intron10-7602 AGCCUAAGGGCAUUCUAAGUAU 22 26482 CFTR-Intron10-7603 UAGCCUAAGGGCAUUCUAAGUAU 23 26483 CFTR-Intron10-7604 UUAGCCUAAGGGCAUUCUAAGUAU 24 26484 CFTR-Intron10-7605 GCUGCCUUUUAGUAGUAU 18 26485 CFTR-Intron10-7606 GGCUGCCUUUUAGUAGUAU 19 26486 CFTR-Intron10-7607 AGGCUGCCUUUUAGUAGUAU 20 26487 CFTR-Intron10-7608 GAGGCUGCCUUUUAGUAGUAU 21 26488 CFTR-Intron10-7609 GGAGGCUGCCUUUUAGUAGUAU 22 26489 CFTR-Intron10-7610 AGGAGGCUGCCUUUUAGUAGUAU 23 26490 CFTR-Intron10-7611 UAGGAGGCUGCCUUUUAGUAGUAU 24 26491 CFTR-Intron10-7612 CUUUUUCAUUGAAUGUAU 18 26492 CFTR-Intron10-7613 UCUUUUUCAUUGAAUGUAU 19 26493 CFTR-Intron10-7614 UUCUUUUUCAUUGAAUGUAU 20 26494 CFTR-Intron10-7615 UUUCUUUUUCAUUGAAUGUAU 21 26495 CFTR-Intron10-7616 UUUUCUUUUUCAUUGAAUGUAU 22 26496 CFTR-Intron10-7617 CUUUUCUUUUUCAUUGAAUGUAU 23 26497 CFTR-Intron10-7618 CCUUUUCUUUUUCAUUGAAUGUAU 24 26498 CFTR-Intron10-7619 CAAUUUGGUAAUUUGUAU 18 26499 CFTR-Intron10-7620 ACAAUUUGGUAAUUUGUAU 19 26500 CFTR-Intron10-7621 UACAAUUUGGUAAUUUGUAU 20 26501 CFTR-Intron10-7622 AUACAAUUUGGUAAUUUGUAU 21 26502 CFTR-Intron10-7623 AAUACAAUUUGGUAAUUUGUAU 22 26503 CFTR-Intron10-7624 CAAUACAAUUUGGUAAUUUGUAU 23 26504 CFTR-Intron10-7625 UCAAUACAAUUUGGUAAUUUGUAU 24 26505 CFTR-Intron10-7626 AUUUUUAACCUGGAUUAU 18 26506 CFTR-Intron10-7627 UAUUUUUAACCUGGAUUAU 19 26507 CFTR-Intron10-7628 AUAUUUUUAACCUGGAUUAU 20 26508 CFTR-Intron10-7629 UAUAUUUUUAACCUGGAUUAU 21 26509 CFTR-Intron10-7630 AUAUAUUUUUAACCUGGAUUAU 22 26510 CFTR-Intron10-7631 UAUAUAUUUUUAACCUGGAUUAU 23 26511 CFTR-Intron10-7632 AUAUAUAUUUUUAACCUGGAUUAU 24 26512 CFTR-Intron10-7633 AAAAGUUUCUCAUCUUAU 18 26513 CFTR-Intron10-7634 AAAAAGUUUCUCAUCUUAU 19 26514 CFTR-Intron10-1339 UAAAAAGUUUCUCAUCUUAU 20 20224 CFTR-Intron10-7635 UUAAAAAGUUUCUCAUCUUAU 21 26515 CFTR-Intron10-7636 UUUAAAAAGUUUCUCAUCUUAU 22 26516 CFTR-Intron10-7637 AUUUAAAAAGUUUCUCAUCUUAU 23 26517 CFTR-Intron10-7638 AAUUUAAAAAGUUUCUCAUCUUAU 24 26518 CFTR-Intron10-7639 UUCCCAGCCUCCAGAACU 18 26519 CFTR-Intron10-7640 CUUCCCAGCCUCCAGAACU 19 26520 CFTR-Intron10-7641 ACUUCCCAGCCUCCAGAACU 20 26521 CFTR-Intron10-7642 GACUUCCCAGCCUCCAGAACU 21 26522 CFTR-Intron10-7643 GGACUUCCCAGCCUCCAGAACU 22 26523 CFTR-Intron10-7644 UGGACUUCCCAGCCUCCAGAACU 23 26524 CFTR-Intron10-7645 UUGGACUUCCCAGCCUCCAGAACU 24 26525 CFTR-Intron10-7646 GAUUAGGGAAUGCAGACU 18 26526 CFTR-Intron10-7647 GGAUUAGGGAAUGCAGACU 19 26527 CFTR-Intron10-7648 GGGAUUAGGGAAUGCAGACU 20 26528 CFTR-Intron10-7649 AGGGAUUAGGGAAUGCAGACU 21 26529 CFTR-Intron10-7650 GAGGGAUUAGGGAAUGCAGACU 22 26530 CFTR-Intron10-7651 UGAGGGAUUAGGGAAUGCAGACU 23 26531 CFTR-Intron10-7652 GUGAGGGAUUAGGGAAUGCAGACU 24 26532 CFTR-Intron10-7653 AGAAUUGAAUAUGAGACU 18 26533 CFTR-Intron10-7654 AAGAAUUGAAUAUGAGACU 19 26534 CFTR-Intron10-114 GAAGAAUUGAAUAUGAGACU 20 19000 CFTR-Intron10-7655 UGAAGAAUUGAAUAUGAGACU 21 26535 CFTR-Intron10-7656 UUGAAGAAUUGAAUAUGAGACU 22 26536 CFTR-Intron10-7657 UUUGAAGAAUUGAAUAUGAGACU 23 26537 CFTR-Intron10-7658 UUUUGAAGAAUUGAAUAUGAGACU 24 26538 CFTR-Intron10-7659 UAGAUUAGCUUAUAUACU 18 26539 CFTR-Intron10-7660 AUAGAUUAGCUUAUAUACU 19 26540 CFTR-Intron10-7661 AAUAGAUUAGCUUAUAUACU 20 26541 CFTR-Intron10-7662 GAAUAGAUUAGCUUAUAUACU 21 26542 CFTR-Intron10-7663 UGAAUAGAUUAGCUUAUAUACU 22 26543 CFTR-Intron10-7664 UUGAAUAGAUUAGCUUAUAUACU 23 26544 CFTR-Intron10-7665 UUUGAAUAGAUUAGCUUAUAUACU 24 26545 CFTR-Intron10-7666 CCCGUAGUCCCAGCUACU 18 26546 CFTR-Intron10-7667 GCCCGUAGUCCCAGCUACU 19 26547 CFTR-Intron10-1343 UGCCCGUAGUCCCAGCUACU 20 20228 CFTR-Intron10-7668 GUGCCCGUAGUCCCAGCUACU 21 26548 CFTR-Intron10-7669 GGUGCCCGUAGUCCCAGCUACU 22 26549 CFTR-Intron10-7670 GGGUGCCCGUAGUCCCAGCUACU 23 26550 CFTR-Intron10-7671 CGGGUGCCCGUAGUCCCAGCUACU 24 26551 CFTR-Intron10-7672 GUGCCUGUAGUCCCAGCUACU 21 26552 CFTR-Intron10-7673 UGUGCCUGUAGUCCCAGCUACU 22 26553 CFTR-Intron10-7674 GUGUGCCUGUAGUCCCAGCUACU 23 26554 CFTR-Intron10-7675 UGUGUGCCUGUAGUCCCAGCUACU 24 26555 CFTR-Intron10-7676 UCUUUAUAAAAGAAACCU 18 26556 CFTR-Intron10-7677 GUCUUUAUAAAAGAAACCU 19 26557 CFTR-Intron10-7678 UGUCUUUAUAAAAGAAACCU 20 26558 CFTR-Intron10-7679 GUGUCUUUAUAAAAGAAACCU 21 26559 CFTR-Intron10-7680 AGUGUCUUUAUAAAAGAAACCU 22 26560 CFTR-Intron10-7681 UAGUGUCUUUAUAAAAGAAACCU 23 26561 CFTR-Intron10-7682 UUAGUGUCUUUAUAAAAGAAACCU 24 26562 CFTR-Intron10-7683 AGAGAGACCCUCACACCU 18 26563 CFTR-Intron10-7684 UAGAGAGACCCUCACACCU 19 26564 CFTR-Intron10-7685 UUAGAGAGACCCUCACACCU 20 26565 CFTR-Intron10-7686 CUUAGAGAGACCCUCACACCU 21 26566 CFTR-Intron10-7687 CCUUAGAGAGACCCUCACACCU 22 26567 CFTR-Intron10-7688 ACCUUAGAGAGACCCUCACACCU 23 26568 CFTR-Intron10-7689 AACCUUAGAGAGACCCUCACACCU 24 26569 CFTR-Intron10-7690 UUCUCCAUAUCCCACCCU 18 26570 CFTR-Intron10-7691 CUUCUCCAUAUCCCACCCU 19 26571 CFTR-Intron10-7692 UCUUCUCCAUAUCCCACCCU 20 26572 CFTR-Intron10-7693 CUCUUCUCCAUAUCCCACCCU 21 26573 CFTR-Intron10-7694 CCUCUUCUCCAUAUCCCACCCU 22 26574 CFTR-Intron10-7695 UCCUCUUCUCCAUAUCCCACCCU 23 26575 CFTR-Intron10-7696 AUCCUCUUCUCCAUAUCCCACCCU 24 26576 CFTR-Intron10-7697 AGGAAGGCAGUGGUCCCU 18 26577 CFTR-Intron10-7698 GAGGAAGGCAGUGGUCCCU 19 26578 CFTR-Intron10-515 AGAGGAAGGCAGUGGUCCCU 20 19401 CFTR-Intron10-7699 UAGAGGAAGGCAGUGGUCCCU 21 26579 CFTR-Intron10-7700 UUAGAGGAAGGCAGUGGUCCCU 22 26580 CFTR-Intron10-7701 GUUAGAGGAAGGCAGUGGUCCCU 23 26581 CFTR-Intron10-7702 AGUUAGAGGAAGGCAGUGGUCCCU 24 26582 CFTR-Intron10-7703 GGAGGAUCACCUGAGCCU 18 26583 CFTR-Intron10-7704 GGGAGGAUCACCUGAGCCU 19 26584 CFTR-Intron10-7705 UGGGAGGAUCACCUGAGCCU 20 26585 CFTR-Intron10-7706 GUGGGAGGAUCACCUGAGCCU 21 26586 CFTR-Intron10-7707 GGUGGGAGGAUCACCUGAGCCU 22 26587 CFTR-Intron10-7708 AGGUGGGAGGAUCACCUGAGCCU 23 26588 CFTR-Intron10-7709 GAGGUGGGAGGAUCACCUGAGCCU 24 26589 CFTR-Intron10-7710 GGGUGUAGGGGUUAGCCU 18 26590 CFTR-Intron10-7711 GGGGUGUAGGGGUUAGCCU 19 26591 CFTR-Intron10-7712 AGGGGUGUAGGGGUUAGCCU 20 26592 CFTR-Intron10-7713 AAGGGGUGUAGGGGUUAGCCU 21 26593 CFTR-Intron10-7714 AAAGGGGUGUAGGGGUUAGCCU 22 26594 CFTR-Intron10-7715 GAAAGGGGUGUAGGGGUUAGCCU 23 26595 CFTR-Intron10-7716 AGAAAGGGGUGUAGGGGUUAGCCU 24 26596 CFTR-Intron10-7717 UAUUGCAGGGUGGGGCCU 18 26597 CFTR-Intron10-7718 GUAUUGCAGGGUGGGGCCU 19 26598 CFTR-Intron10-7719 GGUAUUGCAGGGUGGGGCCU 20 26599 CFTR-Intron10-7720 UGGUAUUGCAGGGUGGGGCCU 21 26600 CFTR-Intron10-7721 AUGGUAUUGCAGGGUGGGGCCU 22 26601 CFTR-Intron10-7722 GAUGGUAUUGCAGGGUGGGGCCU 23 26602 CFTR-Intron10-7723 UGAUGGUAUUGCAGGGUGGGGCCU 24 26603 CFTR-Intron10-7724 UUUGACCUAAGAUAUCCU 18 26604 CFTR-Intron10-7725 CUUUGACCUAAGAUAUCCU 19 26605 CFTR-Intron10-7726 UCUUUGACCUAAGAUAUCCU 20 26606 CFTR-Intron10-7727 CUCUUUGACCUAAGAUAUCCU 21 26607 CFTR-Intron10-7728 CCUCUUUGACCUAAGAUAUCCU 22 26608 CFTR-Intron10-7729 UCCUCUUUGACCUAAGAUAUCCU 23 26609 CFTR-Intron10-7730 UUCCUCUUUGACCUAAGAUAUCCU 24 26610 CFTR-Intron10-7731 AGCUUAUGAAAAGCAGCU 18 26611 CFTR-Intron10-7732 UAGCUUAUGAAAAGCAGCU 19 26612 CFTR-Intron10-7733 AUAGCUUAUGAAAAGCAGCU 20 26613 CFTR-Intron10-7734 UAUAGCUUAUGAAAAGCAGCU 21 26614 CFTR-Intron10-7735 UUAUAGCUUAUGAAAAGCAGCU 22 26615 CFTR-Intron10-7736 GUUAUAGCUUAUGAAAAGCAGCU 23 26616 CFTR-Intron10-7737 AGUUAUAGCUUAUGAAAAGCAGCU 24 26617 CFTR-Intron10-7738 AGAUGUGCAAAAAUAGCU 18 26618 CFTR-Intron10-7739 UAGAUGUGCAAAAAUAGCU 19 26619 CFTR-Intron10-7740 AUAGAUGUGCAAAAAUAGCU 20 26620 CFTR-Intron10-7741 GAUAGAUGUGCAAAAAUAGCU 21 26621 CFTR-Intron10-7742 UGAUAGAUGUGCAAAAAUAGCU 22 26622 CFTR-Intron10-7743 AUGAUAGAUGUGCAAAAAUAGCU 23 26623 CFTR-Intron10-7744 UAUGAUAGAUGUGCAAAAAUAGCU 24 26624 CFTR-Intron10-7745 UCAGAUUCAGGACAUGCU 18 26625 CFTR-Intron10-7746 AUCAGAUUCAGGACAUGCU 19 26626 CFTR-Intron10-7747 GAUCAGAUUCAGGACAUGCU 20 26627 CFTR-Intron10-7748 UGAUCAGAUUCAGGACAUGCU 21 26628 CFTR-Intron10-7749 GUGAUCAGAUUCAGGACAUGCU 22 26629 CFTR-Intron10-7750 AGUGAUCAGAUUCAGGACAUGCU 23 26630 CFTR-Intron10-7751 AAGUGAUCAGAUUCAGGACAUGCU 24 26631 CFTR-Intron10-7752 AGUUUACUAACUCAAUCU 18 26632 CFTR-Intron10-7753 GAGUUUACUAACUCAAUCU 19 26633 CFTR-Intron10-118 GGAGUUUACUAACUCAAUCU 20 19004 CFTR-Intron10-7754 CGGAGUUUACUAACUCAAUCU 21 26634 CFTR-Intron10-7755 ACGGAGUUUACUAACUCAAUCU 22 26635 CFTR-Intron10-7756 AACGGAGUUUACUAACUCAAUCU 23 26636 CFTR-Intron10-7757 AAACGGAGUUUACUAACUCAAUCU 24 26637 CFTR-Intron10-7758 UUUAUCAAGUUGUUAUCU 18 26638 CFTR-Intron10-7759 AUUUAUCAAGUUGUUAUCU 19 26639 CFTR-Intron10-7760 AAUUUAUCAAGUUGUUAUCU 20 26640 CFTR-Intron10-7761 AAAUUUAUCAAGUUGUUAUCU 21 26641 CFTR-Intron10-7762 UAAAUUUAUCAAGUUGUUAUCU 22 26642 CFTR-Intron10-7763 AUAAAUUUAUCAAGUUGUUAUCU 23 26643 CFTR-Intron10-7764 GAUAAAUUUAUCAAGUUGUUAUCU 24 26644 CFTR-Intron10-7765 UUAGGGAAUGCAGACUCU 18 26645 CFTR-Intron10-7766 AUUAGGGAAUGCAGACUCU 19 26646 CFTR-Intron10-119 GAUUAGGGAAUGCAGACUCU 20 19005 CFTR-Intron10-7767 GGAUUAGGGAAUGCAGACUCU 21 26647 CFTR-Intron10-7768 GGGAUUAGGGAAUGCAGACUCU 22 26648 CFTR-Intron10-7769 AGGGAUUAGGGAAUGCAGACUCU 23 26649 CFTR-Intron10-7770 GAGGGAUUAGGGAAUGCAGACUCU 24 26650 CFTR-Intron10-7771 CCAAUAAAAUAAAAGUCU 18 26651 CFTR-Intron10-7772 CCCAAUAAAAUAAAAGUCU 19 26652 CFTR-Intron10-7773 ACCCAAUAAAAUAAAAGUCU 20 26653 CFTR-Intron10-7774 AACCCAAUAAAAUAAAAGUCU 21 26654 CFTR-Intron10-7775 AAACCCAAUAAAAUAAAAGUCU 22 26655 CFTR-Intron10-7776 AAAACCCAAUAAAAUAAAAGUCU 23 26656 CFTR-Intron10-7777 GAAAACCCAAUAAAAUAAAAGUCU 24 26657 CFTR-Intron10-7778 GAAUAUUUAAACACUUCU 18 26658 CFTR-Intron10-7779 GGAAUAUUUAAACACUUCU 19 26659 CFTR-Intron10-7780 GGGAAUAUUUAAACACUUCU 20 26660 CFTR-Intron10-7781 UGGGAAUAUUUAAACACUUCU 21 26661 CFTR-Intron10-7782 UUGGGAAUAUUUAAACACUUCU 22 26662 CFTR-Intron10-7783 CUUGGGAAUAUUUAAACACUUCU 23 26663 CFTR-Intron10-7784 CCUUGGGAAUAUUUAAACACUUCU 24 26664 CFTR-Intron10-7785 ACCCAAUAAAAUAAAAGU 18 26665 CFTR-Intron10-7786 AACCCAAUAAAAUAAAAGU 19 26666 CFTR-Intron10-7787 AAACCCAAUAAAAUAAAAGU 20 26667 CFTR-Intron10-7788 AAAACCCAAUAAAAUAAAAGU 21 26668 CFTR-Intron10-7789 GAAAACCCAAUAAAAUAAAAGU 22 26669 CFTR-Intron10-7790 AGAAAACCCAAUAAAAUAAAAGU 23 26670 CFTR-Intron10-7791 AAGAAAACCCAAUAAAAUAAAAGU 24 26671 CFTR-Intron10-7792 AUGAGGAAGAAAGGAAGU 18 26672 CFTR-Intron10-7793 AAUGAGGAAGAAAGGAAGU 19 26673 CFTR-Intron10-1369 AAAUGAGGAAGAAAGGAAGU 20 20253 CFTR-Intron10-7794 GAAAUGAGGAAGAAAGGAAGU 21 26674 CFTR-Intron10-7795 GGAAAUGAGGAAGAAAGGAAGU 22 26675 CFTR-Intron10-7796 AGGAAAUGAGGAAGAAAGGAAGU 23 26676 CFTR-Intron10-7797 AAGGAAAUGAGGAAGAAAGGAAGU 24 26677 CFTR-Intron10-7798 GGAAAGAAGGAAGGAAGU 18 26678 CFTR-Intron10-7799 AGGAAAGAAGGAAGGAAGU 19 26679 CFTR-Intron10-7800 AAGGAAAGAAGGAAGGAAGU 20 26680 CFTR-Intron10-7801 GAAGGAAAGAAGGAAGGAAGU 21 26681 CFTR-Intron10-7802 GGAAGGAAAGAAGGAAGGAAGU 22 26682 CFTR-Intron10-7803 AGGAAGGAAAGAAGGAAGGAAGU 23 26683 CFTR-Intron10-7804 AAGGAAGGAAAGAAGGAAGGAAGU 24 26684 CFTR-Intron10-7805 GGUUUGGGAAUAUUAAGU 18 26685 CFTR-Intron10-7806 UGGUUUGGGAAUAUUAAGU 19 26686 CFTR-Intron10-7807 UUGGUUUGGGAAUAUUAAGU 20 26687 CFTR-Intron10-7808 CUUGGUUUGGGAAUAUUAAGU 21 26688 CFTR-Intron10-7809 GCUUGGUUUGGGAAUAUUAAGU 22 26689 CFTR-Intron10-7810 AGCUUGGUUUGGGAAUAUUAAGU 23 26690 CFTR-Intron10-7811 GAGCUUGGUUUGGGAAUAUUAAGU 24 26691 CFTR-Intron10-7812 UCUGGUUUGAAGAACAGU 18 26692 CFTR-Intron10-7813 GUCUGGUUUGAAGAACAGU 19 26693 CFTR-Intron10-7814 UGUCUGGUUUGAAGAACAGU 20 26694 CFTR-Intron10-7815 CUGUCUGGUUUGAAGAACAGU 21 26695 CFTR-Intron10-7816 CCUGUCUGGUUUGAAGAACAGU 22 26696 CFTR-Intron10-7817 ACCUGUCUGGUUUGAAGAACAGU 23 26697 CFTR-Intron10-7818 UACCUGUCUGGUUUGAAGAACAGU 24 26698 CFTR-Intron10-7819 CAGCUAUGAAGGCAGAGU 18 26699 CFTR-Intron10-7820 GCAGCUAUGAAGGCAGAGU 19 26700 CFTR-Intron10-7821 AGCAGCUAUGAAGGCAGAGU 20 26701 CFTR-Intron10-7822 AAGCAGCUAUGAAGGCAGAGU 21 26702 CFTR-Intron10-7823 AAAGCAGCUAUGAAGGCAGAGU 22 26703 CFTR-Intron10-7824 AAAAGCAGCUAUGAAGGCAGAGU 23 26704 CFTR-Intron10-7825 GAAAAGCAGCUAUGAAGGCAGAGU 24 26705 CFTR-Intron10-7826 UUGCUUGAGUCCAGGAGU 18 26706 CFTR-Intron10-7827 AUUGCUUGAGUCCAGGAGU 19 26707 CFTR-Intron10-7828 AAUUGCUUGAGUCCAGGAGU 20 26708 CFTR-Intron10-7829 GAAUUGCUUGAGUCCAGGAGU 21 26709 CFTR-Intron10-7830 UGAAUUGCUUGAGUCCAGGAGU 22 26710 CFTR-Intron10-7831 GUGAAUUGCUUGAGUCCAGGAGU 23 26711 CFTR-Intron10-7832 GGUGAAUUGCUUGAGUCCAGGAGU 24 26712 CFTR-Intron10-7833 GGAAGCAAGGAGAUGAGU 18 26713 CFTR-Intron10-7834 AGGAAGCAAGGAGAUGAGU 19 26714 CFTR-Intron10-7835 GAGGAAGCAAGGAGAUGAGU 20 26715 CFTR-Intron10-7836 GGAGGAAGCAAGGAGAUGAGU 21 26716 CFTR-Intron10-7837 GGGAGGAAGCAAGGAGAUGAGU 22 26717 CFTR-Intron10-7838 AGGGAGGAAGCAAGGAGAUGAGU 23 26718 CFTR-Intron10-7839 AAGGGAGGAAGCAAGGAGAUGAGU 24 26719 CFTR-Intron10-7840 UAGUGGAAGUAGUAUAGU 18 26720 CFTR-Intron10-7841 GUAGUGGAAGUAGUAUAGU 19 26721 CFTR-Intron10-533 AGUAGUGGAAGUAGUAUAGU 20 19419 CFTR-Intron10-7842 UAGUAGUGGAAGUAGUAUAGU 21 26722 CFTR-Intron10-7843 GUAGUAGUGGAAGUAGUAUAGU 22 26723 CFTR-Intron10-7844 GGUAGUAGUGGAAGUAGUAUAGU 23 26724 CFTR-Intron10-7845 AGGUAGUAGUGGAAGUAGUAUAGU 24 26725 CFTR-Intron10-7846 GAAGAGGGGGCUGGUAGU 18 26726 CFTR-Intron10-7847 GGAAGAGGGGGCUGGUAGU 19 26727 CFTR-Intron10-7848 AGGAAGAGGGGGCUGGUAGU 20 26728 CFTR-Intron10-7849 AAGGAAGAGGGGGCUGGUAGU 21 26729 CFTR-Intron10-7850 CAAGGAAGAGGGGGCUGGUAGU 22 26730 CFTR-Intron10-7851 UCAAGGAAGAGGGGGCUGGUAGU 23 26731 CFTR-Intron10-7852 UUCAAGGAAGAGGGGGCUGGUAGU 24 26732 CFTR-Intron10-7853 GAUGCUAAUCAUCUCCGU 18 26733 CFTR-Intron10-7854 UGAUGCUAAUCAUCUCCGU 19 26734 CFTR-Intron10-7855 GUGAUGCUAAUCAUCUCCGU 20 26735 CFTR-Intron10-7856 CGUGAUGCUAAUCAUCUCCGU 21 26736 CFTR-Intron10-7857 ACGUGAUGCUAAUCAUCUCCGU 22 26737 CFTR-Intron10-7858 CACGUGAUGCUAAUCAUCUCCGU 23 26738 CFTR-Intron10-7859 CCACGUGAUGCUAAUCAUCUCCGU 24 26739 CFTR-Intron10-7860 GCAGCUAUGCCAGCAGGU 18 26740 CFTR-Intron10-7861 UGCAGCUAUGCCAGCAGGU 19 26741 CFTR-Intron10-7862 GUGCAGCUAUGCCAGCAGGU 20 26742 CFTR-Intron10-7863 AGUGCAGCUAUGCCAGCAGGU 21 26743 CFTR-Intron10-7864 CAGUGCAGCUAUGCCAGCAGGU 22 26744 CFTR-Intron10-7865 UCAGUGCAGCUAUGCCAGCAGGU 23 26745 CFTR-Intron10-7866 AUCAGUGCAGCUAUGCCAGCAGGU 24 26746 CFTR-Intron10-7867 UCAGUGCUUUUUCGAGGU 18 26747 CFTR-Intron10-7868 AUCAGUGCUUUUUCGAGGU 19 26748 CFTR-Intron10-7869 AAUCAGUGCUUUUUCGAGGU 20 26749 CFTR-Intron10-7870 AAAUCAGUGCUUUUUCGAGGU 21 26750 CFTR-Intron10-7871 AAAAUCAGUGCUUUUUCGAGGU 22 26751 CFTR-Intron10-7872 UAAAAUCAGUGCUUUUUCGAGGU 23 26752 CFTR-Intron10-7873 AUAAAAUCAGUGCUUUUUCGAGGU 24 26753 CFTR-Intron10-7874 CAAAGACUUGCAGGAGGU 18 26754 CFTR-Intron10-7875 ACAAAGACUUGCAGGAGGU 19 26755 CFTR-Intron10-7876 AACAAAGACUUGCAGGAGGU 20 26756 CFTR-Intron10-7877 GAACAAAGACUUGCAGGAGGU 21 26757 CFTR-Intron10-7878 UGAACAAAGACUUGCAGGAGGU 22 26758 CFTR-Intron10-7879 UUGAACAAAGACUUGCAGGAGGU 23 26759 CFTR-Intron10-7880 UUUGAACAAAGACUUGCAGGAGGU 24 26760 CFTR-Intron10-7881 GUAAUCGGCGGUGGAGGU 18 26761 CFTR-Intron10-7882 AGUAAUCGGCGGUGGAGGU 19 26762 CFTR-Intron10-536 AAGUAAUCGGCGGUGGAGGU 20 19422 CFTR-Intron10-7883 GAAGUAAUCGGCGGUGGAGGU 21 26763 CFTR-Intron10-7884 AGAAGUAAUCGGCGGUGGAGGU 22 26764 CFTR-Intron10-7885 GAGAAGUAAUCGGCGGUGGAGGU 23 26765 CFTR-Intron10-7886 AGAGAAGUAAUCGGCGGUGGAGGU 24 26766 CFTR-Intron10-7887 UACUUGGGAGGCUGAGGU 18 26767 CFTR-Intron10-7888 CUACUUGGGAGGCUGAGGU 19 26768 CFTR-Intron10-713 GCUACUUGGGAGGCUGAGGU 20 19599 CFTR-Intron10-7889 AGCUACUUGGGAGGCUGAGGU 21 26769 CFTR-Intron10-7890 CAGCUACUUGGGAGGCUGAGGU 22 26770 CFTR-Intron10-7891 CCAGCUACUUGGGAGGCUGAGGU 23 26771 CFTR-Intron10-7892 CCCAGCUACUUGGGAGGCUGAGGU 24 26772 CFTR-Intron10-7893 AGGAGCCAAAAAUUGGGU 18 26773 CFTR-Intron10-7894 CAGGAGCCAAAAAUUGGGU 19 26774 CFTR-Intron10-537 UCAGGAGCCAAAAAUUGGGU 20 19423 CFTR-Intron10-7895 UUCAGGAGCCAAAAAUUGGGU 21 26775 CFTR-Intron10-7896 UUUCAGGAGCCAAAAAUUGGGU 22 26776 CFTR-Intron10-7897 CUUUCAGGAGCCAAAAAUUGGGU 23 26777 CFTR-Intron10-7898 GCUUUCAGGAGCCAAAAAUUGGGU 24 26778 CFTR-Intron10-7899 UGACUAUACCUGUCUGGU 18 26779 CFTR-Intron10-7900 CUGACUAUACCUGUCUGGU 19 26780 CFTR-Intron10-7901 ACUGACUAUACCUGUCUGGU 20 26781 CFTR-Intron10-7902 GACUGACUAUACCUGUCUGGU 21 26782 CFTR-Intron10-7903 GGACUGACUAUACCUGUCUGGU 22 26783 CFTR-Intron10-7904 GGGACUGACUAUACCUGUCUGGU 23 26784 CFTR-Intron10-7905 UGGGACUGACUAUACCUGUCUGGU 24 26785 CFTR-Intron10-7906 UUUUGGAUGGAGCUUGGU 18 26786 CFTR-Intron10-7907 GUUUUGGAUGGAGCUUGGU 19 26787 CFTR-Intron10-7908 GGUUUUGGAUGGAGCUUGGU 20 26788 CFTR-Intron10-7909 AGGUUUUGGAUGGAGCUUGGU 21 26789 CFTR-Intron10-7910 CAGGUUUUGGAUGGAGCUUGGU 22 26790 CFTR-Intron10-7911 ACAGGUUUUGGAUGGAGCUUGGU 23 26791 CFTR-Intron10-7912 AACAGGUUUUGGAUGGAGCUUGGU 24 26792 CFTR-Intron10-7913 GGUACUUUGUAGAAAUGU 18 26793 CFTR-Intron10-7914 UGGUACUUUGUAGAAAUGU 19 26794 CFTR-Intron10-7915 GUGGUACUUUGUAGAAAUGU 20 26795 CFTR-Intron10-7916 UGUGGUACUUUGUAGAAAUGU 21 26796 CFTR-Intron10-7917 CUGUGGUACUUUGUAGAAAUGU 22 26797 CFTR-Intron10-7918 GCUGUGGUACUUUGUAGAAAUGU 23 26798 CFTR-Intron10-7919 AGCUGUGGUACUUUGUAGAAAUGU 24 26799 CFTR-Intron10-7920 CACCCCUUUCUGCCAUGU 18 26800 CFTR-Intron10-7921 UCACCCCUUUCUGCCAUGU 19 26801 CFTR-Intron10-7922 CUCACCCCUUUCUGCCAUGU 20 26802 CFTR-Intron10-7923 CCUCACCCCUUUCUGCCAUGU 21 26803 CFTR-Intron10-7924 CCCUCACCCCUUUCUGCCAUGU 22 26804 CFTR-Intron10-7925 ACCCUCACCCCUUUCUGCCAUGU 23 26805 CFTR-Intron10-7926 GACCCUCACCCCUUUCUGCCAUGU 24 26806 CFTR-Intron10-7927 CCCAGCCUCCAGAACUGU 18 26807 CFTR-Intron10-7928 UCCCAGCCUCCAGAACUGU 19 26808 CFTR-Intron10-7929 UUCCCAGCCUCCAGAACUGU 20 26809 CFTR-Intron10-7930 CUUCCCAGCCUCCAGAACUGU 21 26810 CFTR-Intron10-7931 ACUUCCCAGCCUCCAGAACUGU 22 26811 CFTR-Intron10-7932 GACUUCCCAGCCUCCAGAACUGU 23 26812 CFTR-Intron10-7933 GGACUUCCCAGCCUCCAGAACUGU 24 26813 CFTR-Intron10-7934 GGGAGGGUAGAAUACUGU 18 26814 CFTR-Intron10-7935 AGGGAGGGUAGAAUACUGU 19 26815 CFTR-Intron10-7936 CAGGGAGGGUAGAAUACUGU 20 26816 CFTR-Intron10-7937 ACAGGGAGGGUAGAAUACUGU 21 26817 CFTR-Intron10-7938 GACAGGGAGGGUAGAAUACUGU 22 26818 CFTR-Intron10-7939 AGACAGGGAGGGUAGAAUACUGU 23 26819 CFTR-Intron10-7940 AAGACAGGGAGGGUAGAAUACUGU 24 26820 CFTR-Intron10-7941 GUUUUUAGGCUAUUCUGU 18 26821 CFTR-Intron10-7942 UGUUUUUAGGCUAUUCUGU 19 26822 CFTR-Intron10-541 AUGUUUUUAGGCUAUUCUGU 20 19427 CFTR-Intron10-7943 AAUGUUUUUAGGCUAUUCUGU 21 26823 CFTR-Intron10-7944 UAAUGUUUUUAGGCUAUUCUGU 22 26824 CFTR-Intron10-7945 CUAAUGUUUUUAGGCUAUUCUGU 23 26825 CFTR-Intron10-7946 GCUAAUGUUUUUAGGCUAUUCUGU 24 26826 CFTR-Intron10-7947 AUGGCAUCUCACCAGUGU 18 26827 CFTR-Intron10-7948 UAUGGCAUCUCACCAGUGU 19 26828 CFTR-Intron10-7949 UUAUGGCAUCUCACCAGUGU 20 26829 CFTR-Intron10-7950 CUUAUGGCAUCUCACCAGUGU 21 26830 CFTR-Intron10-7951 GCUUAUGGCAUCUCACCAGUGU 22 26831 CFTR-Intron10-7952 GGCUUAUGGCAUCUCACCAGUGU 23 26832 CFTR-Intron10-7953 UGGCUUAUGGCAUCUCACCAGUGU 24 26833 CFTR-Intron10-7954 GGCAUCUCACCAGUGUGU 18 26834 CFTR-Intron10-7955 UGGCAUCUCACCAGUGUGU 19 26835 CFTR-Intron10-542 AUGGCAUCUCACCAGUGUGU 20 19428 CFTR-Intron10-7956 UAUGGCAUCUCACCAGUGUGU 21 26836 CFTR-Intron10-7957 UUAUGGCAUCUCACCAGUGUGU 22 26837 CFTR-Intron10-7958 CUUAUGGCAUCUCACCAGUGUGU 23 26838 CFTR-Intron10-7959 GCUUAUGGCAUCUCACCAGUGUGU 24 26839 CFTR-Intron10-7960 GUAUGUAUAUAUGUGUGU 18 26840 CFTR-Intron10-7961 UGUAUGUAUAUAUGUGUGU 19 26841 CFTR-Intron10-7962 AUGUAUGUAUAUAUGUGUGU 20 26842 CFTR-Intron10-7963 UAUGUAUGUAUAUAUGUGUGU 21 26843 CFTR-Intron10-7964 AUAUGUAUGUAUAUAUGUGUGU 22 26844 CFTR-Intron10-7965 CAUAUGUAUGUAUAUAUGUGUGU 23 26845 CFTR-Intron10-7966 UCAUAUGUAUGUAUAUAUGUGUGU 24 26846 CFTR-Intron10-7967 UCUAACUUUUCUUAUUGU 18 26847 CFTR-Intron10-7968 UUCUAACUUUUCUUAUUGU 19 26848 CFTR-Intron10-7969 CUUCUAACUUUUCUUAUUGU 20 26849 CFTR-Intron10-7970 ACUUCUAACUUUUCUUAUUGU 21 26850 CFTR-Intron10-7971 UACUUCUAACUUUUCUUAUUGU 22 26851 CFTR-Intron10-7972 UUACUUCUAACUUUUCUUAUUGU 23 26852 CFTR-Intron10-7973 UUUACUUCUAACUUUUCUUAUUGU 24 26853 CFTR-Intron10-7974 GGACCAAAACUUUAUUGU 18 26854 CFTR-Intron10-7975 AGGACCAAAACUUUAUUGU 19 26855 CFTR-Intron10-7976 AAGGACCAAAACUUUAUUGU 20 26856 CFTR-Intron10-7977 AAAGGACCAAAACUUUAUUGU 21 26857 CFTR-Intron10-7978 AAAAGGACCAAAACUUUAUUGU 22 26858 CFTR-Intron10-7979 CAAAAGGACCAAAACUUUAUUGU 23 26859 CFTR-Intron10-7980 GCAAAAGGACCAAAACUUUAUUGU 24 26860 CFTR-Intron10-7981 UACCCAAUAAAAAAAAUU 18 26861 CFTR-Intron10-7982 UUACCCAAUAAAAAAAAUU 19 26862 CFTR-Intron10-124 GUUACCCAAUAAAAAAAAUU 20 19010 CFTR-Intron10-7983 UGUUACCCAAUAAAAAAAAUU 21 26863 CFTR-Intron10-7984 UUGUUACCCAAUAAAAAAAAUU 22 26864 CFTR-Intron10-7985 AUUGUUACCCAAUAAAAAAAAUU 23 26865 CFTR-Intron10-7986 UAUUGUUACCCAAUAAAAAAAAUU 24 26866 CFTR-Intron10-7987 AGAAAUACCGAGAAAAUU 18 26867 CFTR-Intron10-7988 UAGAAAUACCGAGAAAAUU 19 26868 CFTR-Intron10-7989 CUAGAAAUACCGAGAAAAUU 20 26869 CFTR-Intron10-7990 CCUAGAAAUACCGAGAAAAUU 21 26870 CFTR-Intron10-7991 GCCUAGAAAUACCGAGAAAAUU 22 26871 CFTR-Intron10-7992 AGCCUAGAAAUACCGAGAAAAUU 23 26872 CFTR-Intron10-7993 UAGCCUAGAAAUACCGAGAAAAUU 24 26873 CFTR-Intron10-7994 UUAAUGAAAAUAGAAAUU 18 26874 CFTR-Intron10-7995 GUUAAUGAAAAUAGAAAUU 19 26875 CFTR-Intron10-7996 UGUUAAUGAAAAUAGAAAUU 20 26876 CFTR-Intron10-7997 AUGUUAAUGAAAAUAGAAAUU 21 26877 CFTR-Intron10-7998 AAUGUUAAUGAAAAUAGAAAUU 22 26878 CFTR-Intron10-7999 AAAUGUUAAUGAAAAUAGAAAUU 23 26879 CFTR-Intron10-8000 AAAAUGUUAAUGAAAAUAGAAAUU 24 26880 CFTR-Intron10-8001 CUACAGUUGCCUGCAAUU 18 26881 CFTR-Intron10-8002 GCUACAGUUGCCUGCAAUU 19 26882 CFTR-Intron10-8003 AGCUACAGUUGCCUGCAAUU 20 26883 CFTR-Intron10-8004 CAGCUACAGUUGCCUGCAAUU 21 26884 CFTR-Intron10-8005 GCAGCUACAGUUGCCUGCAAUU 22 26885 CFTR-Intron10-8006 UGCAGCUACAGUUGCCUGCAAUU 23 26886 CFTR-Intron10-8007 CUGCAGCUACAGUUGCCUGCAAUU 24 26887 CFTR-Intron10-8008 UAUCAAUAUUUUGGAAUU 18 26888 CFTR-Intron10-8009 UUAUCAAUAUUUUGGAAUU 19 26889 CFTR-Intron10-8010 UUUAUCAAUAUUUUGGAAUU 20 26890 CFTR-Intron10-8011 UUUUAUCAAUAUUUUGGAAUU 21 26891 CFTR-Intron10-8012 GUUUUAUCAAUAUUUUGGAAUU 22 26892 CFTR-Intron10-8013 AGUUUUAUCAAUAUUUUGGAAUU 23 26893 CFTR-Intron10-8014 UAGUUUUAUCAAUAUUUUGGAAUU 24 26894 CFTR-Intron10-8015 GGUACUACUGUAAUAAUU 18 26895 CFTR-Intron10-8016 UGGUACUACUGUAAUAAUU 19 26896 CFTR-Intron10-1381 AUGGUACUACUGUAAUAAUU 20 20265 CFTR-Intron10-8017 UAUGGUACUACUGUAAUAAUU 21 26897 CFTR-Intron10-8018 AUAUGGUACUACUGUAAUAAUU 22 26898 CFTR-Intron10-8019 CAUAUGGUACUACUGUAAUAAUU 23 26899 CFTR-Intron10-8020 ACAUAUGGUACUACUGUAAUAAUU 24 26900 CFTR-Intron10-8021 AAAUAUCACCAACUCAUU 18 26901 CFTR-Intron10-8022 AAAAUAUCACCAACUCAUU 19 26902 CFTR-Intron10-544 AAAAAUAUCACCAACUCAUU 20 19430 CFTR-Intron10-8023 GAAAAAUAUCACCAACUCAUU 21 26903 CFTR-Intron10-8024 UGAAAAAUAUCACCAACUCAUU 22 26904 CFTR-Intron10-8025 AUGAAAAAUAUCACCAACUCAUU 23 26905 CFTR-Intron10-8026 AAUGAAAAAUAUCACCAACUCAUU 24 26906 CFTR-Intron10-8027 GUAGGAAGUGAUCAGAUU 18 26907 CFTR-Intron10-8028 AGUAGGAAGUGAUCAGAUU 19 26908 CFTR-Intron10-8029 UAGUAGGAAGUGAUCAGAUU 20 26909 CFTR-Intron10-8030 AUAGUAGGAAGUGAUCAGAUU 21 26910 CFTR-Intron10-8031 UAUAGUAGGAAGUGAUCAGAUU 22 26911 CFTR-Intron10-8032 GUAUAGUAGGAAGUGAUCAGAUU 23 26912 CFTR-Intron10-8033 AGUAUAGUAGGAAGUGAUCAGAUU 24 26913 CFTR-Intron10-8034 AGCUGGCUAUCCAGGAUU 18 26914 CFTR-Intron10-8035 CAGCUGGCUAUCCAGGAUU 19 26915 CFTR-Intron10-8036 ACAGCUGGCUAUCCAGGAUU 20 26916 CFTR-Intron10-8037 GACAGCUGGCUAUCCAGGAUU 21 26917 CFTR-Intron10-8038 AGACAGCUGGCUAUCCAGGAUU 22 26918 CFTR-Intron10-8039 AAGACAGCUGGCUAUCCAGGAUU 23 26919 CFTR-Intron10-8040 GAAGACAGCUGGCUAUCCAGGAUU 24 26920 CFTR-Intron10-8041 UGCAGGAGGUGAGGGAUU 18 26921 CFTR-Intron10-8042 UUGCAGGAGGUGAGGGAUU 19 26922 CFTR-Intron10-1384 CUUGCAGGAGGUGAGGGAUU 20 20268 CFTR-Intron10-8043 ACUUGCAGGAGGUGAGGGAUU 21 26923 CFTR-Intron10-8044 GACUUGCAGGAGGUGAGGGAUU 22 26924 CFTR-Intron10-8045 AGACUUGCAGGAGGUGAGGGAUU 23 26925 CFTR-Intron10-8046 AAGACUUGCAGGAGGUGAGGGAUU 24 26926 CFTR-Intron10-8047 AAUAGUUUUAUCAAUAUU 18 26927 CFTR-Intron10-8048 AAAUAGUUUUAUCAAUAUU 19 26928 CFTR-Intron10-8049 CAAAUAGUUUUAUCAAUAUU 20 26929 CFTR-Intron10-8050 GCAAAUAGUUUUAUCAAUAUU 21 26930 CFTR-Intron10-8051 UGCAAAUAGUUUUAUCAAUAUU 22 26931 CFTR-Intron10-8052 CUGCAAAUAGUUUUAUCAAUAUU 23 26932 CFTR-Intron10-8053 UCUGCAAAUAGUUUUAUCAAUAUU 24 26933 CFTR-Intron10-8054 GAUGAGGAGAACCAUAUU 18 26934 CFTR-Intron10-8055 AGAUGAGGAGAACCAUAUU 19 26935 CFTR-Intron10-8056 AAGAUGAGGAGAACCAUAUU 20 26936 CFTR-Intron10-8057 UAAGAUGAGGAGAACCAUAUU 21 26937 CFTR-Intron10-8058 CUAAGAUGAGGAGAACCAUAUU 22 26938 CFTR-Intron10-8059 UCUAAGAUGAGGAGAACCAUAUU 23 26939 CFTR-Intron10-8060 AUCUAAGAUGAGGAGAACCAUAUU 24 26940 CFTR-Intron10-8061 AACUUAACCUGGCAUAUU 18 26941 CFTR-Intron10-8062 CAACUUAACCUGGCAUAUU 19 26942 CFTR-Intron10-546 ACAACUUAACCUGGCAUAUU 20 19432 CFTR-Intron10-8063 AACAACUUAACCUGGCAUAUU 21 26943 CFTR-Intron10-8064 GAACAACUUAACCUGGCAUAUU 22 26944 CFTR-Intron10-8065 AGAACAACUUAACCUGGCAUAUU 23 26945 CFTR-Intron10-8066 AAGAACAACUUAACCUGGCAUAUU 24 26946 CFTR-Intron10-8067 UGCUCUCUUUUAACUAUU 18 26947 CFTR-Intron10-8068 UUGCUCUCUUUUAACUAUU 19 26948 CFTR-Intron10-8069 CUUGCUCUCUUUUAACUAUU 20 26949 CFTR-Intron10-8070 ACUUGCUCUCUUUUAACUAUU 21 26950 CFTR-Intron10-8071 AACUUGCUCUCUUUUAACUAUU 22 26951 CFTR-Intron10-8072 AAACUUGCUCUCUUUUAACUAUU 23 26952 CFTR-Intron10-8073 AAAACUUGCUCUCUUUUAACUAUU 24 26953 CFTR-Intron10-8074 GUUUUUCUUUCCUUUAUU 18 26954 CFTR-Intron10-8075 UGUUUUUCUUUCCUUUAUU 19 26955 CFTR-Intron10-8076 AUGUUUUUCUUUCCUUUAUU 20 26956 CFTR-Intron10-8077 UAUGUUUUUCUUUCCUUUAUU 21 26957 CFTR-Intron10-8078 UUAUGUUUUUCUUUCCUUUAUU 22 26958 CFTR-Intron10-8079 UUUAUGUUUUUCUUUCCUUUAUU 23 26959 CFTR-Intron10-8080 UUUUAUGUUUUUCUUUCCUUUAUU 24 26960 CFTR-Intron10-8081 GGGAAUAUUUAAACACUU 18 26961 CFTR-Intron10-8082 UGGGAAUAUUUAAACACUU 19 26962 CFTR-Intron10-8083 UUGGGAAUAUUUAAACACUU 20 26963 CFTR-Intron10-8084 CUUGGGAAUAUUUAAACACUU 21 26964 CFTR-Intron10-8085 CCUUGGGAAUAUUUAAACACUU 22 26965 CFTR-Intron10-8086 CCCUUGGGAAUAUUUAAACACUU 23 26966 CFTR-Intron10-8087 UCCCUUGGGAAUAUUUAAACACUU 24 26967 CFTR-Intron10-8088 CUUGUAAUCCUAGCACUU 18 26968 CFTR-Intron10-8089 ACUUGUAAUCCUAGCACUU 19 26969 CFTR-Intron10-8090 CACUUGUAAUCCUAGCACUU 20 26970 CFTR-Intron10-8091 ACACUUGUAAUCCUAGCACUU 21 26971 CFTR-Intron10-8092 CACACUUGUAAUCCUAGCACUU 22 26972 CFTR-Intron10-8093 UCACACUUGUAAUCCUAGCACUU 23 26973 CFTR-Intron10-8094 CUCACACUUGUAAUCCUAGCACUU 24 26974 CFTR-Intron10-8095 GAAUUGAAUAUGAGACUU 18 26975 CFTR-Intron10-8096 AGAAUUGAAUAUGAGACUU 19 26976 CFTR-Intron10-1394 AAGAAUUGAAUAUGAGACUU 20 20278 CFTR-Intron10-8097 GAAGAAUUGAAUAUGAGACUU 21 26977 CFTR-Intron10-8098 UGAAGAAUUGAAUAUGAGACUU 22 26978 CFTR-Intron10-8099 UUGAAGAAUUGAAUAUGAGACUU 23 26979 CFTR-Intron10-8100 UUUGAAGAAUUGAAUAUGAGACUU 24 26980 CFTR-Intron10-8101 UGUGCCUGUAGUCCCAGCUACUU 23 26981 CFTR-Intron10-8102 GUGUGCCUGUAGUCCCAGCUACUU 24 26982 CFTR-Intron10-8103 AUUGCAGGGUGGGGCCUU 18 26983 CFTR-Intron10-8104 UAUUGCAGGGUGGGGCCUU 19 26984 CFTR-Intron10-721 GUAUUGCAGGGUGGGGCCUU 20 19607 CFTR-Intron10-8105 GGUAUUGCAGGGUGGGGCCUU 21 26985 CFTR-Intron10-8106 UGGUAUUGCAGGGUGGGGCCUU 22 26986 CFTR-Intron10-8107 AUGGUAUUGCAGGGUGGGGCCUU 23 26987 CFTR-Intron10-8108 GAUGGUAUUGCAGGGUGGGGCCUU 24 26988 CFTR-Intron10-8109 ACAGUGCAGUUAUAGCUU 18 26989 CFTR-Intron10-8110 GACAGUGCAGUUAUAGCUU 19 26990 CFTR-Intron10-8111 UGACAGUGCAGUUAUAGCUU 20 26991 CFTR-Intron10-8112 CUGACAGUGCAGUUAUAGCUU 21 26992 CFTR-Intron10-8113 GCUGACAGUGCAGUUAUAGCUU 22 26993 CFTR-Intron10-8114 GGCUGACAGUGCAGUUAUAGCUU 23 26994 CFTR-Intron10-8115 UGGCUGACAGUGCAGUUAUAGCUU 24 26995 CFTR-Intron10-8116 AUUAAAUGUCUUGCGCUU 18 26996 CFTR-Intron10-8117 CAUUAAAUGUCUUGCGCUU 19 26997 CFTR-Intron10-8118 ACAUUAAAUGUCUUGCGCUU 20 26998 CFTR-Intron10-8119 UACAUUAAAUGUCUUGCGCUU 21 26999 CFTR-Intron10-8120 CUACAUUAAAUGUCUUGCGCUU 22 27000 CFTR-Intron10-8121 UCUACAUUAAAUGUCUUGCGCUU 23 27001 CFTR-Intron10-8122 GUCUACAUUAAAUGUCUUGCGCUU 24 27002 CFTR-Intron10-8123 GGCAAUAGGUAUUUGCUU 18 27003 CFTR-Intron10-8124 GGGCAAUAGGUAUUUGCUU 19 27004 CFTR-Intron10-8125 AGGGCAAUAGGUAUUUGCUU 20 27005 CFTR-Intron10-8126 AAGGGCAAUAGGUAUUUGCUU 21 27006 CFTR-Intron10-8127 AAAGGGCAAUAGGUAUUUGCUU 22 27007 CFTR-Intron10-8128 UAAAGGGCAAUAGGUAUUUGCUU 23 27008 CFTR-Intron10-8129 CUAAAGGGCAAUAGGUAUUUGCUU 24 27009 CFTR-Intron10-8130 AAUUUAACUGAAUAUCUU 18 27010 CFTR-Intron10-8131 AAAUUUAACUGAAUAUCUU 19 27011 CFTR-Intron10-8132 GAAAUUUAACUGAAUAUCUU 20 27012 CFTR-Intron10-8133 AGAAAUUUAACUGAAUAUCUU 21 27013 CFTR-Intron10-8134 UAGAAAUUUAACUGAAUAUCUU 22 27014 CFTR-Intron10-8135 AUAGAAAUUUAACUGAAUAUCUU 23 27015 CFTR-Intron10-8136 UAUAGAAAUUUAACUGAAUAUCUU 24 27016 CFTR-Intron10-8137 AUAAUUAACCGGUGUCUU 18 27017 CFTR-Intron10-8138 UAUAAUUAACCGGUGUCUU 19 27018 CFTR-Intron10-8139 UUAUAAUUAACCGGUGUCUU 20 27019 CFTR-Intron10-8140 GUUAUAAUUAACCGGUGUCUU 21 27020 CFTR-Intron10-8141 UGUUAUAAUUAACCGGUGUCUU 22 27021 CFTR-Intron10-8142 CUGUUAUAAUUAACCGGUGUCUU 23 27022 CFTR-Intron10-8143 ACUGUUAUAAUUAACCGGUGUCUU 24 27023 CFTR-Intron10-8144 UUCUAAGUAUUAGAGGUU 18 27024 CFTR-Intron10-8145 AUUCUAAGUAUUAGAGGUU 19 27025 CFTR-Intron10-8146 CAUUCUAAGUAUUAGAGGUU 20 27026 CFTR-Intron10-8147 GCAUUCUAAGUAUUAGAGGUU 21 27027 CFTR-Intron10-8148 GGCAUUCUAAGUAUUAGAGGUU 22 27028 CFTR-Intron10-8149 GGGCAUUCUAAGUAUUAGAGGUU 23 27029 CFTR-Intron10-8150 AGGGCAUUCUAAGUAUUAGAGGUU 24 27030 CFTR-Intron10-8151 CAGUGCUUUUUCGAGGUU 18 27031 CFTR-Intron10-8152 UCAGUGCUUUUUCGAGGUU 19 27032 CFTR-Intron10-556 AUCAGUGCUUUUUCGAGGUU 20 19442 CFTR-Intron10-8153 AAUCAGUGCUUUUUCGAGGUU 21 27033 CFTR-Intron10-8154 AAAUCAGUGCUUUUUCGAGGUU 22 27034 CFTR-Intron10-8155 AAAAUCAGUGCUUUUUCGAGGUU 23 27035 CFTR-Intron10-8156 UAAAAUCAGUGCUUUUUCGAGGUU 24 27036 CFTR-Intron10-8157 UUUGGAUGGAGCUUGGUU 18 27037 CFTR-Intron10-8158 UUUUGGAUGGAGCUUGGUU 19 27038 CFTR-Intron10-128 GUUUUGGAUGGAGCUUGGUU 20 19014 CFTR-Intron10-8159 GGUUUUGGAUGGAGCUUGGUU 21 27039 CFTR-Intron10-8160 AGGUUUUGGAUGGAGCUUGGUU 22 27040 CFTR-Intron10-8161 CAGGUUUUGGAUGGAGCUUGGUU 23 27041 CFTR-Intron10-8162 ACAGGUUUUGGAUGGAGCUUGGUU 24 27042 CFTR-Intron10-8163 UAAUACAUUGGAAAAUUU 18 27043 CFTR-Intron10-8164 UUAAUACAUUGGAAAAUUU 19 27044 CFTR-Intron10-8165 GUUAAUACAUUGGAAAAUUU 20 27045 CFTR-Intron10-8166 AGUUAAUACAUUGGAAAAUUU 21 27046 CFTR-Intron10-8167 CAGUUAAUACAUUGGAAAAUUU 22 27047 CFTR-Intron10-8168 UCAGUUAAUACAUUGGAAAAUUU 23 27048 CFTR-Intron10-8169 UUCAGUUAAUACAUUGGAAAAUUU 24 27049 CFTR-Intron10-8170 AUCAAUAUUUUGGAAUUU 18 27050 CFTR-Intron10-8171 UAUCAAUAUUUUGGAAUUU 19 27051 CFTR-Intron10-1402 UUAUCAAUAUUUUGGAAUUU 20 20286 CFTR-Intron10-8172 UUUAUCAAUAUUUUGGAAUUU 21 27052 CFTR-Intron10-8173 UUUUAUCAAUAUUUUGGAAUUU 22 27053 CFTR-Intron10-8174 GUUUUAUCAAUAUUUUGGAAUUU 23 27054 CFTR-Intron10-8175 AGUUUUAUCAAUAUUUUGGAAUUU 24 27055 CFTR-Intron10-8176 UUAAUAUUACUAUUAUUU 18 27056 CFTR-Intron10-8177 AUUAAUAUUACUAUUAUUU 19 27057 CFTR-Intron10-8178 UAUUAAUAUUACUAUUAUUU 20 27058 CFTR-Intron10-8179 UUAUUAAUAUUACUAUUAUUU 21 27059 CFTR-Intron10-8180 GUUAUUAAUAUUACUAUUAUUU 22 27060 CFTR-Intron10-8181 UGUUAUUAAUAUUACUAUUAUUU 23 27061 CFTR-Intron10-8182 UUGUUAUUAAUAUUACUAUUAUUU 24 27062 CFTR-Intron10-8183 AAACAAGGAUGUUUAUUU 18 27063 CFTR-Intron10-8184 UAAACAAGGAUGUUUAUUU 19 27064 CFTR-Intron10-8185 CUAAACAAGGAUGUUUAUUU 20 27065 CFTR-Intron10-8186 UCUAAACAAGGAUGUUUAUUU 21 27066 CFTR-Intron10-8187 GUCUAAACAAGGAUGUUUAUUU 22 27067 CFTR-Intron10-8188 GGUCUAAACAAGGAUGUUUAUUU 23 27068 CFTR-Intron10-8189 UGGUCUAAACAAGGAUGUUUAUUU 24 27069 CFTR-Intron10-8190 UUGUAAUCCUAGCACUUU 18 27070 CFTR-Intron10-8191 CUUGUAAUCCUAGCACUUU 19 27071 CFTR-Intron10-1408 ACUUGUAAUCCUAGCACUUU 20 20292 CFTR-Intron10-8192 CACUUGUAAUCCUAGCACUUU 21 27072 CFTR-Intron10-8193 ACACUUGUAAUCCUAGCACUUU 22 27073 CFTR-Intron10-8194 CACACUUGUAAUCCUAGCACUUU 23 27074 CFTR-Intron10-8195 UCACACUUGUAAUCCUAGCACUUU 24 27075 CFTR-Intron10-8196 UUGCAGGGUGGGGCCUUU 18 27076 CFTR-Intron10-8197 AUUGCAGGGUGGGGCCUUU 19 27077 CFTR-Intron10-1409 UAUUGCAGGGUGGGGCCUUU 20 20293 CFTR-Intron10-8198 GUAUUGCAGGGUGGGGCCUUU 21 27078 CFTR-Intron10-8199 GGUAUUGCAGGGUGGGGCCUUU 22 27079 CFTR-Intron10-8200 UGGUAUUGCAGGGUGGGGCCUUU 23 27080 CFTR-Intron10-8201 AUGGUAUUGCAGGGUGGGGCCUUU 24 27081 CFTR-Intron10-8202 AAGAUGAUUCCAAGCUUU 18 27082 CFTR-Intron10-8203 AAAGAUGAUUCCAAGCUUU 19 27083 CFTR-Intron10-8204 CAAAGAUGAUUCCAAGCUUU 20 27084 CFTR-Intron10-8205 UCAAAGAUGAUUCCAAGCUUU 21 27085 CFTR-Intron10-8206 GUCAAAGAUGAUUCCAAGCUUU 22 27086 CFTR-Intron10-8207 AGUCAAAGAUGAUUCCAAGCUUU 23 27087 CFTR-Intron10-8208 GAGUCAAAGAUGAUUCCAAGCUUU 24 27088 CFTR-Intron10-8209 UCAUUAUAACACUGCUUU 18 27089 CFTR-Intron10-8210 UUCAUUAUAACACUGCUUU 19 27090 CFTR-Intron10-8211 CUUCAUUAUAACACUGCUUU 20 27091 CFTR-Intron10-8212 UCUUCAUUAUAACACUGCUUU 21 27092 CFTR-Intron10-8213 CUCUUCAUUAUAACACUGCUUU 22 27093 CFTR-Intron10-8214 GCUCUUCAUUAUAACACUGCUUU 23 27094 CFTR-Intron10-8215 AGCUCUUCAUUAUAACACUGCUUU 24 27095 CFTR-Intron10-8216 AUUUAACUGAAUAUCUUU 18 27096 CFTR-Intron10-8217 AAUUUAACUGAAUAUCUUU 19 27097 CFTR-Intron10-1410 AAAUUUAACUGAAUAUCUUU 20 20294 CFTR-Intron10-8218 GAAAUUUAACUGAAUAUCUUU 21 27098 CFTR-Intron10-8219 AGAAAUUUAACUGAAUAUCUUU 22 27099 CFTR-Intron10-8220 UAGAAAUUUAACUGAAUAUCUUU 23 27100 CFTR-Intron10-8221 AUAGAAAUUUAACUGAAUAUCUUU 24 27101 CFTR-Intron10-8222 UCAAUAUUUUGGAAUUUU 18 27102 CFTR-Intron10-8223 AUCAAUAUUUUGGAAUUUU 19 27103 CFTR-Intron10-1412 UAUCAAUAUUUUGGAAUUUU 20 20296 CFTR-Intron10-8224 UUAUCAAUAUUUUGGAAUUUU 21 27104 CFTR-Intron10-8225 UUUAUCAAUAUUUUGGAAUUUU 22 27105 CFTR-Intron10-8226 UUUUAUCAAUAUUUUGGAAUUUU 23 27106 CFTR-Intron10-8227 GUUUUAUCAAUAUUUUGGAAUUUU 24 27107 CFTR-Intron10-8228 GAUAAAAUCAGUGCUUUU 18 27108 CFTR-Intron10-8229 UGAUAAAAUCAGUGCUUUU 19 27109 CFTR-Intron10-8230 CUGAUAAAAUCAGUGCUUUU 20 27110 CFTR-Intron10-8231 UCUGAUAAAAUCAGUGCUUUU 21 27111 CFTR-Intron10-8232 CUCUGAUAAAAUCAGUGCUUUU 22 27112 CFTR-Intron10-8233 GCUCUGAUAAAAUCAGUGCUUUU 23 27113 CFTR-Intron10-8234 AGCUCUGAUAAAAUCAGUGCUUUU 24 27114 CFTR-Intron10-8235 UUAAAAUUUUAUUCUUUU 18 27115 CFTR-Intron10-8236 UUUAAAAUUUUAUUCUUUU 19 27116 CFTR-Intron10-8237 UUUUAAAAUUUUAUUCUUUU 20 27117 CFTR-Intron10-8238 UUUUUAAAAUUUUAUUCUUUU 21 27118 CFTR-Intron10-8239 AUUUUUAAAAUUUUAUUCUUUU 22 27119 CFTR-Intron10-8240 AAUUUUUAAAAUUUUAUUCUUUU 23 27120 CFTR-Intron10-8241 UAAUUUUUAAAAUUUUAUUCUUUU 24 27121 CFTR-Intron10-8242 AUCAUUUUGACCAUUUUU 18 27122 CFTR-Intron10-8243 UAUCAUUUUGACCAUUUUU 19 27123 CFTR-Intron10-8244 UUAUCAUUUUGACCAUUUUU 20 27124 CFTR-Intron10-8245 UUUAUCAUUUUGACCAUUUUU 21 27125 CFTR-Intron10-8246 AUUUAUCAUUUUGACCAUUUUU 22 27126 CFTR-Intron10-8247 AAUUUAUCAUUUUGACCAUUUUU 23 27127 CFTR-Intron10-8248 AAAUUUAUCAUUUUGACCAUUUUU 24 27128 CFTR-Intron10-8249 AUUAGUAGUUAAGUUUUU 18 27129 CFTR-Intron10-8250 UAUUAGUAGUUAAGUUUUU 19 27130 CFTR-Intron10-8251 CUAUUAGUAGUUAAGUUUUU 20 27131 CFTR-Intron10-8252 GCUAUUAGUAGUUAAGUUUUU 21 27132 CFTR-Intron10-8253 GGCUAUUAGUAGUUAAGUUUUU 22 27133 CFTR-Intron10-8254 AGGCUAUUAGUAGUUAAGUUUUU 23 27134 CFTR-Intron10-8255 UAGGCUAUUAGUAGUUAAGUUUUU 24 27135 CFTR-Intron10-8256 AACACUUUAUAGUUUUUU 18 27136 CFTR-Intron10-8257 GAACACUUUAUAGUUUUUU 19 27137 CFTR-Intron10-8258 GGAACACUUUAUAGUUUUUU 20 27138 CFTR-Intron10-8259 UGGAACACUUUAUAGUUUUUU 21 27139 CFTR-Intron10-8260 AUGGAACACUUUAUAGUUUUUU 22 27140 CFTR-Intron10-8261 AAUGGAACACUUUAUAGUUUUUU 23 27141 CFTR-Intron10-8262 GAAUGGAACACUUUAUAGUUUUUU 24 27142 CFTR-Intron10-8263 UUUUUUUUUUUUUUUUUU 18 27143 CFTR-Intron10-8264 UUUUUUUUUUUUUUUUUUU 19 27144 CFTR-Intron10-8265 UUUUUUUUUUUUUUUUUUUU 20 27145 CFTR-Intron10-8266 UUUUUUUUUUUUUUUUUUUUU 21 27146 CFTR-Intron10-8267 UUUUUUUUUUUUUUUUUUUUUU 22 27147 CFTR-Intron10-8268 UUUUUUUUUUUUUUUUUUUUUUU 23 27148 CFTR-Intron10-8269 CUUUUUUUUUUUUUUUUUUUUUUU 24 27149

Table 42A provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the first tier parameters. The targeting domains bind within intron 10, have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 42A 1st Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-8270 GGUGAAGUCUUUAGUAA 17 27150 CFTR-Intron10-8271 + GUUGGUGAUAUUUUUCA 17 27151 CFTR-Intron10-8272 GUCAAGCAUUUGUGUAC 17 27152 CFTR-Intron10-8273 GAUACAUCUGAAAAAAU 17 27153 CFTR-Intron10-8274 + GGAGUGUAAAGGAAAUU 17 27154 CFTR-Intron10-5827 GAGGGUGAAGUCUUUAGUAA 20 24707 CFTR-Intron10-8275 + GGGGAAUAAUAAAAAAUGUA 20 27155 CFTR-Intron10-8276 + GGUUUACCCCCUACCUCCAC 20 27156 CFTR-Intron10-8277 GUGGUCAAGCAUUUGUGUAC 20 27157 CFTR-Intron10-8278 + GGUAGCAGAGGAAGAAAAAG 20 27158 CFTR-Intron10-8279 GCCAUACACUCUAAAUAGAG 20 27159 CFTR-Intron10-8280 GUUUUCUAGAAAAUCUGUAG 20 27160 CFTR-Intron10-8281 GGAGAUACAUCUGAAAAAAU 20 27161 CFTR-Intron10-8282 GCAGGAAGACAGCUGGCUAU 20 27162

Table 42B provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the second tier parameters. The targeting domains bind within intron 10 and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 42B 2nd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-8283 + UAGAGAUUACUUGGAAA 17 27163 CFTR-Intron10-8284 AGUCACAGAGGAGUCAA 17 27164 CFTR-Intron10-8285 + AAAGGACUAUCAGUGAA 17 27165 CFTR-Intron10-8286 ACUGAAUAUCUUUAGGA 17 27166 CFTR-Intron10-8287 + UUACCCCCUACCUCCAC 17 27167 CFTR-Intron10-8288 UCAUUAGGAAAAUGUAC 17 27168 CFTR-Intron10-8289 AAUGGUUCCUUGUUCCC 17 27169 CFTR-Intron10-8290 AAACUUGUCUUCUUUUC 17 27170 CFTR-Intron10-8291 + UCCUAACCUCGAAAAAG 17 27171 CFTR-Intron10-8292 AUACACUCUAAAUAGAG 17 27172 CFTR-Intron10-8293 UUCUAGAAAAUCUGUAG 17 27173 CFTR-Intron10-8294 AAGGCUUAUUUCUCUGG 17 27174 CFTR-Intron10-8295 + CAAAUUGUAUUGAGUGG 17 27175 CFTR-Intron10-8296 UAUAUAUAUGACACUAU 17 27176 CFTR-Intron10-8297 + CUACUAAAAGGCAGCCU 17 27177 CFTR-Intron10-8298 + UGAUCCUUUUGCAGCCU 17 27178 CFTR-Intron10-8299 CUUUCCAUGAAUUAGCU 17 27179 CFTR-Intron10-8300 AUUUCCAAGUAAUCUCU 17 27180 CFTR-Intron10-8301 UUCGUGUAGUUUCUAUU 17 27181 CFTR-Intron10-8302 AAAAGUCACAGAGGAGUCAA 20 27182 CFTR-Intron10-8303 + ACAAAAGGACUAUCAGUGAA 20 27183 CFTR-Intron10-8304 + UGAGUUGGUGAUAUUUUUCA 20 27184 CFTR-Intron10-8305 UUAACUGAAUAUCUUUAGGA 20 27185 CFTR-Intron10-8306 + AAUAAAGUAAUAGAAGCAUA 20 27186 CFTR-Intron10-8307 + AAAGCUCUUUCUCAUCUCUA 20 27187 CFTR-Intron10-3944 + AUAUUAAUAACAAAAUCUUA 20 22826 CFTR-Intron10-8308 UCUAUGAUAUAAUGAAUCAC 20 27188 CFTR-Intron10-8309 UAAAAUGGUUCCUUGUUCCC 20 27189 CFTR-Intron10-8310 UGGAAACUUGUCUUCUUUUC 20 27190 CFTR-Intron10-8311 UAGUGUGAAGAUGGGGCUGG 20 27191 CFTR-Intron10-7212 ACUAAGGCUUAUUUCUCUGG 20 26092 CFTR-Intron10-8312 + UACCAAAUUGUAUUGAGUGG 20 27192 CFTR-Intron10-8313 + AUACUACUAAAAGGCAGCCU 20 27193 CFTR-Intron10-8314 UAUAUUUCCAAGUAAUCUCU 20 27194 CFTR-Intron10-8315 + UGUGGAGUGUAAAGGAAAUU 20 27195 CFTR-Intron10-8316 AUAUUCGUGUAGUUUCUAUU 20 27196

Table 42C provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the third tier parameters. The targeting domains bind within intron 10 and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 42C 3rd Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-8317 + GCUCUUUCUCAUCUCUA 17 27197 CFTR-Intron10-8318 + GAAUAAUAAAAAAUGUA 17 27198 CFTR-Intron10-8319 + GAUACUAAAAAAAGUUA 17 27199 CFTR-Intron10-8320 GUGCAACUAUCACCUCC 17 27200 CFTR-Intron10-8321 GUGGAGGCUGCAGUGAG 17 27201 CFTR-Intron10-8322 + GAGAACUGCUCACACGG 17 27202 CFTR-Intron10-8323 GGAAGACAGCUGGCUAU 17 27203 CFTR-Intron10-8324 + GAAGAUACUAAAAAAAGUUA 20 27204 CFTR-Intron10-8325 GUUGUGCAACUAUCACCUCC 20 27205 CFTR-Intron10-8326 GAAGUGGAGGCUGCAGUGAG 20 27206 CFTR-Intron10-8327 + GCAUCACUAGUGGCACUUUG 20 27207 CFTR-Intron10-8328 + GAUAAAUUUUAACUUUUUAU 20 27208

Table 42D provides exemplary targeting domains for correcting a mutation (e.g., 3272-26->G) in the CFTR gene selected according to the fourth tier parameters. The targeting domains bind within intron 10. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the Table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 42D 4th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID CFTR-Intron10-8329 CUUUGGAAUUUGUUAAA 17 27209 CFTR-Intron10-8330 + ACCCAAAUGUCAAUCAA 17 27210 CFTR-Intron10-8331 + UACCAUCACCUUGGGAA 17 27211 CFTR-Intron10-8332 UGUAUUUAUAUUCAUAA 17 27212 CFTR-Intron10-8333 AUAUAGAAAUGAGGUAA 17 27213 CFTR-Intron10-8334 CAUAUAUAUAUUUUUAA 17 27214 CFTR-Intron10-8335 CUUUGAAGGAAGAUCCA 17 27215 CFTR-Intron10-8336 + AAAGUAAUAGAAGCAUA 17 27216 CFTR-Intron10-8337 UGGAGUCAAAAAUUAUA 17 27217 CFTR-Intron10-8338 + UUAAUAACAAAAUCUUA 17 27218 CFTR-Intron10-8339 AUGAUAUAAUGAAUCAC 17 27219 CFTR-Intron10-8340 + CACACAUAUAUACAUAC 17 27220 CFTR-Intron10-8341 + UCCAAGAUCAAGGUGCC 17 27221 CFTR-Intron10-8342 + CAAAUAUAAAUCAAAGC 17 27222 CFTR-Intron10-8343 + AGCAGAGGAAGAAAAAG 17 27223 CFTR-Intron10-8344 AAUGUUGAAUAAUAGGG 17 27224 CFTR-Intron10-956 AGGGUGGGGCCUUUGGG 17 19841 CFTR-Intron10-8345 UGUGAAGAUGGGGCUGG 17 27225 CFTR-Intron10-8346 + CUCUGCCUCCAAAAGUG 17 27226 CFTR-Intron10-8347 CUCGGCCUCCCAAAGUG 17 27227 CFTR-Intron10-8348 UAGUAUAGUAGGAAGUG 17 27228 CFTR-Intron10-8349 + UCACUAGUGGCACUUUG 17 27229 CFTR-Intron10-8350 UCCACAAAUAUUUUUUG 17 27230 CFTR-Intron10-8351 AAAGAUCUAGCUAAAAU 17 27231 CFTR-Intron10-8352 + AAAUUUUAACUUUUUAU 17 27232 CFTR-Intron10-8353 UUUAUUGAUACUUUUCU 17 27233 CFTR-Intron10-8354 AAAGACUUGCAGGAGGU 17 27234 CFTR-Intron10-8355 + UUUCUUUUUCUGUUUGU 17 27235 CFTR-Intron10-8356 UGGGUAUAUUUUAUAUU 17 27236 CFTR-Intron10-8357 CAGUAGUAUUAUCUUUU 17 27237 CFTR-Intron10-8358 UAAAAUUUUAUUCUUUU 17 27238 CFTR-Intron10-8359 + UUAUAGAGAUUACUUGGAAA 20 27239 CFTR-Intron10-8360 AUACUUUGGAAUUUGUUAAA 20 27240 CFTR-Intron10-8361 + ACAACCCAAAUGUCAAUCAA 20 27241 CFTR-Intron10-8362 + CAAUACCAUCACCUUGGGAA 20 27242 CFTR-Intron10-8363 UUUUGUAUUUAUAUUCAUAA 20 27243 CFTR-Intron10-8364 UUUAUAUAGAAAUGAGGUAA 20 27244 CFTR-Intron10-8365 AUGCAUAUAUAUAUUUUUAA 20 27245 CFTR-Intron10-8366 AUGCUUUGAAGGAAGAUCCA 20 27246 CFTR-Intron10-8367 UUGUGGAGUCAAAAAUUAUA 20 27247 CFTR-Intron10-8368 + AGACACACAUAUAUACAUAC 20 27248 CFTR-Intron10-8369 AACUCAUUAGGAAAAUGUAC 20 27249 CFTR-Intron10-8370 + AAGUCCAAGAUCAAGGUGCC 20 27250 CFTR-Intron10-8371 + AAACAAAUAUAAAUCAAAGC 20 27251 CFTR-Intron10-8372 + AUCUCCUAACCUCGAAAAAG 20 27252 CFTR-Intron10-8373 + AGAGAGAACUGCUCACACGG 20 27253 CFTR-Intron10-8374 AUAAAUGUUGAAUAAUAGGG 20 27254 CFTR-Intron10-1300 UGCAGGGUGGGGCCUUUGGG 20 20185 CFTR-Intron10-8375 + UGCCUCUGCCUCCAAAAGUG 20 27255 CFTR-Intron10-7272 CGCCUCGGCCUCCCAAAGUG 20 26152 CFTR-Intron10-7277 UGCCUCGGCCUCCCAAAGUG 20 26157 CFTR-Intron10-8376 AAGUAGUAUAGUAGGAAGUG 20 27256 CFTR-Intron10-8377 UCCUCCACAAAUAUUUUUUG 20 27257 CFTR-Intron10-8378 ACAAAAGAUCUAGCUAAAAU 20 27258 CFTR-Intron10-8379 ACAUAUAUAUAUGACACUAU 20 27259 CFTR-Intron10-8380 + ACAUGAUCCUUUUGCAGCCU 20 27260 CFTR-Intron10-8381 AAGCUUUCCAUGAAUUAGCU 20 27261 CFTR-Intron10-8382 UCCUUUAUUGAUACUUUUCU 20 27262 CFTR-Intron10-7876 AACAAAGACUUGCAGGAGGU 20 26756 CFTR-Intron10-8383 + CUCUUUCUUUUUCUGUUUGU 20 27263 CFTR-Intron10-8384 UUUUGGGUAUAUUUUAUAUU 20 27264 CFTR-Intron10-8385 AGUCAGUAGUAUUAUCUUUU 20 27265 CFTR-Intron10-8237 UUUUAAAAUUUUAUUCUUUU 20 27117

Table 43A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 43A 1st Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID SCNN1A-327 + GAUACCUCCCCUUGGAA 17 4176 SCNN1A-328 GGGCGCAGGGUGGGACA 17 4177 SCNN1A-99 GGCGCCCCAGCAGCCCA 17  536 SCNN1A-329 GCCUCACUCGGGUUCCA 17 4178 SCNN1A-330 GGGAGAAUGUGGGCGCA 17 4179 SCNN1A-141 + GCGGUGGAACUCGAUCA 17  551 SCNN1A-80 GCCCAUACCAGGUCUCA 17  529 SCNN1A-106 GCACAACCGCAUGAAGA 17  540 SCNN1A-132 + GGAGCACACCAGGCGGA 17  547 SCNN1A-121 + GUUGAUGUUGAGGCUGA 17  545 SCNN1A-331 + GGACUAACCGACCUGUA 17 4180 SCNN1A-332 GCACCCUCAAUCCCUAC 17 4181 SCNN1A-93 GAACAAGCGUGAGGAGC 17  533 SCNN1A-147 + GGCUGCUGGGGCGCCGC 17  554 SCNN1A-117 + GUGCAGAUGGUCACUGC 17  544 SCNN1A-333 GAUGGGAGAGGGCACUC 17 4182 SCNN1A-107 GCAUGAAGACGGCCUUC 17  541 SCNN1A-334 GACAUGGGCAUGGCCAG 17 4183 SCNN1A-142 + GGCCUCCUCCUCCGCCG 17  552 SCNN1A-150 + GGGGCGCCGCAGGUUCG 17  555 SCNN1A-131 + GCUGGGAGCACACCAGG 17  546 SCNN1A-103 GCCCACGGCGGAGGAGG 17  539 SCNN1A-102 GCAGCCCACGGCGGAGG 17  538 SCNN1A-139 + GCUCUCGGUAGGAGCGG 17  550 SCNN1A-116 + GGUGCAGAUGGUCACUG 17  543 SCNN1A-98 GCUGGGCCCCGAACCUG 17  535 SCNN1A-335 GGCGCAGGGUGGGACAU 17 4184 SCNN1A-336 + GGUCAAGGCUGAGCUCU 17 4185 SCNN1A-143 + GCCUCCUCCUCCGCCGU 17  553 SCNN1A-337 GAAUGUGGGCGCAGGGU 17 4186 SCNN1A-338 + GGGACUAACCGACCUGU 17 4187 SCNN1A-339 + GAGCCCCGGAGUGGAUU 17 4188 SCNN1A-340 GUGGGACAUGGGCAUGGCCA 20 4189 SCNN1A-341 GCAGCCUCACUCGGGUUCCA 20 4190 SCNN1A-342 GAGCAGUAUCAAGGUAAGCA 20 4191 SCNN1A-15 GGGAACAAGCGUGAGGAGCA 20  507 SCNN1A-62 + GGAGCGGUGGAACUCGAUCA 20  525 SCNN1A-343 GUGAUGGGAGAGGGCACUCA 20 4192 SCNN1A-1 GCAGCCCAUACCAGGUCUCA 20  503 SCNN1A-36 + GUAGGGAUUGAGGGUGCAGA 20  516 SCNN1A-76 + GCCCUGGAGUGGACUGUGGA 20  528 SCNN1A-10 GUCCACUCCAGGGCUCAUGA 20  505 SCNN1A-42 + GAGGUUGAUGUUGAGGCUGA 20  519 SCNN1A-344 + GUAUGGGCUGCAGAGGUCUA 20 4193 SCNN1A-345 + GAGGGACUAACCGACCUGUA 20 4194 SCNN1A-32 GCACCUUUGGCAUGAUGUAC 20  514 SCNN1A-51 + GGUUGUGCUGGGAGCACACC 20  522 SCNN1A-346 + GUGCCCUCUCCCAUCACCCC 20 4195 SCNN1A-347 GGUGGGACAUGGGCAUGGCC 20 4196 SCNN1A-348 GGCAGCCUCACUCGGGUUCC 20 4197 SCNN1A-176 GCUCAUGAAGGGGAACAAGC 20  811 SCNN1A-68 + GUGGGCUGCUGGGGCGCCGC 20  526 SCNN1A-349 GAGUGGGAGAAUGUGGGCGC 20 4198 SCNN1A-350 GGUGAUGGGAGAGGGCACUC 20 4199 SCNN1A-351 GGCCAGGGGCAGCCUCACUC 20 4200 SCNN1A-352 + GAUUGGGGAGAGCAAGGGUC 20 4201 SCNN1A-16 GGAACAAGCGUGAGGAGCAG 20  508 SCNN1A-44 + GGUUGAUGUUGAGGCUGACG 20  520 SCNN1A-353 GCUCUCCCCAAUCCACUCCG 20 4202 SCNN1A-39 + GGGUGCAGAUGGUCACUGCG 20  518 SCNN1A-71 + GCUGGGGCGCCGCAGGUUCG 20  527 SCNN1A-21 GGCGCCCCAGCAGCCCACGG 20  510 SCNN1A-22 GCCCCAGCAGCCCACGGCGG 20  511 SCNN1A-354 GGGAGAAUGUGGGCGCAGGG 20 4203 SCNN1A-2 GCCCAUACCAGGUCUCAUGG 20  497 SCNN1A-37 + GAGGGUGCAGAUGGUCACUG 20  517 SCNN1A-19 GGGGCUGGGCCCCGAACCUG 20  509 SCNN1A-355 GUGGGCGCAGGGUGGGACAU 20 4204 SCNN1A-356 + GGUAUGGGCUGCAGAGGUCU 20 4205 SCNN1A-58 + GAACUCGAAGAGCUCUCGGU 20  524 SCNN1A-357 GGAGAAUGUGGGCGCAGGGU 20 4206 SCNN1A-33 GGCAUGAUGUACUGGCAAUU 20  515 SCNN1A-31 GUGCUGUGGCUCUGCACCUU 20  513

Table 43B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 43B 2nd Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID SCNN1A-125 + CCAGUACAUCAUGCCAA 17  632 SCNN1A-358 CCAGCUGUCCCUUCCAA 17 4207 SCNN1A-359 AGUAUCAAGGUAAGCAA 17 4208 SCNN1A-90 ACUCCAGGGCUCAUGAA 17  611 SCNN1A-360 ACUCCGGGGCUCAUGAA 17 4209 SCNN1A-104 AACAACACCACCAUCCA 17  617 SCNN1A-88 CUCCACAGUCCACUCCA 17  609 SCNN1A-361 CAGUAUCAAGGUAAGCA 17 4210 SCNN1A-94 AACAAGCGUGAGGAGCA 17  613 SCNN1A-362 UAUCAUGAGCAGUAUCA 17 4211 SCNN1A-363 AUGGGAGAGGGCACUCA 17 4212 SCNN1A-126 + CCACAGCACUGCCCAGA 17  633 SCNN1A-82 AUACCAGGUCUCAUGGA 17  501 SCNN1A-364 + UGAUACCUCCCCUUGGA 17 4213 SCNN1A-89 CACUCCAGGGCUCAUGA 17  610 SCNN1A-365 CACUCCGGGGCUCAUGA 17 4214 SCNN1A-366 UCGGGUUCCAGGGGUGA 17 4215 SCNN1A-367 + CGACCUGUAGGGAUUGA 17 4216 SCNN1A-157 + CUCCAUGAGACCUGGUA 17  502 SCNN1A-122 + UUGAUGUUGAGGCUGAC 17  629 SCNN1A-111 CCUUUGGCAUGAUGUAC 17  622 SCNN1A-130 + UGUGCUGGGAGCACACC 17  637 SCNN1A-156 + UUCCCCUCCAUGAGACC 17  653 SCNN1A-368 CCUCUGCAGCCCAUACC 17 4217 SCNN1A-369 + CCGAGUGAGGCUGCCCC 17 4218 SCNN1A-370 UCUCCCCAAUCCACUCC 17 4219 SCNN1A-87 CCUCCACAGUCCACUCC 17 608 SCNN1A-371 AGCCUCACUCGGGUUCC 17 4220 SCNN1A-124 + AGUACUCUCCGAAAAGC 17 631 SCNN1A-260 CAUGAAGGGGAACAAGC 17 868 SCNN1A-84 CAUGGAGGGGAACAAGC 17 607 SCNN1A-372 + CCCUUGGAAGGGACAGC 17 4221 SCNN1A-373 UGGGAGAAUGUGGGCGC 17 4222 SCNN1A-144 + CCUCCGCCGUGGGCUGC 17  643 SCNN1A-128 + UCUUCAUGCGGUUGUGC 17  635 SCNN1A-140 + AGCGGUGGAACUCGAUC 17  642 SCNN1A-374 CUCUCCCCAAUCCACUC 17 4223 SCNN1A-375 CAGGGGCAGCCUCACUC 17 4224 SCNN1A-376 + UGGGGAGAGCAAGGGUC 17 4225 SCNN1A-149 + UGGGGCGCCGCAGGUUC 17  647 SCNN1A-377 CAGCUGUCCCUUCCAAG 17 4226 SCNN1A-91 CUCCAGGGCUCAUGAAG 17  612 SCNN1A-378 CUCCGGGGCUCAUGAAG 17 4227 SCNN1A-379 CCUCACUCGGGUUCCAG 17 4228 SCNN1A-95 ACAAGCGUGAGGAGCAG 17  614 SCNN1A-380 + CCUGGUAUGGGCUGCAG 17 4229 SCNN1A-138 + AGAGCUCUCGGUAGGAG 17  641 SCNN1A-381 + CUUCAUGAGCCCCGGAG 17 4230 SCNN1A-152 + CUUCAUGAGCCCUGGAG 17  649 SCNN1A-123 + UGAUGUUGAGGCUGACG 17  630 SCNN1A-382 CUCCCCAAUCCACUCCG 17 4231 SCNN1A-118 + UGCAGAUGGUCACUGCG 17  626 SCNN1A-101 CCAGCAGCCCACGGCGG 17  616 SCNN1A-383 AGAAUGUGGGCGCAGGG 17 4232 SCNN1A-384 CUGUCCCUUCCAAGGGG 17 4233 SCNN1A-81 CAUACCAGGUCUCAUGG 17  605 SCNN1A-127 + AGAAGGCCGUCUUCAUG 17  634 SCNN1A-146 + UCCGCCGUGGGCUGCUG 17  645 SCNN1A-385 + CCCCUGGAACCCGAGUG 17 4234 SCNN1A-386 + CCGACCUGUAGGGAUUG 17 4235 SCNN1A-387 + AGCCCCGGAGUGGAUUG 17 4236 SCNN1A-119 + CGAGCUUGUCCGAGUUG 17  627 SCNN1A-120 + AGUUGAGGUUGAUGUUG 17  628 SCNN1A-388 + UGAGCCCCGGAGUGGAU 17 4237 SCNN1A-389 CGGGUUCCAGGGGUGAU 17 4238 SCNN1A-158 + UCCAUGAGACCUGGUAU 17  654 SCNN1A-114 CAACAUCAACCUCAACU 17  625 SCNN1A-97 CGUGAGGAGCAGGGGCU 17  615 SCNN1A-145 + CUCCGCCGUGGGCUGCU 17  644 SCNN1A-129 + CUUCAUGCGGUUGUGCU 17  636 SCNN1A-136 + AGAACUCGAAGAGCUCU 17  639 SCNN1A-390 + AUGGGCUGCAGAGGUCU 17 4239 SCNN1A-108 CAUGAAGACGGCCUUCU 17  619 SCNN1A-391 CCUCAAUCCCUACAGGU 17 4240 SCNN1A-137 + CUCGAAGAGCUCUCGGU 17  640 SCNN1A-112 AUGAUGUACUGGCAAUU 17  623 SCNN1A-110 CUGUGGCUCUGCACCUU 17  621 SCNN1A-148 + CUGGGGCGCCGCAGGUU 17  646 SCNN1A-392 AGCAAGGGAACCUGGUU 17 4241 SCNN1A-113 CAAUUCGGCCUGCUUUU 17  624 SCNN1A-46 + UUGCCAGUACAUCAUGCCAA 20  580 SCNN1A-393 AGCAGUAUCAAGGUAAGCAA 20 4242 SCNN1A-394 + CAUGAUACCUCCCCUUGGAA 20 4243 SCNN1A-395 UGUGGGCGCAGGGUGGGACA 20 4244 SCNN1A-20 UGCGGCGCCCCAGCAGCCCA 20  565 SCNN1A-25 UGCAACAACACCACCAUCCA 20  567 SCNN1A-396 AGUGGGAGAAUGUGGGCGCA 20 4245 SCNN1A-397 AGGUAUCAUGAGCAGUAUCA 20 4246 SCNN1A-398 + AUUGGGGAGAGCAAGGGUCA 20 4247 SCNN1A-27 CCAGCACAACCGCAUGAAGA 20  569 SCNN1A-53 + CUGGGAGCACACCAGGCGGA 20  585 SCNN1A-3 CCCAUACCAGGUCUCAUGGA 20  556 SCNN1A-399 + UCAUGAUACCUCCCCUUGGA 20 4248 SCNN1A-400 AUCCACUCCGGGGCUCAUGA 20 4249 SCNN1A-401 CACUCGGGUUCCAGGGGUGA 20 4250 SCNN1A-402 + AACCGACCUGUAGGGAUUGA 20 4251 SCNN1A-78 + CCCCUCCAUGAGACCUGGUA 20  500 SCNN1A-43 + AGGUUGAUGUUGAGGCUGAC 20  578 SCNN1A-403 UCUGCACCCUCAAUCCCUAC 20 4252 SCNN1A-404 UCAAGGUAAGCAAGGGAACC 20 4253 SCNN1A-405 AGACCUCUGCAGCCCAUACC 20 4254 SCNN1A-406 + AACCCGAGUGAGGCUGCCCC 20 4255 SCNN1A-407 UAGUCCCUCUGCCCCUUCCC 20 4256 SCNN1A-408 UGCUCUCCCCAAUCCACUCC 20 4257 SCNN1A-8 AGCCCUCCACAGUCCACUCC 20  559 SCNN1A-45 + UGAAGUACUCUCCGAAAAGC 20  579 SCNN1A-5 UCUCAUGGAGGGGAACAAGC 20  557 SCNN1A-409 + CUCCCCUUGGAAGGGACAGC 20 4258 SCNN1A-17 CAAGCGUGAGGAGCAGGGGC 20  563 SCNN1A-38 + AGGGUGCAGAUGGUCACUGC 20  575 SCNN1A-65 + CCUCCUCCGCCGUGGGCUGC 20  594 SCNN1A-49 + CCGUCUUCAUGCGGUUGUGC 20  582 SCNN1A-61 + AGGAGCGGUGGAACUCGAUC 20  591 SCNN1A-410 UUGCUCUCCCCAAUCCACUC 20 4259 SCNN1A-411 + UCAGGGUCAAGGCUGAGCUC 20 4260 SCNN1A-28 ACCGCAUGAAGACGGCCUUC 20  570 SCNN1A-70 + UGCUGGGGCGCCGCAGGUUC 20  598 SCNN1A-412 AUCCAGCUGUCCCUUCCAAG 20 4261 SCNN1A-413 UGGGACAUGGGCAUGGCCAG 20 4262 SCNN1A-414 CAGCCUCACUCGGGUUCCAG 20 4263 SCNN1A-415 + AGACCUGGUAUGGGCUGCAG 20 4264 SCNN1A-59 + CGAAGAGCUCUCGGUAGGAG 20  589 SCNN1A-4 CCAUACCAGGUCUCAUGGAG 20  498 SCNN1A-63 + CAGGGCCUCCUCCUCCGCCG 20  592 SCNN1A-52 + UGUGCUGGGAGCACACCAGG 20  584 SCNN1A-23 CCAGCAGCCCACGGCGGAGG 20  566 SCNN1A-60 + AGAGCUCUCGGUAGGAGCGG 20  590 SCNN1A-416 CAGCUGUCCCUUCCAAGGGG 20 4265 SCNN1A-75 + AGCCCUGGAGUGGACUGUGG 20  602 SCNN1A-48 + CCCAGAAGGCCGUCUUCAUG 20  581 SCNN1A-74 + AUGAGCCCUGGAGUGGACUG 20  601 SCNN1A-67 + UCCUCCGCCGUGGGCUGCUG 20  596 SCNN1A-417 + UCACCCCUGGAACCCGAGUG 20 4266 SCNN1A-13 CAUGAAGGGGAACAAGCGUG 20  562 SCNN1A-418 + UAACCGACCUGUAGGGAUUG 20 4267 SCNN1A-419 + AUGAGCCCCGGAGUGGAUUG 20 4268 SCNN1A-40 + AGACGAGCUUGUCCGAGUUG 20  576 SCNN1A-41 + CCGAGUUGAGGUUGAUGUUG 20  577 SCNN1A-420 + UCAUGAGCCCCGGAGUGGAU 20 4269 SCNN1A-421 ACUCGGGUUCCAGGGGUGAU 20 4270 SCNN1A-79 + CCCUCCAUGAGACCUGGUAU 20  604 SCNN1A-35 CCUCAACAUCAACCUCAACU 20  574 SCNN1A-18 AAGCGUGAGGAGCAGGGGCU 20  564 SCNN1A-66 + CUCCUCCGCCGUGGGCUGCU 20  595 SCNN1A-50 + CGUCUUCAUGCGGUUGUGCU 20  583 SCNN1A-57 + AGAAGAACUCGAAGAGCUCU 20  588 SCNN1A-422 + CAGGGUCAAGGCUGAGCUCU 20 4271 SCNN1A-29 CCGCAUGAAGACGGCCUUCU 20  571 SCNN1A-64 + AGGGCCUCCUCCUCCGCCGU 20  593 SCNN1A-423 CACCCUCAAUCCCUACAGGU 20 4272 SCNN1A-424 + AGAGGGACUAACCGACCUGU 20 4273 SCNN1A-425 + CAUGAGCCCCGGAGUGGAUU 20 4274 SCNN1A-69 + CUGCUGGGGCGCCGCAGGUU 20  597 SCNN1A-34 UGGCAAUUCGGCCUGCUUUU 20  573

Table 43C provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 43C 3rd Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID SCNN1A-426 GGACAUGGGCAUGGCCA 17 4275 SCNN1A-427 + GUGGAUUGGGGAGAGCA 17 4276 SCNN1A-428 + GGGGAGAGCAAGGGUCA 17 4277 SCNN1A-115 + GGGAUUGAGGGUGCAGA 17  542 SCNN1A-134 + GCGGAUGGCGCCGUGGA 17  548 SCNN1A-429 GGGACAUGGGCAUGGCC 17 4278 SCNN1A-86 GAACAAGCUGGAGGAGC 17  531 SCNN1A-96 GCGUGAGGAGCAGGGGC 17  534 SCNN1A-430 + GGGUCAAGGCUGAGCUC 17 4279 SCNN1A-100 GCCCCAGCAGCCCACGG 17  537 SCNN1A-135 + GAUGGCGCCGUGGAUGG 17  549 SCNN1A-431 GAAGGGGAACAAGCUGG 17 4280 SCNN1A-85 GGAGGGGAACAAGCUGG 17  530 SCNN1A-92 GAAGGGGAACAAGCGUG 17  532 SCNN1A-432 + GAGUGGAUUGGGGAGAGCAA 20 4281 SCNN1A-9 GCCCUCCACAGUCCACUCCA 20  499 SCNN1A-433 + GGAGUGGAUUGGGGAGAGCA 20 4282 SCNN1A-434 + GAGAGCAAGGGUCAGGGUCA 20 4283 SCNN1A-47 + GAGCCACAGCACUGCCCAGA 20  521 SCNN1A-435 GUUCCAGGGGUGAUGGGAGA 20 4284 SCNN1A-7 GGGGAACAAGCUGGAGGAGC 20  504 SCNN1A-14 GGGGAACAAGCGUGAGGAGC 20  506 SCNN1A-436 GGUUCCAGGGGUGAUGGGAG 20 4285 SCNN1A-24 GCAGCCCACGGCGGAGGAGG 20  512 SCNN1A-56 + GCGGAUGGCGCCGUGGAUGG 20  523 SCNN1A-437 GUAAGCAAGGGAACCUGGUU 20 4286

Table 43D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 43D 4th Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID SCNN1A-438 + UGGAUUGGGGAGAGCAA 17 4287 SCNN1A-439 UCCAGCUGUCCCUUCCA 17 4288 SCNN1A-440 AGGGUGGGACAUGGGCA 17 4289 SCNN1A-441 + AGCAAGGGUCAGGGUCA 17 4290 SCNN1A-442 + ACCAGGGAAGGGGCAGA 17 4291 SCNN1A-443 CCAGGGGUGAUGGGAGA 17 4292 SCNN1A-155 + CUGGAGUGGACUGUGGA 17  652 SCNN1A-444 + UGGGCUGCAGAGGUCUA 17 4293 SCNN1A-445 AGGUAAGCAAGGGAACC 17 4294 SCNN1A-446 + CCCUCUCCCAUCACCCC 17 4295 SCNN1A-151 + UUCCCCUUCAUGAGCCC 17  648 SCNN1A-447 UCCCUCUGCCCCUUCCC 17 4296 SCNN1A-105 CCACGGCGCCAUCCGCC 17  618 SCNN1A-448 UCCAGGGGUGAUGGGAG 17 4297 SCNN1A-83 UACCAGGUCUCAUGGAG 17  606 SCNN1A-133 + CCAGGCGGAUGGCGCCG 17  638 SCNN1A-154 + CCUGGAGUGGACUGUGG 17  651 SCNN1A-153 + AGCCCUGGAGUGGACUG 17  650 SCNN1A-109 CCUUCUGGGCAGUGCUG 17  620 SCNN1A-449 CCAGGGGCAGCCUCACU 17 4298 SCNN1A-450 + CUCAUGAUACCUCCCCU 17 4299 SCNN1A-11 UCCACUCCAGGGCUCAUGAA 20  560 SCNN1A-451 UCCACUCCGGGGCUCAUGAA 20 4300 SCNN1A-452 CGCAGGGUGGGACAUGGGCA 20 4301 SCNN1A-55 + CAGGCGGAUGGCGCCGUGGA 20  587 SCNN1A-77 + UUGUUCCCCUCCAUGAGACC 20  603 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20  599 SCNN1A-26 CAUCCACGGCGCCAUCCGCC 20  568 SCNN1A-12 CCACUCCAGGGCUCAUGAAG 20  561 SCNN1A-453 CCACUCCGGGGCUCAUGAAG 20 4302 SCNN1A-454 + CCCCUUCAUGAGCCCCGGAG 20 4303 SCNN1A-73 + CCCCUUCAUGAGCCCUGGAG 20  600 SCNN1A-54 + ACACCAGGCGGAUGGCGCCG 20  586 SCNN1A-455 CAUGAAGGGGAACAAGCUGG 20 4304 SCNN1A-6 CAUGGAGGGGAACAAGCUGG 20  558 SCNN1A-30 CGGCCUUCUGGGCAGUGCUG 20  572 SCNN1A-456 UGGCCAGGGGCAGCCUCACU 20 4305 SCNN1A-457 + CUGCUCAUGAUACCUCCCCU 20 4306

Table 43E provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fifth tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogeness Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 43E 5th Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID SCNN1A-458 GCCCCACACCUAAGAAA 17 4307 SCNN1A-459 AUGCCUGGAAUCAACAA 17 4308 SCNN1A-460 + ACCCUCAGGCGCUGCAA 17 4309 SCNN1A-461 + CCAUUCCUAGGAAAGAA 17 4310 SCNN1A-462 GGCGACUGCACCAAGAA 17 4311 SCNN1A-463 + ACGCUGGGGAUGGAGAA 17 4312 SCNN1A-464 CCAUUCUUUCCUAGGAA 17 4313 SCNN1A-465 + AACCUGUACCCGGGGAA 17 4314 SCNN1A-466 AGGUAGAGUGUGGGGAA 17 4315 SCNN1A-467 + UGAAUACACACCUGGAA 17 4316 SCNN1A-468 + AUUUCCGGGUACCUGAA 17 4317 SCNN1A-469 + GCUGUGUGUACUUUGAA 17 4318 SCNN1A-470 + GCCACCAUCAUCCAUAA 17 4319 SCNN1A-471 + UGUACUUUGAAGGGUAA 17 4320 SCNN1A-472 GACUGGGGCCCGGGUAA 17 4321 SCNN1A-473 AUCUCUCUGUACCCACA 17 4322 SCNN1A-474 + GGACAAGGACAGAGACA 17 4323 SCNN1A-475 + AGGGCCUGGCUGGGACA 17 4324 SCNN1A-476 AGAGGUUUCUCACACCA 17 4325 SCNN1A-477 + UCUUGUGGCUGGGACCA 17 4326 SCNN1A-478 + AGAUGGGCGGGGGCCCA 17 4327 SCNN1A-479 + AGGAGGGGAGGAUGCCA 17 4328 SCNN1A-480 CCUGGGGUGAGACUCCA 17 4329 SCNN1A-481 + CAGCGUGUCCUCCUCCA 17 4330 SCNN1A-482 GCUCCCUGCUUGCUCCA 17 4331 SCNN1A-483 GCCCCCGCCCAUCUCCA 17 4332 SCNN1A-484 + GCCCCCAAGUCUGUCCA 17 4333 SCNN1A-485 + GCGCCAUGGAGCAAGCA 17 4334 SCNN1A-486 + AGUCACUGUGGACAGCA 17 4335 SCNN1A-487 + AGGCUGGAGAGGGAGCA 17 4336 SCNN1A-488 UCAGCAUGAGGAAGGCA 17 4337 SCNN1A-489 + GUUGUUGAUUCCAGGCA 17 4338 SCNN1A-490 + CCAGGGUGGCAUAGGCA 17 4339 SCNN1A-491 UCCAGGCCGAGGGGGCA 17 4340 SCNN1A-492 + GGGGACACUAACCUGCA 17 4341 SCNN1A-493 + GACCCUCAGGCGCUGCA 17 4342 SCNN1A-494 CUCCAGGGGGCUCUGCA 17 4343 SCNN1A-495 GCCCGGGUAAUGGUGCA 17 4344 SCNN1A-496 + CUCUGCGCGCAGCAUCA 17 4345 SCNN1A-497 ACCAGACAUACUCAUCA 17 4346 SCNN1A-498 + GAAUGGGGGUGUCAUCA 17 4347 SCNN1A-499 CCAGGAGAGCAUGAUCA 17 4348 SCNN1A-500 GUCCCGCCCCCGCCUCA 17 4349 SCNN1A-501 + CCUCUCCUUCCCUCUCA 17 4350 SCNN1A-502 + AGGGGGAGGGGCUGUCA 17 4351 SCNN1A-503 UGAGUCUCCCUCUGUCA 17 4352 SCNN1A-504 AGUCAACAUCUUCUUCA 17 4353 SCNN1A-505 + AAGGGGCGAGGGGAAGA 17 4354 SCNN1A-506 ACCUCUCCUCUCACAGA 17 4355 SCNN1A-507 + CGACCUACCGUGACAGA 17 4356 SCNN1A-508 + CUUAGGUGUGGGGCAGA 17 4357 SCNN1A-509 + CAGAGACUAGAGUCAGA 17 4358 SCNN1A-510 + GGAGGGUGGAGAGGAGA 17 4359 SCNN1A-511 + GCAGAGCCCCCUGGAGA 17 4360 SCNN1A-512 + GCUGUCAAGGCUGGAGA 17 4361 SCNN1A-513 GUUGUCUGUGGUGGAGA 17 4362 SCNN1A-514 CUGGGGGGGCCCUGAGA 17 4363 SCNN1A-515 CUGCUGGUUACUCACGA 17 4364 SCNN1A-516 + GAGAGGUACAUUGACGA 17 4365 SCNN1A-517 + ACCUGGGAUGUCACCGA 17 4366 SCNN1A-518 GAGGCCCGCAGCGCCGA 17 4367 SCNN1A-519 ACUGGUCUCCAGGCCGA 17 4368 SCNN1A-520 UCCUCAUGCUGCUCCGA 17 4369 SCNN1A-521 + UCCCCCGCAGGUCGCGA 17 4370 SCNN1A-522 + GGUACCUGAAGGGGCGA 17 4371 SCNN1A-523 + CCACGCUACGGGCUCGA 17 4372 SCNN1A-524 + GGCAGAAGUGGGAAGGA 17 4373 SCNN1A-525 + GCCCAGGUUGGACAGGA 17 4374 SCNN1A-526 + ACACCUGGAAGGGAGGA 17 4375 SCNN1A-527 CUCCAUCAGCAUGAGGA 17 4376 SCNN1A-528 AGAGUGUGGGGAAGGGA 17 4377 SCNN1A-529 + GUGUCCUCCUCCAGGGA 17 4378 SCNN1A-530 GGGGGCCCUGAGAGGGA 17 4379 SCNN1A-531 + CAACCUGUACCCGGGGA 17 4380 SCNN1A-532 + UGGCAUAGGCAGGGGGA 17 4381 SCNN1A-533 + GCUGGUCACGCUGGGGA 17 4382 SCNN1A-534 CAGGUAGAGUGUGGGGA 17 4383 SCNN1A-535 + UGGGGGCAGAAGUGGGA 17 4384 SCNN1A-536 CCCCCAGGUGGACUGGA 17 4385 SCNN1A-537 + GUGAAUACACACCUGGA 17 4386 SCNN1A-538 UGACUGGGAGGCCUGGA 17 4387 SCNN1A-539 GGUAGGUCGUGCCUGGA 17 4388 SCNN1A-540 CCUGCCUUUAUGGAUGA 17 4389 SCNN1A-541 + AAUUUCCGGGUACCUGA 17 4390 SCNN1A-542 CCCCUUGCAGCGCCUGA 17 4391 SCNN1A-543 + UGCCUUCCUCAUGCUGA 17 4392 SCNN1A-544 AGGGGUGGAUGCGGUGA 17 4393 SCNN1A-545 + GGCCACGAGAGUGGUGA 17 4394 SCNN1A-546 + UGACCUCUUGUUGUUGA 17 4395 SCNN1A-547 + UGCUGUGUGUACUUUGA 17 4396 SCNN1A-548 CUCUCUCUUUCCUGAUA 17 4397 SCNN1A-549 + CAUCAGGGACAGACCUA 17 4398 SCNN1A-550 + AGCUGGAGGCCACGCUA 17 4399 SCNN1A-551 + UCAGGAAAGAGAGAGUA 17 4400 SCNN1A-552 UUCCACCACCCGAUGUA 17 4401 SCNN1A-553 AGACUUGGGGGCGAUUA 17 4402 SCNN1A-554 GGAUGAACCUGCCUUUA 17 4403 SCNN1A-555 + GGGUAAAGGUUCUCAAC 17 4404 SCNN1A-556 + AGGACAGGUGGAGGAAC 17 4405 SCNN1A-557 + CCGAGGAGCCGAACCAC 17 4406 SCNN1A-558 CAUCUCUCUGUACCCAC 17 4407 SCNN1A-559 + CGAACCACAGGCUCCAC 17 4408 SCNN1A-560 CCCGGGUAAUGGUGCAC 17 4409 SCNN1A-561 + AUUUGUUCUGGUUGCAC 17 4410 SCNN1A-562 UCCCGCCCCCGCCUCAC 17 4411 SCNN1A-563 + UCUCUGGCAGCCUCGAC 17 4412 SCNN1A-564 + CACGCUACGGGCUCGAC 17 4413 SCNN1A-565 AGGUGGACUGGAAGGAC 17 4414 SCNN1A-566 + GGGCCCCCCCAGAGGAC 17 4415 SCNN1A-567 ACAACCCCCAGGUGGAC 17 4416 SCNN1A-568 + GGCUGCCCAGGUUGGAC 17 4417 SCNN1A-569 AAGGCAAGGAUGCUGAC 17 4418 SCNN1A-570 CUGCUGUCCACAGUGAC 17 4419 SCNN1A-571 GGUUCCGAAGCCGAUAC 17 4420 SCNN1A-572 + GCUGGAGGCCACGCUAC 17 4421 SCNN1A-573 UCCCCUUCCCCGGGUAC 17 4422 SCNN1A-574 + AGGAGCUGUAUUUGUAC 17 4423 SCNN1A-575 CACCCUCCUGUCCAACC 17 4424 SCNN1A-576 CCAGGUCUCCUGCAACC 17 4425 SCNN1A-577 + CUGAGGAGAAGUCAACC 17 4426 SCNN1A-578 CGCCUGCCGCUUCAACC 17 4427 SCNN1A-579 + AGGAGUGAAUACACACC 17 4428 SCNN1A-580 CUUCUCCUCAGACCACC 17 4429 SCNN1A-581 + AGUCCUUCCAGUCCACC 17 4430 SCNN1A-582 + CCUGGUUGCAGGAGACC 17 4431 SCNN1A-583 + CUUCCCCACACUCUACC 17 4432 SCNN1A-584 UCGCCCCUUCAGGUACC 17 4433 SCNN1A-585 + GCCCGUGCACCAUUACC 17 4434 SCNN1A-586 GGGUUCAUAGGAAACCC 17 4435 SCNN1A-587 CCCUGCCUAUGCCACCC 17 4436 SCNN1A-588 GGAGGUAGCCUCCACCC 17 4437 SCNN1A-589 + CCCGUGCACCAUUACCC 17 4438 SCNN1A-590 + CCCUGGAGUCUCACCCC 17 4439 SCNN1A-591 GCGGGACAACAACCCCC 17 4440 SCNN1A-592 + GCCCCUGCAGAGCCCCC 17 4441 SCNN1A-593 UUAGUGUCCCCUUCCCC 17 4442 SCNN1A-594 + ACUUGGUGAAACAGCCC 17 4443 SCNN1A-595 + GAGAUGGGCGGGGGCCC 17 4444 SCNN1A-596 CACAGUGACUGGGGCCC 17 4445 SCNN1A-597 AGAGGUCAGUCCUGCCC 17 4446 SCNN1A-598 + GGCUCCACUGGCUGCCC 17 4447 SCNN1A-599 GCCCUCGGUGACAUCCC 17 4448 SCNN1A-600 AGAGACUCUGCCAUCCC 17 4449 SCNN1A-601 + GCAGGGUGGGGGCUCCC 17 4450 SCNN1A-602 GUUAGUGUCCCCUUCCC 17 4451 SCNN1A-603 CUGUCCUUGUCCCAGCC 17 4452 SCNN1A-604 + AUGGAGGUCUCCACGCC 17 4453 SCNN1A-605 + CAGGACUGACUCACGCC 17 4454 SCNN1A-606 AUGCUGACUGGGAGGCC 17 4455 SCNN1A-607 GGCUUUAACUUGCGGCC 17 4456 SCNN1A-608 + CCCCUGCCCCCUCGGCC 17 4457 SCNN1A-609 + GGAGAGGGAGCAGGGCC 17 4458 SCNN1A-610 CCACAGUGACUGGGGCC 17 4459 SCNN1A-611 UGGAUGUCUUCCAUGCC 17 4460 SCNN1A-612 + AAGGAGGGGAGGAUGCC 17 4461 SCNN1A-613 CGUGAGUCAGUCCUGCC 17 4462 SCNN1A-614 UCACGGUAGGUCGUGCC 17 4463 SCNN1A-615 + CAUCACAGGCUCCAUCC 17 4464 SCNN1A-616 UCCUGGGGUGAGACUCC 17 4465 SCNN1A-617 + CCAGCGUGUCCUCCUCC 17 4466 SCNN1A-618 CUGCUACUAUAAGCUCC 17 4467 SCNN1A-619 GGCCCCCGCCCAUCUCC 17 4468 SCNN1A-620 + CCUUGAUCAUGCUCUCC 17 4469 SCNN1A-621 AGCCGAUACUGGUCUCC 17 4470 SCNN1A-622 + CGCCCCCAAGUCUGUCC 17 4471 SCNN1A-623 + UCACCGUUGUUGAUUCC 17 4472 SCNN1A-624 CCACCCUCCUCCCUUCC 17 4473 SCNN1A-625 UAUUCACUCCUGCUUCC 17 4474 SCNN1A-626 ACAGAAAGCACAGUUCC 17 4475 SCNN1A-627 + GCUCCUCUUUAAUUUCC 17 4476 SCNN1A-628 + GGCGCCAUGGAGCAAGC 17 4477 SCNN1A-629 + GUUGUUGUCCCGCAAGC 17 4478 SCNN1A-630 + CAUGCUCUCCUGGAAGC 17 4479 SCNN1A-631 UUCAAAGUACACACAGC 17 4480 SCNN1A-632 + CAGUCACUGUGGACAGC 17 4481 SCNN1A-633 + CUGCGGGCCUCACCAGC 17 4482 SCNN1A-634 + GGAACAUGAUGACCAGC 17 4483 SCNN1A-635 GAAGAUCGGCUUCCAGC 17 4484 SCNN1A-636 + AGUAACCAGCAGAGAGC 17 4485 SCNN1A-637 GGAAAUUAAAGAGGAGC 17 4486 SCNN1A-638 AGAGGAGCUGGAGGAGC 17 4487 SCNN1A-639 + AAGGCUGGAGAGGGAGC 17 4488 SCNN1A-640 + GCGACGGCUGCGGGAGC 17 4489 SCNN1A-641 + AGCAGAGAGCUGGUAGC 17 4490 SCNN1A-642 CCUGGAGGAGGACACGC 17 4491 SCNN1A-643 + CUGGUAGCUGGUCACGC 17 4492 SCNN1A-644 + GCGGCAGAGUCCCCCGC 17 4493 SCNN1A-645 + CCAUCAUCCAUAAAGGC 17 4494 SCNN1A-646 + GGAGGGGCUGUCAAGGC 17 4495 SCNN1A-647 + AGAGCAAGGAGCCAGGC 17 4496 SCNN1A-648 + GACGGGCCCCGUGAGGC 17 4497 SCNN1A-649 + CCCAGGGUGGCAUAGGC 17 4498 SCNN1A-650 + GACCUGGUUGAAGCGGC 17 4499 SCNN1A-651 + GUGGCUGGGACCAGGGC 17 4500 SCNN1A-652 GGUAAUGGUGCACGGGC 17 4501 SCNN1A-653 CUCCAGGCCGAGGGGGC 17 4502 SCNN1A-654 + CCCCGUGAGGCGGGGGC 17 4503 SCNN1A-655 + GCCCCCUGGAGAUGGGC 17 4504 SCNN1A-656 + AGGGAGCAGGGCCUGGC 17 4505 SCNN1A-657 UUCACCACUCUCGUGGC 17 4506 SCNN1A-658 AGUGCCGGAAGCCAUGC 17 4507 SCNN1A-659 CAGCCGUCGCGACCUGC 17 4508 SCNN1A-660 GCUCGUCUUUGACCUGC 17 4509 SCNN1A-661 + GGGCCCCUCGGCGCUGC 17 4510 SCNN1A-662 + CAGGUCGCGACGGCUGC 17 4511 SCNN1A-663 UCUCCAGGGGGCUCUGC 17 4512 SCNN1A-664 AGCUACCAGCUCUCUGC 17 4513 SCNN1A-665 GCUGUUUCACCAAGUGC 17 4514 SCNN1A-666 CGUGGCCUCCAGCUUGC 17 4515 SCNN1A-667 + GACUCACGCCUGGUUGC 17 4516 SCNN1A-668 + AGCAGUUUCCAUACAUC 17 4517 SCNN1A-669 + GCUCUGCGCGCAGCAUC 17 4518 SCNN1A-670 + UCUGUCGCGAUAGCAUC 17 4519 SCNN1A-671 UACCAGACAUACUCAUC 17 4520 SCNN1A-672 + GAGAGUAAUUCCUUAUC 17 4521 SCNN1A-673 AGAACAACUCCAACCUC 17 4522 SCNN1A-674 + GCGGGGGCGGGACCCUC 17 4523 SCNN1A-675 UUCCUCCACCUGUCCUC 17 4524 SCNN1A-676 AGGGGGCAGGGGUGCUC 17 4525 SCNN1A-677 + ACCUCUCCUUCCCUCUC 17 4526 SCNN1A-678 + AGGGAUGGCAGAGUCUC 17 4527 SCNN1A-679 + GCGAGGGGAAGAGGGUC 17 4528 SCNN1A-680 + CCCCUGAUGAGUAUGUC 17 4529 SCNN1A-681 CUUCCCCUCGCCCCUUC 17 4530 SCNN1A-682 + CUAACCUGCAUGGCUUC 17 4531 SCNN1A-683 + CACAGUACUCCACGUUC 17 4532 SCNN1A-684 + AGCAGUCCGAUUUGUUC 17 4533 SCNN1A-685 + AGCUCCUCUUUAAUUUC 17 4534 SCNN1A-686 GUACCCGGAAAUUAAAG 17 4535 SCNN1A-687 ACACCGUCAACAACAAG 17 4536 SCNN1A-688 + CCCUCAGGCGCUGCAAG 17 4537 SCNN1A-689 + UGGGGUGGGGGCAGAAG 17 4538 SCNN1A-690 + GAAGGGGCGAGGGGAAG 17 4539 SCNN1A-691 + ACCUGUACCCGGGGAAG 17 4540 SCNN1A-692 + UGUUGAUGUAGUGGAAG 17 4541 SCNN1A-693 + UUUCCGGGUACCUGAAG 17 4542 SCNN1A-694 + AGGAGACCUGGUUGAAG 17 4543 SCNN1A-695 + ACGACCUACCGUGACAG 17 4544 SCNN1A-696 + UCUCAGGGCCCCCCCAG 17 4545 SCNN1A-697 CCAACCUGGGCAGCCAG 17 4546 SCNN1A-698 + GCAUGGAAGACAUCCAG 17 4547 SCNN1A-699 CCCCCGCCCAUCUCCAG 17 4548 SCNN1A-700 + GUCACUGUGGACAGCAG 17 4549 SCNN1A-701 + CAGGGUGGCAUAGGCAG 17 4550 SCNN1A-702 CCAGGCCGAGGGGGCAG 17 4551 SCNN1A-703 + UCUUAGGUGUGGGGCAG 17 4552 SCNN1A-704 UCCAGGGGGCUCUGCAG 17 4553 SCNN1A-705 CCAGACAUACUCAUCAG 17 4554 SCNN1A-706 + ACAGAGACUAGAGUCAG 17 4555 SCNN1A-707 + AGAGACUAGAGUCAGAG 17 4556 SCNN1A-708 + GGAGCCGGCCACGAGAG 17 4557 SCNN1A-709 AGGCCCGCAGCGCCGAG 17 4558 SCNN1A-710 CUGGUCUCCAGGCCGAG 17 4559 SCNN1A-711 + GUACCUGAAGGGGCGAG 17 4560 SCNN1A-712 CCCUGAGAGGGAAGGAG 17 4561 SCNN1A-713 + GCAGAAGUGGGAAGGAG 17 4562 SCNN1A-714 + AGGAGGGUGGAGAGGAG 17 4563 SCNN1A-715 + ACCAUCUGUGAGAGGAG 17 4564 SCNN1A-716 UGGAUGCGGUGAGGGAG 17 4565 SCNN1A-717 + GGCAUAGGCAGGGGGAG 17 4566 SCNN1A-718 ACACCUAAGAAAUGGAG 17 4567 SCNN1A-719 + GGCUGUCAAGGCUGGAG 17 4568 SCNN1A-720 + AAGGGAGGAGGGUGGAG 17 4569 SCNN1A-721 UCUGGGGGGGCCCUGAG 17 4570 SCNN1A-722 + GGGUGACCAUCUGUGAG 17 4571 SCNN1A-723 + AUCAGGGACAGACCUAG 17 4572 SCNN1A-724 + ACAGGAUGUUGAUGUAG 17 4573 SCNN1A-725 UCCGCGGCCCCAGAACG 17 4574 SCNN1A-726 CCCGCCCCCGCCUCACG 17 4575 SCNN1A-727 + CACCACAGACAACACCG 17 4576 SCNN1A-728 + UACCUGGGAUGUCACCG 17 4577 SCNN1A-729 UGAGGCCCGCAGCGCCG 17 4578 SCNN1A-730 UACUGGUCUCCAGGCCG 17 4579 SCNN1A-731 + UCCACGUUCUGGGGCCG 17 4580 SCNN1A-732 CCUACAUCUUCUAUCCG 17 4581 SCNN1A-733 GGCCCAACCUGAUUCCG 17 4582 SCNN1A-734 CCGUCGAGCCCGUAGCG 17 4583 SCNN1A-735 + ACGGGCCCCGUGAGGCG 17 4584 SCNN1A-736 + GGGUACCUGAAGGGGCG 17 4585 SCNN1A-737 + CCCCCUGGAGAUGGGCG 17 4586 SCNN1A-738 UAACUUGCGGCCUGGCG 17 4587 SCNN1A-739 AGCCGUCGCGACCUGCG 17 4588 SCNN1A-740 CUCCUUCACCACUCUCG 17 4589 SCNN1A-741 ACAUCAACAUCCUGUCG 17 4590 SCNN1A-742 + GGGCAGAAGUGGGAAGG 17 4591 SCNN1A-743 + CCCCCCCAGAGGACAGG 17 4592 SCNN1A-744 + UGCCCAGGUUGGACAGG 17 4593 SCNN1A-745 GGACAACAACCCCCAGG 17 4594 SCNN1A-746 + UGGUGAAACAGCCCAGG 17 4595 SCNN1A-747 CCCCGCCCAUCUCCAGG 17 4596 SCNN1A-748 + AGGGUGGCAUAGGCAGG 17 4597 SCNN1A-749 GGGCAGGGGUGCUCAGG 17 4598 SCNN1A-750 UGGUCUCCAGGCCGAGG 17 4599 SCNN1A-751 + CACACCUGGAAGGGAGG 17 4600 SCNN1A-752 UCUGCCAUCCCUGGAGG 17 4601 SCNN1A-753 + CGACGGGCCCCGUGAGG 17 4602 SCNN1A-754 + CGGGCCCCGUGAGGCGG 17 4603 SCNN1A-755 + CCCCUGGAGAUGGGCGG 17 4604 SCNN1A-756 GCCGUCGCGACCUGCGG 17 4605 SCNN1A-757 + AUACACACCUGGAAGGG 17 4606 SCNN1A-758 + UGGGCGGGGGCCCAGGG 17 4607 SCNN1A-759 + AGGGGAGGAUGCCAGGG 17 4608 SCNN1A-760 + AGGUGUGGGGCAGAGGG 17 4609 SCNN1A-761 + CCUGGAAGGGAGGAGGG 17 4610 SCNN1A-762 + AGUUUCCAUACAUCGGG 17 4611 SCNN1A-763 GACAUACUCAUCAGGGG 17 4612 SCNN1A-764 + GAAGUGGGAAGGAGGGG 17 4613 SCNN1A-765 + GUGGCAUAGGCAGGGGG 17 4614 SCNN1A-766 + GCCCCGUGAGGCGGGGG 17 4615 SCNN1A-767 + AGGACAGAGACAUGGGG 17 4616 SCNN1A-768 CCACCUGUCCUCUGGGG 17 4617 SCNN1A-769 + AGCCCCCUGGAGAUGGG 17 4618 SCNN1A-770 UGUGGGGAAGGGAUGGG 17 4619 SCNN1A-771 CAAGGAUGCUGACUGGG 17 4620 SCNN1A-772 UCCACCUGUCCUCUGGG 17 4621 SCNN1A-773 + UUCCUAGGAAAGAAUGG 17 4622 SCNN1A-774 GCCUUUAUGGAUGAUGG 17 4623 SCNN1A-775 + CUUCCUCAUGCUGAUGG 17 4624 SCNN1A-776 + CCUUCCAGUCCACCUGG 17 4625 SCNN1A-777 GACUCUGCCAUCCCUGG 17 4626 SCNN1A-778 + GUUGUCCCGCAAGCUGG 17 4627 SCNN1A-779 AAUUAAAGAGGAGCUGG 17 4628 SCNN1A-780 CUCCACCUGUCCUCUGG 17 4629 SCNN1A-781 + CCCCAGAGGACAGGUGG 17 4630 SCNN1A-782 + GGAGGAUGCCAGGGUGG 17 4631 SCNN1A-783 + UUCCAUACAUCGGGUGG 17 4632 SCNN1A-784 + ACAGAGACAUGGGGUGG 17 4633 SCNN1A-785 GGGGAAGGGAUGGGUGG 17 4634 SCNN1A-786 CUCGGUGUUGUCUGUGG 17 4635 SCNN1A-787 ACCCUGGACAGACUUGG 17 4636 SCNN1A-788 + AUUCCUAGGAAAGAAUG 17 4637 SCNN1A-789 + ACAAGGACAGAGACAUG 17 4638 SCNN1A-790 + ACCUUCGGAGCAGCAUG 17 4639 SCNN1A-791 AGACCUCCAUCAGCAUG 17 4640 SCNN1A-792 CUCAUCAGGGGUGGAUG 17 4641 SCNN1A-793 + GCGUCUGCUCUGUGAUG 17 4642 SCNN1A-794 UGAUCUCUUGGUGUAUG 17 4643 SCNN1A-795 + CCGGGCCCCAGUCACUG 17 4644 SCNN1A-796 GCUGUCCACAGUGACUG 17 4645 SCNN1A-797 + UCCUUCCAGUCCACCUG 17 4646 SCNN1A-798 GCAGCCGUCGCGACCUG 17 4647 SCNN1A-799 + AUAGUAGCAGUACCCUG 17 4648 SCNN1A-800 GCAGCCAGUGGAGCCUG 17 4649 SCNN1A-801 ACCCCUUGCAGCGCCUG 17 4650 SCNN1A-802 AGAAAGCACAGUUCCUG 17 4651 SCNN1A-803 + GGUAGCUGGUCACGCUG 17 4652 SCNN1A-804 + CGGGCCCCUCGGCGCUG 17 4653 SCNN1A-805 + GCAGGUCGCGACGGCUG 17 4654 SCNN1A-806 CCUCCACCUGUCCUCUG 17 4655 SCNN1A-807 + ACAGCCCAGGUGGUCUG 17 4656 SCNN1A-808 CUCCUCGGUGUUGUCUG 17 4657 SCNN1A-809 + CAGUACUCCACGUUCUG 17 4658 SCNN1A-810 ACAUCCCAGGUAGAGUG 17 4659 SCNN1A-811 AGCAUGAUCAAGGAGUG 17 4660 SCNN1A-812 + GCUCGACGGGCCCCGUG 17 4661 SCNN1A-813 AGUACACACAGCAGGUG 17 4662 SCNN1A-814 + ACUCCAUUUCUUAGGUG 17 4663 SCNN1A-815 CAGGGGUGGAUGCGGUG 17 4664 SCNN1A-816 + AGGCGCUGCAAGGGGUG 17 4665 SCNN1A-817 + GACAGAGACAUGGGGUG 17 4666 SCNN1A-818 UGGGGAAGGGAUGGGUG 17 4667 SCNN1A-819 UCGGCUUCCAGCUGGUG 17 4668 SCNN1A-820 AUCCCAGGUAGAGUGUG 17 4669 SCNN1A-821 + UCCAUUUCUUAGGUGUG 17 4670 SCNN1A-822 AUGGUGGCUUUAACUUG 17 4671 SCNN1A-823 AACCCUGGACAGACUUG 17 4672 SCNN1A-824 GCGUGGCCUCCAGCUUG 17 4673 SCNN1A-825 GUGCAACCAGAACAAAU 17 4674 SCNN1A-826 + CAUUCCUAGGAAAGAAU 17 4675 SCNN1A-827 + AGAGGGAGACUCAGAAU 17 4676 SCNN1A-828 CAUUCUUUCCUAGGAAU 17 4677 SCNN1A-829 + GACAAGGACAGAGACAU 17 4678 SCNN1A-830 + UAGCAGUUUCCAUACAU 17 4679 SCNN1A-831 + GGGGCCCAGGGUGGCAU 17 4680 SCNN1A-832 GGUGUAUGUGGGUUCAU 17 4681 SCNN1A-833 UGGAAGGACUGGAAGAU 17 4682 SCNN1A-834 + CAGAGCCCCCUGGAGAU 17 4683 SCNN1A-835 + AGAGGUACAUUGACGAU 17 4684 SCNN1A-836 GAGUGUGGGGAAGGGAU 17 4685 SCNN1A-837 + GGCCUGGAGACCAGUAU 17 4686 SCNN1A-838 + GCAUGGCUUCCGGCACU 17 4687 SCNN1A-839 GAAACCCUGGACAGACU 17 4688 SCNN1A-840 AGGCAAGGAUGCUGACU 17 4689 SCNN1A-841 UGCUGUCCACAGUGACU 17 4690 SCNN1A-842 ACCCUCCUGUCCAACCU 17 4691 SCNN1A-843 UUCUCCUCAGACCACCU 17 4692 SCNN1A-844 + GUCCUUCCAGUCCACCU 17 4693 SCNN1A-845 + GCAUCAGGGACAGACCU 17 4694 SCNN1A-846 + UUCCCCACACUCUACCU 17 4695 SCNN1A-847 CCUGCCUAUGCCACCCU 17 4696 SCNN1A-848 GCUCUCUCUGCACCCCU 17 4697 SCNN1A-849 + GAGCACCCCUGCCCCCU 17 4698 SCNN1A-850 UUACUCACGAUGGCCCU 17 4699 SCNN1A-851 CCUGUGGUUCGGCUCCU 17 4700 SCNN1A-852 + CUGGAAGACCCAUUCCU 17 4701 SCNN1A-853 CAGAAAGCACAGUUCCU 17 4702 SCNN1A-854 CACCCCCAUUCUUUCCU 17 4703 SCNN1A-855 CUGGAGGAGGACACGCU 17 4704 SCNN1A-856 + UGGUAGCUGGUCACGCU 17 4705 SCNN1A-857 + GGGAGCAGGGCCUGGCU 17 4706 SCNN1A-858 UCCUCCACCUGUCCUCU 17 4707 SCNN1A-859 + AACAUCACUGCCAUUCU 17 4708 SCNN1A-860 + ACAGUACUCCACGUUCU 17 4709 SCNN1A-861 + GGGGUGGGGGCAGAAGU 17 4710 SCNN1A-862 + UGCAGAGAGAGCAGAGU 17 4711 SCNN1A-863 + AUCAGGAAAGAGAGAGU 17 4712 SCNN1A-864 + CCACUGGCUGCCCAGGU 17 4713 SCNN1A-865 + CUGCCACGGAAUCAGGU 17 4714 SCNN1A-866 + GGAAGACAUCCAGAGGU 17 4715 SCNN1A-867 UCUCCCUCUGUCACGGU 17 4716 SCNN1A-868 + GGUGUGGGGCAGAGGGU 17 4717 SCNN1A-869 + GGACAGAGACAUGGGGU 17 4718 SCNN1A-870 GUGGGGAAGGGAUGGGU 17 4719 SCNN1A-871 + CCGCGGAUAGAAGAUGU 17 4720 SCNN1A-872 GAUCUCUUGGUGUAUGU 17 4721 SCNN1A-873 + UAGUAGCAGUACCCUGU 17 4722 SCNN1A-874 + AGAAAGGUGCUCAGUGU 17 4723 SCNN1A-875 CAUCCCAGGUAGAGUGU 17 4724 SCNN1A-876 + CUCCAUUUCUUAGGUGU 17 4725 SCNN1A-877 AAACCCUGGACAGACUU 17 4726 SCNN1A-878 + GAAGAAGAUGUUGACUU 17 4727 SCNN1A-879 + AUCGGCUUCGGAACCUU 17 4728 SCNN1A-880 + GAGACCAGUAUCGGCUU 17 4729 SCNN1A-881 + UGGCCACUCCAUUUCUU 17 4730 SCNN1A-882 + UGCCACGGAAUCAGGUU 17 4731 SCNN1A-883 CAGUGGAGCCUGUGGUU 17 4732 SCNN1A-884 UCUGCCCCACACCUAAGAAA 20 4733 SCNN1A-885 UCCAUGCCUGGAAUCAACAA 20 4734 SCNN1A-886 + GGGACCCUCAGGCGCUGCAA 20 4735 SCNN1A-887 + GACCCAUUCCUAGGAAAGAA 20 4736 SCNN1A-888 UAUGGCGACUGCACCAAGAA 20 4737 SCNN1A-889 + GUCACGCUGGGGAUGGAGAA 20 4738 SCNN1A-890 CCCCCAUUCUUUCCUAGGAA 20 4739 SCNN1A-891 CCCAGGUAGAGUGUGGGGAA 20 4740 SCNN1A-892 + GAGUGAAUACACACCUGGAA 20 4741 SCNN1A-893 + UUAAUUUCCGGGUACCUGAA 20 4742 SCNN1A-894 + CCUGCUGUGUGUACUUUGAA 20 4743 SCNN1A-895 + AAAGCCACCAUCAUCCAUAA 20 4744 SCNN1A-896 + GUGUGUACUUUGAAGGGUAA 20 4745 SCNN1A-897 AGUGACUGGGGCCCGGGUAA 20 4746 SCNN1A-898 GGCAUCUCUCUGUACCCACA 20 4747 SCNN1A-899 + CUGGGACAAGGACAGAGACA 20 4748 SCNN1A-900 + AGCAGGGCCUGGCUGGGACA 20 4749 SCNN1A-901 AGGAGAGGUUUCUCACACCA 20 4750 SCNN1A-902 + UGGAGAUGGGCGGGGGCCCA 20 4751 SCNN1A-903 + GGAAGGAGGGGAGGAUGCCA 20 4752 SCNN1A-904 GUUCCUGGGGUGAGACUCCA 20 4753 SCNN1A-905 + GCCCAGCGUGUCCUCCUCCA 20 4754 SCNN1A-906 GAAGCUCCCUGCUUGCUCCA 20 4755 SCNN1A-907 UGGGCCCCCGCCCAUCUCCA 20 4756 SCNN1A-908 + AUCGCCCCCAAGUCUGUCCA 20 4757 SCNN1A-909 + AGGGCGCCAUGGAGCAAGCA 20 4758 SCNN1A-910 + CCCAGUCACUGUGGACAGCA 20 4759 SCNN1A-911 + UCAAGGCUGGAGAGGGAGCA 20 4760 SCNN1A-912 CCAUCAGCAUGAGGAAGGCA 20 4761 SCNN1A-913 + ACCGUUGUUGAUUCCAGGCA 20 4762 SCNN1A-914 + GGCCCAGGGUGGCAUAGGCA 20 4763 SCNN1A-915 GUCUCCAGGCCGAGGGGGCA 20 4764 SCNN1A-916 + GAAGGGGACACUAACCUGCA 20 4765 SCNN1A-917 + CGGGACCCUCAGGCGCUGCA 20 4766 SCNN1A-918 CAUCUCCAGGGGGCUCUGCA 20 4767 SCNN1A-919 GGGGCCCGGGUAAUGGUGCA 20 4768 SCNN1A-920 + CUGCUCUGCGCGCAGCAUCA 20 4769 SCNN1A-921 UCUACCAGACAUACUCAUCA 20 4770 SCNN1A-922 + AAAGAAUGGGGGUGUCAUCA 20 4771 SCNN1A-923 CUUCCAGGAGAGCAUGAUCA 20 4772 SCNN1A-924 AGGGUCCCGCCCCCGCCUCA 20 4773 SCNN1A-925 + AAACCUCUCCUUCCCUCUCA 20 4774 SCNN1A-926 + GGCAGGGGGAGGGGCUGUCA 20 4775 SCNN1A-927 UUCUGAGUCUCCCUCUGUCA 20 4776 SCNN1A-928 CAAAGUCAACAUCUUCUUCA 20 4777 SCNN1A-929 + CUGAAGGGGCGAGGGGAAGA 20 4778 SCNN1A-930 UGUACCUCUCCUCUCACAGA 20 4779 SCNN1A-931 + GCACGACCUACCGUGACAGA 20 4780 SCNN1A-932 + UUUCUUAGGUGUGGGGCAGA 20 4781 SCNN1A-933 + ACACAGAGACUAGAGUCAGA 20 4782 SCNN1A-934 + GGAGGAGGGUGGAGAGGAGA 20 4783 SCNN1A-935 + CCUGCAGAGCCCCCUGGAGA 20 4784 SCNN1A-936 + GGGGCUGUCAAGGCUGGAGA 20 4785 SCNN1A-937 GGUGUUGUCUGUGGUGGAGA 20 4786 SCNN1A-938 CCUCUGGGGGGGCCCUGAGA 20 4787 SCNN1A-939 UCUCUGCUGGUUACUCACGA 20 4788 SCNN1A-940 + GAGGAGAGGUACAUUGACGA 20 4789 SCNN1A-941 + UCUACCUGGGAUGUCACCGA 20 4790 SCNN1A-942 GGUGAGGCCCGCAGCGCCGA 20 4791 SCNN1A-943 GAUACUGGUCUCCAGGCCGA 20 4792 SCNN1A-944 UGUUCCUCAUGCUGCUCCGA 20 4793 SCNN1A-945 + GAGUCCCCCGCAGGUCGCGA 20 4794 SCNN1A-946 + CCGGGUACCUGAAGGGGCGA 20 4795 SCNN1A-947 + AGGCCACGCUACGGGCUCGA 20 4796 SCNN1A-948 + GGGGGCAGAAGUGGGAAGGA 20 4797 SCNN1A-949 + GCUGCCCAGGUUGGACAGGA 20 4798 SCNN1A-950 + UACACACCUGGAAGGGAGGA 20 4799 SCNN1A-951 GACCUCCAUCAGCAUGAGGA 20 4800 SCNN1A-952 GGUAGAGUGUGGGGAAGGGA 20 4801 SCNN1A-953 + AGCGUGUCCUCCUCCAGGGA 20 4802 SCNN1A-954 UGGGGGGGCCCUGAGAGGGA 20 4803 SCNN1A-955 + GGGUGGCAUAGGCAGGGGGA 20 4804 SCNN1A-956 + GUAGCUGGUCACGCUGGGGA 20 4805 SCNN1A-957 UCCCAGGUAGAGUGUGGGGA 20 4806 SCNN1A-958 + GGGUGGGGGCAGAAGUGGGA 20 4807 SCNN1A-959 CAACCCCCAGGUGGACUGGA 20 4808 SCNN1A-960 + GGAGUGAAUACACACCUGGA 20 4809 SCNN1A-961 UGCUGACUGGGAGGCCUGGA 20 4810 SCNN1A-962 CACGGUAGGUCGUGCCUGGA 20 4811 SCNN1A-963 GAACCUGCCUUUAUGGAUGA 20 4812 SCNN1A-964 + UUUAAUUUCCGGGUACCUGA 20 4813 SCNN1A-965 GCACCCCUUGCAGCGCCUGA 20 4814 SCNN1A-966 + CCUUGCCUUCCUCAUGCUGA 20 4815 SCNN1A-967 AUCAGGGGUGGAUGCGGUGA 20 4816 SCNN1A-968 + GCCGGCCACGAGAGUGGUGA 20 4817 SCNN1A-969 + GACUGACCUCUUGUUGUUGA 20 4818 SCNN1A-970 + ACCUGCUGUGUGUACUUUGA 20 4819 SCNN1A-971 CUACUCUCUCUUUCCUGAUA 20 4820 SCNN1A-972 + CAGCAUCAGGGACAGACCUA 20 4821 SCNN1A-973 + GCAAGCUGGAGGCCACGCUA 20 4822 SCNN1A-974 + UUAUCAGGAAAGAGAGAGUA 20 4823 SCNN1A-975 CACUUCCACCACCCGAUGUA 20 4824 SCNN1A-976 GACAGACUUGGGGGCGAUUA 20 4825 SCNN1A-977 GCAGGAUGAACCUGCCUUUA 20 4826 SCNN1A-978 + GAAGGGUAAAGGUUCUCAAC 20 4827 SCNN1A-979 + CAGAGGACAGGUGGAGGAAC 20 4828 SCNN1A-980 + ACACCGAGGAGCCGAACCAC 20 4829 SCNN1A-981 AGGCAUCUCUCUGUACCCAC 20 4830 SCNN1A-982 + AGCCGAACCACAGGCUCCAC 20 4831 SCNN1A-983 GGGCCCGGGUAAUGGUGCAC 20 4832 SCNN1A-984 + CCGAUUUGUUCUGGUUGCAC 20 4833 SCNN1A-985 GGGUCCCGCCCCCGCCUCAC 20 4834 SCNN1A-986 + GAGUCUCUGGCAGCCUCGAC 20 4835 SCNN1A-987 + GGCCACGCUACGGGCUCGAC 20 4836 SCNN1A-988 CCCAGGUGGACUGGAAGGAC 20 4837 SCNN1A-989 + UCAGGGCCCCCCCAGAGGAC 20 4838 SCNN1A-990 ACAACAACCCCCAGGUGGAC 20 4839 SCNN1A-991 + ACUGGCUGCCCAGGUUGGAC 20 4840 SCNN1A-992 AGGAAGGCAAGGAUGCUGAC 20 4841 SCNN1A-993 CCCCUGCUGUCCACAGUGAC 20 4842 SCNN1A-994 GAAGGUUCCGAAGCCGAUAC 20 4843 SCNN1A-995 + CAAGCUGGAGGCCACGCUAC 20 4844 SCNN1A-996 GUGUCCCCUUCCCCGGGUAC 20 4845 SCNN1A-997 + UGAAGGAGCUGUAUUUGUAC 20 4846 SCNN1A-998 GGUCACCCUCCUGUCCAACC 20 4847 SCNN1A-999 CAACCAGGUCUCCUGCAACC 20 4848 SCNN1A-1000 + GGUCUGAGGAGAAGUCAACC 20 4849 SCNN1A-1001 CUUCGCCUGCCGCUUCAACC 20 4850 SCNN1A-1002 + AGCAGGAGUGAAUACACACC 20 4851 SCNN1A-1003 UGACUUCUCCUCAGACCACC 20 4852 SCNN1A-1004 + UCCAGUCCUUCCAGUCCACC 20 4853 SCNN1A-1005 + ACGCCUGGUUGCAGGAGACC 20 4854 SCNN1A-1006 + UCCCUUCCCCACACUCUACC 20 4855 SCNN1A-1007 CCCUCGCCCCUUCAGGUACC 20 4856 SCNN1A-1008 + CCUGCCCGUGCACCAUUACC 20 4857 SCNN1A-1009 UGUGGGUUCAUAGGAAACCC 20 4858 SCNN1A-1010 UCCCCCUGCCUAUGCCACCC 20 4859 SCNN1A-1011 UCAGGAGGUAGCCUCCACCC 20 4860 SCNN1A-1012 + CUGCCCGUGCACCAUUACCC 20 4861 SCNN1A-1013 + GCUCCCUGGAGUCUCACCCC 20 4862 SCNN1A-1014 CUUGCGGGACAACAACCCCC 20 4863 SCNN1A-1015 + CUGGCCCCUGCAGAGCCCCC 20 4864 SCNN1A-1016 AGGUUAGUGUCCCCUUCCCC 20 4865 SCNN1A-1017 + GGCACUUGGUGAAACAGCCC 20 4866 SCNN1A-1018 + CUGGAGAUGGGCGGGGGCCC 20 4867 SCNN1A-1019 GUCCACAGUGACUGGGGCCC 20 4868 SCNN1A-1020 ACAAGAGGUCAGUCCUGCCC 20 4869 SCNN1A-1021 + ACAGGCUCCACUGGCUGCCC 20 4870 SCNN1A-1022 AUGGCCCUCGGUGACAUCCC 20 4871 SCNN1A-1023 GCCAGAGACUCUGCCAUCCC 20 4872 SCNN1A-1024 CAGGUUAGUGUCCCCUUCCC 20 4873 SCNN1A-1025 UCUCUGUCCUUGUCCCAGCC 20 4874 SCNN1A-1026 + CUGAUGGAGGUCUCCACGCC 20 4875 SCNN1A-1027 + AGGCAGGACUGACUCACGCC 20 4876 SCNN1A-1028 AGGAUGCUGACUGGGAGGCC 20 4877 SCNN1A-1029 GGUGGCUUUAACUUGCGGCC 20 4878 SCNN1A-1030 + GCACCCCUGCCCCCUCGGCC 20 4879 SCNN1A-1031 + GCUGGAGAGGGAGCAGGGCC 20 4880 SCNN1A-1032 UGUCCACAGUGACUGGGGCC 20 4881 SCNN1A-1033 CUCUGGAUGUCUUCCAUGCC 20 4882 SCNN1A-1034 + GGGAAGGAGGGGAGGAUGCC 20 4883 SCNN1A-1035 AGGCGUGAGUCAGUCCUGCC 20 4884 SCNN1A-1036 CUGUCACGGUAGGUCGUGCC 20 4885 SCNN1A-1037 AGUUCCUGGGGUGAGACUCC 20 4886 SCNN1A-1038 + UGCCCAGCGUGUCCUCCUCC 20 4887 SCNN1A-1039 GUACUGCUACUAUAAGCUCC 20 4888 SCNN1A-1040 CUGGGCCCCCGCCCAUCUCC 20 4889 SCNN1A-1041 + ACUCCUUGAUCAUGCUCUCC 20 4890 SCNN1A-1042 CGAAGCCGAUACUGGUCUCC 20 4891 SCNN1A-1043 + AAUCGCCCCCAAGUCUGUCC 20 4892 SCNN1A-1044 + UUCUCACCGUUGUUGAUUCC 20 4893 SCNN1A-1045 UCUCCACCCUCCUCCCUUCC 20 4894 SCNN1A-1046 GUGUAUUCACUCCUGCUUCC 20 4895 SCNN1A-1047 ACUACAGAAAGCACAGUUCC 20 4896 SCNN1A-1048 + CCAGCUCCUCUUUAAUUUCC 20 4897 SCNN1A-1049 + GAGGGCGCCAUGGAGCAAGC 20 4898 SCNN1A-1050 + GGGGUUGUUGUCCCGCAAGC 20 4899 SCNN1A-1051 + GAUCAUGCUCUCCUGGAAGC 20 4900 SCNN1A-1052 CCCUUCAAAGUACACACAGC 20 4901 SCNN1A-1053 + CCCCAGUCACUGUGGACAGC 20 4902 SCNN1A-1054 + GCGCUGCGGGCCUCACCAGC 20 4903 SCNN1A-1055 + UGAGGAACAUGAUGACCAGC 20 4904 SCNN1A-1056 CUGGAAGAUCGGCUUCCAGC 20 4905 SCNN1A-1057 + GUGAGUAACCAGCAGAGAGC 20 4906 SCNN1A-1058 CCCGGAAAUUAAAGAGGAGC 20 4907 SCNN1A-1059 UAAAGAGGAGCUGGAGGAGC 20 4908 SCNN1A-1060 + GUCAAGGCUGGAGAGGGAGC 20 4909 SCNN1A-1061 + GUCGCGACGGCUGCGGGAGC 20 4910 SCNN1A-1062 + ACCAGCAGAGAGCUGGUAGC 20 4911 SCNN1A-1063 AUCCCUGGAGGAGGACACGC 20 4912 SCNN1A-1064 + GAGCUGGUAGCUGGUCACGC 20 4913 SCNN1A-1065 + GGUGCGGCAGAGUCCCCCGC 20 4914 SCNN1A-1066 + CCACCAUCAUCCAUAAAGGC 20 4915 SCNN1A-1067 + GGGGGAGGGGCUGUCAAGGC 20 4916 SCNN1A-1068 + CUCGACGGGCCCCGUGAGGC 20 4917 SCNN1A-1069 + GGGCCCAGGGUGGCAUAGGC 20 4918 SCNN1A-1070 + GGAGACCUGGUUGAAGCGGC 20 4919 SCNN1A-1071 + CUUGUGGCUGGGACCAGGGC 20 4920 SCNN1A-1072 CCGGGUAAUGGUGCACGGGC 20 4921 SCNN1A-1073 GGUCUCCAGGCCGAGGGGGC 20 4922 SCNN1A-1074 + GGGCCCCGUGAGGCGGGGGC 20 4923 SCNN1A-1075 + AGAGCCCCCUGGAGAUGGGC 20 4924 SCNN1A-1076 + GAGAGGGAGCAGGGCCUGGC 20 4925 SCNN1A-1077 UCCUUCACCACUCUCGUGGC 20 4926 SCNN1A-1078 CCAAGUGCCGGAAGCCAUGC 20 4927 SCNN1A-1079 CCGCAGCCGUCGCGACCUGC 20 4928 SCNN1A-1080 UGAGCUCGUCUUUGACCUGC 20 4929 SCNN1A-1081 + GGCGGGCCCCUCGGCGCUGC 20 4930 SCNN1A-1082 + CCGCAGGUCGCGACGGCUGC 20 4931 SCNN1A-1083 CCAUCUCCAGGGGGCUCUGC 20 4932 SCNN1A-1084 ACCAGCUACCAGCUCUCUGC 20 4933 SCNN1A-1085 UGGGCUGUUUCACCAAGUGC 20 4934 SCNN1A-1086 UAGCGUGGCCUCCAGCUUGC 20 4935 SCNN1A-1087 + ACUGACUCACGCCUGGUUGC 20 4936 SCNN1A-1088 + UAUAGCAGUUUCCAUACAUC 20 4937 SCNN1A-1089 + UCUGCUCUGCGCGCAGCAUC 20 4938 SCNN1A-1090 + UGUUCUGUCGCGAUAGCAUC 20 4939 SCNN1A-1091 UUCUACCAGACAUACUCAUC 20 4940 SCNN1A-1092 + AGUGAGAGUAAUUCCUUAUC 20 4941 SCNN1A-1093 ACAAGAACAACUCCAACCUC 20 4942 SCNN1A-1094 + GAGGCGGGGGCGGGACCCUC 20 4943 SCNN1A-1095 CAGUUCCUCCACCUGUCCUC 20 4944 SCNN1A-1096 CCGAGGGGGCAGGGGUGCUC 20 4945 SCNN1A-1097 + GAAACCUCUCCUUCCCUCUC 20 4946 SCNN1A-1098 + UCCAGGGAUGGCAGAGUCUC 20 4947 SCNN1A-1099 + GGGGCGAGGGGAAGAGGGUC 20 4948 SCNN1A-1100 + CCACCCCUGAUGAGUAUGUC 20 4949 SCNN1A-1101 CCUCUUCCCCUCGCCCCUUC 20 4950 SCNN1A-1102 + ACACUAACCUGCAUGGCUUC 20 4951 SCNN1A-1103 + AGUCACAGUACUCCACGUUC 20 4952 SCNN1A-1104 + AGAAGCAGUCCGAUUUGUUC 20 4953 SCNN1A-1105 + UCCAGCUCCUCUUUAAUUUC 20 4954 SCNN1A-1106 CAGGUACCCGGAAAUUAAAG 20 4955 SCNN1A-1107 AUUACACCGUCAACAACAAG 20 4956 SCNN1A-1108 + GGACCCUCAGGCGCUGCAAG 20 4957 SCNN1A-1109 + ACAUGGGGUGGGGGCAGAAG 20 4958 SCNN1A-1110 + CCUGAAGGGGCGAGGGGAAG 20 4959 SCNN1A-1111 + GGAUGUUGAUGUAGUGGAAG 20 4960 SCNN1A-1112 + UAAUUUCCGGGUACCUGAAG 20 4961 SCNN1A-1113 + UGCAGGAGACCUGGUUGAAG 20 4962 SCNN1A-1114 + GGCACGACCUACCGUGACAG 20 4963 SCNN1A-1115 + CCCUCUCAGGGCCCCCCCAG 20 4964 SCNN1A-1116 UGUCCAACCUGGGCAGCCAG 20 4965 SCNN1A-1117 + CAGGCAUGGAAGACAUCCAG 20 4966 SCNN1A-1118 GGGCCCCCGCCCAUCUCCAG 20 4967 SCNN1A-1119 + CCAGUCACUGUGGACAGCAG 20 4968 SCNN1A-1120 + GCCCAGGGUGGCAUAGGCAG 20 4969 SCNN1A-1121 UCUCCAGGCCGAGGGGGCAG 20 4970 SCNN1A-1122 + AUUUCUUAGGUGUGGGGCAG 20 4971 SCNN1A-1123 AUCUCCAGGGGGCUCUGCAG 20 4972 SCNN1A-1124 CUACCAGACAUACUCAUCAG 20 4973 SCNN1A-1125 + GACACAGAGACUAGAGUCAG 20 4974 SCNN1A-1126 + CACAGAGACUAGAGUCAGAG 20 4975 SCNN1A-1127 + GCGGGAGCCGGCCACGAGAG 20 4976 SCNN1A-1128 GUGAGGCCCGCAGCGCCGAG 20 4977 SCNN1A-1129 AUACUGGUCUCCAGGCCGAG 20 4978 SCNN1A-1130 + CGGGUACCUGAAGGGGCGAG 20 4979 SCNN1A-1131 GGGCCCUGAGAGGGAAGGAG 20 4980 SCNN1A-1132 + GGGGCAGAAGUGGGAAGGAG 20 4981 SCNN1A-1133 + GGGAGGAGGGUGGAGAGGAG 20 4982 SCNN1A-1134 + GUGACCAUCUGUGAGAGGAG 20 4983 SCNN1A-1135 GGGUGGAUGCGGUGAGGGAG 20 4984 SCNN1A-1136 + GGUGGCAUAGGCAGGGGGAG 20 4985 SCNN1A-1137 CCCACACCUAAGAAAUGGAG 20 4986 SCNN1A-1138 + AGGGGCUGUCAAGGCUGGAG 20 4987 SCNN1A-1139 + UGGAAGGGAGGAGGGUGGAG 20 4988 SCNN1A-1140 UCCUCUGGGGGGGCCCUGAG 20 4989 SCNN1A-1141 + GGAGGGUGACCAUCUGUGAG 20 4990 SCNN1A-1142 + AGCAUCAGGGACAGACCUAG 20 4991 SCNN1A-1143 + UCGACAGGAUGUUGAUGUAG 20 4992 SCNN1A-1144 CUAUCCGCGGCCCCAGAACG 20 4993 SCNN1A-1145 GGUCCCGCCCCCGCCUCACG 20 4994 SCNN1A-1146 + CUCCACCACAGACAACACCG 20 4995 SCNN1A-1147 + CUCUACCUGGGAUGUCACCG 20 4996 SCNN1A-1148 UGGUGAGGCCCGCAGCGCCG 20 4997 SCNN1A-1149 CGAUACUGGUCUCCAGGCCG 20 4998 SCNN1A-1150 + UACUCCACGUUCUGGGGCCG 20 4999 SCNN1A-1151 GUGCCUACAUCUUCUAUCCG 20 5000 SCNN1A-1152 UGAGGCCCAACCUGAUUCCG 20 5001 SCNN1A-1153 GGCCCGUCGAGCCCGUAGCG 20 5002 SCNN1A-1154 + UCGACGGGCCCCGUGAGGCG 20 5003 SCNN1A-1155 + UCCGGGUACCUGAAGGGGCG 20 5004 SCNN1A-1156 + GAGCCCCCUGGAGAUGGGCG 20 5005 SCNN1A-1157 CUUUAACUUGCGGCCUGGCG 20 5006 SCNN1A-1158 CGCAGCCGUCGCGACCUGCG 20 5007 SCNN1A-1159 CAGCUCCUUCACCACUCUCG 20 5008 SCNN1A-1160 ACUACAUCAACAUCCUGUCG 20 5009 SCNN1A-1161 + UGGGGGCAGAAGUGGGAAGG 20 5010 SCNN1A-1162 + GGGCCCCCCCAGAGGACAGG 20 5011 SCNN1A-1163 + GGCUGCCCAGGUUGGACAGG 20 5012 SCNN1A-1164 GCGGGACAACAACCCCCAGG 20 5013 SCNN1A-1165 + ACUUGGUGAAACAGCCCAGG 20 5014 SCNN1A-1166 GGCCCCCGCCCAUCUCCAGG 20 5015 SCNN1A-1167 + CCCAGGGUGGCAUAGGCAGG 20 5016 SCNN1A-1168 AGGGGGCAGGGGUGCUCAGG 20 5017 SCNN1A-1169 UACUGGUCUCCAGGCCGAGG 20 5018 SCNN1A-1170 + AUACACACCUGGAAGGGAGG 20 5019 SCNN1A-1171 GACUCUGCCAUCCCUGGAGG 20 5020 SCNN1A-1172 + GCUCGACGGGCCCCGUGAGG 20 5021 SCNN1A-1173 + CGACGGGCCCCGUGAGGCGG 20 5022 SCNN1A-1174 + AGCCCCCUGGAGAUGGGCGG 20 5023 SCNN1A-1175 GCAGCCGUCGCGACCUGCGG 20 5024 SCNN1A-1176 + UGAAUACACACCUGGAAGGG 20 5025 SCNN1A-1177 + AGAUGGGCGGGGGCCCAGGG 20 5026 SCNN1A-1178 + AGGAGGGGAGGAUGCCAGGG 20 5027 SCNN1A-1179 + CUUAGGUGUGGGGCAGAGGG 20 5028 SCNN1A-1180 + ACACCUGGAAGGGAGGAGGG 20 5029 SCNN1A-1181 + AGCAGUUUCCAUACAUCGGG 20 5030 SCNN1A-1182 CCAGACAUACUCAUCAGGGG 20 5031 SCNN1A-1183 + GCAGAAGUGGGAAGGAGGGG 20 5032 SCNN1A-1184 + AGGGUGGCAUAGGCAGGGGG 20 5033 SCNN1A-1185 + CGGGCCCCGUGAGGCGGGGG 20 5034 SCNN1A-1186 + ACAAGGACAGAGACAUGGGG 20 5035 SCNN1A-1187 CCUCCACCUGUCCUCUGGGG 20 5036 SCNN1A-1188 + CAGAGCCCCCUGGAGAUGGG 20 5037 SCNN1A-1189 GAGUGUGGGGAAGGGAUGGG 20 5038 SCNN1A-1190 AGGCAAGGAUGCUGACUGGG 20 5039 SCNN1A-1191 UCCUCCACCUGUCCUCUGGG 20 5040 SCNN1A-1192 + CCAUUCCUAGGAAAGAAUGG 20 5041 SCNN1A-1193 CCUGCCUUUAUGGAUGAUGG 20 5042 SCNN1A-1194 + UGCCUUCCUCAUGCUGAUGG 20 5043 SCNN1A-1195 + AGUCCUUCCAGUCCACCUGG 20 5044 SCNN1A-1196 AGAGACUCUGCCAUCCCUGG 20 5045 SCNN1A-1197 + GUUGUUGUCCCGCAAGCUGG 20 5046 SCNN1A-1198 GGAAAUUAAAGAGGAGCUGG 20 5047 SCNN1A-1199 UUCCUCCACCUGUCCUCUGG 20 5048 SCNN1A-1200 + CCCCCCCAGAGGACAGGUGG 20 5049 SCNN1A-1201 + AGGGGAGGAUGCCAGGGUGG 20 5050 SCNN1A-1202 + AGUUUCCAUACAUCGGGUGG 20 5051 SCNN1A-1203 + AGGACAGAGACAUGGGGUGG 20 5052 SCNN1A-1204 UGUGGGGAAGGGAUGGGUGG 20 5053 SCNN1A-1205 CUCCUCGGUGUUGUCUGUGG 20 5054 SCNN1A-1206 GAAACCCUGGACAGACUUGG 20 5055 SCNN1A-1207 + CCCAUUCCUAGGAAAGAAUG 20 5056 SCNN1A-1208 + GGGACAAGGACAGAGACAUG 20 5057 SCNN1A-1209 + GGAACCUUCGGAGCAGCAUG 20 5058 SCNN1A-1210 UGGAGACCUCCAUCAGCAUG 20 5059 SCNN1A-1211 AUACUCAUCAGGGGUGGAUG 20 5060 SCNN1A-1212 + AGAGCGUCUGCUCUGUGAUG 20 5061 SCNN1A-1213 + UACCCGGGCCCCAGUCACUG 20 5062 SCNN1A-1214 CCUGCUGUCCACAGUGACUG 20 5063 SCNN1A-1215 + CAGUCCUUCCAGUCCACCUG 20 5064 SCNN1A-1216 CCCGCAGCCGUCGCGACCUG 20 5065 SCNN1A-1217 + CUUAUAGUAGCAGUACCCUG 20 5066 SCNN1A-1218 UGGGCAGCCAGUGGAGCCUG 20 5067 SCNN1A-1219 CGCACCCCUUGCAGCGCCUG 20 5068 SCNN1A-1220 UACAGAAAGCACAGUUCCUG 20 5069 SCNN1A-1221 + GCUGGUAGCUGGUCACGCUG 20 5070 SCNN1A-1222 + GGGCGGGCCCCUCGGCGCUG 20 5071 SCNN1A-1223 + CCCGCAGGUCGCGACGGCUG 20 5072 SCNN1A-1224 GUUCCUCCACCUGUCCUCUG 20 5073 SCNN1A-1225 + GAAACAGCCCAGGUGGUCUG 20 5074 SCNN1A-1226 CGGCUCCUCGGUGUUGUCUG 20 5075 SCNN1A-1227 + UCACAGUACUCCACGUUCUG 20 5076 SCNN1A-1228 GUGACAUCCCAGGUAGAGUG 20 5077 SCNN1A-1229 GAGAGCAUGAUCAAGGAGUG 20 5078 SCNN1A-1230 + CGGGCUCGACGGGCCCCGUG 20 5079 SCNN1A-1231 CAAAGUACACACAGCAGGUG 20 5080 SCNN1A-1232 + GCCACUCCAUUUCUUAGGUG 20 5081 SCNN1A-1233 CAUCAGGGGUGGAUGCGGUG 20 5082 SCNN1A-1234 + CUCAGGCGCUGCAAGGGGUG 20 5083 SCNN1A-1235 + AAGGACAGAGACAUGGGGUG 20 5084 SCNN1A-1236 GUGUGGGGAAGGGAUGGGUG 20 5085 SCNN1A-1237 AGAUCGGCUUCCAGCUGGUG 20 5086 SCNN1A-1238 GACAUCCCAGGUAGAGUGUG 20 5087 SCNN1A-1239 + CACUCCAUUUCUUAGGUGUG 20 5088 SCNN1A-1240 AUGAUGGUGGCUUUAACUUG 20 5089 SCNN1A-1241 GGAAACCCUGGACAGACUUG 20 5090 SCNN1A-1242 GUAGCGUGGCCUCCAGCUUG 20 5091 SCNN1A-1243 CCAGUGCAACCAGAACAAAU 20 5092 SCNN1A-1244 + ACCCAUUCCUAGGAAAGAAU 20 5093 SCNN1A-1245 + GACAGAGGGAGACUCAGAAU 20 5094 SCNN1A-1246 CCCCAUUCUUUCCUAGGAAU 20 5095 SCNN1A-1247 + UGGGACAAGGACAGAGACAU 20 5096 SCNN1A-1248 + GUAUAGCAGUUUCCAUACAU 20 5097 SCNN1A-1249 + GCGGGGGCCCAGGGUGGCAU 20 5098 SCNN1A-1250 CUUGGUGUAUGUGGGUUCAU 20 5099 SCNN1A-1251 GACUGGAAGGACUGGAAGAU 20 5100 SCNN1A-1252 + CUGCAGAGCCCCCUGGAGAU 20 5101 SCNN1A-1253 + AGGAGAGGUACAUUGACGAU 20 5102 SCNN1A-1254 GUAGAGUGUGGGGAAGGGAU 20 5103 SCNN1A-1255 + CUCGGCCUGGAGACCAGUAU 20 5104 SCNN1A-1256 + CCUGCAUGGCUUCCGGCACU 20 5105 SCNN1A-1257 UAGGAAACCCUGGACAGACU 20 5106 SCNN1A-1258 GGAAGGCAAGGAUGCUGACU 20 5107 SCNN1A-1259 CCCUGCUGUCCACAGUGACU 20 5108 SCNN1A-1260 GUCACCCUCCUGUCCAACCU 20 5109 SCNN1A-1261 GACUUCUCCUCAGACCACCU 20 5110 SCNN1A-1262 + CCAGUCCUUCCAGUCCACCU 20 5111 SCNN1A-1263 + GCAGCAUCAGGGACAGACCU 20 5112 SCNN1A-1264 + CCCUUCCCCACACUCUACCU 20 5113 SCNN1A-1265 CCCCCUGCCUAUGCCACCCU 20 5114 SCNN1A-1266 UCUGCUCUCUCUGCACCCCU 20 5115 SCNN1A-1267 + CCUGAGCACCCCUGCCCCCU 20 5116 SCNN1A-1268 UGGUUACUCACGAUGGCCCU 20 5117 SCNN1A-1269 GAGCCUGUGGUUCGGCUCCU 20 5118 SCNN1A-1270 + CAUCUGGAAGACCCAUUCCU 20 5119 SCNN1A-1271 CUACAGAAAGCACAGUUCCU 20 5120 SCNN1A-1272 UGACACCCCCAUUCUUUCCU 20 5121 SCNN1A-1273 UCCCUGGAGGAGGACACGCU 20 5122 SCNN1A-1274 + AGCUGGUAGCUGGUCACGCU 20 5123 SCNN1A-1275 + AGAGGGAGCAGGGCCUGGCU 20 5124 SCNN1A-1276 AGUUCCUCCACCUGUCCUCU 20 5125 SCNN1A-1277 + AGGAACAUCACUGCCAUUCU 20 5126 SCNN1A-1278 + GUCACAGUACUCCACGUUCU 20 5127 SCNN1A-1279 + CAUGGGGUGGGGGCAGAAGU 20 5128 SCNN1A-1280 + GGGUGCAGAGAGAGCAGAGU 20 5129 SCNN1A-1281 + CUUAUCAGGAAAGAGAGAGU 20 5130 SCNN1A-1282 + GCUCCACUGGCUGCCCAGGU 20 5131 SCNN1A-1283 + UGGCUGCCACGGAAUCAGGU 20 5132 SCNN1A-1284 + CAUGGAAGACAUCCAGAGGU 20 5133 SCNN1A-1285 GAGUCUCCCUCUGUCACGGU 20 5134 SCNN1A-1286 + UUAGGUGUGGGGCAGAGGGU 20 5135 SCNN1A-1287 + CAAGGACAGAGACAUGGGGU 20 5136 SCNN1A-1288 AGUGUGGGGAAGGGAUGGGU 20 5137 SCNN1A-1289 + GGGCCGCGGAUAGAAGAUGU 20 5138 SCNN1A-1290 UCUGAUCUCUUGGUGUAUGU 20 5139 SCNN1A-1291 + UUAUAGUAGCAGUACCCUGU 20 5140 SCNN1A-1292 + UGGAGAAAGGUGCUCAGUGU 20 5141 SCNN1A-1293 UGACAUCCCAGGUAGAGUGU 20 5142 SCNN1A-1294 + CCACUCCAUUUCUUAGGUGU 20 5143 SCNN1A-1295 AGGAAACCCUGGACAGACUU 20 5144 SCNN1A-1296 + CUUGAAGAAGAUGUUGACUU 20 5145 SCNN1A-1297 + AGUAUCGGCUUCGGAACCUU 20 5146 SCNN1A-1298 + CUGGAGACCAGUAUCGGCUU 20 5147 SCNN1A-1299 + CUUUGGCCACUCCAUUUCUU 20 5148 SCNN1A-1300 + GGCUGCCACGGAAUCAGGUU 20 5149 SCNN1A-1301 AGCCAGUGGAGCCUGUGGUU 20 5150

Table 44A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 44A  1st Tier Target  gRNA Name DNA Strand Targeting Domain Site Length Seq ID SCNN1A-1302 + GGUUGAUGUUGAGGCUGA 18 5151 SCNN1A-42 + GAGGUUGAUGUUGAGGCUGA 20  519 SCNN1A-1303 + GUUGAGGUUGAUGUUGAGGCUGA 23 5152 SCNN1A-1304 + GCCCUCUCCCAUCACCCCUGGAAC 24 5153 SCNN1A-1305 + GUCAAGGCUGAGCUCUGGGCC 21 5154 SCNN1A-1306 + GGUCAAGGCUGAGCUCUGGGCC 22 5155 SCNN1A-1307 + GGGUCAAGGCUGAGCUCUGGGCC 23 5156 SCNN1A-1308 + GAGUGGAUUGGGGAGAGC 18 5157 SCNN1A-1309 + GGAGUGGAUUGGGGAGAGC 19 5158 SCNN1A-1310 + GCCCCGGAGUGGAUUGGGGAGAGC 24 5159 SCNN1A-1311 + GCCCUGGAGUGGACUGUGGAGGGC 24 5160 SCNN1A-1312 + GUAUGGGCUGCAGAGGUC 18 5161 SCNN1A-1313 + GGUAUGGGCUGCAGAGGUC 19 5162 SCNN1A-1314 + GACCUGGUAUGGGCUGCAGAGGUC 24 5163 SCNN1A-1315 + GAUACCUCCCCUUGGAAGGGACAG 24 5164 SCNN1A-1316 + GUGCUGGGAGCACACCAG 18 5165 SCNN1A-1317 + GUUGUGCUGGGAGCACACCAG 21 5166 SCNN1A-1318 + GGUUGUGCUGGGAGCACACCAG 22 5167 SCNN1A-1319 + GCGGUUGUGCUGGGAGCACACCAG 24 5168 SCNN1A-1320 + GUACUCUCCGAAAAGCAGG 19 5169 SCNN1A-1321 + GAAGUACUCUCCGAAAAGCAGG 22 5170 SCNN1A-1322 + GAUUGGGGAGAGCAAGGGU 19 5171 SCNN1A-1323 + GGAUUGGGGAGAGCAAGGGU 20 5172 SCNN1A-1324 + GUGGAUUGGGGAGAGCAAGGGU 22 5173 SCNN1A-1325 + GAGUGGAUUGGGGAGAGCAAGGGU 24 5174 SCNN1A-1326 + GAGGGACUAACCGACCUGU 19 5175 SCNN1A-1327 + GCAGAGGGACUAACCGACCUGU 22 5176 SCNN1A-1328 + GGCAGAGGGACUAACCGACCUGU 23 5177 SCNN1A-1329 + GGGCAGAGGGACUAACCGACCUGU 24 5178 SCNN1A-1330 + GCGGGGAAGACGAGCUUGU 19 5179 SCNN1A-1331 + GACUAACCGACCUGUAGGGAUU 22 5180 SCNN1A-1332 + GGACUAACCGACCUGUAGGGAUU 23 5181 SCNN1A-1333 + GGGACUAACCGACCUGUAGGGAUU 24 5182 SCNN1A-1334 GCGGAGGAGGAGGCCCUGA 19 5183 SCNN1A-189 GGCGGAGGAGGAGGCCCUGA 20  819 SCNN1A-1335 GGCCAGGGGCAGCCUCAC 18 5184 SCNN1A-1336 GCAGCCUCACUCGGGUUCC 19 5185 SCNN1A-348 GGCAGCCUCACUCGGGUUCC 20 4197 SCNN1A-197 GCAAUUCGGCCUGCUUUUCG 20  826 SCNN1A-1337 GGCAAUUCGGCCUGCUUUUCG 21 5186 SCNN1A-1338 GCUCCUACCGAGAGCUCU 18 5187 SCNN1A-437 GUAAGCAAGGGAACCUGGUU 20 4286 SCNN1A-1339 GGUAAGCAAGGGAACCUGGUU 21 5188

Table 44B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 44B 2nd Tier Target gRNA Name DNA Strand Targeting Domain Site Length Seq ID SCNN1A-1340 + AGGUUGAUGUUGAGGCUGA 19 5189 SCNN1A-1341 + UGAGGUUGAUGUUGAGGCUGA 21 5190 SCNN1A-1342 + UUGAGGUUGAUGUUGAGGCUGA 22 5191 SCNN1A-1343 + AGUUGAGGUUGAUGUUGAGGCUGA 24 5192 SCNN1A-1344 + UCCCAUCACCCCUGGAAC 18 5193 SCNN1A-1345 + CUCCCAUCACCCCUGGAAC 19 5194 SCNN1A-1346 + UCUCCCAUCACCCCUGGAAC 20 5195 SCNN1A-1347 + CUCUCCCAUCACCCCUGGAAC 21 5196 SCNN1A-1348 + CCUCUCCCAUCACCCCUGGAAC 22 5197 SCNN1A-1349 + CCCUCUCCCAUCACCCCUGGAAC 23 5198 SCNN1A-1350 + AAGGCUGAGCUCUGGGCC 18 5199 SCNN1A-1351 + CAAGGCUGAGCUCUGGGCC 19 5200 SCNN1A-1352 + UCAAGGCUGAGCUCUGGGCC 20 5201 SCNN1A-1353 + AGGGUCAAGGCUGAGCUCUGGGCC 24 5202 SCNN1A-1354 + CGGAGUGGAUUGGGGAGAGC 20 5203 SCNN1A-1355 + CCGGAGUGGAUUGGGGAGAGC 21 5204 SCNN1A-1356 + CCCGGAGUGGAUUGGGGAGAGC 22 5205 SCNN1A-1357 + CCCCGGAGUGGAUUGGGGAGAGC 23 5206 SCNN1A-1358 + CUGGAGUGGACUGUGGAGGGC 21 5207 SCNN1A-1359 + CCUGGAGUGGACUGUGGAGGGC 22 5208 SCNN1A-1360 + CCCUGGAGUGGACUGUGGAGGGC 23 5209 SCNN1A-1361 + UGGUAUGGGCUGCAGAGGUC 20 5210 SCNN1A-1362 + CUGGUAUGGGCUGCAGAGGUC 21 5211 SCNN1A-1363 + CCUGGUAUGGGCUGCAGAGGUC 22 5212 SCNN1A-1364 + ACCUGGUAUGGGCUGCAGAGGUC 23 5213 SCNN1A-1365 + UCCCCUUGGAAGGGACAG 18 5214 SCNN1A-1366 + CUCCCCUUGGAAGGGACAG 19 5215 SCNN1A-1367 + CCUCCCCUUGGAAGGGACAG 20 5216 SCNN1A-1368 + ACCUCCCCUUGGAAGGGACAG 21 5217 SCNN1A-1369 + UACCUCCCCUUGGAAGGGACAG 22 5218 SCNN1A-1370 + AUACCUCCCCUUGGAAGGGACAG 23 5219 SCNN1A-1371 + UGUGCUGGGAGCACACCAG 19 5220 SCNN1A-224 + UUGUGCUGGGAGCACACCAG 20  847 SCNN1A-1372 + CGGUUGUGCUGGGAGCACACCAG 23 5221 SCNN1A-1373 + UACUCUCCGAAAAGCAGG 18 5222 SCNN1A-230 + AGUACUCUCCGAAAAGCAGG 20  851 SCNN1A-1374 + AAGUACUCUCCGAAAAGCAGG 21 5223 SCNN1A-1375 + UGAAGUACUCUCCGAAAAGCAGG 23 5224 SCNN1A-1376 + CUGAAGUACUCUCCGAAAAGCAGG 24 5225 SCNN1A-1377 + AUUGGGGAGAGCAAGGGU 18 5226 SCNN1A-1378 + UGGAUUGGGGAGAGCAAGGGU 21 5227 SCNN1A-1379 + AGUGGAUUGGGGAGAGCAAGGGU 23 5228 SCNN1A-1380 + AGGGACUAACCGACCUGU 18 5229 SCNN1A-424 + AGAGGGACUAACCGACCUGU 20 4273 SCNN1A-1381 + CAGAGGGACUAACCGACCUGU 21 5230 SCNN1A-1382 + CGGGGAAGACGAGCUUGU 18 5231 SCNN1A-237 + UGCGGGGAAGACGAGCUUGU 20  857 SCNN1A-1383 + CUGCGGGGAAGACGAGCUUGU 21 5232 SCNN1A-1384 + ACUGCGGGGAAGACGAGCUUGU 22 5233 SCNN1A-1385 + CACUGCGGGGAAGACGAGCUUGU 23 5234 SCNN1A-1386 + UCACUGCGGGGAAGACGAGCUUGU 24 5235 SCNN1A-1387 + AACCGACCUGUAGGGAUU 18 5236 SCNN1A-1388 + UAACCGACCUGUAGGGAUU 19 5237 SCNN1A-1389 + CUAACCGACCUGUAGGGAUU 20 5238 SCNN1A-1390 + ACUAACCGACCUGUAGGGAUU 21 5239 SCNN1A-1391 CGGAGGAGGAGGCCCUGA 18 5240 SCNN1A-1392 UGGCCAGGGGCAGCCUCAC 19 5241 SCNN1A-1393 AUGGCCAGGGGCAGCCUCAC 20 5242 SCNN1A-1394 CAGCCUCACUCGGGUUCC 18 5243 SCNN1A-1395 AAUUCGGCCUGCUUUUCG 18 5244 SCNN1A-1396 CAAUUCGGCCUGCUUUUCG 19 5245 SCNN1A-1397 UGGCAAUUCGGCCUGCUUUUCG 22 5246 SCNN1A-1398 CUGGCAAUUCGGCCUGCUUUUCG 23 5247 SCNN1A-1399 ACUGGCAAUUCGGCCUGCUUUUCG 24 5248 SCNN1A-1400 CGCUCCUACCGAGAGCUCU 19 5249 SCNN1A-192 CCGCUCCUACCGAGAGCUCU 20  822 SCNN1A-1401 ACCGCUCCUACCGAGAGCUCU 21 5250 SCNN1A-1402 CACCGCUCCUACCGAGAGCUCU 22 5251 SCNN1A-1403 CCACCGCUCCUACCGAGAGCUCU 23 5252 SCNN1A-1404 UCCACCGCUCCUACCGAGAGCUCU 24 5253 SCNN1A-1405 AAGCAAGGGAACCUGGUU 18 5254 SCNN1A-1406 UAAGCAAGGGAACCUGGUU 19 5255 SCNN1A-1407 AGGUAAGCAAGGGAACCUGGUU 22 5256 SCNN1A-1408 AAGGUAAGCAAGGGAACCUGGUU 23 5257 SCNN1A-1409 CAAGGUAAGCAAGGGAACCUGGUU 24 5258

Table 44C provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 44C  3rd Tier Target gRNA Name DNA Strand Targeting Domain Site Length Seq ID SCNN1A-1410 + CCCUUCAUGAGCCCCGGA 18 5259 SCNN1A-1411 + CCCCUUCAUGAGCCCCGGA 19 5260 SCNN1A-1412 + UCCCCUUCAUGAGCCCCGGA 20 5261 SCNN1A-1413 + UUCCCCUUCAUGAGCCCCGGA 21 5262 SCNN1A-1414 + GUUCCCCUUCAUGAGCCCCGGA 22 5263 SCNN1A-1415 + UGUUCCCCUUCAUGAGCCCCGGA 23 5264 SCNN1A-1416 + UUGUUCCCCUUCAUGAGCCCCGGA 24 5265 SCNN1A-1417 + GUUCCCCUUCAUGAGCCC 18 5266 SCNN1A-1418 + UGUUCCCCUUCAUGAGCCC 19 5267 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20  599 SCNN1A-1419 + CUUGUUCCCCUUCAUGAGCCC 21 5268 SCNN1A-1420 + GCUUGUUCCCCUUCAUGAGCCC 22 5269 SCNN1A-1421 + AGCUUGUUCCCCUUCAUGAGCCC 23 5270 SCNN1A-1422 + CAGCUUGUUCCCCUUCAUGAGCCC 24 5271 SCNN1A-1423 + CGCUUGUUCCCCUUCAUGAGCCC 23 5272 SCNN1A-1424 + ACGCUUGUUCCCCUUCAUGAGCCC 24 5273 SCNN1A-1425 + CACCAGGCGGAUGGCGCC 18 5274 SCNN1A-1426 + ACACCAGGCGGAUGGCGCC 19 5275 SCNN1A-223 + CACACCAGGCGGAUGGCGCC 20  846 SCNN1A-1427 + GCACACCAGGCGGAUGGCGCC 21 5276 SCNN1A-1428 + AGCACACCAGGCGGAUGGCGCC 22 5277 SCNN1A-1429 + GAGCACACCAGGCGGAUGGCGCC 23 5278 SCNN1A-1430 + GGAGCACACCAGGCGGAUGGCGCC 24 5279 SCNN1A-1431 + GAGUGGACUGUGGAGGGC 18 5280 SCNN1A-1432 + GGAGUGGACUGUGGAGGGC 19 5281 SCNN1A-201 + UGGAGUGGACUGUGGAGGGC 20  830 SCNN1A-1433 CGGCGGAGGAGGAGGCCCUGA 21 5282 SCNN1A-1434 ACGGCGGAGGAGGAGGCCCUGA 22 5283 SCNN1A-1435 CACGGCGGAGGAGGAGGCCCUGA 23 5284 SCNN1A-1436 CCACGGCGGAGGAGGAGGCCCUGA 24 5285 SCNN1A-1437 CAUGGCCAGGGGCAGCCUCAC 21 5286 SCNN1A-1438 GCAUGGCCAGGGGCAGCCUCAC 22 5287 SCNN1A-1439 GGCAUGGCCAGGGGCAGCCUCAC 23 5288 SCNN1A-1440 GGGCAUGGCCAGGGGCAGCCUCAC 24 5289 SCNN1A-1441 GGGCAGCCUCACUCGGGUUCC 21 5290 SCNN1A-1442 GGGGCAGCCUCACUCGGGUUCC 22 5291 SCNN1A-1443 AGGGGCAGCCUCACUCGGGUUCC 23 5292 SCNN1A-1444 CAGGGGCAGCCUCACUCGGGUUCC 24 5293

Table 44D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 44D  4th Tier Target gRNA Name DNA Strand Targeting Domain Site Length Seq ID SCNN1A-1445 + AUCACCCCUGGAACCCGA 18 5294 SCNN1A-1446 + CAUCACCCCUGGAACCCGA 19 5295 SCNN1A-1447 + CCAUCACCCCUGGAACCCGA 20 5296 SCNN1A-1448 + CCCAUCACCCCUGGAACCCGA 21 5297 SCNN1A-1449 + UCCCAUCACCCCUGGAACCCGA 22 5298 SCNN1A-1450 + CUCCCAUCACCCCUGGAACCCGA 23 5299 SCNN1A-1451 + UCUCCCAUCACCCCUGGAACCCGA 24 5300 SCNN1A-1452 + CUAACCGACCUGUAGGGA 18 5301 SCNN1A-1453 + ACUAACCGACCUGUAGGGA 19 5302 SCNN1A-1454 + GACUAACCGACCUGUAGGGA 20 5303 SCNN1A-1455 + GGACUAACCGACCUGUAGGGA 21 5304 SCNN1A-1456 + GGGACUAACCGACCUGUAGGGA 22 5305 SCNN1A-1457 + AGGGACUAACCGACCUGUAGGGA 23 5306 SCNN1A-1458 + GAGGGACUAACCGACCUGUAGGGA 24 5307 SCNN1A-1459 + CCCUUCAUGAGCCCUGGA 18 5308 SCNN1A-1460 + CCCCUUCAUGAGCCCUGGA 19 5309 SCNN1A-205 + UCCCCUUCAUGAGCCCUGGA 20  833 SCNN1A-1461 + UUCCCCUUCAUGAGCCCUGGA 21 5310 SCNN1A-1462 + GUUCCCCUUCAUGAGCCCUGGA 22 5311 SCNN1A-1463 + UGUUCCCCUUCAUGAGCCCUGGA 23 5312 SCNN1A-1464 + UUGUUCCCCUUCAUGAGCCCUGGA 24 5313 SCNN1A-1465 + CAUGAGCCCCGGAGUGGA 18 5314 SCNN1A-1466 + UCAUGAGCCCCGGAGUGGA 19 5315 SCNN1A-1467 + UUCAUGAGCCCCGGAGUGGA 20 5316 SCNN1A-1468 + CUUCAUGAGCCCCGGAGUGGA 21 5317 SCNN1A-1469 + CCUUCAUGAGCCCCGGAGUGGA 22 5318 SCNN1A-1470 + CCCUUCAUGAGCCCCGGAGUGGA 23 5319 SCNN1A-1471 + CCCCUUCAUGAGCCCCGGAGUGGA 24 5320 SCNN1A-1472 + AUGAUACCUCCCCUUGGA 18 5321 SCNN1A-1473 + CAUGAUACCUCCCCUUGGA 19 5322 SCNN1A-399 + UCAUGAUACCUCCCCUUGGA 20 4248 SCNN1A-1474 + CUCAUGAUACCUCCCCUUGGA 21 5323 SCNN1A-1475 + GCUCAUGAUACCUCCCCUUGGA 22 5324 SCNN1A-1476 + UGCUCAUGAUACCUCCCCUUGGA 23 5325 SCNN1A-1477 + CUGCUCAUGAUACCUCCCCUUGGA 24 5326 SCNN1A-1478 + GUGUUGUUGCAGAAGAAC 18 5327 SCNN1A-1479 + GGUGUUGUUGCAGAAGAAC 19 5328 SCNN1A-220 + UGGUGUUGUUGCAGAAGAAC 20  843 SCNN1A-1480 + GUGGUGUUGUUGCAGAAGAAC 21 5329 SCNN1A-1481 + GGUGGUGUUGUUGCAGAAGAAC 22 5330 SCNN1A-1482 + UGGUGGUGUUGUUGCAGAAGAAC 23 5331 SCNN1A-1483 + AUGGUGGUGUUGUUGCAGAAGAAC 24 5332 SCNN1A-1484 + UGCCCUCUCCCAUCACCC 18 5333 SCNN1A-1485 + GUGCCCUCUCCCAUCACCC 19 5334 SCNN1A-1486 + AGUGCCCUCUCCCAUCACCC 20 5335 SCNN1A-1487 + GAGUGCCCUCUCCCAUCACCC 21 5336 SCNN1A-1488 + UGAGUGCCCUCUCCCAUCACCC 22 5337 SCNN1A-1489 + CUGAGUGCCCUCUCCCAUCACCC 23 5338 SCNN1A-1490 + CCUGAGUGCCCUCUCCCAUCACCC 24 5339 SCNN1A-1491 + GCCCUCUCCCAUCACCCC 18 5340 SCNN1A-1492 + UGCCCUCUCCCAUCACCCC 19 5341 SCNN1A-346 + GUGCCCUCUCCCAUCACCCC 20 4195 SCNN1A-1493 + AGUGCCCUCUCCCAUCACCCC 21 5342 SCNN1A-1494 + GAGUGCCCUCUCCCAUCACCCC 22 5343 SCNN1A-1495 + UGAGUGCCCUCUCCCAUCACCCC 23 5344 SCNN1A-1496 + CUGAGUGCCCUCUCCCAUCACCCC 24 5345 SCNN1A-1497 + UGCUCAUGAUACCUCCCC 18 5346 SCNN1A-1498 + CUGCUCAUGAUACCUCCCC 19 5347 SCNN1A-1499 + ACUGCUCAUGAUACCUCCCC 20 5348 SCNN1A-1500 + UACUGCUCAUGAUACCUCCCC 21 5349 SCNN1A-1501 + AUACUGCUCAUGAUACCUCCCC 22 5350 SCNN1A-1502 + GAUACUGCUCAUGAUACCUCCCC 23 5351 SCNN1A-1503 + UGAUACUGCUCAUGAUACCUCCCC 24 5352 SCNN1A-1504 + UGUUCCCCUUCAUGAGCC 18 5353 SCNN1A-1505 + UUGUUCCCCUUCAUGAGCC 19 5354 SCNN1A-207 + CUUGUUCCCCUUCAUGAGCC 20  834 SCNN1A-1506 + GCUUGUUCCCCUUCAUGAGCC 21 5355 SCNN1A-1507 + AGCUUGUUCCCCUUCAUGAGCC 22 5356 SCNN1A-1508 + CAGCUUGUUCCCCUUCAUGAGCC 23 5357 SCNN1A-1509 + CCAGCUUGUUCCCCUUCAUGAGCC 24 5358 SCNN1A-1510 + CGCUUGUUCCCCUUCAUGAGCC 22 5359 SCNN1A-1511 + ACGCUUGUUCCCCUUCAUGAGCC 23 5360 SCNN1A-1512 + CACGCUUGUUCCCCUUCAUGAGCC 24 5361 SCNN1A-1513 + AGGGCCUCCUCCUCCGCC 18 5362 SCNN1A-1514 + CAGGGCCUCCUCCUCCGCC 19 5363 SCNN1A-213 + UCAGGGCCUCCUCCUCCGCC 20  838 SCNN1A-1515 + AUCAGGGCCUCCUCCUCCGCC 21 5364 SCNN1A-1516 + GAUCAGGGCCUCCUCCUCCGCC 22 5365 SCNN1A-1517 + CGAUCAGGGCCUCCUCCUCCGCC 23 5366 SCNN1A-1518 + UCGAUCAGGGCCUCCUCCUCCGCC 24 5367 SCNN1A-1519 + CAGAGCCACAGCACUGCC 18 5368 SCNN1A-1520 + GCAGAGCCACAGCACUGCC 19 5369 SCNN1A-228 + UGCAGAGCCACAGCACUGCC 20  849 SCNN1A-1521 + GUGCAGAGCCACAGCACUGCC 21 5370 SCNN1A-1522 + GGUGCAGAGCCACAGCACUGCC 22 5371 SCNN1A-1523 + AGGUGCAGAGCCACAGCACUGCC 23 5372 SCNN1A-1524 + AAGGUGCAGAGCCACAGCACUGCC 24 5373 SCNN1A-1525 + UCCAGCUUGUUCCCCUCC 18 5374 SCNN1A-1526 + CUCCAGCUUGUUCCCCUCC 19 5375 SCNN1A-200 + CCUCCAGCUUGUUCCCCUCC 20  829 SCNN1A-1527 + UCCUCCAGCUUGUUCCCCUCC 21 5376 SCNN1A-1528 + CUCCUCCAGCUUGUUCCCCUCC 22 5377 SCNN1A-1529 + GCUCCUCCAGCUUGUUCCCCUCC 23 5378 SCNN1A-1530 + UGCUCCUCCAGCUUGUUCCCCUCC 24 5379 SCNN1A-1531 + GGUGCAGAUGGUCACUGC 18 5380 SCNN1A-1532 + GGGUGCAGAUGGUCACUGC 19 5381 SCNN1A-38 + AGGGUGCAGAUGGUCACUGC 20  575 SCNN1A-1533 + GAGGGUGCAGAUGGUCACUGC 21 5382 SCNN1A-1534 + UGAGGGUGCAGAUGGUCACUGC 22 5383 SCNN1A-1535 + UUGAGGGUGCAGAUGGUCACUGC 23 5384 SCNN1A-1536 + AUUGAGGGUGCAGAUGGUCACUGC 24 5385 SCNN1A-1537 + UCCUCCGCCGUGGGCUGC 18 5386 SCNN1A-1538 + CUCCUCCGCCGUGGGCUGC 19 5387 SCNN1A-65 + CCUCCUCCGCCGUGGGCUGC 20  594 SCNN1A-1539 + UCCUCCUCCGCCGUGGGCUGC 21 5388 SCNN1A-1540 + CUCCUCCUCCGCCGUGGGCUGC 22 5389 SCNN1A-1541 + CCUCCUCCUCCGCCGUGGGCUGC 23 5390 SCNN1A-1542 + GCCUCCUCCUCCGCCGUGGGCUGC 24 5391 SCNN1A-1543 + GUCUUCAUGCGGUUGUGC 18 5392 SCNN1A-1544 + CGUCUUCAUGCGGUUGUGC 19 5393 SCNN1A-49 + CCGUCUUCAUGCGGUUGUGC 20  582 SCNN1A-1545 + GCCGUCUUCAUGCGGUUGUGC 21 5394 SCNN1A-1546 + GGCCGUCUUCAUGCGGUUGUGC 22 5395 SCNN1A-1547 + AGGCCGUCUUCAUGCGGUUGUGC 23 5396 SCNN1A-1548 + AAGGCCGUCUUCAUGCGGUUGUGC 24 5397 SCNN1A-1549 + UCCAGCUUGUUCCCCUUC 18 5398 SCNN1A-1550 + CUCCAGCUUGUUCCCCUUC 19 5399 SCNN1A-1551 + CCUCCAGCUUGUUCCCCUUC 20 5400 SCNN1A-1552 + UCCUCCAGCUUGUUCCCCUUC 21 5401 SCNN1A-1553 + CUCCUCCAGCUUGUUCCCCUUC 22 5402 SCNN1A-1554 + GCUCCUCCAGCUUGUUCCCCUUC 23 5403 SCNN1A-1555 + UGCUCCUCCAGCUUGUUCCCCUUC 24 5404 SCNN1A-1556 + UCACGCUUGUUCCCCUUC 18 5405 SCNN1A-1557 + CUCACGCUUGUUCCCCUUC 19 5406 SCNN1A-208 + CCUCACGCUUGUUCCCCUUC 20  835 SCNN1A-1558 + UCCUCACGCUUGUUCCCCUUC 21 5407 SCNN1A-1559 + CUCCUCACGCUUGUUCCCCUUC 22 5408 SCNN1A-1560 + GCUCCUCACGCUUGUUCCCCUUC 23 5409 SCNN1A-1561 + UGCUCCUCACGCUUGUUCCCCUUC 24 5410 SCNN1A-1562 + AUGGUCACUGCGGGGAAG 18 5411 SCNN1A-1563 + GAUGGUCACUGCGGGGAAG 19 5412 SCNN1A-238 + AGAUGGUCACUGCGGGGAAG 20  858 SCNN1A-1564 + CAGAUGGUCACUGCGGGGAAG 21 5413 SCNN1A-1565 + GCAGAUGGUCACUGCGGGGAAG 22 5414 SCNN1A-1566 + UGCAGAUGGUCACUGCGGGGAAG 23 5415 SCNN1A-1567 + GUGCAGAUGGUCACUGCGGGGAAG 24 5416 SCNN1A-1568 + AUGGUGGUGUUGUUGCAG 18 5417 SCNN1A-1569 + GAUGGUGGUGUUGUUGCAG 19 5418 SCNN1A-221 + GGAUGGUGGUGUUGUUGCAG 20  844 SCNN1A-1570 + UGGAUGGUGGUGUUGUUGCAG 21 5419 SCNN1A-1571 + GUGGAUGGUGGUGUUGUUGCAG 22 5420 SCNN1A-1572 + CGUGGAUGGUGGUGUUGUUGCAG 23 5421 SCNN1A-1573 + CCGUGGAUGGUGGUGUUGUUGCAG 24 5422 SCNN1A-1574 + AAGACGAGCUUGUCCGAG 18 5423 SCNN1A-1575 + GAAGACGAGCUUGUCCGAG 19 5424 SCNN1A-236 + GGAAGACGAGCUUGUCCGAG 20  856 SCNN1A-1576 + GGGAAGACGAGCUUGUCCGAG 21 5425 SCNN1A-1577 + GGGGAAGACGAGCUUGUCCGAG 22 5426 SCNN1A-1578 + CGGGGAAGACGAGCUUGUCCGAG 23 5427 SCNN1A-1579 + GCGGGGAAGACGAGCUUGUCCGAG 24 5428 SCNN1A-1580 + UUGAGGCUGACGGGGUAG 18 5429 SCNN1A-1581 + GUUGAGGCUGACGGGGUAG 19 5430 SCNN1A-232 + UGUUGAGGCUGACGGGGUAG 20  853 SCNN1A-1582 + AUGUUGAGGCUGACGGGGUAG 21 5431 SCNN1A-1583 + GAUGUUGAGGCUGACGGGGUAG 22 5432 SCNN1A-1584 + UGAUGUUGAGGCUGACGGGGUAG 23 5433 SCNN1A-1585 + UUGAUGUUGAGGCUGACGGGGUAG 24 5434 SCNN1A-1586 + GAGCUCUCGGUAGGAGCG 18 5435 SCNN1A-1587 + AGAGCUCUCGGUAGGAGCG 19 5436 SCNN1A-216 + AAGAGCUCUCGGUAGGAGCG 20  840 SCNN1A-1588 + GAAGAGCUCUCGGUAGGAGCG 21 5437 SCNN1A-1589 + CGAAGAGCUCUCGGUAGGAGCG 22 5438 SCNN1A-1590 + UCGAAGAGCUCUCGGUAGGAGCG 23 5439 SCNN1A-1591 + CUCGAAGAGCUCUCGGUAGGAGCG 24 5440 SCNN1A-1592 + GUGCAGAUGGUCACUGCG 18 5441 SCNN1A-1593 + GGUGCAGAUGGUCACUGCG 19 5442 SCNN1A-39 + GGGUGCAGAUGGUCACUGCG 20  518 SCNN1A-1594 + AGGGUGCAGAUGGUCACUGCG 21 5443 SCNN1A-1595 + GAGGGUGCAGAUGGUCACUGCG 22 5444 SCNN1A-1596 + UGAGGGUGCAGAUGGUCACUGCG 23 5445 SCNN1A-1597 + UUGAGGGUGCAGAUGGUCACUGCG 24 5446 SCNN1A-1598 + UUGUUGCAGAAGAACUCG 18 5447 SCNN1A-1599 + GUUGUUGCAGAAGAACUCG 19 5448 SCNN1A-219 + UGUUGUUGCAGAAGAACUCG 20  842 SCNN1A-1600 + GUGUUGUUGCAGAAGAACUCG 21 5449 SCNN1A-1601 + GGUGUUGUUGCAGAAGAACUCG 22 5450 SCNN1A-1602 + UGGUGUUGUUGCAGAAGAACUCG 23 5451 SCNN1A-1603 + GUGGUGUUGUUGCAGAAGAACUCG 24 5452 SCNN1A-1604 + CAAGGGUCAGGGUCAAGG 18 5453 SCNN1A-1605 + GCAAGGGUCAGGGUCAAGG 19 5454 SCNN1A-1606 + AGCAAGGGUCAGGGUCAAGG 20 5455 SCNN1A-1607 + GAGCAAGGGUCAGGGUCAAGG 21 5456 SCNN1A-1608 + AGAGCAAGGGUCAGGGUCAAGG 22 5457 SCNN1A-1609 + GAGAGCAAGGGUCAGGGUCAAGG 23 5458 SCNN1A-1610 + GGAGAGCAAGGGUCAGGGUCAAGG 24 5459 SCNN1A-1611 + AGCUCUCGGUAGGAGCGG 18 5460 SCNN1A-1612 + GAGCUCUCGGUAGGAGCGG 19 5461 SCNN1A-60 + AGAGCUCUCGGUAGGAGCGG 20  590 SCNN1A-1613 + AAGAGCUCUCGGUAGGAGCGG 21 5462 SCNN1A-1614 + GAAGAGCUCUCGGUAGGAGCGG 22 5463 SCNN1A-1615 + CGAAGAGCUCUCGGUAGGAGCGG 23 5464 SCNN1A-1616 + UCGAAGAGCUCUCGGUAGGAGCGG 24 5465 SCNN1A-1617 + AACUCGAAGAGCUCUCGG 18 5466 SCNN1A-1618 + GAACUCGAAGAGCUCUCGG 19 5467 SCNN1A-218 + AGAACUCGAAGAGCUCUCGG 20  841 SCNN1A-1619 + AAGAACUCGAAGAGCUCUCGG 21 5468 SCNN1A-1620 + GAAGAACUCGAAGAGCUCUCGG 22 5469 SCNN1A-1621 + AGAAGAACUCGAAGAGCUCUCGG 23 5470 SCNN1A-1622 + CAGAAGAACUCGAAGAGCUCUCGG 24 5471 SCNN1A-1623 + GCCCCGGAGUGGAUUGGG 18 5472 SCNN1A-1624 + AGCCCCGGAGUGGAUUGGG 19 5473 SCNN1A-1625 + GAGCCCCGGAGUGGAUUGGG 20 5474 SCNN1A-1626 + UGAGCCCCGGAGUGGAUUGGG 21 5475 SCNN1A-1627 + AUGAGCCCCGGAGUGGAUUGGG 22 5476 SCNN1A-1628 + CAUGAGCCCCGGAGUGGAUUGGG 23 5477 SCNN1A-1629 + UCAUGAGCCCCGGAGUGGAUUGGG 24 5478 SCNN1A-1630 + CAUGAUACCUCCCCUUGG 18 5479 SCNN1A-1631 + UCAUGAUACCUCCCCUUGG 19 5480 SCNN1A-1632 + CUCAUGAUACCUCCCCUUGG 20 5481 SCNN1A-1633 + GCUCAUGAUACCUCCCCUUGG 21 5482 SCNN1A-1634 + UGCUCAUGAUACCUCCCCUUGG 22 5483 SCNN1A-1635 + CUGCUCAUGAUACCUCCCCUUGG 23 5484 SCNN1A-1636 + ACUGCUCAUGAUACCUCCCCUUGG 24 5485 SCNN1A-1637 + UCCGAGUUGAGGUUGAUG 18 5486 SCNN1A-1638 + GUCCGAGUUGAGGUUGAUG 19 5487 SCNN1A-235 + UGUCCGAGUUGAGGUUGAUG 20  855 SCNN1A-1639 + UUGUCCGAGUUGAGGUUGAUG 21 5488 SCNN1A-1640 + CUUGUCCGAGUUGAGGUUGAUG 22 5489 SCNN1A-1641 + GCUUGUCCGAGUUGAGGUUGAUG 23 5490 SCNN1A-1642 + AGCUUGUCCGAGUUGAGGUUGAUG 24 5491 SCNN1A-1643 + GGGUGCAGAUGGUCACUG 18 5492 SCNN1A-1644 + AGGGUGCAGAUGGUCACUG 19 5493 SCNN1A-37 + GAGGGUGCAGAUGGUCACUG 20  517 SCNN1A-1645 + UGAGGGUGCAGAUGGUCACUG 21 5494 SCNN1A-1646 + UUGAGGGUGCAGAUGGUCACUG 22 5495 SCNN1A-1647 + AUUGAGGGUGCAGAUGGUCACUG 23 5496 SCNN1A-1648 + GAUUGAGGGUGCAGAUGGUCACUG 24 5497 SCNN1A-1649 + GAGCCCUGGAGUGGACUG 18 5498 SCNN1A-1650 + UGAGCCCUGGAGUGGACUG 19 5499 SCNN1A-74 + AUGAGCCCUGGAGUGGACUG 20  601 SCNN1A-1651 + CAUGAGCCCUGGAGUGGACUG 21 5500 SCNN1A-1652 + UCAUGAGCCCUGGAGUGGACUG 22 5501 SCNN1A-1653 + UUCAUGAGCCCUGGAGUGGACUG 23 5502 SCNN1A-1654 + CUUCAUGAGCCCUGGAGUGGACUG 24 5503 SCNN1A-1655 + GAGGGACUAACCGACCUG 18 5504 SCNN1A-1656 + AGAGGGACUAACCGACCUG 19 5505 SCNN1A-1657 + CAGAGGGACUAACCGACCUG 20 5506 SCNN1A-1658 + GCAGAGGGACUAACCGACCUG 21 5507 SCNN1A-1659 + GGCAGAGGGACUAACCGACCUG 22 5508 SCNN1A-1660 + GGGCAGAGGGACUAACCGACCUG 23 5509 SCNN1A-1661 + GGGGCAGAGGGACUAACCGACCUG 24 5510 SCNN1A-1662 + AGGUUGAUGUUGAGGCUG 18 5511 SCNN1A-1663 + GAGGUUGAUGUUGAGGCUG 19 5512 SCNN1A-234 + UGAGGUUGAUGUUGAGGCUG 20  854 SCNN1A-1664 + UUGAGGUUGAUGUUGAGGCUG 21 5513 SCNN1A-1665 + GUUGAGGUUGAUGUUGAGGCUG 22 5514 SCNN1A-1666 + AGUUGAGGUUGAUGUUGAGGCUG 23 5515 SCNN1A-1667 + GAGUUGAGGUUGAUGUUGAGGCUG 24 5516 SCNN1A-1668 + GAGACCUGGUAUGGGCUG 18 5517 SCNN1A-1669 + UGAGACCUGGUAUGGGCUG 19 5518 SCNN1A-1670 + AUGAGACCUGGUAUGGGCUG 20 5519 SCNN1A-1671 + CAUGAGACCUGGUAUGGGCUG 21 5520 SCNN1A-1672 + CCAUGAGACCUGGUAUGGGCUG 22 5521 SCNN1A-1673 + UCCAUGAGACCUGGUAUGGGCUG 23 5522 SCNN1A-1674 + CUCCAUGAGACCUGGUAUGGGCUG 24 5523 SCNN1A-1675 + CUCCUCCGCCGUGGGCUG 18 5524 SCNN1A-1676 + CCUCCUCCGCCGUGGGCUG 19 5525 SCNN1A-212 + UCCUCCUCCGCCGUGGGCUG 20  837 SCNN1A-1677 + CUCCUCCUCCGCCGUGGGCUG 21 5526 SCNN1A-1678 + CCUCCUCCUCCGCCGUGGGCUG 22 5527 SCNN1A-1679 + GCCUCCUCCUCCGCCGUGGGCUG 23 5528 SCNN1A-1680 + GGCCUCCUCCUCCGCCGUGGGCUG 24 5529 SCNN1A-1681 + UACAUCAUGCCAAAGGUG 18 5530 SCNN1A-1682 + GUACAUCAUGCCAAAGGUG 19 5531 SCNN1A-229 + AGUACAUCAUGCCAAAGGUG 20  850 SCNN1A-1683 + CAGUACAUCAUGCCAAAGGUG 21 5532 SCNN1A-1684 + CCAGUACAUCAUGCCAAAGGUG 22 5533 SCNN1A-1685 + GCCAGUACAUCAUGCCAAAGGUG 23 5534 SCNN1A-1686 + UGCCAGUACAUCAUGCCAAAGGUG 24 5535 SCNN1A-1687 + GCCCUGGAGUGGACUGUG 18 5536 SCNN1A-1688 + AGCCCUGGAGUGGACUGUG 19 5537 SCNN1A-202 + GAGCCCUGGAGUGGACUGUG 20  831 SCNN1A-1689 + UGAGCCCUGGAGUGGACUGUG 21 5538 SCNN1A-1690 + AUGAGCCCUGGAGUGGACUGUG 22 5539 SCNN1A-1691 + CAUGAGCCCUGGAGUGGACUGUG 23 5540 SCNN1A-1692 + UCAUGAGCCCUGGAGUGGACUGUG 24 5541 SCNN1A-1693 + CGUCUUCAUGCGGUUGUG 18 5542 SCNN1A-1694 + CCGUCUUCAUGCGGUUGUG 19 5543 SCNN1A-227 + GCCGUCUUCAUGCGGUUGUG 20  848 SCNN1A-1695 + GGCCGUCUUCAUGCGGUUGUG 21 5544 SCNN1A-1696 + AGGCCGUCUUCAUGCGGUUGUG 22 5545 SCNN1A-1697 + AAGGCCGUCUUCAUGCGGUUGUG 23 5546 SCNN1A-1698 + GAAGGCCGUCUUCAUGCGGUUGUG 24 5547 SCNN1A-1699 + GAGCCCCGGAGUGGAUUG 18 5548 SCNN1A-1700 + UGAGCCCCGGAGUGGAUUG 19 5549 SCNN1A-419 + AUGAGCCCCGGAGUGGAUUG 20 4268 SCNN1A-1701 + CAUGAGCCCCGGAGUGGAUUG 21 5550 SCNN1A-1702 + UCAUGAGCCCCGGAGUGGAUUG 22 5551 SCNN1A-1703 + UUCAUGAGCCCCGGAGUGGAUUG 23 5552 SCNN1A-1704 + CUUCAUGAGCCCCGGAGUGGAUUG 24 5553 SCNN1A-1705 + UGGAUGGUGGUGUUGUUG 18 5554 SCNN1A-1706 + GUGGAUGGUGGUGUUGUUG 19 5555 SCNN1A-222 + CGUGGAUGGUGGUGUUGUUG 20  845 SCNN1A-1707 + CCGUGGAUGGUGGUGUUGUUG 21 5556 SCNN1A-1708 + GCCGUGGAUGGUGGUGUUGUUG 22 5557 SCNN1A-1709 + CGCCGUGGAUGGUGGUGUUGUUG 23 5558 SCNN1A-1710 + GCGCCGUGGAUGGUGGUGUUGUUG 24 5559 SCNN1A-1711 + GGAGCGGUGGAACUCGAU 18 5560 SCNN1A-1712 + AGGAGCGGUGGAACUCGAU 19 5561 SCNN1A-214 + UAGGAGCGGUGGAACUCGAU 20  839 SCNN1A-1713 + GUAGGAGCGGUGGAACUCGAU 21 5562 SCNN1A-1714 + GGUAGGAGCGGUGGAACUCGAU 22 5563 SCNN1A-1715 + CGGUAGGAGCGGUGGAACUCGAU 23 5564 SCNN1A-1716 + UCGGUAGGAGCGGUGGAACUCGAU 24 5565 SCNN1A-1717 + AUGAGCCCCGGAGUGGAU 18 5566 SCNN1A-1718 + CAUGAGCCCCGGAGUGGAU 19 5567 SCNN1A-420 + UCAUGAGCCCCGGAGUGGAU 20 4269 SCNN1A-1719 + UUCAUGAGCCCCGGAGUGGAU 21 5568 SCNN1A-1720 + CUUCAUGAGCCCCGGAGUGGAU 22 5569 SCNN1A-1721 + CCUUCAUGAGCCCCGGAGUGGAU 23 5570 SCNN1A-1722 + CCCUUCAUGAGCCCCGGAGUGGAU 24 5571 SCNN1A-1723 + AGGGUGCAGAUGGUCACU 18 5572 SCNN1A-1724 + GAGGGUGCAGAUGGUCACU 19 5573 SCNN1A-242 + UGAGGGUGCAGAUGGUCACU 20  859 SCNN1A-1725 + UUGAGGGUGCAGAUGGUCACU 21 5574 SCNN1A-1726 + AUUGAGGGUGCAGAUGGUCACU 22 5575 SCNN1A-1727 + GAUUGAGGGUGCAGAUGGUCACU 23 5576 SCNN1A-1728 + GGAUUGAGGGUGCAGAUGGUCACU 24 5577 SCNN1A-1729 + UGAGCCCUGGAGUGGACU 18 5578 SCNN1A-1730 + AUGAGCCCUGGAGUGGACU 19 5579 SCNN1A-204 + CAUGAGCCCUGGAGUGGACU 20  832 SCNN1A-1731 + UCAUGAGCCCUGGAGUGGACU 21 5580 SCNN1A-1732 + UUCAUGAGCCCUGGAGUGGACU 22 5581 SCNN1A-1733 + CUUCAUGAGCCCUGGAGUGGACU 23 5582 SCNN1A-1734 + CCUUCAUGAGCCCUGGAGUGGACU 24 5583 SCNN1A-1735 + GCUCAUGAUACCUCCCCU 18 5584 SCNN1A-1736 + UGCUCAUGAUACCUCCCCU 19 5585 SCNN1A-457 + CUGCUCAUGAUACCUCCCCU 20 4306 SCNN1A-1737 + ACUGCUCAUGAUACCUCCCCU 21 5586 SCNN1A-1738 + UACUGCUCAUGAUACCUCCCCU 22 5587 SCNN1A-1739 + AUACUGCUCAUGAUACCUCCCCU 23 5588 SCNN1A-1740 + GAUACUGCUCAUGAUACCUCCCCU 24 5589 SCNN1A-1741 + CAGGGUCAAGGCUGAGCU 18 5590 SCNN1A-1742 + UCAGGGUCAAGGCUGAGCU 19 5591 SCNN1A-1743 + GUCAGGGUCAAGGCUGAGCU 20 5592 SCNN1A-1744 + GGUCAGGGUCAAGGCUGAGCU 21 5593 SCNN1A-1745 + GGGUCAGGGUCAAGGCUGAGCU 22 5594 SCNN1A-1746 + AGGGUCAGGGUCAAGGCUGAGCU 23 5595 SCNN1A-1747 + AAGGGUCAGGGUCAAGGCUGAGCU 24 5596 SCNN1A-1748 + UCUUCAUGCGGUUGUGCU 18 5597 SCNN1A-1749 + GUCUUCAUGCGGUUGUGCU 19 5598 SCNN1A-50 + CGUCUUCAUGCGGUUGUGCU 20  583 SCNN1A-1750 + CCGUCUUCAUGCGGUUGUGCU 21 5599 SCNN1A-1751 + GCCGUCUUCAUGCGGUUGUGCU 22 5600 SCNN1A-1752 + GGCCGUCUUCAUGCGGUUGUGCU 23 5601 SCNN1A-1753 + AGGCCGUCUUCAUGCGGUUGUGCU 24 5602 SCNN1A-1754 + GGGUAGCUGAAGUACUCU 18 5603 SCNN1A-1755 + GGGGUAGCUGAAGUACUCU 19 5604 SCNN1A-231 + CGGGGUAGCUGAAGUACUCU 20  852 SCNN1A-1756 + ACGGGGUAGCUGAAGUACUCU 21 5605 SCNN1A-1757 + GACGGGGUAGCUGAAGUACUCU 22 5606 SCNN1A-1758 + UGACGGGGUAGCUGAAGUACUCU 23 5607 SCNN1A-1759 + CUGACGGGGUAGCUGAAGUACUCU 24 5608 SCNN1A-1760 + UGCUGGGGCGCCGCAGGU 18 5609 SCNN1A-1761 + CUGCUGGGGCGCCGCAGGU 19 5610 SCNN1A-210 + GCUGCUGGGGCGCCGCAGGU 20  836 SCNN1A-1762 + GGCUGCUGGGGCGCCGCAGGU 21 5611 SCNN1A-1763 + GGGCUGCUGGGGCGCCGCAGGU 22 5612 SCNN1A-1764 + UGGGCUGCUGGGGCGCCGCAGGU 23 5613 SCNN1A-1765 + GUGGGCUGCUGGGGCGCCGCAGGU 24 5614 SCNN1A-1766 + ACUCGAAGAGCUCUCGGU 18 5615 SCNN1A-1767 + AACUCGAAGAGCUCUCGGU 19 5616 SCNN1A-58 + GAACUCGAAGAGCUCUCGGU 20  524 SCNN1A-1768 + AGAACUCGAAGAGCUCUCGGU 21 5617 SCNN1A-1769 + AAGAACUCGAAGAGCUCUCGGU 22 5618 SCNN1A-1770 + GAAGAACUCGAAGAGCUCUCGGU 23 5619 SCNN1A-1771 + AGAAGAACUCGAAGAGCUCUCGGU 24 5620 SCNN1A-1772 + CCCUCCAUGAGACCUGGU 18 5621 SCNN1A-1773 + CCCCUCCAUGAGACCUGGU 19 5622 SCNN1A-199 + UCCCCUCCAUGAGACCUGGU 20  828 SCNN1A-1774 + UUCCCCUCCAUGAGACCUGGU 21 5623 SCNN1A-1775 + GUUCCCCUCCAUGAGACCUGGU 22 5624 SCNN1A-1776 + UGUUCCCCUCCAUGAGACCUGGU 23 5625 SCNN1A-1777 + UUGUUCCCCUCCAUGAGACCUGGU 24 5626 SCNN1A-1778 + UGAGCCCCGGAGUGGAUU 18 5627 SCNN1A-1779 + AUGAGCCCCGGAGUGGAUU 19 5628 SCNN1A-425 + CAUGAGCCCCGGAGUGGAUU 20 4274 SCNN1A-1780 + UCAUGAGCCCCGGAGUGGAUU 21 5629 SCNN1A-1781 + UUCAUGAGCCCCGGAGUGGAUU 22 5630 SCNN1A-1782 + CUUCAUGAGCCCCGGAGUGGAUU 23 5631 SCNN1A-1783 + CCUUCAUGAGCCCCGGAGUGGAUU 24 5632 SCNN1A-1784 + GCUGGGGCGCCGCAGGUU 18 5633 SCNN1A-1785 + UGCUGGGGCGCCGCAGGUU 19 5634 SCNN1A-69 + CUGCUGGGGCGCCGCAGGUU 20  597 SCNN1A-1786 + GCUGCUGGGGCGCCGCAGGUU 21 5635 SCNN1A-1787 + GGCUGCUGGGGCGCCGCAGGUU 22 5636 SCNN1A-1788 + GGGCUGCUGGGGCGCCGCAGGUU 23 5637 SCNN1A-1789 + UGGGCUGCUGGGGCGCCGCAGGUU 24 5638 SCNN1A-1790 CAGUAUCAAGGUAAGCAA 18 5639 SCNN1A-1791 GCAGUAUCAAGGUAAGCAA 19 5640 SCNN1A-393 AGCAGUAUCAAGGUAAGCAA 20 4242 SCNN1A-1792 GAGCAGUAUCAAGGUAAGCAA 21 5641 SCNN1A-1793 UGAGCAGUAUCAAGGUAAGCAA 22 5642 SCNN1A-1794 AUGAGCAGUAUCAAGGUAAGCAA 23 5643 SCNN1A-1795 CAUGAGCAGUAUCAAGGUAAGCAA 24 5644 SCNN1A-1796 CACUCCAGGGCUCAUGAA 18 5645 SCNN1A-1797 CCACUCCAGGGCUCAUGAA 19 5646 SCNN1A-11 UCCACUCCAGGGCUCAUGAA 20  560 SCNN1A-1798 GUCCACUCCAGGGCUCAUGAA 21 5647 SCNN1A-1799 AGUCCACUCCAGGGCUCAUGAA 22 5648 SCNN1A-1800 CAGUCCACUCCAGGGCUCAUGAA 23 5649 SCNN1A-1801 ACAGUCCACUCCAGGGCUCAUGAA 24 5650 SCNN1A-1802 CACUCCGGGGCUCAUGAA 18 5651 SCNN1A-1803 CCACUCCGGGGCUCAUGAA 19 5652 SCNN1A-451 UCCACUCCGGGGCUCAUGAA 20 4300 SCNN1A-1804 AUCCACUCCGGGGCUCAUGAA 21 5653 SCNN1A-1805 AAUCCACUCCGGGGCUCAUGAA 22 5654 SCNN1A-1806 CAAUCCACUCCGGGGCUCAUGAA 23 5655 SCNN1A-1807 CCAAUCCACUCCGGGGCUCAUGAA 24 5656 SCNN1A-1808 GCAGUAUCAAGGUAAGCA 18 5657 SCNN1A-1809 AGCAGUAUCAAGGUAAGCA 19 5658 SCNN1A-342 GAGCAGUAUCAAGGUAAGCA 20 4191 SCNN1A-1810 UGAGCAGUAUCAAGGUAAGCA 21 5659 SCNN1A-1811 AUGAGCAGUAUCAAGGUAAGCA 22 5660 SCNN1A-1812 CAUGAGCAGUAUCAAGGUAAGCA 23 5661 SCNN1A-1813 UCAUGAGCAGUAUCAAGGUAAGCA 24 5662 SCNN1A-1814 AGCCCAUACCAGGUCUCA 18 5663 SCNN1A-1815 CAGCCCAUACCAGGUCUCA 19 5664 SCNN1A-1 GCAGCCCAUACCAGGUCUCA 20  503 SCNN1A-1816 UGCAGCCCAUACCAGGUCUCA 21 5665 SCNN1A-1817 CUGCAGCCCAUACCAGGUCUCA 22 5666 SCNN1A-1818 UCUGCAGCCCAUACCAGGUCUCA 23 5667 SCNN1A-1819 CUCUGCAGCCCAUACCAGGUCUCA 24 5668 SCNN1A-1820 GUUCCAGGGGUGAUGGGA 18 5669 SCNN1A-1821 GGUUCCAGGGGUGAUGGGA 19 5670 SCNN1A-1822 GGGUUCCAGGGGUGAUGGGA 20 5671 SCNN1A-1823 CGGGUUCCAGGGGUGAUGGGA 21 5672 SCNN1A-1824 UCGGGUUCCAGGGGUGAUGGGA 22 5673 SCNN1A-1825 CUCGGGUUCCAGGGGUGAUGGGA 23 5674 SCNN1A-1826 ACUCGGGUUCCAGGGGUGAUGGGA 24 5675 SCNN1A-1827 CAUACCAGGUCUCAUGGA 18 5676 SCNN1A-1828 CCAUACCAGGUCUCAUGGA 19 5677 SCNN1A-3 CCCAUACCAGGUCUCAUGGA 20  556 SCNN1A-1829 GCCCAUACCAGGUCUCAUGGA 21 5678 SCNN1A-1830 AGCCCAUACCAGGUCUCAUGGA 22 5679 SCNN1A-1831 CAGCCCAUACCAGGUCUCAUGGA 23 5680 SCNN1A-1832 GCAGCCCAUACCAGGUCUCAUGGA 24 5681 SCNN1A-1833 CCACUCCAGGGCUCAUGA 18 5682 SCNN1A-1834 UCCACUCCAGGGCUCAUGA 19 5683 SCNN1A-10 GUCCACUCCAGGGCUCAUGA 20  505 SCNN1A-1835 AGUCCACUCCAGGGCUCAUGA 21 5684 SCNN1A-1836 CAGUCCACUCCAGGGCUCAUGA 22 5685 SCNN1A-1837 ACAGUCCACUCCAGGGCUCAUGA 23 5686 SCNN1A-1838 CACAGUCCACUCCAGGGCUCAUGA 24 5687 SCNN1A-1839 CCACUCCGGGGCUCAUGA 18 5688 SCNN1A-1840 UCCACUCCGGGGCUCAUGA 19 5689 SCNN1A-400 AUCCACUCCGGGGCUCAUGA 20 4249 SCNN1A-1841 AAUCCACUCCGGGGCUCAUGA 21 5690 SCNN1A-1842 CAAUCCACUCCGGGGCUCAUGA 22 5691 SCNN1A-1843 CCAAUCCACUCCGGGGCUCAUGA 23 5692 SCNN1A-1844 CCCAAUCCACUCCGGGGCUCAUGA 24 5693 SCNN1A-1845 CUCGGGUUCCAGGGGUGA 18 5694 SCNN1A-1846 ACUCGGGUUCCAGGGGUGA 19 5695 SCNN1A-401 CACUCGGGUUCCAGGGGUGA 20 4250 SCNN1A-1847 UCACUCGGGUUCCAGGGGUGA 21 5696 SCNN1A-1848 CUCACUCGGGUUCCAGGGGUGA 22 5697 SCNN1A-1849 CCUCACUCGGGUUCCAGGGGUGA 23 5698 SCNN1A-1850 GCCUCACUCGGGUUCCAGGGGUGA 24 5699 SCNN1A-1851 CGAGUUCCACCGCUCCUA 18 5700 SCNN1A-1852 UCGAGUUCCACCGCUCCUA 19 5701 SCNN1A-190 AUCGAGUUCCACCGCUCCUA 20  820 SCNN1A-1853 GAUCGAGUUCCACCGCUCCUA 21 5702 SCNN1A-1854 UGAUCGAGUUCCACCGCUCCUA 22 5703 SCNN1A-1855 CUGAUCGAGUUCCACCGCUCCUA 23 5704 SCNN1A-1856 CCUGAUCGAGUUCCACCGCUCCUA 24 5705 SCNN1A-1857 CUCAACAUCAACCUCAAC 18 5706 SCNN1A-1858 CCUCAACAUCAACCUCAAC 19 5707 SCNN1A-198 GCCUCAACAUCAACCUCAAC 20  827 SCNN1A-1859 AGCCUCAACAUCAACCUCAAC 21 5708 SCNN1A-1860 CAGCCUCAACAUCAACCUCAAC 22 5709 SCNN1A-1861 UCAGCCUCAACAUCAACCUCAAC 23 5710 SCNN1A-1862 GUCAGCCUCAACAUCAACCUCAAC 24 5711 SCNN1A-1863 GUGGGCGCAGGGUGGGAC 18 5712 SCNN1A-1864 UGUGGGCGCAGGGUGGGAC 19 5713 SCNN1A-1865 AUGUGGGCGCAGGGUGGGAC 20 5714 SCNN1A-1866 AAUGUGGGCGCAGGGUGGGAC 21 5715 SCNN1A-1867 GAAUGUGGGCGCAGGGUGGGAC 22 5716 SCNN1A-1868 AGAAUGUGGGCGCAGGGUGGGAC 23 5717 SCNN1A-1869 GAGAAUGUGGGCGCAGGGUGGGAC 24 5718 SCNN1A-1870 AGUUCCACCGCUCCUACC 18 5719 SCNN1A-1871 GAGUUCCACCGCUCCUACC 19 5720 SCNN1A-191 CGAGUUCCACCGCUCCUACC 20  821 SCNN1A-1872 UCGAGUUCCACCGCUCCUACC 21 5721 SCNN1A-1873 AUCGAGUUCCACCGCUCCUACC 22 5722 SCNN1A-1874 GAUCGAGUUCCACCGCUCCUACC 23 5723 SCNN1A-1875 UGAUCGAGUUCCACCGCUCCUACC 24 5724 SCNN1A-1876 GAGAGGGCACUCAGGGCC 18 5725 SCNN1A-1877 GGAGAGGGCACUCAGGGCC 19 5726 SCNN1A-1878 GGGAGAGGGCACUCAGGGCC 20 5727 SCNN1A-1879 UGGGAGAGGGCACUCAGGGCC 21 5728 SCNN1A-1880 AUGGGAGAGGGCACUCAGGGCC 22 5729 SCNN1A-1881 GAUGGGAGAGGGCACUCAGGGCC 23 5730 SCNN1A-1882 UGAUGGGAGAGGGCACUCAGGGCC 24 5731 SCNN1A-1883 AGGAGCAGGGGCUGGGCC 18 5732 SCNN1A-1884 GAGGAGCAGGGGCUGGGCC 19 5733 SCNN1A-182 UGAGGAGCAGGGGCUGGGCC 20  815 SCNN1A-1885 GUGAGGAGCAGGGGCUGGGCC 21 5734 SCNN1A-1886 CGUGAGGAGCAGGGGCUGGGCC 22 5735 SCNN1A-1887 GCGUGAGGAGCAGGGGCUGGGCC 23 5736 SCNN1A-1888 AGCGUGAGGAGCAGGGGCUGGGCC 24 5737 SCNN1A-1889 UGGGACAUGGGCAUGGCC 18 5738 SCNN1A-1890 GUGGGACAUGGGCAUGGCC 19 5739 SCNN1A-347 GGUGGGACAUGGGCAUGGCC 20 4196 SCNN1A-1891 GGGUGGGACAUGGGCAUGGCC 21 5740 SCNN1A-1892 AGGGUGGGACAUGGGCAUGGCC 22 5741 SCNN1A-1893 CAGGGUGGGACAUGGGCAUGGCC 23 5742 SCNN1A-1894 GCAGGGUGGGACAUGGGCAUGGCC 24 5743 SCNN1A-1895 UCAUGAAGGGGAACAAGC 18 5744 SCNN1A-1896 CUCAUGAAGGGGAACAAGC 19 5745 SCNN1A-176 GCUCAUGAAGGGGAACAAGC 20  811 SCNN1A-1897 GGCUCAUGAAGGGGAACAAGC 21 5746 SCNN1A-1898 GGGCUCAUGAAGGGGAACAAGC 22 5747 SCNN1A-1899 AGGGCUCAUGAAGGGGAACAAGC 23 5748 SCNN1A-1900 CAGGGCUCAUGAAGGGGAACAAGC 24 5749 SCNN1A-1901 GGGGCUCAUGAAGGGGAACAAGC 23 5750 SCNN1A-1902 CGGGGCUCAUGAAGGGGAACAAGC 24 5751 SCNN1A-1903 UCAUGGAGGGGAACAAGC 18 5752 SCNN1A-1904 CUCAUGGAGGGGAACAAGC 19 5753 SCNN1A-5 UCUCAUGGAGGGGAACAAGC 20  557 SCNN1A-1905 GUCUCAUGGAGGGGAACAAGC 21 5754 SCNN1A-1906 GGUCUCAUGGAGGGGAACAAGC 22 5755 SCNN1A-1907 AGGUCUCAUGGAGGGGAACAAGC 23 5756 SCNN1A-1908 CAGGUCUCAUGGAGGGGAACAAGC 24 5757 SCNN1A-1909 AGCAGUAUCAAGGUAAGC 18 5758 SCNN1A-1910 GAGCAGUAUCAAGGUAAGC 19 5759 SCNN1A-1911 UGAGCAGUAUCAAGGUAAGC 20 5760 SCNN1A-1912 AUGAGCAGUAUCAAGGUAAGC 21 5761 SCNN1A-1913 CAUGAGCAGUAUCAAGGUAAGC 22 5762 SCNN1A-1914 UCAUGAGCAGUAUCAAGGUAAGC 23 5763 SCNN1A-1915 AUCAUGAGCAGUAUCAAGGUAAGC 24 5764 SCNN1A-1916 GGAACAAGCGUGAGGAGC 18 5765 SCNN1A-1917 GGGAACAAGCGUGAGGAGC 19 5766 SCNN1A-14 GGGGAACAAGCGUGAGGAGC 20  506 SCNN1A-1918 AGGGGAACAAGCGUGAGGAGC 21 5767 SCNN1A-1919 AAGGGGAACAAGCGUGAGGAGC 22 5768 SCNN1A-1920 GAAGGGGAACAAGCGUGAGGAGC 23 5769 SCNN1A-1921 UGAAGGGGAACAAGCGUGAGGAGC 24 5770 SCNN1A-1922 UGCUCCCAGCACAACCGC 18 5771 SCNN1A-1923 GUGCUCCCAGCACAACCGC 19 5772 SCNN1A-193 UGUGCUCCCAGCACAACCGC 20  823 SCNN1A-1924 GUGUGCUCCCAGCACAACCGC 21 5773 SCNN1A-1925 GGUGUGCUCCCAGCACAACCGC 22 5774 SCNN1A-1926 UGGUGUGCUCCCAGCACAACCGC 23 5775 SCNN1A-1927 CUGGUGUGCUCCCAGCACAACCGC 24 5776 SCNN1A-1928 GUGGGACAUGGGCAUGGC 18 5777 SCNN1A-1929 GGUGGGACAUGGGCAUGGC 19 5778 SCNN1A-1930 GGGUGGGACAUGGGCAUGGC 20 5779 SCNN1A-1931 AGGGUGGGACAUGGGCAUGGC 21 5780 SCNN1A-1932 CAGGGUGGGACAUGGGCAUGGC 22 5781 SCNN1A-1933 GCAGGGUGGGACAUGGGCAUGGC 23 5782 SCNN1A-1934 CGCAGGGUGGGACAUGGGCAUGGC 24 5783 SCNN1A-1935 CUUCCAAGGGGAGGUAUC 18 5784 SCNN1A-1936 CCUUCCAAGGGGAGGUAUC 19 5785 SCNN1A-1937 CCCUUCCAAGGGGAGGUAUC 20 5786 SCNN1A-1938 UCCCUUCCAAGGGGAGGUAUC 21 5787 SCNN1A-1939 GUCCCUUCCAAGGGGAGGUAUC 22 5788 SCNN1A-1940 UGUCCCUUCCAAGGGGAGGUAUC 23 5789 SCNN1A-1941 CUGUCCCUUCCAAGGGGAGGUAUC 24 5790 SCNN1A-1942 GCUCUCCCCAAUCCACUC 18 5791 SCNN1A-1943 UGCUCUCCCCAAUCCACUC 19 5792 SCNN1A-410 UUGCUCUCCCCAAUCCACUC 20 4259 SCNN1A-1944 CUUGCUCUCCCCAAUCCACUC 21 5793 SCNN1A-1945 CCUUGCUCUCCCCAAUCCACUC 22 5794 SCNN1A-1946 CCCUUGCUCUCCCCAAUCCACUC 23 5795 SCNN1A-1947 ACCCUUGCUCUCCCCAAUCCACUC 24 5796 SCNN1A-1948 GCCCUCCACAGUCCACUC 18 5797 SCNN1A-1949 AGCCCUCCACAGUCCACUC 19 5798 SCNN1A-170 UAGCCCUCCACAGUCCACUC 20  808 SCNN1A-1950 CUAGCCCUCCACAGUCCACUC 21 5799 SCNN1A-1951 UCUAGCCCUCCACAGUCCACUC 22 5800 SCNN1A-1952 CUCUAGCCCUCCACAGUCCACUC 23 5801 SCNN1A-1953 ACUCUAGCCCUCCACAGUCCACUC 24 5802 SCNN1A-1954 CAGUCCACUCCAGGGCUC 18 5803 SCNN1A-1955 ACAGUCCACUCCAGGGCUC 19 5804 SCNN1A-171 CACAGUCCACUCCAGGGCUC 20  809 SCNN1A-1956 CCACAGUCCACUCCAGGGCUC 21 5805 SCNN1A-1957 UCCACAGUCCACUCCAGGGCUC 22 5806 SCNN1A-1958 CUCCACAGUCCACUCCAGGGCUC 23 5807 SCNN1A-1959 CCUCCACAGUCCACUCCAGGGCUC 24 5808 SCNN1A-1960 CAAUCCACUCCGGGGCUC 18 5809 SCNN1A-1961 CCAAUCCACUCCGGGGCUC 19 5810 SCNN1A-1962 CCCAAUCCACUCCGGGGCUC 20 5811 SCNN1A-1963 CCCCAAUCCACUCCGGGGCUC 21 5812 SCNN1A-1964 UCCCCAAUCCACUCCGGGGCUC 22 5813 SCNN1A-1965 CUCCCCAAUCCACUCCGGGGCUC 23 5814 SCNN1A-1966 UCUCCCCAAUCCACUCCGGGGCUC 24 5815 SCNN1A-1967 CAGCCCAUACCAGGUCUC 18 5816 SCNN1A-1968 GCAGCCCAUACCAGGUCUC 19 5817 SCNN1A-159 UGCAGCCCAUACCAGGUCUC 20  803 SCNN1A-1969 CUGCAGCCCAUACCAGGUCUC 21 5818 SCNN1A-1970 UCUGCAGCCCAUACCAGGUCUC 22 5819 SCNN1A-1971 CUCUGCAGCCCAUACCAGGUCUC 23 5820 SCNN1A-1972 CCUCUGCAGCCCAUACCAGGUCUC 24 5821 SCNN1A-1973 GCAGCCUCACUCGGGUUC 18 5822 SCNN1A-1974 GGCAGCCUCACUCGGGUUC 19 5823 SCNN1A-1975 GGGCAGCCUCACUCGGGUUC 20 5824 SCNN1A-1976 GGGGCAGCCUCACUCGGGUUC 21 5825 SCNN1A-1977 AGGGGCAGCCUCACUCGGGUUC 22 5826 SCNN1A-1978 CAGGGGCAGCCUCACUCGGGUUC 23 5827 SCNN1A-1979 CCAGGGGCAGCCUCACUCGGGUUC 24 5828 SCNN1A-1980 CUCAUGAAGGGGAACAAG 18 5829 SCNN1A-1981 GCUCAUGAAGGGGAACAAG 19 5830 SCNN1A-1982 GGCUCAUGAAGGGGAACAAG 20 5831 SCNN1A-1983 GGGCUCAUGAAGGGGAACAAG 21 5832 SCNN1A-1984 GGGGCUCAUGAAGGGGAACAAG 22 5833 SCNN1A-1985 CGGGGCUCAUGAAGGGGAACAAG 23 5834 SCNN1A-1986 CCGGGGCUCAUGAAGGGGAACAAG 24 5835 SCNN1A-1987 CUCAUGGAGGGGAACAAG 18 5836 SCNN1A-1988 UCUCAUGGAGGGGAACAAG 19 5837 SCNN1A-165 GUCUCAUGGAGGGGAACAAG 20  805 SCNN1A-1989 GGUCUCAUGGAGGGGAACAAG 21 5838 SCNN1A-1990 AGGUCUCAUGGAGGGGAACAAG 22 5839 SCNN1A-1991 CAGGUCUCAUGGAGGGGAACAAG 23 5840 SCNN1A-1992 CCAGGUCUCAUGGAGGGGAACAAG 24 5841 SCNN1A-1993 CCAGCUGUCCCUUCCAAG 18 5842 SCNN1A-1994 UCCAGCUGUCCCUUCCAAG 19 5843 SCNN1A-412 AUCCAGCUGUCCCUUCCAAG 20 4261 SCNN1A-1995 ACUCCAGGGCUCAUGAAG 18 5844 SCNN1A-1996 CACUCCAGGGCUCAUGAAG 19 5845 SCNN1A-12 CCACUCCAGGGCUCAUGAAG 20  561 SCNN1A-1997 UCCACUCCAGGGCUCAUGAAG 21 5846 SCNN1A-1998 GUCCACUCCAGGGCUCAUGAAG 22 5847 SCNN1A-1999 AGUCCACUCCAGGGCUCAUGAAG 23 5848 SCNN1A-2000 CAGUCCACUCCAGGGCUCAUGAAG 24 5849 SCNN1A-2001 ACUCCGGGGCUCAUGAAG 18 5850 SCNN1A-2002 CACUCCGGGGCUCAUGAAG 19 5851 SCNN1A-453 CCACUCCGGGGCUCAUGAAG 20 4302 SCNN1A-2003 UCCACUCCGGGGCUCAUGAAG 21 5852 SCNN1A-2004 AUCCACUCCGGGGCUCAUGAAG 22 5853 SCNN1A-2005 AAUCCACUCCGGGGCUCAUGAAG 23 5854 SCNN1A-2006 CAAUCCACUCCGGGGCUCAUGAAG 24 5855 SCNN1A-2007 GGGAACAAGCUGGAGGAG 18 5856 SCNN1A-2008 GGGGAACAAGCUGGAGGAG 19 5857 SCNN1A-169 AGGGGAACAAGCUGGAGGAG 20  807 SCNN1A-2009 AAGGGGAACAAGCUGGAGGAG 21 5858 SCNN1A-2010 GAAGGGGAACAAGCUGGAGGAG 22 5859 SCNN1A-2011 UGAAGGGGAACAAGCUGGAGGAG 23 5860 SCNN1A-2012 AUGAAGGGGAACAAGCUGGAGGAG 24 5861 SCNN1A-2013 GAGGGGAACAAGCUGGAGGAG 21 5862 SCNN1A-2014 GGAGGGGAACAAGCUGGAGGAG 22 5863 SCNN1A-2015 UGGAGGGGAACAAGCUGGAGGAG 23 5864 SCNN1A-2016 AUGGAGGGGAACAAGCUGGAGGAG 24 5865 SCNN1A-2017 GGGAACAAGCGUGAGGAG 18 5866 SCNN1A-2018 GGGGAACAAGCGUGAGGAG 19 5867 SCNN1A-179 AGGGGAACAAGCGUGAGGAG 20  813 SCNN1A-2019 AAGGGGAACAAGCGUGAGGAG 21 5868 SCNN1A-2020 GAAGGGGAACAAGCGUGAGGAG 22 5869 SCNN1A-2021 UGAAGGGGAACAAGCGUGAGGAG 23 5870 SCNN1A-2022 AUGAAGGGGAACAAGCGUGAGGAG 24 5871 SCNN1A-2023 CAGCAGCCCACGGCGGAG 18 5872 SCNN1A-2024 CCAGCAGCCCACGGCGGAG 19 5873 SCNN1A-187 CCCAGCAGCCCACGGCGGAG 20  818 SCNN1A-2025 CCCCAGCAGCCCACGGCGGAG 21 5874 SCNN1A-2026 GCCCCAGCAGCCCACGGCGGAG 22 5875 SCNN1A-2027 CGCCCCAGCAGCCCACGGCGGAG 23 5876 SCNN1A-2028 GCGCCCCAGCAGCCCACGGCGGAG 24 5877 SCNN1A-2029 AUACCAGGUCUCAUGGAG 18 5878 SCNN1A-2030 CAUACCAGGUCUCAUGGAG 19 5879 SCNN1A-4 CCAUACCAGGUCUCAUGGAG 20  498 SCNN1A-2031 CCCAUACCAGGUCUCAUGGAG 21 5880 SCNN1A-2032 GCCCAUACCAGGUCUCAUGGAG 22 5881 SCNN1A-2033 AGCCCAUACCAGGUCUCAUGGAG 23 5882 SCNN1A-2034 CAGCCCAUACCAGGUCUCAUGGAG 24 5883 SCNN1A-2035 GCGCCCCAGCAGCCCACG 18 5884 SCNN1A-2036 GGCGCCCCAGCAGCCCACG 19 5885 SCNN1A-183 CGGCGCCCCAGCAGCCCACG 20  816 SCNN1A-2037 GCGGCGCCCCAGCAGCCCACG 21 5886 SCNN1A-2038 UGCGGCGCCCCAGCAGCCCACG 22 5887 SCNN1A-2039 CUGCGGCGCCCCAGCAGCCCACG 23 5888 SCNN1A-2040 CCUGCGGCGCCCCAGCAGCCCACG 24 5889 SCNN1A-2041 CCCCAGCAGCCCACGGCG 18 5890 SCNN1A-2042 GCCCCAGCAGCCCACGGCG 19 5891 SCNN1A-185 CGCCCCAGCAGCCCACGGCG 20  817 SCNN1A-2043 GCGCCCCAGCAGCCCACGGCG 21 5892 SCNN1A-2044 GGCGCCCCAGCAGCCCACGGCG 22 5893 SCNN1A-2045 CGGCGCCCCAGCAGCCCACGGCG 23 5894 SCNN1A-2046 GCGGCGCCCCAGCAGCCCACGGCG 24 5895 SCNN1A-2047 GGAGAAUGUGGGCGCAGG 18 5896 SCNN1A-2048 GGGAGAAUGUGGGCGCAGG 19 5897 SCNN1A-2049 UGGGAGAAUGUGGGCGCAGG 20 5898 SCNN1A-2050 AGCAGCCCACGGCGGAGG 18 5899 SCNN1A-2051 CAGCAGCCCACGGCGGAGG 19 5900 SCNN1A-23 CCAGCAGCCCACGGCGGAGG 20  566 SCNN1A-2052 CCCAGCAGCCCACGGCGGAGG 21 5901 SCNN1A-2053 CCCCAGCAGCCCACGGCGGAGG 22 5902 SCNN1A-2054 GCCCCAGCAGCCCACGGCGGAGG 23 5903 SCNN1A-2055 CGCCCCAGCAGCCCACGGCGGAGG 24 5904 SCNN1A-2056 CGCCCCAGCAGCCCACGG 18 5905 SCNN1A-2057 GCGCCCCAGCAGCCCACGG 19 5906 SCNN1A-21 GGCGCCCCAGCAGCCCACGG 20  510 SCNN1A-2058 CGGCGCCCCAGCAGCCCACGG 21 5907 SCNN1A-2059 GCGGCGCCCCAGCAGCCCACGG 22 5908 SCNN1A-2060 UGCGGCGCCCCAGCAGCCCACGG 23 5909 SCNN1A-2061 CUGCGGCGCCCCAGCAGCCCACGG 24 5910 SCNN1A-2062 CCCAGCAGCCCACGGCGG 18 5911 SCNN1A-2063 CCCCAGCAGCCCACGGCGG 19 5912 SCNN1A-22 GCCCCAGCAGCCCACGGCGG 20  511 SCNN1A-2064 CGCCCCAGCAGCCCACGGCGG 21 5913 SCNN1A-2065 GCGCCCCAGCAGCCCACGGCGG 22 5914 SCNN1A-2066 GGCGCCCCAGCAGCCCACGGCGG 23 5915 SCNN1A-2067 CGGCGCCCCAGCAGCCCACGGCGG 24 5916 SCNN1A-2068 GAGAAUGUGGGCGCAGGG 18 5917 SCNN1A-2069 GGAGAAUGUGGGCGCAGGG 19 5918 SCNN1A-354 GGGAGAAUGUGGGCGCAGGG 20 4203 SCNN1A-2070 UGGGAGAAUGUGGGCGCAGGG 21 5919 SCNN1A-2071 GUGGGAGAAUGUGGGCGCAGGG 22 5920 SCNN1A-2072 AGUGGGAGAAUGUGGGCGCAGGG 23 5921 SCNN1A-2073 GAGUGGGAGAAUGUGGGCGCAGGG 24 5922 SCNN1A-2074 AAGCGUGAGGAGCAGGGG 18 5923 SCNN1A-2075 CAAGCGUGAGGAGCAGGGG 19 5924 SCNN1A-181 ACAAGCGUGAGGAGCAGGGG 20  814 SCNN1A-2076 AACAAGCGUGAGGAGCAGGGG 21 5925 SCNN1A-2077 GAACAAGCGUGAGGAGCAGGGG 22 5926 SCNN1A-2078 GGAACAAGCGUGAGGAGCAGGGG 23 5927 SCNN1A-2079 GGGAACAAGCGUGAGGAGCAGGGG 24 5928 SCNN1A-2080 CCAUACCAGGUCUCAUGG 18 5929 SCNN1A-2081 CCCAUACCAGGUCUCAUGG 19 5930 SCNN1A-2 GCCCAUACCAGGUCUCAUGG 20  497 SCNN1A-2082 AGCCCAUACCAGGUCUCAUGG 21 5931 SCNN1A-2083 CAGCCCAUACCAGGUCUCAUGG 22 5932 SCNN1A-2084 GCAGCCCAUACCAGGUCUCAUGG 23 5933 SCNN1A-2085 UGCAGCCCAUACCAGGUCUCAUGG 24 5934 SCNN1A-2086 GGGUUCCAGGGGUGAUGG 18 5935 SCNN1A-2087 CGGGUUCCAGGGGUGAUGG 19 5936 SCNN1A-2088 UCGGGUUCCAGGGGUGAUGG 20 5937 SCNN1A-2089 CUCGGGUUCCAGGGGUGAUGG 21 5938 SCNN1A-2090 ACUCGGGUUCCAGGGGUGAUGG 22 5939 SCNN1A-2091 CACUCGGGUUCCAGGGGUGAUGG 23 5940 SCNN1A-2092 UCACUCGGGUUCCAGGGGUGAUGG 24 5941 SCNN1A-2093 UGAAGGGGAACAAGCUGG 18 5942 SCNN1A-2094 AUGAAGGGGAACAAGCUGG 19 5943 SCNN1A-455 CAUGAAGGGGAACAAGCUGG 20 4304 SCNN1A-2095 UCAUGAAGGGGAACAAGCUGG 21 5944 SCNN1A-2096 CUCAUGAAGGGGAACAAGCUGG 22 5945 SCNN1A-2097 GCUCAUGAAGGGGAACAAGCUGG 23 5946 SCNN1A-2098 GGCUCAUGAAGGGGAACAAGCUGG 24 5947 SCNN1A-2099 UGGAGGGGAACAAGCUGG 18 5948 SCNN1A-2100 AUGGAGGGGAACAAGCUGG 19 5949 SCNN1A-6 CAUGGAGGGGAACAAGCUGG 20  558 SCNN1A-2101 UCAUGGAGGGGAACAAGCUGG 21 5950 SCNN1A-2102 CUCAUGGAGGGGAACAAGCUGG 22 5951 SCNN1A-2103 UCUCAUGGAGGGGAACAAGCUGG 23 5952 SCNN1A-2104 GUCUCAUGGAGGGGAACAAGCUGG 24 5953 SCNN1A-2105 UCCACUCCAGGGCUCAUG 18 5954 SCNN1A-2106 GUCCACUCCAGGGCUCAUG 19 5955 SCNN1A-172 AGUCCACUCCAGGGCUCAUG 20  810 SCNN1A-2107 CAGUCCACUCCAGGGCUCAUG 21 5956 SCNN1A-2108 ACAGUCCACUCCAGGGCUCAUG 22 5957 SCNN1A-2109 CACAGUCCACUCCAGGGCUCAUG 23 5958 SCNN1A-2110 CCACAGUCCACUCCAGGGCUCAUG 24 5959 SCNN1A-2111 UCCACUCCGGGGCUCAUG 18 5960 SCNN1A-2112 AUCCACUCCGGGGCUCAUG 19 5961 SCNN1A-2113 AAUCCACUCCGGGGCUCAUG 20 5962 SCNN1A-2114 CAAUCCACUCCGGGGCUCAUG 21 5963 SCNN1A-2115 CCAAUCCACUCCGGGGCUCAUG 22 5964 SCNN1A-2116 CCCAAUCCACUCCGGGGCUCAUG 23 5965 SCNN1A-2117 CCCCAAUCCACUCCGGGGCUCAUG 24 5966 SCNN1A-2118 CCCAUACCAGGUCUCAUG 18 5967 SCNN1A-2119 GCCCAUACCAGGUCUCAUG 19 5968 SCNN1A-161 AGCCCAUACCAGGUCUCAUG 20  804 SCNN1A-2120 CAGCCCAUACCAGGUCUCAUG 21 5969 SCNN1A-2121 GCAGCCCAUACCAGGUCUCAUG 22 5970 SCNN1A-2122 UGCAGCCCAUACCAGGUCUCAUG 23 5971 SCNN1A-2123 CUGCAGCCCAUACCAGGUCUCAUG 24 5972 SCNN1A-2124 AUGAAGGGGAACAAGCUG 18 5973 SCNN1A-2125 CAUGAAGGGGAACAAGCUG 19 5974 SCNN1A-2126 UCAUGAAGGGGAACAAGCUG 20 5975 SCNN1A-2127 CUCAUGAAGGGGAACAAGCUG 21 5976 SCNN1A-2128 GCUCAUGAAGGGGAACAAGCUG 22 5977 SCNN1A-2129 GGCUCAUGAAGGGGAACAAGCUG 23 5978 SCNN1A-2130 GGGCUCAUGAAGGGGAACAAGCUG 24 5979 SCNN1A-2131 AUGGAGGGGAACAAGCUG 18 5980 SCNN1A-2132 CAUGGAGGGGAACAAGCUG 19 5981 SCNN1A-167 UCAUGGAGGGGAACAAGCUG 20  806 SCNN1A-2133 CUCAUGGAGGGGAACAAGCUG 21 5982 SCNN1A-2134 UCUCAUGGAGGGGAACAAGCUG 22 5983 SCNN1A-2135 GUCUCAUGGAGGGGAACAAGCUG 23 5984 SCNN1A-2136 GGUCUCAUGGAGGGGAACAAGCUG 24 5985 SCNN1A-2137 UGAAGGGGAACAAGCGUG 18 5986 SCNN1A-2138 AUGAAGGGGAACAAGCGUG 19 5987 SCNN1A-13 CAUGAAGGGGAACAAGCGUG 20  562 SCNN1A-2139 UCAUGAAGGGGAACAAGCGUG 21 5988 SCNN1A-2140 CUCAUGAAGGGGAACAAGCGUG 22 5989 SCNN1A-2141 GCUCAUGAAGGGGAACAAGCGUG 23 5990 SCNN1A-2142 GGCUCAUGAAGGGGAACAAGCGUG 24 5991 SCNN1A-2143 ACUCGGGUUCCAGGGGUG 18 5992 SCNN1A-2144 CACUCGGGUUCCAGGGGUG 19 5993 SCNN1A-2145 UCACUCGGGUUCCAGGGGUG 20 5994 SCNN1A-2146 CUCACUCGGGUUCCAGGGGUG 21 5995 SCNN1A-2147 CCUCACUCGGGUUCCAGGGGUG 22 5996 SCNN1A-2148 GCCUCACUCGGGUUCCAGGGGUG 23 5997 SCNN1A-2149 AGCCUCACUCGGGUUCCAGGGGUG 24 5998 SCNN1A-2150 UCGGGUUCCAGGGGUGAU 18 5999 SCNN1A-2151 CUCGGGUUCCAGGGGUGAU 19 6000 SCNN1A-421 ACUCGGGUUCCAGGGGUGAU 20 4270 SCNN1A-2152 CACUCGGGUUCCAGGGGUGAU 21 6001 SCNN1A-2153 UCACUCGGGUUCCAGGGGUGAU 22 6002 SCNN1A-2154 CUCACUCGGGUUCCAGGGGUGAU 23 6003 SCNN1A-2155 CCUCACUCGGGUUCCAGGGGUGAU 24 6004 SCNN1A-2156 UGCUCUCCCCAAUCCACU 18 6005 SCNN1A-2157 UUGCUCUCCCCAAUCCACU 19 6006 SCNN1A-2158 CUUGCUCUCCCCAAUCCACU 20 6007 SCNN1A-2159 CCUUGCUCUCCCCAAUCCACU 21 6008 SCNN1A-2160 CCCUUGCUCUCCCCAAUCCACU 22 6009 SCNN1A-2161 ACCCUUGCUCUCCCCAAUCCACU 23 6010 SCNN1A-2162 GACCCUUGCUCUCCCCAAUCCACU 24 6011 SCNN1A-2163 GUGAUGGGAGAGGGCACU 18 6012 SCNN1A-2164 GGUGAUGGGAGAGGGCACU 19 6013 SCNN1A-2165 GGGUGAUGGGAGAGGGCACU 20 6014 SCNN1A-2166 GGGGUGAUGGGAGAGGGCACU 21 6015 SCNN1A-2167 AGGGGUGAUGGGAGAGGGCACU 22 6016 SCNN1A-2168 CAGGGGUGAUGGGAGAGGGCACU 23 6017 SCNN1A-2169 CCAGGGGUGAUGGGAGAGGGCACU 24 6018 SCNN1A-2170 AUGAAGGGGAACAAGCGU 18 6019 SCNN1A-2171 CAUGAAGGGGAACAAGCGU 19 6020 SCNN1A-177 UCAUGAAGGGGAACAAGCGU 20  812 SCNN1A-2172 CUCAUGAAGGGGAACAAGCGU 21 6021 SCNN1A-2173 GCUCAUGAAGGGGAACAAGCGU 22 6022 SCNN1A-2174 GGCUCAUGAAGGGGAACAAGCGU 23 6023 SCNN1A-2175 GGGCUCAUGAAGGGGAACAAGCGU 24 6024 SCNN1A-2176 UAAGCAAGGGAACCUGGU 18 6025 SCNN1A-2177 GUAAGCAAGGGAACCUGGU 19 6026 SCNN1A-2178 GGUAAGCAAGGGAACCUGGU 20 6027 SCNN1A-2179 AGGUAAGCAAGGGAACCUGGU 21 6028 SCNN1A-2180 AAGGUAAGCAAGGGAACCUGGU 22 6029 SCNN1A-2181 CAAGGUAAGCAAGGGAACCUGGU 23 6030 SCNN1A-2182 UCAAGGUAAGCAAGGGAACCUGGU 24 6031 SCNN1A-2183 CCGCAUGAAGACGGCCUU 18 6032 SCNN1A-2184 ACCGCAUGAAGACGGCCUU 19 6033 SCNN1A-194 AACCGCAUGAAGACGGCCUU 20  824 SCNN1A-2185 CAACCGCAUGAAGACGGCCUU 21 6034 SCNN1A-2186 ACAACCGCAUGAAGACGGCCUU 22 6035 SCNN1A-2187 CACAACCGCAUGAAGACGGCCUU 23 6036 SCNN1A-2188 GCACAACCGCAUGAAGACGGCCUU 24 6037 SCNN1A-2189 GGCAAUUCGGCCUGCUUU 18 6038 SCNN1A-2190 UGGCAAUUCGGCCUGCUUU 19 6039 SCNN1A-195 CUGGCAAUUCGGCCUGCUUU 20  825 SCNN1A-2191 ACUGGCAAUUCGGCCUGCUUU 21 6040 SCNN1A-2192 UACUGGCAAUUCGGCCUGCUUU 22 6041 SCNN1A-2193 GUACUGGCAAUUCGGCCUGCUUU 23 6042 SCNN1A-2194 UGUACUGGCAAUUCGGCCUGCUUU 24 6043 SCNN1A-2195 GCAAUUCGGCCUGCUUUU 18 6044 SCNN1A-2196 GGCAAUUCGGCCUGCUUUU 19 6045 SCNN1A-34 UGGCAAUUCGGCCUGCUUUU 20  573 SCNN1A-2197 CUGGCAAUUCGGCCUGCUUUU 21 6046 SCNN1A-2198 ACUGGCAAUUCGGCCUGCUUUU 22 6047 SCNN1A-2199 UACUGGCAAUUCGGCCUGCUUUU 23 6048 SCNN1A-2200 GUACUGGCAAUUCGGCCUGCUUUU 24 6049

Table 44E provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fifth tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene), starts with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 44E 5th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-2201 + GUACCUGAAGGGGCGAGGGGAA 22 6050 SCNN1A-2202 + GGUACCUGAAGGGGCGAGGGGAA 23 6051 SCNN1A-2203 + GGGUACCUGAAGGGGCGAGGGGAA 24 6052 SCNN1A-2204 + GGGACAAGGACAGAGACA 18 6053 SCNN1A-2205 + GCUGGGACAAGGACAGAGACA 21 6054 SCNN1A-2206 + GGCUGGGACAAGGACAGAGACA 22 6055 SCNN1A-2207 + GUAUAGCAGUUUCCAUACA 19 6056 SCNN1A-2208 + GAAAGUAUAGCAGUUUCCAUACA 23 6057 SCNN1A-2209 + GGACCCUCAGGCGCUGCA 18 6058 SCNN1A-2210 + GGGACCCUCAGGCGCUGCA 19 6059 SCNN1A-2211 + GCGGGACCCUCAGGCGCUGCA 21 6060 SCNN1A-2212 + GGCGGGACCCUCAGGCGCUGCA 22 6061 SCNN1A-2213 + GGGCGGGACCCUCAGGCGCUGCA 23 6062 SCNN1A-2214 + GGGGCGGGACCCUCAGGCGCUGCA 24 6063 SCNN1A-2215 + GUAAUUCCUUAUCAGGAAAGA 21 6064 SCNN1A-2216 + GAGUAAUUCCUUAUCAGGAAAGA 23 6065 SCNN1A-2217 + GAGUCUCUGGCAGCCUCGA 19 6066 SCNN1A-2218 + GCAGAGUCUCUGGCAGCCUCGA 22 6067 SCNN1A-2219 + GGCAGAGUCUCUGGCAGCCUCGA 23 6068 SCNN1A-2220 + GCUCUCCUGGAAGCAGGA 18 6069 SCNN1A-2221 + GAUCAUGCUCUCCUGGAAGCAGGA 24 6070 SCNN1A-2222 + GAAGACCCAUUCCUAGGA 18 6071 SCNN1A-2223 + GGAAGACCCAUUCCUAGGA 19 6072 SCNN1A-2224 + GCUGCGGGAGCCGGCCAC 18 6073 SCNN1A-2225 + GGCUGCGGGAGCCGGCCAC 19 6074 SCNN1A-2226 + GACGGCUGCGGGAGCCGGCCAC 22 6075 SCNN1A-2227 + GCGACGGCUGCGGGAGCCGGCCAC 24 6076 SCNN1A-2228 + GUUGCACUGGACACAGAGAC 20 6077 SCNN1A-2229 + GGUUGCACUGGACACAGAGAC 21 6078 SCNN1A-2230 + GCCCCCUGGAGAUGGGCGGGGGCC 24 6079 SCNN1A-2231 + GUACUCCACGUUCUGGGGCC 20 6080 SCNN1A-2232 + GCCCAGCGUGUCCUCCUCC 19 6081 SCNN1A-2233 + GUUGCCCAGCGUGUCCUCCUCC 22 6082 SCNN1A-1051 + GAUCAUGCUCUCCUGGAAGC 20 4900 SCNN1A-2234 + GGAAGGAGGGGAGGAUGC 18 6083 SCNN1A-2235 + GGGAAGGAGGGGAGGAUGC 19 6084 SCNN1A-2236 + GUGGGAAGGAGGGGAGGAUGC 21 6085 SCNN1A-2237 + GAAGUGGGAAGGAGGGGAGGAUGC 24 6086 SCNN1A-2238 + GAUGUCACCGAGGGCCAUC 19 6087 SCNN1A-2239 + GGAUGUCACCGAGGGCCAUC 20 6088 SCNN1A-2240 + GGGAUGUCACCGAGGGCCAUC 21 6089 SCNN1A-2241 + GCCAUAAUCGCCCCCAAGUCUGUC 24 6090 SCNN1A-2242 + GCUGCCCAGGUUGGACAG 18 6091 SCNN1A-2243 + GGCUGCCCAGGUUGGACAG 19 6092 SCNN1A-2244 + GCCCCAGUCACUGUGGACAGCAG 23 6093 SCNN1A-2245 + GGCCCCAGUCACUGUGGACAGCAG 24 6094 SCNN1A-2246 + GACCUAGGGGUGCAGAGAGAG 21 6095 SCNN1A-2247 + GAAUACACACCUGGAAGGGAG 21 6096 SCNN1A-2248 + GUGAAUACACACCUGGAAGGGAG 23 6097 SCNN1A-2249 + GCGCUGCAAGGGGUGCGG 18 6098 SCNN1A-2250 + GGCGCUGCAAGGGGUGCGG 19 6099 SCNN1A-2251 + GCAGAAGUGGGAAGGAGGG 19 6100 SCNN1A-2252 + GGCAGAAGUGGGAAGGAGGG 20 6101 SCNN1A-2253 + GGGCAGAAGUGGGAAGGAGGG 21 6102 SCNN1A-2254 + GGGGCAGAAGUGGGAAGGAGGG 22 6103 SCNN1A-2255 + GGGGGCAGAAGUGGGAAGGAGGG 23 6104 SCNN1A-2256 + GUCCUCCUCCAGGGAUGG 18 6105 SCNN1A-2257 + GUGUCCUCCUCCAGGGAUGG 20 6106 SCNN1A-2258 + GCGUGUCCUCCUCCAGGGAUGG 22 6107 SCNN1A-2259 + GCCUCACCUGCUGUGUGUACUUUG 24 6108 SCNN1A-2260 + GACCCAUUCCUAGGAAAGAAU 21 6109 SCNN1A-2261 + GAAGACCCAUUCCUAGGAAAGAAU 24 6110 SCNN1A-2262 + GACCUACCGUGACAGAGGGAGACU 24 6111 SCNN1A-1263 + GCAGCAUCAGGGACAGACCU 20 5112 SCNN1A-2263 + GCGCAGCAUCAGGGACAGACCU 22 6112 SCNN1A-2264 + GCGCGCAGCAUCAGGGACAGACCU 24 6113 SCNN1A-2265 + GCUUAUAGUAGCAGUACCCU 20 6114 SCNN1A-2266 + GAGCUUAUAGUAGCAGUACCCU 22 6115 SCNN1A-2267 + GGAGCUUAUAGUAGCAGUACCCU 23 6116 SCNN1A-2268 + GCUGGUAGCUGGUCACGCU 19 6117 SCNN1A-2269 + GAGCUGGUAGCUGGUCACGCU 21 6118 SCNN1A-2270 + GAGAGCUGGUAGCUGGUCACGCU 23 6119 SCNN1A-2271 + GCAUGGAAGACAUCCAGAGGU 21 6120 SCNN1A-2272 + GGCAUGGAAGACAUCCAGAGGU 22 6121 SCNN1A-2273 + GCUCCUCCAGCUCCUCUUUAAUUU 24 6122 SCNN1A-2274 GGCAUCUCUCUGUACCCA 18 6123 SCNN1A-2275 GAACAGGCAUCUCUCUGUACCCA 23 6124 SCNN1A-2276 GCUUCCAGGAGAGCAUGAUCA 21 6125 SCNN1A-2277 GACACCCCCAUUCUUUCCUAGGA 23 6126 SCNN1A-2278 GACAUCCCAGGUAGAGUGUGGGGA 24 6127 SCNN1A-2279 GACCCUACUCUCUCUUUCCUGAUA 24 6128 SCNN1A-2280 GAUUAUGGCGACUGCACC 18 6129 SCNN1A-2281 GCGAUUAUGGCGACUGCACC 20 6130 SCNN1A-2282 GGCGAUUAUGGCGACUGCACC 21 6131 SCNN1A-2283 GGGCGAUUAUGGCGACUGCACC 22 6132 SCNN1A-2284 GGGGCGAUUAUGGCGACUGCACC 23 6133 SCNN1A-2285 GGGGGCGAUUAUGGCGACUGCACC 24 6134 SCNN1A-2286 GCAGGUUAGUGUCCCCUUCC 20 6135 SCNN1A-2287 GACUACAGAAAGCACAGUUCC 21 6136 SCNN1A-2288 GUGACUACAGAAAGCACAGUUCC 23 6137 SCNN1A-2289 GACCUCCAUCAGCAUGAGGAAGGC 24 6138 SCNN1A-2290 GGUCUCCUGCAACCAGGC 18 6139 SCNN1A-2291 GUCUCCAGGCCGAGGGGGC 19 6140 SCNN1A-1073 GGUCUCCAGGCCGAGGGGGC 20 4922 SCNN1A-2292 GUCCACAGUGACUGGGGC 18 6141 SCNN1A-2293 GCUGUCCACAGUGACUGGGGC 21 6142 SCNN1A-2294 GCUUCUACCAGACAUACUCAUC 22 6143 SCNN1A-2295 GUCCCUGAUGCUGCGCGCAGAG 22 6144 SCNN1A-2296 GCCCUCGGUGACAUCCCAGG 20 6145 SCNN1A-2297 GGCCCUCGGUGACAUCCCAGG 21 6146 SCNN1A-2298 GAUGGCCCUCGGUGACAUCCCAGG 24 6147 SCNN1A-2299 GUAGAGUGUGGGGAAGGG 18 6148 SCNN1A-2300 GGUAGAGUGUGGGGAAGGG 19 6149 SCNN1A-2301 GCCCGGGUAAUGGUGCACGGG 21 6150 SCNN1A-2302 GGCCCGGGUAAUGGUGCACGGG 22 6151 SCNN1A-2303 GGGCCCGGGUAAUGGUGCACGGG 23 6152 SCNN1A-2304 GGGGCCCGGGUAAUGGUGCACGGG 24 6153 SCNN1A-2305 GUGGGGAAGGGAUGGGUG 18 6154 SCNN1A-1236 GUGUGGGGAAGGGAUGGGUG 20 5085 SCNN1A-2306 GAGUGUGGGGAAGGGAUGGGUG 22 6155 SCNN1A-2307 GACAAGAACAACUCCAACCU 20 6156 SCNN1A-2308 GCACCCCUUGCAGCGCCU 18 6157 SCNN1A-2309 GCCGCACCCCUUGCAGCGCCU 21 6158 SCNN1A-2310 GACACCCCCAUUCUUUCCU 19 6159 SCNN1A-2311 GAUGACACCCCCAUUCUUUCCU 22 6160 SCNN1A-2312 GCUGAACUACAAAACCAAUU 20 6161 SCNN1A-2313 GAGCUGAACUACAAAACCAAUU 22 6162 SCNN1A-2314 GGAGCUGAACUACAAAACCAAUU 23 6163 SCNN1A-2315 GCAGGAUGAACCUGCCUUU 19 6164 SCNN1A-2316 GGCAGGAUGAACCUGCCUUU 20 6165 SCNN1A-2317 GGGCAGGAUGAACCUGCCUUU 21 6166

Table 44F provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the six tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene) and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 44F 6th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-2318 + CUGAAGGGGCGAGGGGAA 18 6167 SCNN1A-2319 + CCUGAAGGGGCGAGGGGAA 19 6168 SCNN1A-2320 + ACCUGAAGGGGCGAGGGGAA 20 6169 SCNN1A-2321 + UACCUGAAGGGGCGAGGGGAA 21 6170 SCNN1A-2322 + UGGGACAAGGACAGAGACA 19 6171 SCNN1A-899 + CUGGGACAAGGACAGAGACA 20 4748 SCNN1A-2323 + UGGCUGGGACAAGGACAGAGACA 23 6172 SCNN1A-2324 + CUGGCUGGGACAAGGACAGAGACA 24 6173 SCNN1A-2325 + UAUAGCAGUUUCCAUACA 18 6174 SCNN1A-2326 + AGUAUAGCAGUUUCCAUACA 20 6175 SCNN1A-2327 + AAGUAUAGCAGUUUCCAUACA 21 6176 SCNN1A-2328 + AAAGUAUAGCAGUUUCCAUACA 22 6177 SCNN1A-2329 + UGAAAGUAUAGCAGUUUCCAUACA 24 6178 SCNN1A-2330 + UUUCUUAGGUGUGGGGCA 18 6179 SCNN1A-2331 + AUUUCUUAGGUGUGGGGCA 19 6180 SCNN1A-2332 + CAUUUCUUAGGUGUGGGGCA 20 6181 SCNN1A-2333 + CCAUUUCUUAGGUGUGGGGCA 21 6182 SCNN1A-2334 + UCCAUUUCUUAGGUGUGGGGCA 22 6183 SCNN1A-2335 + CUCCAUUUCUUAGGUGUGGGGCA 23 6184 SCNN1A-2336 + ACUCCAUUUCUUAGGUGUGGGGCA 24 6185 SCNN1A-917 + CGGGACCCUCAGGCGCUGCA 20 4766 SCNN1A-2337 + AUUCCUUAUCAGGAAAGA 18 6186 SCNN1A-2338 + AAUUCCUUAUCAGGAAAGA 19 6187 SCNN1A-2339 + UAAUUCCUUAUCAGGAAAGA 20 6188 SCNN1A-2340 + AGUAAUUCCUUAUCAGGAAAGA 22 6189 SCNN1A-2341 + AGAGUAAUUCCUUAUCAGGAAAGA 24 6190 SCNN1A-2342 + AGUCUCUGGCAGCCUCGA 18 6191 SCNN1A-2343 + AGAGUCUCUGGCAGCCUCGA 20 6192 SCNN1A-2344 + CAGAGUCUCUGGCAGCCUCGA 21 6193 SCNN1A-2345 + UGGCAGAGUCUCUGGCAGCCUCGA 24 6194 SCNN1A-2346 + UGCUCUCCUGGAAGCAGGA 19 6195 SCNN1A-2347 + AUGCUCUCCUGGAAGCAGGA 20 6196 SCNN1A-2348 + CAUGCUCUCCUGGAAGCAGGA 21 6197 SCNN1A-2349 + UCAUGCUCUCCUGGAAGCAGGA 22 6198 SCNN1A-2350 + AUCAUGCUCUCCUGGAAGCAGGA 23 6199 SCNN1A-2351 + UGGAAGACCCAUUCCUAGGA 20 6200 SCNN1A-2352 + CUGGAAGACCCAUUCCUAGGA 21 6201 SCNN1A-2353 + UCUGGAAGACCCAUUCCUAGGA 22 6202 SCNN1A-2354 + AUCUGGAAGACCCAUUCCUAGGA 23 6203 SCNN1A-2355 + CAUCUGGAAGACCCAUUCCUAGGA 24 6204 SCNN1A-2356 + CGGCUGCGGGAGCCGGCCAC 20 6205 SCNN1A-2357 + ACGGCUGCGGGAGCCGGCCAC 21 6206 SCNN1A-2358 + CGACGGCUGCGGGAGCCGGCCAC 23 6207 SCNN1A-2359 + UGCACUGGACACAGAGAC 18 6208 SCNN1A-2360 + UUGCACUGGACACAGAGAC 19 6209 SCNN1A-2361 + UGGUUGCACUGGACACAGAGAC 22 6210 SCNN1A-2362 + CUGGUUGCACUGGACACAGAGAC 23 6211 SCNN1A-2363 + UCUGGUUGCACUGGACACAGAGAC 24 6212 SCNN1A-2364 + CCUUCCCCACACUCUACC 18 6213 SCNN1A-2365 + CCCUUCCCCACACUCUACC 19 6214 SCNN1A-1006 + UCCCUUCCCCACACUCUACC 20 4855 SCNN1A-2366 + AUCCCUUCCCCACACUCUACC 21 6215 SCNN1A-2367 + CAUCCCUUCCCCACACUCUACC 22 6216 SCNN1A-2368 + CCAUCCCUUCCCCACACUCUACC 23 6217 SCNN1A-2369 + CCCAUCCCUUCCCCACACUCUACC 24 6218 SCNN1A-2370 + UGGAGAUGGGCGGGGGCC 18 6219 SCNN1A-2371 + CUGGAGAUGGGCGGGGGCC 19 6220 SCNN1A-2372 + CCUGGAGAUGGGCGGGGGCC 20 6221 SCNN1A-2373 + CCCUGGAGAUGGGCGGGGGCC 21 6222 SCNN1A-2374 + CCCCUGGAGAUGGGCGGGGGCC 22 6223 SCNN1A-2375 + CCCCCUGGAGAUGGGCGGGGGCC 23 6224 SCNN1A-2376 + ACUCCACGUUCUGGGGCC 18 6225 SCNN1A-2377 + UACUCCACGUUCUGGGGCC 19 6226 SCNN1A-2378 + AGUACUCCACGUUCUGGGGCC 21 6227 SCNN1A-2379 + CAGUACUCCACGUUCUGGGGCC 22 6228 SCNN1A-2380 + ACAGUACUCCACGUUCUGGGGCC 23 6229 SCNN1A-2381 + CACAGUACUCCACGUUCUGGGGCC 24 6230 SCNN1A-2382 + CCCAGCGUGUCCUCCUCC 18 6231 SCNN1A-1038 + UGCCCAGCGUGUCCUCCUCC 20 4887 SCNN1A-2383 + UUGCCCAGCGUGUCCUCCUCC 21 6232 SCNN1A-2384 + AGUUGCCCAGCGUGUCCUCCUCC 23 6233 SCNN1A-2385 + AAGUUGCCCAGCGUGUCCUCCUCC 24 6234 SCNN1A-2386 + UCAUGCUCUCCUGGAAGC 18 6235 SCNN1A-2387 + AUCAUGCUCUCCUGGAAGC 19 6236 SCNN1A-2388 + UGAUCAUGCUCUCCUGGAAGC 21 6237 SCNN1A-2389 + UUGAUCAUGCUCUCCUGGAAGC 22 6238 SCNN1A-2390 + CUUGAUCAUGCUCUCCUGGAAGC 23 6239 SCNN1A-2391 + CCUUGAUCAUGCUCUCCUGGAAGC 24 6240 SCNN1A-2392 + UGGGAAGGAGGGGAGGAUGC 20 6241 SCNN1A-2393 + AGUGGGAAGGAGGGGAGGAUGC 22 6242 SCNN1A-2394 + AAGUGGGAAGGAGGGGAGGAUGC 23 6243 SCNN1A-2395 + AUGUCACCGAGGGCCAUC 18 6244 SCNN1A-2396 + UGGGAUGUCACCGAGGGCCAUC 22 6245 SCNN1A-2397 + CUGGGAUGUCACCGAGGGCCAUC 23 6246 SCNN1A-2398 + CCUGGGAUGUCACCGAGGGCCAUC 24 6247 SCNN1A-2399 + AUCGCCCCCAAGUCUGUC 18 6248 SCNN1A-2400 + AAUCGCCCCCAAGUCUGUC 19 6249 SCNN1A-2401 + UAAUCGCCCCCAAGUCUGUC 20 6250 SCNN1A-2402 + AUAAUCGCCCCCAAGUCUGUC 21 6251 SCNN1A-2403 + CAUAAUCGCCCCCAAGUCUGUC 22 6252 SCNN1A-2404 + CCAUAAUCGCCCCCAAGUCUGUC 23 6253 SCNN1A-2405 + UGGCUGCCCAGGUUGGACAG 20 6254 SCNN1A-2406 + CUGGCUGCCCAGGUUGGACAG 21 6255 SCNN1A-2407 + ACUGGCUGCCCAGGUUGGACAG 22 6256 SCNN1A-2408 + CACUGGCUGCCCAGGUUGGACAG 23 6257 SCNN1A-2409 + CCACUGGCUGCCCAGGUUGGACAG 24 6258 SCNN1A-2410 + AGUCACUGUGGACAGCAG 18 6259 SCNN1A-2411 + CAGUCACUGUGGACAGCAG 19 6260 SCNN1A-1119 + CCAGUCACUGUGGACAGCAG 20 4968 SCNN1A-2412 + CCCAGUCACUGUGGACAGCAG 21 6261 SCNN1A-2413 + CCCCAGUCACUGUGGACAGCAG 22 6262 SCNN1A-2414 + UUAUCAGGAAAGAGAGAG 18 6263 SCNN1A-2415 + CUUAUCAGGAAAGAGAGAG 19 6264 SCNN1A-2416 + CCUUAUCAGGAAAGAGAGAG 20 6265 SCNN1A-2417 + UCCUUAUCAGGAAAGAGAGAG 21 6266 SCNN1A-2418 + UUCCUUAUCAGGAAAGAGAGAG 22 6267 SCNN1A-2419 + AUUCCUUAUCAGGAAAGAGAGAG 23 6268 SCNN1A-2420 + AAUUCCUUAUCAGGAAAGAGAGAG 24 6269 SCNN1A-2421 + CUAGGGGUGCAGAGAGAG 18 6270 SCNN1A-2422 + CCUAGGGGUGCAGAGAGAG 19 6271 SCNN1A-2423 + ACCUAGGGGUGCAGAGAGAG 20 6272 SCNN1A-2424 + AGACCUAGGGGUGCAGAGAGAG 22 6273 SCNN1A-2425 + CAGACCUAGGGGUGCAGAGAGAG 23 6274 SCNN1A-2426 + ACAGACCUAGGGGUGCAGAGAGAG 24 6275 SCNN1A-2427 + UACACACCUGGAAGGGAG 18 6276 SCNN1A-2428 + AUACACACCUGGAAGGGAG 19 6277 SCNN1A-2429 + AAUACACACCUGGAAGGGAG 20 6278 SCNN1A-2430 + UGAAUACACACCUGGAAGGGAG 22 6279 SCNN1A-2431 + AGUGAAUACACACCUGGAAGGGAG 24 6280 SCNN1A-2432 + AGGCGCUGCAAGGGGUGCGG 20 6281 SCNN1A-2433 + CAGGCGCUGCAAGGGGUGCGG 21 6282 SCNN1A-2434 + UCAGGCGCUGCAAGGGGUGCGG 22 6283 SCNN1A-2435 + CUCAGGCGCUGCAAGGGGUGCGG 23 6284 SCNN1A-2436 + CCUCAGGCGCUGCAAGGGGUGCGG 24 6285 SCNN1A-2437 + CAGAAGUGGGAAGGAGGG 18 6286 SCNN1A-2438 + UGGGGGCAGAAGUGGGAAGGAGGG 24 6287 SCNN1A-2439 + UGUCCUCCUCCAGGGAUGG 19 6288 SCNN1A-2440 + CGUGUCCUCCUCCAGGGAUGG 21 6289 SCNN1A-2441 + AGCGUGUCCUCCUCCAGGGAUGG 23 6290 SCNN1A-2442 + CAGCGUGUCCUCCUCCAGGGAUGG 24 6291 SCNN1A-2443 + UCACCGCAUCCACCCCUG 18 6292 SCNN1A-2444 + CUCACCGCAUCCACCCCUG 19 6293 SCNN1A-2445 + CCUCACCGCAUCCACCCCUG 20 6294 SCNN1A-2446 + CCCUCACCGCAUCCACCCCUG 21 6295 SCNN1A-2447 + UCCCUCACCGCAUCCACCCCUG 22 6296 SCNN1A-2448 + CUCCCUCACCGCAUCCACCCCUG 23 6297 SCNN1A-2449 + ACUCCCUCACCGCAUCCACCCCUG 24 6298 SCNN1A-2450 + CCUGCUGUGUGUACUUUG 18 6299 SCNN1A-2451 + ACCUGCUGUGUGUACUUUG 19 6300 SCNN1A-2452 + CACCUGCUGUGUGUACUUUG 20 6301 SCNN1A-2453 + UCACCUGCUGUGUGUACUUUG 21 6302 SCNN1A-2454 + CUCACCUGCUGUGUGUACUUUG 22 6303 SCNN1A-2455 + CCUCACCUGCUGUGUGUACUUUG 23 6304 SCNN1A-2456 + CCAUUCCUAGGAAAGAAU 18 6305 SCNN1A-2457 + CCCAUUCCUAGGAAAGAAU 19 6306 SCNN1A-1244 + ACCCAUUCCUAGGAAAGAAU 20 5093 SCNN1A-2458 + AGACCCAUUCCUAGGAAAGAAU 22 6307 SCNN1A-2459 + AAGACCCAUUCCUAGGAAAGAAU 23 6308 SCNN1A-2460 + CCGUGACAGAGGGAGACU 18 6309 SCNN1A-2461 + ACCGUGACAGAGGGAGACU 19 6310 SCNN1A-2462 + UACCGUGACAGAGGGAGACU 20 6311 SCNN1A-2463 + CUACCGUGACAGAGGGAGACU 21 6312 SCNN1A-2464 + CCUACCGUGACAGAGGGAGACU 22 6313 SCNN1A-2465 + ACCUACCGUGACAGAGGGAGACU 23 6314 SCNN1A-2466 + AGUCCUUCCAGUCCACCU 18 6315 SCNN1A-2467 + CAGUCCUUCCAGUCCACCU 19 6316 SCNN1A-1262 + CCAGUCCUUCCAGUCCACCU 20 5111 SCNN1A-2468 + UCCAGUCCUUCCAGUCCACCU 21 6317 SCNN1A-2469 + UUCCAGUCCUUCCAGUCCACCU 22 6318 SCNN1A-2470 + CUUCCAGUCCUUCCAGUCCACCU 23 6319 SCNN1A-2471 + UCUUCCAGUCCUUCCAGUCCACCU 24 6320 SCNN1A-2472 + AGCAUCAGGGACAGACCU 18 6321 SCNN1A-2473 + CAGCAUCAGGGACAGACCU 19 6322 SCNN1A-2474 + CGCAGCAUCAGGGACAGACCU 21 6323 SCNN1A-2475 + CGCGCAGCAUCAGGGACAGACCU 23 6324 SCNN1A-2476 + UUAUAGUAGCAGUACCCU 18 6325 SCNN1A-2477 + CUUAUAGUAGCAGUACCCU 19 6326 SCNN1A-2478 + AGCUUAUAGUAGCAGUACCCU 21 6327 SCNN1A-2479 + UGGAGCUUAUAGUAGCAGUACCCU 24 6328 SCNN1A-2480 + CUGGUAGCUGGUCACGCU 18 6329 SCNN1A-1274 + AGCUGGUAGCUGGUCACGCU 20 5123 SCNN1A-2481 + AGAGCUGGUAGCUGGUCACGCU 22 6330 SCNN1A-2482 + AGAGAGCUGGUAGCUGGUCACGCU 24 6331 SCNN1A-2483 + ACAUCGGGUGGUGGAAGU 18 6332 SCNN1A-2484 + UACAUCGGGUGGUGGAAGU 19 6333 SCNN1A-2485 + AUACAUCGGGUGGUGGAAGU 20 6334 SCNN1A-2486 + CAUACAUCGGGUGGUGGAAGU 21 6335 SCNN1A-2487 + CCAUACAUCGGGUGGUGGAAGU 22 6336 SCNN1A-2488 + UCCAUACAUCGGGUGGUGGAAGU 23 6337 SCNN1A-2489 + UUCCAUACAUCGGGUGGUGGAAGU 24 6338 SCNN1A-2490 + UGGAAGACAUCCAGAGGU 18 6339 SCNN1A-2491 + AUGGAAGACAUCCAGAGGU 19 6340 SCNN1A-1284 + CAUGGAAGACAUCCAGAGGU 20 5133 SCNN1A-2492 + AGGCAUGGAAGACAUCCAGAGGU 23 6341 SCNN1A-2493 + CAGGCAUGGAAGACAUCCAGAGGU 24 6342 SCNN1A-2494 + CCAGCUCCUCUUUAAUUU 18 6343 SCNN1A-2495 + UCCAGCUCCUCUUUAAUUU 19 6344 SCNN1A-2496 + CUCCAGCUCCUCUUUAAUUU 20 6345 SCNN1A-2497 + CCUCCAGCUCCUCUUUAAUUU 21 6346 SCNN1A-2498 + UCCUCCAGCUCCUCUUUAAUUU 22 6347 SCNN1A-2499 + CUCCUCCAGCUCCUCUUUAAUUU 23 6348 SCNN1A-2500 UGCCCCACACCUAAGAAA 18 6349 SCNN1A-2501 CUGCCCCACACCUAAGAAA 19 6350 SCNN1A-884 UCUGCCCCACACCUAAGAAA 20 4733 SCNN1A-2502 CUCUGCCCCACACCUAAGAAA 21 6351 SCNN1A-2503 CCUCUGCCCCACACCUAAGAAA 22 6352 SCNN1A-2504 CCCUCUGCCCCACACCUAAGAAA 23 6353 SCNN1A-2505 ACCCUCUGCCCCACACCUAAGAAA 24 6354 SCNN1A-2506 AGGCAUCUCUCUGUACCCA 19 6355 SCNN1A-2507 CAGGCAUCUCUCUGUACCCA 20 6356 SCNN1A-2508 ACAGGCAUCUCUCUGUACCCA 21 6357 SCNN1A-2509 AACAGGCAUCUCUCUGUACCCA 22 6358 SCNN1A-2510 AGAACAGGCAUCUCUCUGUACCCA 24 6359 SCNN1A-2511 UCCAGGAGAGCAUGAUCA 18 6360 SCNN1A-2512 UUCCAGGAGAGCAUGAUCA 19 6361 SCNN1A-923 CUUCCAGGAGAGCAUGAUCA 20 4772 SCNN1A-2513 UGCUUCCAGGAGAGCAUGAUCA 22 6362 SCNN1A-2514 CUGCUUCCAGGAGAGCAUGAUCA 23 6363 SCNN1A-2515 CCUGCUUCCAGGAGAGCAUGAUCA 24 6364 SCNN1A-2516 CCCCAUUCUUUCCUAGGA 18 6365 SCNN1A-2517 CCCCCAUUCUUUCCUAGGA 19 6366 SCNN1A-2518 ACCCCCAUUCUUUCCUAGGA 20 6367 SCNN1A-2519 CACCCCCAUUCUUUCCUAGGA 21 6368 SCNN1A-2520 ACACCCCCAUUCUUUCCUAGGA 22 6369 SCNN1A-2521 UGACACCCCCAUUCUUUCCUAGGA 24 6370 SCNN1A-2522 CCAGGUAGAGUGUGGGGA 18 6371 SCNN1A-2523 CCCAGGUAGAGUGUGGGGA 19 6372 SCNN1A-957 UCCCAGGUAGAGUGUGGGGA 20 4806 SCNN1A-2524 AUCCCAGGUAGAGUGUGGGGA 21 6373 SCNN1A-2525 CAUCCCAGGUAGAGUGUGGGGA 22 6374 SCNN1A-2526 ACAUCCCAGGUAGAGUGUGGGGA 23 6375 SCNN1A-2527 CAGGGGUGGAUGCGGUGA 18 6376 SCNN1A-2528 UCAGGGGUGGAUGCGGUGA 19 6377 SCNN1A-967 AUCAGGGGUGGAUGCGGUGA 20 4816 SCNN1A-2529 CAUCAGGGGUGGAUGCGGUGA 21 6378 SCNN1A-2530 UCAUCAGGGGUGGAUGCGGUGA 22 6379 SCNN1A-2531 CUCAUCAGGGGUGGAUGCGGUGA 23 6380 SCNN1A-2532 ACUCAUCAGGGGUGGAUGCGGUGA 24 6381 SCNN1A-2533 ACUCUCUCUUUCCUGAUA 18 6382 SCNN1A-2534 UACUCUCUCUUUCCUGAUA 19 6383 SCNN1A-971 CUACUCUCUCUUUCCUGAUA 20 4820 SCNN1A-2535 CCUACUCUCUCUUUCCUGAUA 21 6384 SCNN1A-2536 CCCUACUCUCUCUUUCCUGAUA 22 6385 SCNN1A-2537 ACCCUACUCUCUCUUUCCUGAUA 23 6386 SCNN1A-2538 CGAUUAUGGCGACUGCACC 19 6387 SCNN1A-2539 CUGGAUGUCUUCCAUGCC 18 6388 SCNN1A-2540 UCUGGAUGUCUUCCAUGCC 19 6389 SCNN1A-1033 CUCUGGAUGUCUUCCAUGCC 20 4882 SCNN1A-2541 CCUCUGGAUGUCUUCCAUGCC 21 6390 SCNN1A-2542 ACCUCUGGAUGUCUUCCAUGCC 22 6391 SCNN1A-2543 AACCUCUGGAUGUCUUCCAUGCC 23 6392 SCNN1A-2544 CAACCUCUGGAUGUCUUCCAUGCC 24 6393 SCNN1A-2545 AGGUUAGUGUCCCCUUCC 18 6394 SCNN1A-2546 CAGGUUAGUGUCCCCUUCC 19 6395 SCNN1A-2547 UGCAGGUUAGUGUCCCCUUCC 21 6396 SCNN1A-2548 AUGCAGGUUAGUGUCCCCUUCC 22 6397 SCNN1A-2549 CAUGCAGGUUAGUGUCCCCUUCC 23 6398 SCNN1A-2550 CCAUGCAGGUUAGUGUCCCCUUCC 24 6399 SCNN1A-2551 UACAGAAAGCACAGUUCC 18 6400 SCNN1A-2552 CUACAGAAAGCACAGUUCC 19 6401 SCNN1A-1047 ACUACAGAAAGCACAGUUCC 20 4896 SCNN1A-2553 UGACUACAGAAAGCACAGUUCC 22 6402 SCNN1A-2554 UGUGACUACAGAAAGCACAGUUCC 24 6403 SCNN1A-2555 CAUCAGCAUGAGGAAGGC 18 6404 SCNN1A-2556 CCAUCAGCAUGAGGAAGGC 19 6405 SCNN1A-2557 UCCAUCAGCAUGAGGAAGGC 20 6406 SCNN1A-2558 CUCCAUCAGCAUGAGGAAGGC 21 6407 SCNN1A-2559 CCUCCAUCAGCAUGAGGAAGGC 22 6408 SCNN1A-2560 ACCUCCAUCAGCAUGAGGAAGGC 23 6409 SCNN1A-2561 AGGUCUCCUGCAACCAGGC 19 6410 SCNN1A-2562 CAGGUCUCCUGCAACCAGGC 20 6411 SCNN1A-2563 CCAGGUCUCCUGCAACCAGGC 21 6412 SCNN1A-2564 ACCAGGUCUCCUGCAACCAGGC 22 6413 SCNN1A-2565 AACCAGGUCUCCUGCAACCAGGC 23 6414 SCNN1A-2566 CAACCAGGUCUCCUGCAACCAGGC 24 6415 SCNN1A-2567 UCUCCAGGCCGAGGGGGC 18 6416 SCNN1A-2568 UGGUCUCCAGGCCGAGGGGGC 21 6417 SCNN1A-2569 CUGGUCUCCAGGCCGAGGGGGC 22 6418 SCNN1A-2570 ACUGGUCUCCAGGCCGAGGGGGC 23 6419 SCNN1A-2571 UACUGGUCUCCAGGCCGAGGGGGC 24 6420 SCNN1A-2572 UGUCCACAGUGACUGGGGC 19 6421 SCNN1A-2573 CUGUCCACAGUGACUGGGGC 20 6422 SCNN1A-2574 UGCUGUCCACAGUGACUGGGGC 22 6423 SCNN1A-2575 CUGCUGUCCACAGUGACUGGGGC 23 6424 SCNN1A-2576 CCUGCUGUCCACAGUGACUGGGGC 24 6425 SCNN1A-2577 UGUCACGGUAGGUCGUGC 18 6426 SCNN1A-2578 CUGUCACGGUAGGUCGUGC 19 6427 SCNN1A-2579 UCUGUCACGGUAGGUCGUGC 20 6428 SCNN1A-2580 CUCUGUCACGGUAGGUCGUGC 21 6429 SCNN1A-2581 CCUCUGUCACGGUAGGUCGUGC 22 6430 SCNN1A-2582 CCCUCUGUCACGGUAGGUCGUGC 23 6431 SCNN1A-2583 UCCCUCUGUCACGGUAGGUCGUGC 24 6432 SCNN1A-2584 CUACCAGACAUACUCAUC 18 6433 SCNN1A-2585 UCUACCAGACAUACUCAUC 19 6434 SCNN1A-1091 UUCUACCAGACAUACUCAUC 20 4940 SCNN1A-2586 CUUCUACCAGACAUACUCAUC 21 6435 SCNN1A-2587 UGCUUCUACCAGACAUACUCAUC 23 6436 SCNN1A-2588 CUGCUUCUACCAGACAUACUCAUC 24 6437 SCNN1A-2589 CUGAUGCUGCGCGCAGAG 18 6438 SCNN1A-2590 CCUGAUGCUGCGCGCAGAG 19 6439 SCNN1A-2591 CCCUGAUGCUGCGCGCAGAG 20 6440 SCNN1A-2592 UCCCUGAUGCUGCGCGCAGAG 21 6441 SCNN1A-2593 UGUCCCUGAUGCUGCGCGCAGAG 23 6442 SCNN1A-2594 CUGUCCCUGAUGCUGCGCGCAGAG 24 6443 SCNN1A-2595 AUCCGCGGCCCCAGAACG 18 6444 SCNN1A-2596 UAUCCGCGGCCCCAGAACG 19 6445 SCNN1A-1144 CUAUCCGCGGCCCCAGAACG 20 4993 SCNN1A-2597 UCUAUCCGCGGCCCCAGAACG 21 6446 SCNN1A-2598 UUCUAUCCGCGGCCCCAGAACG 22 6447 SCNN1A-2599 CUUCUAUCCGCGGCCCCAGAACG 23 6448 SCNN1A-2600 UCUUCUAUCCGCGGCCCCAGAACG 24 6449 SCNN1A-2601 CCUCGGUGACAUCCCAGG 18 6450 SCNN1A-2602 CCCUCGGUGACAUCCCAGG 19 6451 SCNN1A-2603 UGGCCCUCGGUGACAUCCCAGG 22 6452 SCNN1A-2604 AUGGCCCUCGGUGACAUCCCAGG 23 6453 SCNN1A-2605 AGGUAGAGUGUGGGGAAGGG 20 6454 SCNN1A-2606 CAGGUAGAGUGUGGGGAAGGG 21 6455 SCNN1A-2607 CCAGGUAGAGUGUGGGGAAGGG 22 6456 SCNN1A-2608 CCCAGGUAGAGUGUGGGGAAGGG 23 6457 SCNN1A-2609 UCCCAGGUAGAGUGUGGGGAAGGG 24 6458 SCNN1A-2610 CAGACAUACUCAUCAGGG 18 6459 SCNN1A-2611 CCAGACAUACUCAUCAGGG 19 6460 SCNN1A-2612 ACCAGACAUACUCAUCAGGG 20 6461 SCNN1A-2613 UACCAGACAUACUCAUCAGGG 21 6462 SCNN1A-2614 CUACCAGACAUACUCAUCAGGG 22 6463 SCNN1A-2615 UCUACCAGACAUACUCAUCAGGG 23 6464 SCNN1A-2616 UUCUACCAGACAUACUCAUCAGGG 24 6465 SCNN1A-2617 CGGGUAAUGGUGCACGGG 18 6466 SCNN1A-2618 CCGGGUAAUGGUGCACGGG 19 6467 SCNN1A-2619 CCCGGGUAAUGGUGCACGGG 20 6468 SCNN1A-2620 UGUGGGGAAGGGAUGGGUG 19 6469 SCNN1A-2621 AGUGUGGGGAAGGGAUGGGUG 21 6470 SCNN1A-2622 AGAGUGUGGGGAAGGGAUGGGUG 23 6471 SCNN1A-2623 UAGAGUGUGGGGAAGGGAUGGGUG 24 6472 SCNN1A-2624 CAAGAACAACUCCAACCU 18 6473 SCNN1A-2625 ACAAGAACAACUCCAACCU 19 6474 SCNN1A-2626 UGACAAGAACAACUCCAACCU 21 6475 SCNN1A-2627 AUGACAAGAACAACUCCAACCU 22 6476 SCNN1A-2628 AAUGACAAGAACAACUCCAACCU 23 6477 SCNN1A-2629 CAAUGACAAGAACAACUCCAACCU 24 6478 SCNN1A-2630 CGCACCCCUUGCAGCGCCU 19 6479 SCNN1A-2631 CCGCACCCCUUGCAGCGCCU 20 6480 SCNN1A-2632 UGCCGCACCCCUUGCAGCGCCU 22 6481 SCNN1A-2633 CUGCCGCACCCCUUGCAGCGCCU 23 6482 SCNN1A-2634 UCUGCCGCACCCCUUGCAGCGCCU 24 6483 SCNN1A-2635 ACACCCCCAUUCUUUCCU 18 6484 SCNN1A-1272 UGACACCCCCAUUCUUUCCU 20 5121 SCNN1A-2636 AUGACACCCCCAUUCUUUCCU 21 6485 SCNN1A-2637 UGAUGACACCCCCAUUCUUUCCU 23 6486 SCNN1A-2638 UUGAUGACACCCCCAUUCUUUCCU 24 6487 SCNN1A-2639 UGAACUACAAAACCAAUU 18 6488 SCNN1A-2640 CUGAACUACAAAACCAAUU 19 6489 SCNN1A-2641 AGCUGAACUACAAAACCAAUU 21 6490 SCNN1A-2642 AGGAGCUGAACUACAAAACCAAUU 24 6491 SCNN1A-2643 CAGGAUGAACCUGCCUUU 18 6492 SCNN1A-2644 CGGGCAGGAUGAACCUGCCUUU 22 6493 SCNN1A-2645 ACGGGCAGGAUGAACCUGCCUUU 23 6494 SCNN1A-2646 CACGGGCAGGAUGAACCUGCCUUU 24 6495

Table 44G provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the seven tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene) and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 44G 7th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-2647 + UAAUUCCUUAUCAGGAAA 18 6496 SCNN1A-2648 + GUAAUUCCUUAUCAGGAAA 19 6497 SCNN1A-2649 + AGUAAUUCCUUAUCAGGAAA 20 6498 SCNN1A-2650 + GAGUAAUUCCUUAUCAGGAAA 21 6499 SCNN1A-2651 + AGAGUAAUUCCUUAUCAGGAAA 22 6500 SCNN1A-2652 + GAGAGUAAUUCCUUAUCAGGAAA 23 6501 SCNN1A-2653 + UGAGAGUAAUUCCUUAUCAGGAAA 24 6502 SCNN1A-2654 + AAGGGUAAAGGUUCUCAA 18 6503 SCNN1A-2655 + GAAGGGUAAAGGUUCUCAA 19 6504 SCNN1A-2656 + UGAAGGGUAAAGGUUCUCAA 20 6505 SCNN1A-2657 + UUGAAGGGUAAAGGUUCUCAA 21 6506 SCNN1A-2658 + UUUGAAGGGUAAAGGUUCUCAA 22 6507 SCNN1A-2659 + CUUUGAAGGGUAAAGGUUCUCAA 23 6508 SCNN1A-2660 + ACUUUGAAGGGUAAAGGUUCUCAA 24 6509 SCNN1A-2661 + CCCAUUCCUAGGAAAGAA 18 6510 SCNN1A-2662 + ACCCAUUCCUAGGAAAGAA 19 6511 SCNN1A-887 + GACCCAUUCCUAGGAAAGAA 20 4736 SCNN1A-2663 + AGACCCAUUCCUAGGAAAGAA 21 6512 SCNN1A-2664 + AAGACCCAUUCCUAGGAAAGAA 22 6513 SCNN1A-2665 + GAAGACCCAUUCCUAGGAAAGAA 23 6514 SCNN1A-2666 + GGAAGACCCAUUCCUAGGAAAGAA 24 6515 SCNN1A-2667 + CAUGGGGUGGGGGCAGAA 18 6516 SCNN1A-2668 + ACAUGGGGUGGGGGCAGAA 19 6517 SCNN1A-2669 + GACAUGGGGUGGGGGCAGAA 20 6518 SCNN1A-2670 + AGACAUGGGGUGGGGGCAGAA 21 6519 SCNN1A-2671 + GAGACAUGGGGUGGGGGCAGAA 22 6520 SCNN1A-2672 + AGAGACAUGGGGUGGGGGCAGAA 23 6521 SCNN1A-2673 + CAGAGACAUGGGGUGGGGGCAGAA 24 6522 SCNN1A-2674 + GUGAAUACACACCUGGAA 18 6523 SCNN1A-2675 + AGUGAAUACACACCUGGAA 19 6524 SCNN1A-892 + GAGUGAAUACACACCUGGAA 20 4741 SCNN1A-2676 + GGAGUGAAUACACACCUGGAA 21 6525 SCNN1A-2677 + AGGAGUGAAUACACACCUGGAA 22 6526 SCNN1A-2678 + CAGGAGUGAAUACACACCUGGAA 23 6527 SCNN1A-2679 + GCAGGAGUGAAUACACACCUGGAA 24 6528 SCNN1A-2680 + AUACAUCGGGUGGUGGAA 18 6529 SCNN1A-2681 + CAUACAUCGGGUGGUGGAA 19 6530 SCNN1A-2682 + CCAUACAUCGGGUGGUGGAA 20 6531 SCNN1A-2683 + UCCAUACAUCGGGUGGUGGAA 21 6532 SCNN1A-2684 + UUCCAUACAUCGGGUGGUGGAA 22 6533 SCNN1A-2685 + UUUCCAUACAUCGGGUGGUGGAA 23 6534 SCNN1A-2686 + GUUUCCAUACAUCGGGUGGUGGAA 24 6535 SCNN1A-2687 + UCUCCACCACAGACAACA 18 6536 SCNN1A-2688 + AUCUCCACCACAGACAACA 19 6537 SCNN1A-2689 + CAUCUCCACCACAGACAACA 20 6538 SCNN1A-2690 + CCAUCUCCACCACAGACAACA 21 6539 SCNN1A-2691 + GCCAUCUCCACCACAGACAACA 22 6540 SCNN1A-2692 + AGCCAUCUCCACCACAGACAACA 23 6541 SCNN1A-2693 + CAGCCAUCUCCACCACAGACAACA 24 6542 SCNN1A-2694 + UUCUGGUUGCACUGGACA 18 6543 SCNN1A-2695 + GUUCUGGUUGCACUGGACA 19 6544 SCNN1A-2696 + UGUUCUGGUUGCACUGGACA 20 6545 SCNN1A-2697 + UUGUUCUGGUUGCACUGGACA 21 6546 SCNN1A-2698 + UUUGUUCUGGUUGCACUGGACA 22 6547 SCNN1A-2699 + AUUUGUUCUGGUUGCACUGGACA 23 6548 SCNN1A-2700 + GAUUUGUUCUGGUUGCACUGGACA 24 6549 SCNN1A-2701 + GCACGACCUACCGUGACA 18 6550 SCNN1A-2702 + GGCACGACCUACCGUGACA 19 6551 SCNN1A-2703 + AGGCACGACCUACCGUGACA 20 6552 SCNN1A-2704 + CAGGCACGACCUACCGUGACA 21 6553 SCNN1A-2705 + CCAGGCACGACCUACCGUGACA 22 6554 SCNN1A-2706 + UCCAGGCACGACCUACCGUGACA 23 6555 SCNN1A-2707 + AUCCAGGCACGACCUACCGUGACA 24 6556 SCNN1A-2708 + CAGUACCCUGUGGGUACA 18 6557 SCNN1A-2709 + GCAGUACCCUGUGGGUACA 19 6558 SCNN1A-2710 + AGCAGUACCCUGUGGGUACA 20 6559 SCNN1A-2711 + UAGCAGUACCCUGUGGGUACA 21 6560 SCNN1A-2712 + GUAGCAGUACCCUGUGGGUACA 22 6561 SCNN1A-2713 + AGUAGCAGUACCCUGUGGGUACA 23 6562 SCNN1A-2714 + UAGUAGCAGUACCCUGUGGGUACA 24 6563 SCNN1A-2715 + CCUCUCAGGGCCCCCCCA 18 6564 SCNN1A-2716 + CCCUCUCAGGGCCCCCCCA 19 6565 SCNN1A-2717 + UCCCUCUCAGGGCCCCCCCA 20 6566 SCNN1A-2718 + UUCCCUCUCAGGGCCCCCCCA 21 6567 SCNN1A-2719 + CUUCCCUCUCAGGGCCCCCCCA 22 6568 SCNN1A-2720 + CCUUCCCUCUCAGGGCCCCCCCA 23 6569 SCNN1A-2721 + UCCUUCCCUCUCAGGGCCCCCCCA 24 6570 SCNN1A-2722 + GGCGCCAUGGAGCAAGCA 18 6571 SCNN1A-2723 + GGGCGCCAUGGAGCAAGCA 19 6572 SCNN1A-909 + AGGGCGCCAUGGAGCAAGCA 20 4758 SCNN1A-2724 + GAGGGCGCCAUGGAGCAAGCA 21 6573 SCNN1A-2725 + AGAGGGCGCCAUGGAGCAAGCA 22 6574 SCNN1A-2726 + CAGAGGGCGCCAUGGAGCAAGCA 23 6575 SCNN1A-2727 + GCAGAGGGCGCCAUGGAGCAAGCA 24 6576 SCNN1A-2728 + CAGUCACUGUGGACAGCA 18 6577 SCNN1A-2729 + CCAGUCACUGUGGACAGCA 19 6578 SCNN1A-910 + CCCAGUCACUGUGGACAGCA 20 4759 SCNN1A-2730 + CCCCAGUCACUGUGGACAGCA 21 6579 SCNN1A-2731 + GCCCCAGUCACUGUGGACAGCA 22 6580 SCNN1A-2732 + GGCCCCAGUCACUGUGGACAGCA 23 6581 SCNN1A-2733 + GGGCCCCAGUCACUGUGGACAGCA 24 6582 SCNN1A-2734 + CAUCGUGAGUAACCAGCA 18 6583 SCNN1A-2735 + CCAUCGUGAGUAACCAGCA 19 6584 SCNN1A-2736 + GCCAUCGUGAGUAACCAGCA 20 6585 SCNN1A-2737 + GGCCAUCGUGAGUAACCAGCA 21 6586 SCNN1A-2738 + GGGCCAUCGUGAGUAACCAGCA 22 6587 SCNN1A-2739 + AGGGCCAUCGUGAGUAACCAGCA 23 6588 SCNN1A-2740 + GAGGGCCAUCGUGAGUAACCAGCA 24 6589 SCNN1A-2741 + CGUUGUUGAUUCCAGGCA 18 6590 SCNN1A-2742 + CCGUUGUUGAUUCCAGGCA 19 6591 SCNN1A-913 + ACCGUUGUUGAUUCCAGGCA 20 4762 SCNN1A-2743 + CACCGUUGUUGAUUCCAGGCA 21 6592 SCNN1A-2744 + UCACCGUUGUUGAUUCCAGGCA 22 6593 SCNN1A-2745 + CUCACCGUUGUUGAUUCCAGGCA 23 6594 SCNN1A-2746 + UCUCACCGUUGUUGAUUCCAGGCA 24 6595 SCNN1A-2747 + CCCAGGGUGGCAUAGGCA 18 6596 SCNN1A-2748 + GCCCAGGGUGGCAUAGGCA 19 6597 SCNN1A-914 + GGCCCAGGGUGGCAUAGGCA 20 4763 SCNN1A-2749 + GGGCCCAGGGUGGCAUAGGCA 21 6598 SCNN1A-2750 + GGGGCCCAGGGUGGCAUAGGCA 22 6599 SCNN1A-2751 + GGGGGCCCAGGGUGGCAUAGGCA 23 6600 SCNN1A-2752 + CGGGGGCCCAGGGUGGCAUAGGCA 24 6601 SCNN1A-2753 + GACAGACCUAGGGGUGCA 18 6602 SCNN1A-2754 + GGACAGACCUAGGGGUGCA 19 6603 SCNN1A-2755 + GGGACAGACCUAGGGGUGCA 20 6604 SCNN1A-2756 + AGGGACAGACCUAGGGGUGCA 21 6605 SCNN1A-2757 + CAGGGACAGACCUAGGGGUGCA 22 6606 SCNN1A-2758 + UCAGGGACAGACCUAGGGGUGCA 23 6607 SCNN1A-2759 + AUCAGGGACAGACCUAGGGGUGCA 24 6608 SCNN1A-2760 + CGAUUUGUUCUGGUUGCA 18 6609 SCNN1A-2761 + CCGAUUUGUUCUGGUUGCA 19 6610 SCNN1A-2762 + UCCGAUUUGUUCUGGUUGCA 20 6611 SCNN1A-2763 + GUCCGAUUUGUUCUGGUUGCA 21 6612 SCNN1A-2764 + AGUCCGAUUUGUUCUGGUUGCA 22 6613 SCNN1A-2765 + CAGUCCGAUUUGUUCUGGUUGCA 23 6614 SCNN1A-2766 + GCAGUCCGAUUUGUUCUGGUUGCA 24 6615 SCNN1A-2767 + ACACAGAGACUAGAGUCA 18 6616 SCNN1A-2768 + GACACAGAGACUAGAGUCA 19 6617 SCNN1A-2769 + GGACACAGAGACUAGAGUCA 20 6618 SCNN1A-2770 + UGGACACAGAGACUAGAGUCA 21 6619 SCNN1A-2771 + CUGGACACAGAGACUAGAGUCA 22 6620 SCNN1A-2772 + ACUGGACACAGAGACUAGAGUCA 23 6621 SCNN1A-2773 + CACUGGACACAGAGACUAGAGUCA 24 6622 SCNN1A-2774 + CUGUAUUUGUACAGGUCA 18 6623 SCNN1A-2775 + GCUGUAUUUGUACAGGUCA 19 6624 SCNN1A-2776 + AGCUGUAUUUGUACAGGUCA 20 6625 SCNN1A-2777 + GAGCUGUAUUUGUACAGGUCA 21 6626 SCNN1A-2778 + GGAGCUGUAUUUGUACAGGUCA 22 6627 SCNN1A-2779 + AGGAGCUGUAUUUGUACAGGUCA 23 6628 SCNN1A-2780 + AAGGAGCUGUAUUUGUACAGGUCA 24 6629 SCNN1A-2781 + ACUCUACCUGGGAUGUCA 18 6630 SCNN1A-2782 + CACUCUACCUGGGAUGUCA 19 6631 SCNN1A-2783 + ACACUCUACCUGGGAUGUCA 20 6632 SCNN1A-2784 + CACACUCUACCUGGGAUGUCA 21 6633 SCNN1A-2785 + CCACACUCUACCUGGGAUGUCA 22 6634 SCNN1A-2786 + CCCACACUCUACCUGGGAUGUCA 23 6635 SCNN1A-2787 + CCCCACACUCUACCUGGGAUGUCA 24 6636 SCNN1A-2788 + UUGGAGUUGUUCUUGUCA 18 6637 SCNN1A-2789 + GUUGGAGUUGUUCUUGUCA 19 6638 SCNN1A-2790 + GGUUGGAGUUGUUCUUGUCA 20 6639 SCNN1A-2791 + AGGUUGGAGUUGUUCUUGUCA 21 6640 SCNN1A-2792 + GAGGUUGGAGUUGUUCUUGUCA 22 6641 SCNN1A-2793 + AGAGGUUGGAGUUGUUCUUGUCA 23 6642 SCNN1A-2794 + CAGAGGUUGGAGUUGUUCUUGUCA 24 6643 SCNN1A-2795 + ACCCAUUCCUAGGAAAGA 18 6644 SCNN1A-2796 + GACCCAUUCCUAGGAAAGA 19 6645 SCNN1A-2797 + AGACCCAUUCCUAGGAAAGA 20 6646 SCNN1A-2798 + AAGACCCAUUCCUAGGAAAGA 21 6647 SCNN1A-2799 + GAAGACCCAUUCCUAGGAAAGA 22 6648 SCNN1A-2800 + GGAAGACCCAUUCCUAGGAAAGA 23 6649 SCNN1A-2801 + UGGAAGACCCAUUCCUAGGAAAGA 24 6650 SCNN1A-2802 + ACGACCUACCGUGACAGA 18 6651 SCNN1A-2803 + CACGACCUACCGUGACAGA 19 6652 SCNN1A-931 + GCACGACCUACCGUGACAGA 20 4780 SCNN1A-2804 + GGCACGACCUACCGUGACAGA 21 6653 SCNN1A-2805 + AGGCACGACCUACCGUGACAGA 22 6654 SCNN1A-2806 + CAGGCACGACCUACCGUGACAGA 23 6655 SCNN1A-2807 + CCAGGCACGACCUACCGUGACAGA 24 6656 SCNN1A-2808 + CAGACCUAGGGGUGCAGA 18 6657 SCNN1A-2809 + ACAGACCUAGGGGUGCAGA 19 6658 SCNN1A-2810 + GACAGACCUAGGGGUGCAGA 20 6659 SCNN1A-2811 + GGACAGACCUAGGGGUGCAGA 21 6660 SCNN1A-2812 + GGGACAGACCUAGGGGUGCAGA 22 6661 SCNN1A-2813 + AGGGACAGACCUAGGGGUGCAGA 23 6662 SCNN1A-2814 + CAGGGACAGACCUAGGGGUGCAGA 24 6663 SCNN1A-2815 + ACAGAGACUAGAGUCAGA 18 6664 SCNN1A-2816 + CACAGAGACUAGAGUCAGA 19 6665 SCNN1A-933 + ACACAGAGACUAGAGUCAGA 20 4782 SCNN1A-2817 + GACACAGAGACUAGAGUCAGA 21 6666 SCNN1A-2818 + GGACACAGAGACUAGAGUCAGA 22 6667 SCNN1A-2819 + UGGACACAGAGACUAGAGUCAGA 23 6668 SCNN1A-2820 + CUGGACACAGAGACUAGAGUCAGA 24 6669 SCNN1A-2821 + GGCUGUCAAGGCUGGAGA 18 6670 SCNN1A-2822 + GGGCUGUCAAGGCUGGAGA 19 6671 SCNN1A-936 + GGGGCUGUCAAGGCUGGAGA 20 4785 SCNN1A-2823 + AGGGGCUGUCAAGGCUGGAGA 21 6672 SCNN1A-2824 + GAGGGGCUGUCAAGGCUGGAGA 22 6673 SCNN1A-2825 + GGAGGGGCUGUCAAGGCUGGAGA 23 6674 SCNN1A-2826 + GGGAGGGGCUGUCAAGGCUGGAGA 24 6675 SCNN1A-2827 + GGGUACCUGAAGGGGCGA 18 6676 SCNN1A-2828 + CGGGUACCUGAAGGGGCGA 19 6677 SCNN1A-946 + CCGGGUACCUGAAGGGGCGA 20 4795 SCNN1A-2829 + UCCGGGUACCUGAAGGGGCGA 21 6678 SCNN1A-2830 + UUCCGGGUACCUGAAGGGGCGA 22 6679 SCNN1A-2831 + UUUCCGGGUACCUGAAGGGGCGA 23 6680 SCNN1A-2832 + AUUUCCGGGUACCUGAAGGGGCGA 24 6681 SCNN1A-2833 + GCCUGGCUGGGACAAGGA 18 6682 SCNN1A-2834 + GGCCUGGCUGGGACAAGGA 19 6683 SCNN1A-2835 + GGGCCUGGCUGGGACAAGGA 20 6684 SCNN1A-2836 + AGGGCCUGGCUGGGACAAGGA 21 6685 SCNN1A-2837 + CAGGGCCUGGCUGGGACAAGGA 22 6686 SCNN1A-2838 + GCAGGGCCUGGCUGGGACAAGGA 23 6687 SCNN1A-2839 + AGCAGGGCCUGGCUGGGACAAGGA 24 6688 SCNN1A-2840 + GGGCAGAAGUGGGAAGGA 18 6689 SCNN1A-2841 + GGGGCAGAAGUGGGAAGGA 19 6690 SCNN1A-948 + GGGGGCAGAAGUGGGAAGGA 20 4797 SCNN1A-2842 + UGGGGGCAGAAGUGGGAAGGA 21 6691 SCNN1A-2843 + GUGGGGGCAGAAGUGGGAAGGA 22 6692 SCNN1A-2844 + GGUGGGGGCAGAAGUGGGAAGGA 23 6693 SCNN1A-2845 + GGGUGGGGGCAGAAGUGGGAAGGA 24 6694 SCNN1A-2846 + AGUAAUUCCUUAUCAGGA 18 6695 SCNN1A-2847 + GAGUAAUUCCUUAUCAGGA 19 6696 SCNN1A-2848 + AGAGUAAUUCCUUAUCAGGA 20 6697 SCNN1A-2849 + GAGAGUAAUUCCUUAUCAGGA 21 6698 SCNN1A-2850 + UGAGAGUAAUUCCUUAUCAGGA 22 6699 SCNN1A-2851 + GUGAGAGUAAUUCCUUAUCAGGA 23 6700 SCNN1A-2852 + AGUGAGAGUAAUUCCUUAUCAGGA 24 6701 SCNN1A-2853 + GGAGGAGGGUGGAGAGGA 18 6702 SCNN1A-2854 + GGGAGGAGGGUGGAGAGGA 19 6703 SCNN1A-2855 + AGGGAGGAGGGUGGAGAGGA 20 6704 SCNN1A-2856 + AAGGGAGGAGGGUGGAGAGGA 21 6705 SCNN1A-2857 + GAAGGGAGGAGGGUGGAGAGGA 22 6706 SCNN1A-2858 + GGAAGGGAGGAGGGUGGAGAGGA 23 6707 SCNN1A-2859 + UGGAAGGGAGGAGGGUGGAGAGGA 24 6708 SCNN1A-2860 + ACGUUCUGGGGCCGCGGA 18 6709 SCNN1A-2861 + CACGUUCUGGGGCCGCGGA 19 6710 SCNN1A-2862 + CCACGUUCUGGGGCCGCGGA 20 6711 SCNN1A-2863 + UCCACGUUCUGGGGCCGCGGA 21 6712 SCNN1A-2864 + CUCCACGUUCUGGGGCCGCGGA 22 6713 SCNN1A-2865 + ACUCCACGUUCUGGGGCCGCGGA 23 6714 SCNN1A-2866 + UACUCCACGUUCUGGGGCCGCGGA 24 6715 SCNN1A-2867 + ACUGUGGACAGCAGGGGA 18 6716 SCNN1A-2868 + CACUGUGGACAGCAGGGGA 19 6717 SCNN1A-2869 + UCACUGUGGACAGCAGGGGA 20 6718 SCNN1A-2870 + GUCACUGUGGACAGCAGGGGA 21 6719 SCNN1A-2871 + AGUCACUGUGGACAGCAGGGGA 22 6720 SCNN1A-2872 + CAGUCACUGUGGACAGCAGGGGA 23 6721 SCNN1A-2873 + CCAGUCACUGUGGACAGCAGGGGA 24 6722 SCNN1A-2874 + AGCUGGUCACGCUGGGGA 18 6723 SCNN1A-2875 + UAGCUGGUCACGCUGGGGA 19 6724 SCNN1A-956 + GUAGCUGGUCACGCUGGGGA 20 4805 SCNN1A-2876 + GGUAGCUGGUCACGCUGGGGA 21 6725 SCNN1A-2877 + UGGUAGCUGGUCACGCUGGGGA 22 6726 SCNN1A-2878 + CUGGUAGCUGGUCACGCUGGGGA 23 6727 SCNN1A-2879 + GCUGGUAGCUGGUCACGCUGGGGA 24 6728 SCNN1A-2880 + GUGGGGGCAGAAGUGGGA 18 6729 SCNN1A-2881 + GGUGGGGGCAGAAGUGGGA 19 6730 SCNN1A-958 + GGGUGGGGGCAGAAGUGGGA 20 4807 SCNN1A-2882 + GGGGUGGGGGCAGAAGUGGGA 21 6731 SCNN1A-2883 + UGGGGUGGGGGCAGAAGUGGGA 22 6732 SCNN1A-2884 + AUGGGGUGGGGGCAGAAGUGGGA 23 6733 SCNN1A-2885 + CAUGGGGUGGGGGCAGAAGUGGGA 24 6734 SCNN1A-2886 + AGUGAAUACACACCUGGA 18 6735 SCNN1A-2887 + GAGUGAAUACACACCUGGA 19 6736 SCNN1A-960 + GGAGUGAAUACACACCUGGA 20 4809 SCNN1A-2888 + AGGAGUGAAUACACACCUGGA 21 6737 SCNN1A-2889 + CAGGAGUGAAUACACACCUGGA 22 6738 SCNN1A-2890 + GCAGGAGUGAAUACACACCUGGA 23 6739 SCNN1A-2891 + AGCAGGAGUGAAUACACACCUGGA 24 6740 SCNN1A-2892 + GGGGCUGUCAAGGCUGGA 18 6741 SCNN1A-2893 + AGGGGCUGUCAAGGCUGGA 19 6742 SCNN1A-2894 + GAGGGGCUGUCAAGGCUGGA 20 6743 SCNN1A-2895 + GGAGGGGCUGUCAAGGCUGGA 21 6744 SCNN1A-2896 + GGGAGGGGCUGUCAAGGCUGGA 22 6745 SCNN1A-2897 + GGGGAGGGGCUGUCAAGGCUGGA 23 6746 SCNN1A-2898 + GGGGGAGGGGCUGUCAAGGCUGGA 24 6747 SCNN1A-2899 + GGAAGGGAGGAGGGUGGA 18 6748 SCNN1A-2900 + UGGAAGGGAGGAGGGUGGA 19 6749 SCNN1A-2901 + CUGGAAGGGAGGAGGGUGGA 20 6750 SCNN1A-2902 + CCUGGAAGGGAGGAGGGUGGA 21 6751 SCNN1A-2903 + ACCUGGAAGGGAGGAGGGUGGA 22 6752 SCNN1A-2904 + CACCUGGAAGGGAGGAGGGUGGA 23 6753 SCNN1A-2905 + ACACCUGGAAGGGAGGAGGGUGGA 24 6754 SCNN1A-2906 + CUGGCUGCCCAGGUUGGA 18 6755 SCNN1A-2907 + ACUGGCUGCCCAGGUUGGA 19 6756 SCNN1A-2908 + CACUGGCUGCCCAGGUUGGA 20 6757 SCNN1A-2909 + CCACUGGCUGCCCAGGUUGGA 21 6758 SCNN1A-2910 + UCCACUGGCUGCCCAGGUUGGA 22 6759 SCNN1A-2911 + CUCCACUGGCUGCCCAGGUUGGA 23 6760 SCNN1A-2912 + GCUCCACUGGCUGCCCAGGUUGGA 24 6761 SCNN1A-2913 + UAAUUUCCGGGUACCUGA 18 6762 SCNN1A-2914 + UUAAUUUCCGGGUACCUGA 19 6763 SCNN1A-964 + UUUAAUUUCCGGGUACCUGA 20 4813 SCNN1A-2915 + CUUUAAUUUCCGGGUACCUGA 21 6764 SCNN1A-2916 + UCUUUAAUUUCCGGGUACCUGA 22 6765 SCNN1A-2917 + CUCUUUAAUUUCCGGGUACCUGA 23 6766 SCNN1A-2918 + CCUCUUUAAUUUCCGGGUACCUGA 24 6767 SCNN1A-2919 + UUGCCUUCCUCAUGCUGA 18 6768 SCNN1A-2920 + CUUGCCUUCCUCAUGCUGA 19 6769 SCNN1A-966 + CCUUGCCUUCCUCAUGCUGA 20 4815 SCNN1A-2921 + UCCUUGCCUUCCUCAUGCUGA 21 6770 SCNN1A-2922 + AUCCUUGCCUUCCUCAUGCUGA 22 6771 SCNN1A-2923 + CAUCCUUGCCUUCCUCAUGCUGA 23 6772 SCNN1A-2924 + GCAUCCUUGCCUUCCUCAUGCUGA 24 6773 SCNN1A-2925 + AGGCACGACCUACCGUGA 18 6774 SCNN1A-2926 + CAGGCACGACCUACCGUGA 19 6775 SCNN1A-2927 + CCAGGCACGACCUACCGUGA 20 6776 SCNN1A-2928 + UCCAGGCACGACCUACCGUGA 21 6777 SCNN1A-2929 + AUCCAGGCACGACCUACCGUGA 22 6778 SCNN1A-2930 + CAUCCAGGCACGACCUACCGUGA 23 6779 SCNN1A-2931 + CCAUCCAGGCACGACCUACCGUGA 24 6780 SCNN1A-2932 + CGGCCACGAGAGUGGUGA 18 6781 SCNN1A-2933 + CCGGCCACGAGAGUGGUGA 19 6782 SCNN1A-968 + GCCGGCCACGAGAGUGGUGA 20 4817 SCNN1A-2934 + AGCCGGCCACGAGAGUGGUGA 21 6783 SCNN1A-2935 + GAGCCGGCCACGAGAGUGGUGA 22 6784 SCNN1A-2936 + GGAGCCGGCCACGAGAGUGGUGA 23 6785 SCNN1A-2937 + GGGAGCCGGCCACGAGAGUGGUGA 24 6786 SCNN1A-2938 + GAGGGUGACCAUCUGUGA 18 6787 SCNN1A-2939 + GGAGGGUGACCAUCUGUGA 19 6788 SCNN1A-2940 + AGGAGGGUGACCAUCUGUGA 20 6789 SCNN1A-2941 + CAGGAGGGUGACCAUCUGUGA 21 6790 SCNN1A-2942 + ACAGGAGGGUGACCAUCUGUGA 22 6791 SCNN1A-2943 + GACAGGAGGGUGACCAUCUGUGA 23 6792 SCNN1A-2944 + GGACAGGAGGGUGACCAUCUGUGA 24 6793 SCNN1A-2945 + AGCAGUACCCUGUGGGUA 18 6794 SCNN1A-2946 + UAGCAGUACCCUGUGGGUA 19 6795 SCNN1A-2947 + GUAGCAGUACCCUGUGGGUA 20 6796 SCNN1A-2948 + AGUAGCAGUACCCUGUGGGUA 21 6797 SCNN1A-2949 + UAGUAGCAGUACCCUGUGGGUA 22 6798 SCNN1A-2950 + AUAGUAGCAGUACCCUGUGGGUA 23 6799 SCNN1A-2951 + UAUAGUAGCAGUACCCUGUGGGUA 24 6800 SCNN1A-2952 + CGACAGGAUGUUGAUGUA 18 6801 SCNN1A-2953 + UCGACAGGAUGUUGAUGUA 19 6802 SCNN1A-2954 + CUCGACAGGAUGUUGAUGUA 20 6803 SCNN1A-2955 + CCUCGACAGGAUGUUGAUGUA 21 6804 SCNN1A-2956 + GCCUCGACAGGAUGUUGAUGUA 22 6805 SCNN1A-2957 + AGCCUCGACAGGAUGUUGAUGUA 23 6806 SCNN1A-2958 + CAGCCUCGACAGGAUGUUGAUGUA 24 6807 SCNN1A-2959 + AGGGUAAAGGUUCUCAAC 18 6808 SCNN1A-2960 + AAGGGUAAAGGUUCUCAAC 19 6809 SCNN1A-978 + GAAGGGUAAAGGUUCUCAAC 20 4827 SCNN1A-2961 + UGAAGGGUAAAGGUUCUCAAC 21 6810 SCNN1A-2962 + UUGAAGGGUAAAGGUUCUCAAC 22 6811 SCNN1A-2963 + UUUGAAGGGUAAAGGUUCUCAAC 23 6812 SCNN1A-2964 + CUUUGAAGGGUAAAGGUUCUCAAC 24 6813 SCNN1A-2965 + GUCUGAGGAGAAGUCAAC 18 6814 SCNN1A-2966 + GGUCUGAGGAGAAGUCAAC 19 6815 SCNN1A-2967 + UGGUCUGAGGAGAAGUCAAC 20 6816 SCNN1A-2968 + GUGGUCUGAGGAGAAGUCAAC 21 6817 SCNN1A-2969 + GGUGGUCUGAGGAGAAGUCAAC 22 6818 SCNN1A-2970 + AGGUGGUCUGAGGAGAAGUCAAC 23 6819 SCNN1A-2971 + CAGGUGGUCUGAGGAGAAGUCAAC 24 6820 SCNN1A-2972 + GCAGGAGUGAAUACACAC 18 6821 SCNN1A-2973 + AGCAGGAGUGAAUACACAC 19 6822 SCNN1A-2974 + AAGCAGGAGUGAAUACACAC 20 6823 SCNN1A-2975 + GAAGCAGGAGUGAAUACACAC 21 6824 SCNN1A-2976 + GGAAGCAGGAGUGAAUACACAC 22 6825 SCNN1A-2977 + UGGAAGCAGGAGUGAAUACACAC 23 6826 SCNN1A-2978 + CUGGAAGCAGGAGUGAAUACACAC 24 6827 SCNN1A-2979 + CCAGUCCUUCCAGUCCAC 18 6828 SCNN1A-2980 + UCCAGUCCUUCCAGUCCAC 19 6829 SCNN1A-2981 + UUCCAGUCCUUCCAGUCCAC 20 6830 SCNN1A-2982 + CUUCCAGUCCUUCCAGUCCAC 21 6831 SCNN1A-2983 + UCUUCCAGUCCUUCCAGUCCAC 22 6832 SCNN1A-2984 + AUCUUCCAGUCCUUCCAGUCCAC 23 6833 SCNN1A-2985 + GAUCUUCCAGUCCUUCCAGUCCAC 24 6834 SCNN1A-2986 + UGGGACAAGGACAGAGAC 18 6835 SCNN1A-2987 + CUGGGACAAGGACAGAGAC 19 6836 SCNN1A-2988 + GCUGGGACAAGGACAGAGAC 20 6837 SCNN1A-2989 + GGCUGGGACAAGGACAGAGAC 21 6838 SCNN1A-2990 + UGGCUGGGACAAGGACAGAGAC 22 6839 SCNN1A-2991 + CUGGCUGGGACAAGGACAGAGAC 23 6840 SCNN1A-2992 + CCUGGCUGGGACAAGGACAGAGAC 24 6841 SCNN1A-2993 + GCAGGGCCUGGCUGGGAC 18 6842 SCNN1A-2994 + AGCAGGGCCUGGCUGGGAC 19 6843 SCNN1A-2995 + GAGCAGGGCCUGGCUGGGAC 20 6844 SCNN1A-2996 + GGAGCAGGGCCUGGCUGGGAC 21 6845 SCNN1A-2997 + GGGAGCAGGGCCUGGCUGGGAC 22 6846 SCNN1A-2998 + AGGGAGCAGGGCCUGGCUGGGAC 23 6847 SCNN1A-2999 + GAGGGAGCAGGGCCUGGCUGGGAC 24 6848 SCNN1A-3000 + UGGCUGCCCAGGUUGGAC 18 6849 SCNN1A-3001 + CUGGCUGCCCAGGUUGGAC 19 6850 SCNN1A-991 + ACUGGCUGCCCAGGUUGGAC 20 4840 SCNN1A-3002 + CACUGGCUGCCCAGGUUGGAC 21 6851 SCNN1A-3003 + CCACUGGCUGCCCAGGUUGGAC 22 6852 SCNN1A-3004 + UCCACUGGCUGCCCAGGUUGGAC 23 6853 SCNN1A-3005 + CUCCACUGGCUGCCCAGGUUGGAC 24 6854 SCNN1A-3006 + CCCUUCCCCACACUCUAC 18 6855 SCNN1A-3007 + UCCCUUCCCCACACUCUAC 19 6856 SCNN1A-3008 + AUCCCUUCCCCACACUCUAC 20 6857 SCNN1A-3009 + CAUCCCUUCCCCACACUCUAC 21 6858 SCNN1A-3010 + CCAUCCCUUCCCCACACUCUAC 22 6859 SCNN1A-3011 + CCCAUCCCUUCCCCACACUCUAC 23 6860 SCNN1A-3012 + ACCCAUCCCUUCCCCACACUCUAC 24 6861 SCNN1A-3013 + UCUUUAAUUUCCGGGUAC 18 6862 SCNN1A-3014 + CUCUUUAAUUUCCGGGUAC 19 6863 SCNN1A-3015 + CCUCUUUAAUUUCCGGGUAC 20 6864 SCNN1A-3016 + UCCUCUUUAAUUUCCGGGUAC 21 6865 SCNN1A-3017 + CUCCUCUUUAAUUUCCGGGUAC 22 6866 SCNN1A-3018 + GCUCCUCUUUAAUUUCCGGGUAC 23 6867 SCNN1A-3019 + AGCUCCUCUUUAAUUUCCGGGUAC 24 6868 SCNN1A-3020 + CUGCCCGUGCACCAUUAC 18 6869 SCNN1A-3021 + CCUGCCCGUGCACCAUUAC 19 6870 SCNN1A-3022 + UCCUGCCCGUGCACCAUUAC 20 6871 SCNN1A-3023 + AUCCUGCCCGUGCACCAUUAC 21 6872 SCNN1A-3024 + CAUCCUGCCCGUGCACCAUUAC 22 6873 SCNN1A-3025 + UCAUCCUGCCCGUGCACCAUUAC 23 6874 SCNN1A-3026 + UUCAUCCUGCCCGUGCACCAUUAC 24 6875 SCNN1A-3027 + UCUGAGGAGAAGUCAACC 18 6876 SCNN1A-3028 + GUCUGAGGAGAAGUCAACC 19 6877 SCNN1A-1000 + GGUCUGAGGAGAAGUCAACC 20 4849 SCNN1A-3029 + UGGUCUGAGGAGAAGUCAACC 21 6878 SCNN1A-3030 + GUGGUCUGAGGAGAAGUCAACC 22 6879 SCNN1A-3031 + GGUGGUCUGAGGAGAAGUCAACC 23 6880 SCNN1A-3032 + AGGUGGUCUGAGGAGAAGUCAACC 24 6881 SCNN1A-3033 + UCCACCACAGACAACACC 18 6882 SCNN1A-3034 + CUCCACCACAGACAACACC 19 6883 SCNN1A-3035 + UCUCCACCACAGACAACACC 20 6884 SCNN1A-3036 + AUCUCCACCACAGACAACACC 21 6885 SCNN1A-3037 + CAUCUCCACCACAGACAACACC 22 6886 SCNN1A-3038 + CCAUCUCCACCACAGACAACACC 23 6887 SCNN1A-3039 + GCCAUCUCCACCACAGACAACACC 24 6888 SCNN1A-3040 + CAGGAGUGAAUACACACC 18 6889 SCNN1A-3041 + GCAGGAGUGAAUACACACC 19 6890 SCNN1A-1002 + AGCAGGAGUGAAUACACACC 20 4851 SCNN1A-3042 + AAGCAGGAGUGAAUACACACC 21 6891 SCNN1A-3043 + GAAGCAGGAGUGAAUACACACC 22 6892 SCNN1A-3044 + GGAAGCAGGAGUGAAUACACACC 23 6893 SCNN1A-3045 + UGGAAGCAGGAGUGAAUACACACC 24 6894 SCNN1A-3046 + UAUGAACCCACAUACACC 18 6895 SCNN1A-3047 + CUAUGAACCCACAUACACC 19 6896 SCNN1A-3048 + CCUAUGAACCCACAUACACC 20 6897 SCNN1A-3049 + UCCUAUGAACCCACAUACACC 21 6898 SCNN1A-3050 + UUCCUAUGAACCCACAUACACC 22 6899 SCNN1A-3051 + UUUCCUAUGAACCCACAUACACC 23 6900 SCNN1A-3052 + GUUUCCUAUGAACCCACAUACACC 24 6901 SCNN1A-3053 + CAGUCCUUCCAGUCCACC 18 6902 SCNN1A-3054 + CCAGUCCUUCCAGUCCACC 19 6903 SCNN1A-1004 + UCCAGUCCUUCCAGUCCACC 20 4853 SCNN1A-3055 + UUCCAGUCCUUCCAGUCCACC 21 6904 SCNN1A-3056 + CUUCCAGUCCUUCCAGUCCACC 22 6905 SCNN1A-3057 + UCUUCCAGUCCUUCCAGUCCACC 23 6906 SCNN1A-3058 + AUCUUCCAGUCCUUCCAGUCCACC 24 6907 SCNN1A-3059 + UCUACCUGGGAUGUCACC 18 6908 SCNN1A-3060 + CUCUACCUGGGAUGUCACC 19 6909 SCNN1A-3061 + ACUCUACCUGGGAUGUCACC 20 6910 SCNN1A-3062 + CACUCUACCUGGGAUGUCACC 21 6911 SCNN1A-3063 + ACACUCUACCUGGGAUGUCACC 22 6912 SCNN1A-3064 + CACACUCUACCUGGGAUGUCACC 23 6913 SCNN1A-3065 + CCACACUCUACCUGGGAUGUCACC 24 6914 SCNN1A-3066 + CAGCAUCAGGGACAGACC 18 6915 SCNN1A-3067 + GCAGCAUCAGGGACAGACC 19 6916 SCNN1A-3068 + CGCAGCAUCAGGGACAGACC 20 6917 SCNN1A-3069 + GCGCAGCAUCAGGGACAGACC 21 6918 SCNN1A-3070 + CGCGCAGCAUCAGGGACAGACC 22 6919 SCNN1A-3071 + GCGCGCAGCAUCAGGGACAGACC 23 6920 SCNN1A-3072 + UGCGCGCAGCAUCAGGGACAGACC 24 6921 SCNN1A-3073 + CUCCCUGGAGUCUCACCC 18 6922 SCNN1A-3074 + GCUCCCUGGAGUCUCACCC 19 6923 SCNN1A-3075 + GGCUCCCUGGAGUCUCACCC 20 6924 SCNN1A-3076 + GGGCUCCCUGGAGUCUCACCC 21 6925 SCNN1A-3077 + GGGGCUCCCUGGAGUCUCACCC 22 6926 SCNN1A-3078 + GGGGGCUCCCUGGAGUCUCACCC 23 6927 SCNN1A-3079 + UGGGGGCUCCCUGGAGUCUCACCC 24 6928 SCNN1A-3080 + UCCCUGGAGUCUCACCCC 18 6929 SCNN1A-3081 + CUCCCUGGAGUCUCACCCC 19 6930 SCNN1A-1013 + GCUCCCUGGAGUCUCACCCC 20 4862 SCNN1A-3082 + GGCUCCCUGGAGUCUCACCCC 21 6931 SCNN1A-3083 + GGGCUCCCUGGAGUCUCACCCC 22 6932 SCNN1A-3084 + GGGGCUCCCUGGAGUCUCACCCC 23 6933 SCNN1A-3085 + GGGGGCUCCCUGGAGUCUCACCCC 24 6934 SCNN1A-3086 + UCCCUCUCAGGGCCCCCC 18 6935 SCNN1A-3087 + UUCCCUCUCAGGGCCCCCC 19 6936 SCNN1A-3088 + CUUCCCUCUCAGGGCCCCCC 20 6937 SCNN1A-3089 + CCUUCCCUCUCAGGGCCCCCC 21 6938 SCNN1A-3090 + UCCUUCCCUCUCAGGGCCCCCC 22 6939 SCNN1A-3091 + CUCCUUCCCUCUCAGGGCCCCCC 23 6940 SCNN1A-3092 + UCUCCUUCCCUCUCAGGGCCCCCC 24 6941 SCNN1A-3093 + GGCCCCUGCAGAGCCCCC 18 6942 SCNN1A-3094 + UGGCCCCUGCAGAGCCCCC 19 6943 SCNN1A-1015 + CUGGCCCCUGCAGAGCCCCC 20 4864 SCNN1A-3095 + ACUGGCCCCUGCAGAGCCCCC 21 6944 SCNN1A-3096 + AACUGGCCCCUGCAGAGCCCCC 22 6945 SCNN1A-3097 + GAACUGGCCCCUGCAGAGCCCCC 23 6946 SCNN1A-3098 + GGAACUGGCCCCUGCAGAGCCCCC 24 6947 SCNN1A-3099 + UGGCCCCUGCAGAGCCCC 18 6948 SCNN1A-3100 + CUGGCCCCUGCAGAGCCCC 19 6949 SCNN1A-3101 + ACUGGCCCCUGCAGAGCCCC 20 6950 SCNN1A-3102 + AACUGGCCCCUGCAGAGCCCC 21 6951 SCNN1A-3103 + GAACUGGCCCCUGCAGAGCCCC 22 6952 SCNN1A-3104 + GGAACUGGCCCCUGCAGAGCCCC 23 6953 SCNN1A-3105 + AGGAACUGGCCCCUGCAGAGCCCC 24 6954 SCNN1A-3106 + ACGGGCUCGACGGGCCCC 18 6955 SCNN1A-3107 + UACGGGCUCGACGGGCCCC 19 6956 SCNN1A-3108 + CUACGGGCUCGACGGGCCCC 20 6957 SCNN1A-3109 + GCUACGGGCUCGACGGGCCCC 21 6958 SCNN1A-3110 + CGCUACGGGCUCGACGGGCCCC 22 6959 SCNN1A-3111 + ACGCUACGGGCUCGACGGGCCCC 23 6960 SCNN1A-3112 + CACGCUACGGGCUCGACGGGCCCC 24 6961 SCNN1A-3113 + CGGCUGCGGGAGCCGGCC 18 6962 SCNN1A-3114 + ACGGCUGCGGGAGCCGGCC 19 6963 SCNN1A-3115 + GACGGCUGCGGGAGCCGGCC 20 6964 SCNN1A-3116 + CGACGGCUGCGGGAGCCGGCC 21 6965 SCNN1A-3117 + GCGACGGCUGCGGGAGCCGGCC 22 6966 SCNN1A-3118 + CGCGACGGCUGCGGGAGCCGGCC 23 6967 SCNN1A-3119 + UCGCGACGGCUGCGGGAGCCGGCC 24 6968 SCNN1A-3120 + ACCCCUGCCCCCUCGGCC 18 6969 SCNN1A-3121 + CACCCCUGCCCCCUCGGCC 19 6970 SCNN1A-1030 + GCACCCCUGCCCCCUCGGCC 20 4879 SCNN1A-3122 + AGCACCCCUGCCCCCUCGGCC 21 6971 SCNN1A-3123 + GAGCACCCCUGCCCCCUCGGCC 22 6972 SCNN1A-3124 + UGAGCACCCCUGCCCCCUCGGCC 23 6973 SCNN1A-3125 + CUGAGCACCCCUGCCCCCUCGGCC 24 6974 SCNN1A-3126 + GUUUUGUAGUUCAGCUCC 18 6975 SCNN1A-3127 + GGUUUUGUAGUUCAGCUCC 19 6976 SCNN1A-3128 + UGGUUUUGUAGUUCAGCUCC 20 6977 SCNN1A-3129 + UUGGUUUUGUAGUUCAGCUCC 21 6978 SCNN1A-3130 + AUUGGUUUUGUAGUUCAGCUCC 22 6979 SCNN1A-3131 + AAUUGGUUUUGUAGUUCAGCUCC 23 6980 SCNN1A-3132 + GAAUUGGUUUUGUAGUUCAGCUCC 24 6981 SCNN1A-3133 + UCCUUGAUCAUGCUCUCC 18 6982 SCNN1A-3134 + CUCCUUGAUCAUGCUCUCC 19 6983 SCNN1A-1041 + ACUCCUUGAUCAUGCUCUCC 20 4890 SCNN1A-3135 + CACUCCUUGAUCAUGCUCUCC 21 6984 SCNN1A-3136 + ACACUCCUUGAUCAUGCUCUCC 22 6985 SCNN1A-3137 + CACACUCCUUGAUCAUGCUCUCC 23 6986 SCNN1A-3138 + CCACACUCCUUGAUCAUGCUCUCC 24 6987 SCNN1A-3139 + AUCUGGAAGACCCAUUCC 18 6988 SCNN1A-3140 + CAUCUGGAAGACCCAUUCC 19 6989 SCNN1A-3141 + GCAUCUGGAAGACCCAUUCC 20 6990 SCNN1A-3142 + AGCAUCUGGAAGACCCAUUCC 21 6991 SCNN1A-3143 + UAGCAUCUGGAAGACCCAUUCC 22 6992 SCNN1A-3144 + AUAGCAUCUGGAAGACCCAUUCC 23 6993 SCNN1A-3145 + GAUAGCAUCUGGAAGACCCAUUCC 24 6994 SCNN1A-3146 + GGGCGCCAUGGAGCAAGC 18 6995 SCNN1A-3147 + AGGGCGCCAUGGAGCAAGC 19 6996 SCNN1A-1049 + GAGGGCGCCAUGGAGCAAGC 20 4898 SCNN1A-3148 + AGAGGGCGCCAUGGAGCAAGC 21 6997 SCNN1A-3149 + CAGAGGGCGCCAUGGAGCAAGC 22 6998 SCNN1A-3150 + GCAGAGGGCGCCAUGGAGCAAGC 23 6999 SCNN1A-3151 + AGCAGAGGGCGCCAUGGAGCAAGC 24 7000 SCNN1A-3152 + GGUUGUUGUCCCGCAAGC 18 7001 SCNN1A-3153 + GGGUUGUUGUCCCGCAAGC 19 7002 SCNN1A-1050 + GGGGUUGUUGUCCCGCAAGC 20 4899 SCNN1A-3154 + GGGGGUUGUUGUCCCGCAAGC 21 7003 SCNN1A-3155 + UGGGGGUUGUUGUCCCGCAAGC 22 7004 SCNN1A-3156 + CUGGGGGUUGUUGUCCCGCAAGC 23 7005 SCNN1A-3157 + CCUGGGGGUUGUUGUCCCGCAAGC 24 7006 SCNN1A-3158 + CCAGUCACUGUGGACAGC 18 7007 SCNN1A-3159 + CCCAGUCACUGUGGACAGC 19 7008 SCNN1A-1053 + CCCCAGUCACUGUGGACAGC 20 4902 SCNN1A-3160 + GCCCCAGUCACUGUGGACAGC 21 7009 SCNN1A-3161 + GGCCCCAGUCACUGUGGACAGC 22 7010 SCNN1A-3162 + GGGCCCCAGUCACUGUGGACAGC 23 7011 SCNN1A-3163 + CGGGCCCCAGUCACUGUGGACAGC 24 7012 SCNN1A-3164 + GCUGCGGGCCUCACCAGC 18 7013 SCNN1A-3165 + CGCUGCGGGCCUCACCAGC 19 7014 SCNN1A-1054 + GCGCUGCGGGCCUCACCAGC 20 4903 SCNN1A-3166 + GGCGCUGCGGGCCUCACCAGC 21 7015 SCNN1A-3167 + CGGCGCUGCGGGCCUCACCAGC 22 7016 SCNN1A-3168 + UCGGCGCUGCGGGCCUCACCAGC 23 7017 SCNN1A-3169 + CUCGGCGCUGCGGGCCUCACCAGC 24 7018 SCNN1A-3170 + CGGAACCUUCGGAGCAGC 18 7019 SCNN1A-3171 + UCGGAACCUUCGGAGCAGC 19 7020 SCNN1A-3172 + UUCGGAACCUUCGGAGCAGC 20 7021 SCNN1A-3173 + CUUCGGAACCUUCGGAGCAGC 21 7022 SCNN1A-3174 + GCUUCGGAACCUUCGGAGCAGC 22 7023 SCNN1A-3175 + GGCUUCGGAACCUUCGGAGCAGC 23 7024 SCNN1A-3176 + CGGCUUCGGAACCUUCGGAGCAGC 24 7025 SCNN1A-3177 + GCUGGUAGCUGGUCACGC 18 7026 SCNN1A-3178 + AGCUGGUAGCUGGUCACGC 19 7027 SCNN1A-1064 + GAGCUGGUAGCUGGUCACGC 20 4913 SCNN1A-3179 + AGAGCUGGUAGCUGGUCACGC 21 7028 SCNN1A-3180 + GAGAGCUGGUAGCUGGUCACGC 22 7029 SCNN1A-3181 + AGAGAGCUGGUAGCUGGUCACGC 23 7030 SCNN1A-3182 + CAGAGAGCUGGUAGCUGGUCACGC 24 7031 SCNN1A-3183 + GGGAGGGGCUGUCAAGGC 18 7032 SCNN1A-3184 + GGGGAGGGGCUGUCAAGGC 19 7033 SCNN1A-1067 + GGGGGAGGGGCUGUCAAGGC 20 4916 SCNN1A-3185 + AGGGGGAGGGGCUGUCAAGGC 21 7034 SCNN1A-3186 + CAGGGGGAGGGGCUGUCAAGGC 22 7035 SCNN1A-3187 + GCAGGGGGAGGGGCUGUCAAGGC 23 7036 SCNN1A-3188 + GGCAGGGGGAGGGGCUGUCAAGGC 24 7037 SCNN1A-3189 + CCGUUGUUGAUUCCAGGC 18 7038 SCNN1A-3190 + ACCGUUGUUGAUUCCAGGC 19 7039 SCNN1A-3191 + CACCGUUGUUGAUUCCAGGC 20 7040 SCNN1A-3192 + UCACCGUUGUUGAUUCCAGGC 21 7041 SCNN1A-3193 + CUCACCGUUGUUGAUUCCAGGC 22 7042 SCNN1A-3194 + UCUCACCGUUGUUGAUUCCAGGC 23 7043 SCNN1A-3195 + UUCUCACCGUUGUUGAUUCCAGGC 24 7044 SCNN1A-3196 + CGACGGGCCCCGUGAGGC 18 7045 SCNN1A-3197 + UCGACGGGCCCCGUGAGGC 19 7046 SCNN1A-1068 + CUCGACGGGCCCCGUGAGGC 20 4917 SCNN1A-3198 + GCUCGACGGGCCCCGUGAGGC 21 7047 SCNN1A-3199 + GGCUCGACGGGCCCCGUGAGGC 22 7048 SCNN1A-3200 + GGGCUCGACGGGCCCCGUGAGGC 23 7049 SCNN1A-3201 + CGGGCUCGACGGGCCCCGUGAGGC 24 7050 SCNN1A-3202 + GCCCAGGGUGGCAUAGGC 18 7051 SCNN1A-3203 + GGCCCAGGGUGGCAUAGGC 19 7052 SCNN1A-1069 + GGGCCCAGGGUGGCAUAGGC 20 4918 SCNN1A-3204 + GGGGCCCAGGGUGGCAUAGGC 21 7053 SCNN1A-3205 + GGGGGCCCAGGGUGGCAUAGGC 22 7054 SCNN1A-3206 + CGGGGGCCCAGGGUGGCAUAGGC 23 7055 SCNN1A-3207 + GCGGGGGCCCAGGGUGGCAUAGGC 24 7056 SCNN1A-3208 + CACCCCUGCCCCCUCGGC 18 7057 SCNN1A-3209 + GCACCCCUGCCCCCUCGGC 19 7058 SCNN1A-3210 + AGCACCCCUGCCCCCUCGGC 20 7059 SCNN1A-3211 + GAGCACCCCUGCCCCCUCGGC 21 7060 SCNN1A-3212 + UGAGCACCCCUGCCCCCUCGGC 22 7061 SCNN1A-3213 + CUGAGCACCCCUGCCCCCUCGGC 23 7062 SCNN1A-3214 + CCUGAGCACCCCUGCCCCCUCGGC 24 7063 SCNN1A-3215 + CCGGGUACCUGAAGGGGC 18 7064 SCNN1A-3216 + UCCGGGUACCUGAAGGGGC 19 7065 SCNN1A-3217 + UUCCGGGUACCUGAAGGGGC 20 7066 SCNN1A-3218 + UUUCCGGGUACCUGAAGGGGC 21 7067 SCNN1A-3219 + AUUUCCGGGUACCUGAAGGGGC 22 7068 SCNN1A-3220 + AAUUUCCGGGUACCUGAAGGGGC 23 7069 SCNN1A-3221 + UAAUUUCCGGGUACCUGAAGGGGC 24 7070 SCNN1A-3222 + AGCCCCCUGGAGAUGGGC 18 7071 SCNN1A-3223 + GAGCCCCCUGGAGAUGGGC 19 7072 SCNN1A-1075 + AGAGCCCCCUGGAGAUGGGC 20 4924 SCNN1A-3224 + CAGAGCCCCCUGGAGAUGGGC 21 7073 SCNN1A-3225 + GCAGAGCCCCCUGGAGAUGGGC 22 7074 SCNN1A-3226 + UGCAGAGCCCCCUGGAGAUGGGC 23 7075 SCNN1A-3227 + CUGCAGAGCCCCCUGGAGAUGGGC 24 7076 SCNN1A-3228 + GAGGGAGCAGGGCCUGGC 18 7077 SCNN1A-3229 + AGAGGGAGCAGGGCCUGGC 19 7078 SCNN1A-1076 + GAGAGGGAGCAGGGCCUGGC 20 4925 SCNN1A-3230 + GGAGAGGGAGCAGGGCCUGGC 21 7079 SCNN1A-3231 + UGGAGAGGGAGCAGGGCCUGGC 22 7080 SCNN1A-3232 + CUGGAGAGGGAGCAGGGCCUGGC 23 7081 SCNN1A-3233 + GCUGGAGAGGGAGCAGGGCCUGGC 24 7082 SCNN1A-3234 + GGGACCCUCAGGCGCUGC 18 7083 SCNN1A-3235 + CGGGACCCUCAGGCGCUGC 19 7084 SCNN1A-3236 + GCGGGACCCUCAGGCGCUGC 20 7085 SCNN1A-3237 + GGCGGGACCCUCAGGCGCUGC 21 7086 SCNN1A-3238 + GGGCGGGACCCUCAGGCGCUGC 22 7087 SCNN1A-3239 + GGGGCGGGACCCUCAGGCGCUGC 23 7088 SCNN1A-3240 + GGGGGCGGGACCCUCAGGCGCUGC 24 7089 SCNN1A-3241 + GCAGGUCGCGACGGCUGC 18 7090 SCNN1A-3242 + CGCAGGUCGCGACGGCUGC 19 7091 SCNN1A-1082 + CCGCAGGUCGCGACGGCUGC 20 4931 SCNN1A-3243 + CCCGCAGGUCGCGACGGCUGC 21 7092 SCNN1A-3244 + CCCCGCAGGUCGCGACGGCUGC 22 7093 SCNN1A-3245 + CCCCCGCAGGUCGCGACGGCUGC 23 7094 SCNN1A-3246 + UCCCCCGCAGGUCGCGACGGCUGC 24 7095 SCNN1A-3247 + UGACUCACGCCUGGUUGC 18 7096 SCNN1A-3248 + CUGACUCACGCCUGGUUGC 19 7097 SCNN1A-1087 + ACUGACUCACGCCUGGUUGC 20 4936 SCNN1A-3249 + GACUGACUCACGCCUGGUUGC 21 7098 SCNN1A-3250 + GGACUGACUCACGCCUGGUUGC 22 7099 SCNN1A-3251 + AGGACUGACUCACGCCUGGUUGC 23 7100 SCNN1A-3252 + CAGGACUGACUCACGCCUGGUUGC 24 7101 SCNN1A-3253 + CCAGGCAUGGAAGACAUC 18 7102 SCNN1A-3254 + UCCAGGCAUGGAAGACAUC 19 7103 SCNN1A-3255 + UUCCAGGCAUGGAAGACAUC 20 7104 SCNN1A-3256 + AUUCCAGGCAUGGAAGACAUC 21 7105 SCNN1A-3257 + GAUUCCAGGCAUGGAAGACAUC 22 7106 SCNN1A-3258 + UGAUUCCAGGCAUGGAAGACAUC 23 7107 SCNN1A-3259 + UUGAUUCCAGGCAUGGAAGACAUC 24 7108 SCNN1A-3260 + UGCUCUGCGCGCAGCAUC 18 7109 SCNN1A-3261 + CUGCUCUGCGCGCAGCAUC 19 7110 SCNN1A-1089 + UCUGCUCUGCGCGCAGCAUC 20 4938 SCNN1A-3262 + UUCUGCUCUGCGCGCAGCAUC 21 7111 SCNN1A-3263 + AUUCUGCUCUGCGCGCAGCAUC 22 7112 SCNN1A-3264 + CAUUCUGCUCUGCGCGCAGCAUC 23 7113 SCNN1A-3265 + UCAUUCUGCUCUGCGCGCAGCAUC 24 7114 SCNN1A-3266 + UUCUGUCGCGAUAGCAUC 18 7115 SCNN1A-3267 + GUUCUGUCGCGAUAGCAUC 19 7116 SCNN1A-1090 + UGUUCUGUCGCGAUAGCAUC 20 4939 SCNN1A-3268 + UUGUUCUGUCGCGAUAGCAUC 21 7117 SCNN1A-3269 + AUUGUUCUGUCGCGAUAGCAUC 22 7118 SCNN1A-3270 + AAUUGUUCUGUCGCGAUAGCAUC 23 7119 SCNN1A-3271 + UAAUUGUUCUGUCGCGAUAGCAUC 24 7120 SCNN1A-3272 + UGAGAGUAAUUCCUUAUC 18 7121 SCNN1A-3273 + GUGAGAGUAAUUCCUUAUC 19 7122 SCNN1A-1092 + AGUGAGAGUAAUUCCUUAUC 20 4941 SCNN1A-3274 + AAGUGAGAGUAAUUCCUUAUC 21 7123 SCNN1A-3275 + GAAGUGAGAGUAAUUCCUUAUC 22 7124 SCNN1A-3276 + GGAAGUGAGAGUAAUUCCUUAUC 23 7125 SCNN1A-3277 + UGGAAGUGAGAGUAAUUCCUUAUC 24 7126 SCNN1A-3278 + CAGGGUGGAGGCUACCUC 18 7127 SCNN1A-3279 + CCAGGGUGGAGGCUACCUC 19 7128 SCNN1A-3280 + GCCAGGGUGGAGGCUACCUC 20 7129 SCNN1A-3281 + UGCCAGGGUGGAGGCUACCUC 21 7130 SCNN1A-3282 + AUGCCAGGGUGGAGGCUACCUC 22 7131 SCNN1A-3283 + GAUGCCAGGGUGGAGGCUACCUC 23 7132 SCNN1A-3284 + GGAUGCCAGGGUGGAGGCUACCUC 24 7133 SCNN1A-3285 + GCCCAGCGUGUCCUCCUC 18 7134 SCNN1A-3286 + UGCCCAGCGUGUCCUCCUC 19 7135 SCNN1A-3287 + UUGCCCAGCGUGUCCUCCUC 20 7136 SCNN1A-3288 + GUUGCCCAGCGUGUCCUCCUC 21 7137 SCNN1A-3289 + AGUUGCCCAGCGUGUCCUCCUC 22 7138 SCNN1A-3290 + AAGUUGCCCAGCGUGUCCUCCUC 23 7139 SCNN1A-3291 + GAAGUUGCCCAGCGUGUCCUCCUC 24 7140 SCNN1A-3292 + CUCCUUGAUCAUGCUCUC 18 7141 SCNN1A-3293 + ACUCCUUGAUCAUGCUCUC 19 7142 SCNN1A-3294 + CACUCCUUGAUCAUGCUCUC 20 7143 SCNN1A-3295 + ACACUCCUUGAUCAUGCUCUC 21 7144 SCNN1A-3296 + CACACUCCUUGAUCAUGCUCUC 22 7145 SCNN1A-3297 + CCACACUCCUUGAUCAUGCUCUC 23 7146 SCNN1A-3298 + GCCACACUCCUUGAUCAUGCUCUC 24 7147 SCNN1A-3299 + UCACAGUACUCCACGUUC 18 7148 SCNN1A-3300 + GUCACAGUACUCCACGUUC 19 7149 SCNN1A-1103 + AGUCACAGUACUCCACGUUC 20 4952 SCNN1A-3301 + UAGUCACAGUACUCCACGUUC 21 7150 SCNN1A-3302 + GUAGUCACAGUACUCCACGUUC 22 7151 SCNN1A-3303 + UGUAGUCACAGUACUCCACGUUC 23 7152 SCNN1A-3304 + CUGUAGUCACAGUACUCCACGUUC 24 7153 SCNN1A-3305 + AUGACCAGCAGGUCAAAG 18 7154 SCNN1A-3306 + GAUGACCAGCAGGUCAAAG 19 7155 SCNN1A-3307 + UGAUGACCAGCAGGUCAAAG 20 7156 SCNN1A-3308 + AUGAUGACCAGCAGGUCAAAG 21 7157 SCNN1A-3309 + CAUGAUGACCAGCAGGUCAAAG 22 7158 SCNN1A-3310 + ACAUGAUGACCAGCAGGUCAAAG 23 7159 SCNN1A-3311 + AACAUGAUGACCAGCAGGUCAAAG 24 7160 SCNN1A-3312 + AGGGCGCCAUGGAGCAAG 18 7161 SCNN1A-3313 + GAGGGCGCCAUGGAGCAAG 19 7162 SCNN1A-3314 + AGAGGGCGCCAUGGAGCAAG 20 7163 SCNN1A-3315 + CAGAGGGCGCCAUGGAGCAAG 21 7164 SCNN1A-3316 + GCAGAGGGCGCCAUGGAGCAAG 22 7165 SCNN1A-3317 + AGCAGAGGGCGCCAUGGAGCAAG 23 7166 SCNN1A-3318 + AAGCAGAGGGCGCCAUGGAGCAAG 24 7167 SCNN1A-3319 + GGGUUGUUGUCCCGCAAG 18 7168 SCNN1A-3320 + GGGGUUGUUGUCCCGCAAG 19 7169 SCNN1A-3321 + GGGGGUUGUUGUCCCGCAAG 20 7170 SCNN1A-3322 + UGGGGGUUGUUGUCCCGCAAG 21 7171 SCNN1A-3323 + CUGGGGGUUGUUGUCCCGCAAG 22 7172 SCNN1A-3324 + CCUGGGGGUUGUUGUCCCGCAAG 23 7173 SCNN1A-3325 + ACCUGGGGGUUGUUGUCCCGCAAG 24 7174 SCNN1A-3326 + AUGGGGUGGGGGCAGAAG 18 7175 SCNN1A-3327 + CAUGGGGUGGGGGCAGAAG 19 7176 SCNN1A-1109 + ACAUGGGGUGGGGGCAGAAG 20 4958 SCNN1A-3328 + GACAUGGGGUGGGGGCAGAAG 21 7177 SCNN1A-3329 + AGACAUGGGGUGGGGGCAGAAG 22 7178 SCNN1A-3330 + GAGACAUGGGGUGGGGGCAGAAG 23 7179 SCNN1A-3331 + AGAGACAUGGGGUGGGGGCAGAAG 24 7180 SCNN1A-3332 + UUGAAGCGGCAGGCGAAG 18 7181 SCNN1A-3333 + GUUGAAGCGGCAGGCGAAG 19 7182 SCNN1A-3334 + GGUUGAAGCGGCAGGCGAAG 20 7183 SCNN1A-3335 + UGGUUGAAGCGGCAGGCGAAG 21 7184 SCNN1A-3336 + CUGGUUGAAGCGGCAGGCGAAG 22 7185 SCNN1A-3337 + CCUGGUUGAAGCGGCAGGCGAAG 23 7186 SCNN1A-3338 + ACCUGGUUGAAGCGGCAGGCGAAG 24 7187 SCNN1A-3339 + GGGGGCAGAAGUGGGAAG 18 7188 SCNN1A-3340 + UGGGGGCAGAAGUGGGAAG 19 7189 SCNN1A-3341 + GUGGGGGCAGAAGUGGGAAG 20 7190 SCNN1A-3342 + GGUGGGGGCAGAAGUGGGAAG 21 7191 SCNN1A-3343 + GGGUGGGGGCAGAAGUGGGAAG 22 7192 SCNN1A-3344 + GGGGUGGGGGCAGAAGUGGGAAG 23 7193 SCNN1A-3345 + UGGGGUGGGGGCAGAAGUGGGAAG 24 7194 SCNN1A-3346 + AUCAUGCUCUCCUGGAAG 18 7195 SCNN1A-3347 + GAUCAUGCUCUCCUGGAAG 19 7196 SCNN1A-3348 + UGAUCAUGCUCUCCUGGAAG 20 7197 SCNN1A-3349 + UUGAUCAUGCUCUCCUGGAAG 21 7198 SCNN1A-3350 + CUUGAUCAUGCUCUCCUGGAAG 22 7199 SCNN1A-3351 + CCUUGAUCAUGCUCUCCUGGAAG 23 7200 SCNN1A-3352 + UCCUUGAUCAUGCUCUCCUGGAAG 24 7201 SCNN1A-3353 + GGCCCCCCCAGAGGACAG 18 7202 SCNN1A-3354 + GGGCCCCCCCAGAGGACAG 19 7203 SCNN1A-3355 + AGGGCCCCCCCAGAGGACAG 20 7204 SCNN1A-3356 + CAGGGCCCCCCCAGAGGACAG 21 7205 SCNN1A-3357 + UCAGGGCCCCCCCAGAGGACAG 22 7206 SCNN1A-3358 + CUCAGGGCCCCCCCAGAGGACAG 23 7207 SCNN1A-3359 + UCUCAGGGCCCCCCCAGAGGACAG 24 7208 SCNN1A-3360 + CCCAGUCACUGUGGACAG 18 7209 SCNN1A-3361 + CCCCAGUCACUGUGGACAG 19 7210 SCNN1A-3362 + GCCCCAGUCACUGUGGACAG 20 7211 SCNN1A-3363 + GGCCCCAGUCACUGUGGACAG 21 7212 SCNN1A-3364 + GGGCCCCAGUCACUGUGGACAG 22 7213 SCNN1A-3365 + CGGGCCCCAGUCACUGUGGACAG 23 7214 SCNN1A-3366 + CCGGGCCCCAGUCACUGUGGACAG 24 7215 SCNN1A-3367 + CACGACCUACCGUGACAG 18 7216 SCNN1A-3368 + GCACGACCUACCGUGACAG 19 7217 SCNN1A-1114 + GGCACGACCUACCGUGACAG 20 4963 SCNN1A-3369 + AGGCACGACCUACCGUGACAG 21 7218 SCNN1A-3370 + CAGGCACGACCUACCGUGACAG 22 7219 SCNN1A-3371 + CCAGGCACGACCUACCGUGACAG 23 7220 SCNN1A-3372 + UCCAGGCACGACCUACCGUGACAG 24 7221 SCNN1A-3373 + GCCAUCGUGAGUAACCAG 18 7222 SCNN1A-3374 + GGCCAUCGUGAGUAACCAG 19 7223 SCNN1A-3375 + GGGCCAUCGUGAGUAACCAG 20 7224 SCNN1A-3376 + AGGGCCAUCGUGAGUAACCAG 21 7225 SCNN1A-3377 + GAGGGCCAUCGUGAGUAACCAG 22 7226 SCNN1A-3378 + CGAGGGCCAUCGUGAGUAACCAG 23 7227 SCNN1A-3379 + CCGAGGGCCAUCGUGAGUAACCAG 24 7228 SCNN1A-3380 + CGCUGCGGGCCUCACCAG 18 7229 SCNN1A-3381 + GCGCUGCGGGCCUCACCAG 19 7230 SCNN1A-3382 + GGCGCUGCGGGCCUCACCAG 20 7231 SCNN1A-3383 + CGGCGCUGCGGGCCUCACCAG 21 7232 SCNN1A-3384 + UCGGCGCUGCGGGCCUCACCAG 22 7233 SCNN1A-3385 + CUCGGCGCUGCGGGCCUCACCAG 23 7234 SCNN1A-3386 + CCUCGGCGCUGCGGGCCUCACCAG 24 7235 SCNN1A-3387 + CCAGGGUGGCAUAGGCAG 18 7236 SCNN1A-3388 + CCCAGGGUGGCAUAGGCAG 19 7237 SCNN1A-1120 + GCCCAGGGUGGCAUAGGCAG 20 4969 SCNN1A-3389 + GGCCCAGGGUGGCAUAGGCAG 21 7238 SCNN1A-3390 + GGGCCCAGGGUGGCAUAGGCAG 22 7239 SCNN1A-3391 + GGGGCCCAGGGUGGCAUAGGCAG 23 7240 SCNN1A-3392 + GGGGGCCCAGGGUGGCAUAGGCAG 24 7241 SCNN1A-3393 + ACCUGGUUGAAGCGGCAG 18 7242 SCNN1A-3394 + GACCUGGUUGAAGCGGCAG 19 7243 SCNN1A-3395 + AGACCUGGUUGAAGCGGCAG 20 7244 SCNN1A-3396 + GAGACCUGGUUGAAGCGGCAG 21 7245 SCNN1A-3397 + GGAGACCUGGUUGAAGCGGCAG 22 7246 SCNN1A-3398 + AGGAGACCUGGUUGAAGCGGCAG 23 7247 SCNN1A-3399 + CAGGAGACCUGGUUGAAGCGGCAG 24 7248 SCNN1A-3400 + CACAGAGACUAGAGUCAG 18 7249 SCNN1A-3401 + ACACAGAGACUAGAGUCAG 19 7250 SCNN1A-1125 + GACACAGAGACUAGAGUCAG 20 4974 SCNN1A-3402 + GGACACAGAGACUAGAGUCAG 21 7251 SCNN1A-3403 + UGGACACAGAGACUAGAGUCAG 22 7252 SCNN1A-3404 + CUGGACACAGAGACUAGAGUCAG 23 7253 SCNN1A-3405 + ACUGGACACAGAGACUAGAGUCAG 24 7254 SCNN1A-3406 + AGGGAGGAGGGUGGAGAG 18 7255 SCNN1A-3407 + AAGGGAGGAGGGUGGAGAG 19 7256 SCNN1A-3408 + GAAGGGAGGAGGGUGGAGAG 20 7257 SCNN1A-3409 + GGAAGGGAGGAGGGUGGAGAG 21 7258 SCNN1A-3410 + UGGAAGGGAGGAGGGUGGAGAG 22 7259 SCNN1A-3411 + CUGGAAGGGAGGAGGGUGGAGAG 23 7260 SCNN1A-3412 + CCUGGAAGGGAGGAGGGUGGAGAG 24 7261 SCNN1A-3413 + GGUGACCAUCUGUGAGAG 18 7262 SCNN1A-3414 + GGGUGACCAUCUGUGAGAG 19 7263 SCNN1A-3415 + AGGGUGACCAUCUGUGAGAG 20 7264 SCNN1A-3416 + GAGGGUGACCAUCUGUGAGAG 21 7265 SCNN1A-3417 + GGAGGGUGACCAUCUGUGAGAG 22 7266 SCNN1A-3418 + AGGAGGGUGACCAUCUGUGAGAG 23 7267 SCNN1A-3419 + CAGGAGGGUGACCAUCUGUGAGAG 24 7268 SCNN1A-3420 + GGUACCUGAAGGGGCGAG 18 7269 SCNN1A-3421 + GGGUACCUGAAGGGGCGAG 19 7270 SCNN1A-1130 + CGGGUACCUGAAGGGGCGAG 20 4979 SCNN1A-3422 + CCGGGUACCUGAAGGGGCGAG 21 7271 SCNN1A-3423 + UCCGGGUACCUGAAGGGGCGAG 22 7272 SCNN1A-3424 + UUCCGGGUACCUGAAGGGGCGAG 23 7273 SCNN1A-3425 + UUUCCGGGUACCUGAAGGGGCGAG 24 7274 SCNN1A-3426 + GGCAGAAGUGGGAAGGAG 18 7275 SCNN1A-3427 + GGGCAGAAGUGGGAAGGAG 19 7276 SCNN1A-1132 + GGGGCAGAAGUGGGAAGGAG 20 4981 SCNN1A-3428 + GGGGGCAGAAGUGGGAAGGAG 21 7277 SCNN1A-3429 + UGGGGGCAGAAGUGGGAAGGAG 22 7278 SCNN1A-3430 + GUGGGGGCAGAAGUGGGAAGGAG 23 7279 SCNN1A-3431 + GGUGGGGGCAGAAGUGGGAAGGAG 24 7280 SCNN1A-3432 + ACAGACAACACCGAGGAG 18 7281 SCNN1A-3433 + CACAGACAACACCGAGGAG 19 7282 SCNN1A-3434 + CCACAGACAACACCGAGGAG 20 7283 SCNN1A-3435 + ACCACAGACAACACCGAGGAG 21 7284 SCNN1A-3436 + CACCACAGACAACACCGAGGAG 22 7285 SCNN1A-3437 + CCACCACAGACAACACCGAGGAG 23 7286 SCNN1A-3438 + UCCACCACAGACAACACCGAGGAG 24 7287 SCNN1A-3439 + UCAAGGCUGGAGAGGGAG 18 7288 SCNN1A-3440 + GUCAAGGCUGGAGAGGGAG 19 7289 SCNN1A-3441 + UGUCAAGGCUGGAGAGGGAG 20 7290 SCNN1A-3442 + CUGUCAAGGCUGGAGAGGGAG 21 7291 SCNN1A-3443 + GCUGUCAAGGCUGGAGAGGGAG 22 7292 SCNN1A-3444 + GGCUGUCAAGGCUGGAGAGGGAG 23 7293 SCNN1A-3445 + GGGCUGUCAAGGCUGGAGAGGGAG 24 7294 SCNN1A-3446 + CUGCAGAGCCCCCUGGAG 18 7295 SCNN1A-3447 + CCUGCAGAGCCCCCUGGAG 19 7296 SCNN1A-3448 + CCCUGCAGAGCCCCCUGGAG 20 7297 SCNN1A-3449 + CCCCUGCAGAGCCCCCUGGAG 21 7298 SCNN1A-3450 + GCCCCUGCAGAGCCCCCUGGAG 22 7299 SCNN1A-3451 + GGCCCCUGCAGAGCCCCCUGGAG 23 7300 SCNN1A-3452 + UGGCCCCUGCAGAGCCCCCUGGAG 24 7301 SCNN1A-3453 + GGGCUGUCAAGGCUGGAG 18 7302 SCNN1A-3454 + GGGGCUGUCAAGGCUGGAG 19 7303 SCNN1A-1138 + AGGGGCUGUCAAGGCUGGAG 20 4987 SCNN1A-3455 + GAGGGGCUGUCAAGGCUGGAG 21 7304 SCNN1A-3456 + GGAGGGGCUGUCAAGGCUGGAG 22 7305 SCNN1A-3457 + GGGAGGGGCUGUCAAGGCUGGAG 23 7306 SCNN1A-3458 + GGGGAGGGGCUGUCAAGGCUGGAG 24 7307 SCNN1A-3459 + GAAGGGAGGAGGGUGGAG 18 7308 SCNN1A-3460 + GGAAGGGAGGAGGGUGGAG 19 7309 SCNN1A-1139 + UGGAAGGGAGGAGGGUGGAG 20 4988 SCNN1A-3461 + CUGGAAGGGAGGAGGGUGGAG 21 7310 SCNN1A-3462 + CCUGGAAGGGAGGAGGGUGGAG 22 7311 SCNN1A-3463 + ACCUGGAAGGGAGGAGGGUGGAG 23 7312 SCNN1A-3464 + CACCUGGAAGGGAGGAGGGUGGAG 24 7313 SCNN1A-3465 + CAGCCCAGGUGGUCUGAG 18 7314 SCNN1A-3466 + ACAGCCCAGGUGGUCUGAG 19 7315 SCNN1A-3467 + AACAGCCCAGGUGGUCUGAG 20 7316 SCNN1A-3468 + AAACAGCCCAGGUGGUCUGAG 21 7317 SCNN1A-3469 + GAAACAGCCCAGGUGGUCUGAG 22 7318 SCNN1A-3470 + UGAAACAGCCCAGGUGGUCUGAG 23 7319 SCNN1A-3471 + GUGAAACAGCCCAGGUGGUCUGAG 24 7320 SCNN1A-3472 + CUCGACGGGCCCCGUGAG 18 7321 SCNN1A-3473 + GCUCGACGGGCCCCGUGAG 19 7322 SCNN1A-3474 + GGCUCGACGGGCCCCGUGAG 20 7323 SCNN1A-3475 + GGGCUCGACGGGCCCCGUGAG 21 7324 SCNN1A-3476 + CGGGCUCGACGGGCCCCGUGAG 22 7325 SCNN1A-3477 + ACGGGCUCGACGGGCCCCGUGAG 23 7326 SCNN1A-3478 + UACGGGCUCGACGGGCCCCGUGAG 24 7327 SCNN1A-3479 + AGGGUGACCAUCUGUGAG 18 7328 SCNN1A-3480 + GAGGGUGACCAUCUGUGAG 19 7329 SCNN1A-1141 + GGAGGGUGACCAUCUGUGAG 20 4990 SCNN1A-3481 + AGGAGGGUGACCAUCUGUGAG 21 7330 SCNN1A-3482 + CAGGAGGGUGACCAUCUGUGAG 22 7331 SCNN1A-3483 + ACAGGAGGGUGACCAUCUGUGAG 23 7332 SCNN1A-3484 + GACAGGAGGGUGACCAUCUGUGAG 24 7333 SCNN1A-3485 + GACAGGAUGUUGAUGUAG 18 7334 SCNN1A-3486 + CGACAGGAUGUUGAUGUAG 19 7335 SCNN1A-1143 + UCGACAGGAUGUUGAUGUAG 20 4992 SCNN1A-3487 + CUCGACAGGAUGUUGAUGUAG 21 7336 SCNN1A-3488 + CCUCGACAGGAUGUUGAUGUAG 22 7337 SCNN1A-3489 + GCCUCGACAGGAUGUUGAUGUAG 23 7338 SCNN1A-3490 + AGCCUCGACAGGAUGUUGAUGUAG 24 7339 SCNN1A-3491 + AGCUGGUAGCUGGUCACG 18 7340 SCNN1A-3492 + GAGCUGGUAGCUGGUCACG 19 7341 SCNN1A-3493 + AGAGCUGGUAGCUGGUCACG 20 7342 SCNN1A-3494 + GAGAGCUGGUAGCUGGUCACG 21 7343 SCNN1A-3495 + AGAGAGCUGGUAGCUGGUCACG 22 7344 SCNN1A-3496 + CAGAGAGCUGGUAGCUGGUCACG 23 7345 SCNN1A-3497 + GCAGAGAGCUGGUAGCUGGUCACG 24 7346 SCNN1A-3498 + AGGAGAGGUACAUUGACG 18 7347 SCNN1A-3499 + GAGGAGAGGUACAUUGACG 19 7348 SCNN1A-3500 + AGAGGAGAGGUACAUUGACG 20 7349 SCNN1A-3501 + GAGAGGAGAGGUACAUUGACG 21 7350 SCNN1A-3502 + UGAGAGGAGAGGUACAUUGACG 22 7351 SCNN1A-3503 + GUGAGAGGAGAGGUACAUUGACG 23 7352 SCNN1A-3504 + UGUGAGAGGAGAGGUACAUUGACG 24 7353 SCNN1A-3505 + CCACCACAGACAACACCG 18 7354 SCNN1A-3506 + UCCACCACAGACAACACCG 19 7355 SCNN1A-1146 + CUCCACCACAGACAACACCG 20 4995 SCNN1A-3507 + UCUCCACCACAGACAACACCG 21 7356 SCNN1A-3508 + AUCUCCACCACAGACAACACCG 22 7357 SCNN1A-3509 + CAUCUCCACCACAGACAACACCG 23 7358 SCNN1A-3510 + CCAUCUCCACCACAGACAACACCG 24 7359 SCNN1A-3511 + CGGGUACCUGAAGGGGCG 18 7360 SCNN1A-3512 + CCGGGUACCUGAAGGGGCG 19 7361 SCNN1A-1155 + UCCGGGUACCUGAAGGGGCG 20 5004 SCNN1A-3513 + UUCCGGGUACCUGAAGGGGCG 21 7362 SCNN1A-3514 + UUUCCGGGUACCUGAAGGGGCG 22 7363 SCNN1A-3515 + AUUUCCGGGUACCUGAAGGGGCG 23 7364 SCNN1A-3516 + AAUUUCCGGGUACCUGAAGGGGCG 24 7365 SCNN1A-3517 + GGCCACGCUACGGGCUCG 18 7366 SCNN1A-3518 + AGGCCACGCUACGGGCUCG 19 7367 SCNN1A-3519 + GAGGCCACGCUACGGGCUCG 20 7368 SCNN1A-3520 + GGAGGCCACGCUACGGGCUCG 21 7369 SCNN1A-3521 + UGGAGGCCACGCUACGGGCUCG 22 7370 SCNN1A-3522 + CUGGAGGCCACGCUACGGGCUCG 23 7371 SCNN1A-3523 + GCUGGAGGCCACGCUACGGGCUCG 24 7372 SCNN1A-3524 + GGGGAGGGGCUGUCAAGG 18 7373 SCNN1A-3525 + GGGGGAGGGGCUGUCAAGG 19 7374 SCNN1A-3526 + AGGGGGAGGGGCUGUCAAGG 20 7375 SCNN1A-3527 + CAGGGGGAGGGGCUGUCAAGG 21 7376 SCNN1A-3528 + GCAGGGGGAGGGGCUGUCAAGG 22 7377 SCNN1A-3529 + GGCAGGGGGAGGGGCUGUCAAGG 23 7378 SCNN1A-3530 + AGGCAGGGGGAGGGGCUGUCAAGG 24 7379 SCNN1A-3531 + GGGGCAGAAGUGGGAAGG 18 7380 SCNN1A-3532 + GGGGGCAGAAGUGGGAAGG 19 7381 SCNN1A-1161 + UGGGGGCAGAAGUGGGAAGG 20 5010 SCNN1A-3533 + GUGGGGGCAGAAGUGGGAAGG 21 7382 SCNN1A-3534 + GGUGGGGGCAGAAGUGGGAAGG 22 7383 SCNN1A-3535 + GGGUGGGGGCAGAAGUGGGAAGG 23 7384 SCNN1A-3536 + GGGGUGGGGGCAGAAGUGGGAAGG 24 7385 SCNN1A-3537 + GAAUACACACCUGGAAGG 18 7386 SCNN1A-3538 + UGAAUACACACCUGGAAGG 19 7387 SCNN1A-3539 + GUGAAUACACACCUGGAAGG 20 7388 SCNN1A-3540 + AGUGAAUACACACCUGGAAGG 21 7389 SCNN1A-3541 + GAGUGAAUACACACCUGGAAGG 22 7390 SCNN1A-3542 + GGAGUGAAUACACACCUGGAAGG 23 7391 SCNN1A-3543 + AGGAGUGAAUACACACCUGGAAGG 24 7392 SCNN1A-3544 + GCCCCCCCAGAGGACAGG 18 7393 SCNN1A-3545 + GGCCCCCCCAGAGGACAGG 19 7394 SCNN1A-1162 + GGGCCCCCCCAGAGGACAGG 20 5011 SCNN1A-3546 + AGGGCCCCCCCAGAGGACAGG 21 7395 SCNN1A-3547 + CAGGGCCCCCCCAGAGGACAGG 22 7396 SCNN1A-3548 + UCAGGGCCCCCCCAGAGGACAGG 23 7397 SCNN1A-3549 + CUCAGGGCCCCCCCAGAGGACAGG 24 7398 SCNN1A-3550 + CUCCACUGGCUGCCCAGG 18 7399 SCNN1A-3551 + GCUCCACUGGCUGCCCAGG 19 7400 SCNN1A-3552 + GGCUCCACUGGCUGCCCAGG 20 7401 SCNN1A-3553 + AGGCUCCACUGGCUGCCCAGG 21 7402 SCNN1A-3554 + CAGGCUCCACUGGCUGCCCAGG 22 7403 SCNN1A-3555 + ACAGGCUCCACUGGCUGCCCAGG 23 7404 SCNN1A-3556 + CACAGGCUCCACUGGCUGCCCAGG 24 7405 SCNN1A-3557 + GGAGGGGAGGAUGCCAGG 18 7406 SCNN1A-3558 + AGGAGGGGAGGAUGCCAGG 19 7407 SCNN1A-3559 + AAGGAGGGGAGGAUGCCAGG 20 7408 SCNN1A-3560 + GAAGGAGGGGAGGAUGCCAGG 21 7409 SCNN1A-3561 + GGAAGGAGGGGAGGAUGCCAGG 22 7410 SCNN1A-3562 + GGGAAGGAGGGGAGGAUGCCAGG 23 7411 SCNN1A-3563 + UGGGAAGGAGGGGAGGAUGCCAGG 24 7412 SCNN1A-3564 + CAGGGUGGCAUAGGCAGG 18 7413 SCNN1A-3565 + CCAGGGUGGCAUAGGCAGG 19 7414 SCNN1A-1167 + CCCAGGGUGGCAUAGGCAGG 20 5016 SCNN1A-3566 + GCCCAGGGUGGCAUAGGCAGG 21 7415 SCNN1A-3567 + GGCCCAGGGUGGCAUAGGCAGG 22 7416 SCNN1A-3568 + GGGCCCAGGGUGGCAUAGGCAGG 23 7417 SCNN1A-3569 + GGGGCCCAGGGUGGCAUAGGCAGG 24 7418 SCNN1A-3570 + AUGGAAGACAUCCAGAGG 18 7419 SCNN1A-3571 + CAUGGAAGACAUCCAGAGG 19 7420 SCNN1A-3572 + GCAUGGAAGACAUCCAGAGG 20 7421 SCNN1A-3573 + GGCAUGGAAGACAUCCAGAGG 21 7422 SCNN1A-3574 + AGGCAUGGAAGACAUCCAGAGG 22 7423 SCNN1A-3575 + CAGGCAUGGAAGACAUCCAGAGG 23 7424 SCNN1A-3576 + CCAGGCAUGGAAGACAUCCAGAGG 24 7425 SCNN1A-3577 + UUAGGUGUGGGGCAGAGG 18 7426 SCNN1A-3578 + CUUAGGUGUGGGGCAGAGG 19 7427 SCNN1A-3579 + UCUUAGGUGUGGGGCAGAGG 20 7428 SCNN1A-3580 + UUCUUAGGUGUGGGGCAGAGG 21 7429 SCNN1A-3581 + UUUCUUAGGUGUGGGGCAGAGG 22 7430 SCNN1A-3582 + AUUUCUUAGGUGUGGGGCAGAGG 23 7431 SCNN1A-3583 + CAUUUCUUAGGUGUGGGGCAGAGG 24 7432 SCNN1A-3584 + CACCUGGAAGGGAGGAGG 18 7433 SCNN1A-3585 + ACACCUGGAAGGGAGGAGG 19 7434 SCNN1A-3586 + CACACCUGGAAGGGAGGAGG 20 7435 SCNN1A-3587 + ACACACCUGGAAGGGAGGAGG 21 7436 SCNN1A-3588 + UACACACCUGGAAGGGAGGAGG 22 7437 SCNN1A-3589 + AUACACACCUGGAAGGGAGGAGG 23 7438 SCNN1A-3590 + AAUACACACCUGGAAGGGAGGAGG 24 7439 SCNN1A-3591 + UCGACGGGCCCCGUGAGG 18 7440 SCNN1A-3592 + CUCGACGGGCCCCGUGAGG 19 7441 SCNN1A-1172 + GCUCGACGGGCCCCGUGAGG 20 5021 SCNN1A-3593 + GGCUCGACGGGCCCCGUGAGG 21 7442 SCNN1A-3594 + GGGCUCGACGGGCCCCGUGAGG 22 7443 SCNN1A-3595 + CGGGCUCGACGGGCCCCGUGAGG 23 7444 SCNN1A-3596 + ACGGGCUCGACGGGCCCCGUGAGG 24 7445 SCNN1A-3597 + GGCCCAGGGUGGCAUAGG 18 7446 SCNN1A-3598 + GGGCCCAGGGUGGCAUAGG 19 7447 SCNN1A-3599 + GGGGCCCAGGGUGGCAUAGG 20 7448 SCNN1A-3600 + GGGGGCCCAGGGUGGCAUAGG 21 7449 SCNN1A-3601 + CGGGGGCCCAGGGUGGCAUAGG 22 7450 SCNN1A-3602 + GCGGGGGCCCAGGGUGGCAUAGG 23 7451 SCNN1A-3603 + GGCGGGGGCCCAGGGUGGCAUAGG 24 7452 SCNN1A-3604 + AAUACACACCUGGAAGGG 18 7453 SCNN1A-3605 + GAAUACACACCUGGAAGGG 19 7454 SCNN1A-1176 + UGAAUACACACCUGGAAGGG 20 5025 SCNN1A-3606 + GUGAAUACACACCUGGAAGGG 21 7455 SCNN1A-3607 + AGUGAAUACACACCUGGAAGGG 22 7456 SCNN1A-3608 + GAGUGAAUACACACCUGGAAGGG 23 7457 SCNN1A-3609 + GGAGUGAAUACACACCUGGAAGGG 24 7458 SCNN1A-3610 + UUCCGGGUACCUGAAGGG 18 7459 SCNN1A-3611 + UUUCCGGGUACCUGAAGGG 19 7460 SCNN1A-3612 + AUUUCCGGGUACCUGAAGGG 20 7461 SCNN1A-3613 + AAUUUCCGGGUACCUGAAGGG 21 7462 SCNN1A-3614 + UAAUUUCCGGGUACCUGAAGGG 22 7463 SCNN1A-3615 + UUAAUUUCCGGGUACCUGAAGGG 23 7464 SCNN1A-3616 + UUUAAUUUCCGGGUACCUGAAGGG 24 7465 SCNN1A-3617 + UUGUGGCUGGGACCAGGG 18 7466 SCNN1A-3618 + CUUGUGGCUGGGACCAGGG 19 7467 SCNN1A-3619 + UCUUGUGGCUGGGACCAGGG 20 7468 SCNN1A-3620 + GAGGGGAGGAUGCCAGGG 18 7469 SCNN1A-3621 + GGAGGGGAGGAUGCCAGGG 19 7470 SCNN1A-1178 + AGGAGGGGAGGAUGCCAGGG 20 5027 SCNN1A-3622 + AAGGAGGGGAGGAUGCCAGGG 21 7471 SCNN1A-3623 + GAAGGAGGGGAGGAUGCCAGGG 22 7472 SCNN1A-3624 + GGAAGGAGGGGAGGAUGCCAGGG 23 7473 SCNN1A-3625 + GGGAAGGAGGGGAGGAUGCCAGGG 24 7474 SCNN1A-3626 + UAGGUGUGGGGCAGAGGG 18 7475 SCNN1A-3627 + UUAGGUGUGGGGCAGAGGG 19 7476 SCNN1A-1179 + CUUAGGUGUGGGGCAGAGGG 20 5028 SCNN1A-3628 + UCUUAGGUGUGGGGCAGAGGG 21 7477 SCNN1A-3629 + UUCUUAGGUGUGGGGCAGAGGG 22 7478 SCNN1A-3630 + UUUCUUAGGUGUGGGGCAGAGGG 23 7479 SCNN1A-3631 + AUUUCUUAGGUGUGGGGCAGAGGG 24 7480 SCNN1A-3632 + ACCUGGAAGGGAGGAGGG 18 7481 SCNN1A-3633 + CACCUGGAAGGGAGGAGGG 19 7482 SCNN1A-1180 + ACACCUGGAAGGGAGGAGGG 20 5029 SCNN1A-3634 + CACACCUGGAAGGGAGGAGGG 21 7483 SCNN1A-3635 + ACACACCUGGAAGGGAGGAGGG 22 7484 SCNN1A-3636 + UACACACCUGGAAGGGAGGAGGG 23 7485 SCNN1A-3637 + AUACACACCUGGAAGGGAGGAGGG 24 7486 SCNN1A-3638 + GGGUGGCAUAGGCAGGGG 18 7487 SCNN1A-3639 + AGGGUGGCAUAGGCAGGGG 19 7488 SCNN1A-3640 + CAGGGUGGCAUAGGCAGGGG 20 7489 SCNN1A-3641 + CCAGGGUGGCAUAGGCAGGGG 21 7490 SCNN1A-3642 + CCCAGGGUGGCAUAGGCAGGGG 22 7491 SCNN1A-3643 + GCCCAGGGUGGCAUAGGCAGGGG 23 7492 SCNN1A-3644 + GGCCCAGGGUGGCAUAGGCAGGGG 24 7493 SCNN1A-3645 + ACCUGAAGGGGCGAGGGG 18 7494 SCNN1A-3646 + UACCUGAAGGGGCGAGGGG 19 7495 SCNN1A-3647 + GUACCUGAAGGGGCGAGGGG 20 7496 SCNN1A-3648 + GGUACCUGAAGGGGCGAGGGG 21 7497 SCNN1A-3649 + GGGUACCUGAAGGGGCGAGGGG 22 7498 SCNN1A-3650 + CGGGUACCUGAAGGGGCGAGGGG 23 7499 SCNN1A-3651 + CCGGGUACCUGAAGGGGCGAGGGG 24 7500 SCNN1A-3652 + GGGCCCCGUGAGGCGGGG 18 7501 SCNN1A-3653 + CGGGCCCCGUGAGGCGGGG 19 7502 SCNN1A-3654 + ACGGGCCCCGUGAGGCGGGG 20 7503 SCNN1A-3655 + GACGGGCCCCGUGAGGCGGGG 21 7504 SCNN1A-3656 + CGACGGGCCCCGUGAGGCGGGG 22 7505 SCNN1A-3657 + UCGACGGGCCCCGUGAGGCGGGG 23 7506 SCNN1A-3658 + CUCGACGGGCCCCGUGAGGCGGGG 24 7507 SCNN1A-3659 + GGUGGCAUAGGCAGGGGG 18 7508 SCNN1A-3660 + GGGUGGCAUAGGCAGGGGG 19 7509 SCNN1A-1184 + AGGGUGGCAUAGGCAGGGGG 20 5033 SCNN1A-3661 + CAGGGUGGCAUAGGCAGGGGG 21 7510 SCNN1A-3662 + CCAGGGUGGCAUAGGCAGGGGG 22 7511 SCNN1A-3663 + CCCAGGGUGGCAUAGGCAGGGGG 23 7512 SCNN1A-3664 + GCCCAGGGUGGCAUAGGCAGGGGG 24 7513 SCNN1A-3665 + GGCCCCGUGAGGCGGGGG 18 7514 SCNN1A-3666 + GGGCCCCGUGAGGCGGGGG 19 7515 SCNN1A-1185 + CGGGCCCCGUGAGGCGGGGG 20 5034 SCNN1A-3667 + ACGGGCCCCGUGAGGCGGGGG 21 7516 SCNN1A-3668 + GACGGGCCCCGUGAGGCGGGGG 22 7517 SCNN1A-3669 + CGACGGGCCCCGUGAGGCGGGGG 23 7518 SCNN1A-3670 + UCGACGGGCCCCGUGAGGCGGGGG 24 7519 SCNN1A-3671 + AGAGACAUGGGGUGGGGG 18 7520 SCNN1A-3672 + CAGAGACAUGGGGUGGGGG 19 7521 SCNN1A-3673 + ACAGAGACAUGGGGUGGGGG 20 7522 SCNN1A-3674 + GACAGAGACAUGGGGUGGGGG 21 7523 SCNN1A-3675 + GGACAGAGACAUGGGGUGGGGG 22 7524 SCNN1A-3676 + AGGACAGAGACAUGGGGUGGGGG 23 7525 SCNN1A-3677 + AAGGACAGAGACAUGGGGUGGGGG 24 7526 SCNN1A-3678 + AAGGACAGAGACAUGGGG 18 7527 SCNN1A-3679 + CAAGGACAGAGACAUGGGG 19 7528 SCNN1A-1186 + ACAAGGACAGAGACAUGGGG 20 5035 SCNN1A-3680 + GACAAGGACAGAGACAUGGGG 21 7529 SCNN1A-3681 + GGACAAGGACAGAGACAUGGGG 22 7530 SCNN1A-3682 + GGGACAAGGACAGAGACAUGGGG 23 7531 SCNN1A-3683 + UGGGACAAGGACAGAGACAUGGGG 24 7532 SCNN1A-3684 + UAGCUGGUCACGCUGGGG 18 7533 SCNN1A-3685 + GUAGCUGGUCACGCUGGGG 19 7534 SCNN1A-3686 + GGUAGCUGGUCACGCUGGGG 20 7535 SCNN1A-3687 + UGGUAGCUGGUCACGCUGGGG 21 7536 SCNN1A-3688 + CUGGUAGCUGGUCACGCUGGGG 22 7537 SCNN1A-3689 + GCUGGUAGCUGGUCACGCUGGGG 23 7538 SCNN1A-3690 + AGCUGGUAGCUGGUCACGCUGGGG 24 7539 SCNN1A-3691 + CAUUUCUUAGGUGUGGGG 18 7540 SCNN1A-3692 + CCAUUUCUUAGGUGUGGGG 19 7541 SCNN1A-3693 + UCCAUUUCUUAGGUGUGGGG 20 7542 SCNN1A-3694 + CUCCAUUUCUUAGGUGUGGGG 21 7543 SCNN1A-3695 + ACUCCAUUUCUUAGGUGUGGGG 22 7544 SCNN1A-3696 + CACUCCAUUUCUUAGGUGUGGGG 23 7545 SCNN1A-3697 + CCACUCCAUUUCUUAGGUGUGGGG 24 7546 SCNN1A-3698 + CAAGGACAGAGACAUGGG 18 7547 SCNN1A-3699 + ACAAGGACAGAGACAUGGG 19 7548 SCNN1A-3700 + GACAAGGACAGAGACAUGGG 20 7549 SCNN1A-3701 + GGACAAGGACAGAGACAUGGG 21 7550 SCNN1A-3702 + GGGACAAGGACAGAGACAUGGG 22 7551 SCNN1A-3703 + UGGGACAAGGACAGAGACAUGGG 23 7552 SCNN1A-3704 + CUGGGACAAGGACAGAGACAUGGG 24 7553 SCNN1A-3705 + GAGCCCCCUGGAGAUGGG 18 7554 SCNN1A-3706 + AGAGCCCCCUGGAGAUGGG 19 7555 SCNN1A-1188 + CAGAGCCCCCUGGAGAUGGG 20 5037 SCNN1A-3707 + GCAGAGCCCCCUGGAGAUGGG 21 7556 SCNN1A-3708 + UGCAGAGCCCCCUGGAGAUGGG 22 7557 SCNN1A-3709 + CUGCAGAGCCCCCUGGAGAUGGG 23 7558 SCNN1A-3710 + CCUGCAGAGCCCCCUGGAGAUGGG 24 7559 SCNN1A-3711 + GGUGGGGGCAGAAGUGGG 18 7560 SCNN1A-3712 + GGGUGGGGGCAGAAGUGGG 19 7561 SCNN1A-3713 + GGGGUGGGGGCAGAAGUGGG 20 7562 SCNN1A-3714 + UGGGGUGGGGGCAGAAGUGGG 21 7563 SCNN1A-3715 + AUGGGGUGGGGGCAGAAGUGGG 22 7564 SCNN1A-3716 + CAUGGGGUGGGGGCAGAAGUGGG 23 7565 SCNN1A-3717 + ACAUGGGGUGGGGGCAGAAGUGGG 24 7566 SCNN1A-3718 + UGUGGGGCAGAGGGUGGG 18 7567 SCNN1A-3719 + GUGUGGGGCAGAGGGUGGG 19 7568 SCNN1A-3720 + GGUGUGGGGCAGAGGGUGGG 20 7569 SCNN1A-3721 + AGGUGUGGGGCAGAGGGUGGG 21 7570 SCNN1A-3722 + UAGGUGUGGGGCAGAGGGUGGG 22 7571 SCNN1A-3723 + UUAGGUGUGGGGCAGAGGGUGGG 23 7572 SCNN1A-3724 + CUUAGGUGUGGGGCAGAGGGUGGG 24 7573 SCNN1A-3725 + AGAGCCCCCUGGAGAUGG 18 7574 SCNN1A-3726 + CAGAGCCCCCUGGAGAUGG 19 7575 SCNN1A-3727 + GCAGAGCCCCCUGGAGAUGG 20 7576 SCNN1A-3728 + UGCAGAGCCCCCUGGAGAUGG 21 7577 SCNN1A-3729 + CUGCAGAGCCCCCUGGAGAUGG 22 7578 SCNN1A-3730 + CCUGCAGAGCCCCCUGGAGAUGG 23 7579 SCNN1A-3731 + CCCUGCAGAGCCCCCUGGAGAUGG 24 7580 SCNN1A-3732 + GAGUGAAUACACACCUGG 18 7581 SCNN1A-3733 + GGAGUGAAUACACACCUGG 19 7582 SCNN1A-3734 + AGGAGUGAAUACACACCUGG 20 7583 SCNN1A-3735 + CAGGAGUGAAUACACACCUGG 21 7584 SCNN1A-3736 + GCAGGAGUGAAUACACACCUGG 22 7585 SCNN1A-3737 + AGCAGGAGUGAAUACACACCUGG 23 7586 SCNN1A-3738 + AAGCAGGAGUGAAUACACACCUGG 24 7587 SCNN1A-3739 + UGGUUGCAGGAGACCUGG 18 7588 SCNN1A-3740 + CUGGUUGCAGGAGACCUGG 19 7589 SCNN1A-3741 + CCUGGUUGCAGGAGACCUGG 20 7590 SCNN1A-3742 + GCCUGGUUGCAGGAGACCUGG 21 7591 SCNN1A-3743 + CGCCUGGUUGCAGGAGACCUGG 22 7592 SCNN1A-3744 + ACGCCUGGUUGCAGGAGACCUGG 23 7593 SCNN1A-3745 + CACGCCUGGUUGCAGGAGACCUGG 24 7594 SCNN1A-3746 + AGAGGGAGCAGGGCCUGG 18 7595 SCNN1A-3747 + GAGAGGGAGCAGGGCCUGG 19 7596 SCNN1A-3748 + GGAGAGGGAGCAGGGCCUGG 20 7597 SCNN1A-3749 + UGGAGAGGGAGCAGGGCCUGG 21 7598 SCNN1A-3750 + CUGGAGAGGGAGCAGGGCCUGG 22 7599 SCNN1A-3751 + GCUGGAGAGGGAGCAGGGCCUGG 23 7600 SCNN1A-3752 + GGCUGGAGAGGGAGCAGGGCCUGG 24 7601 SCNN1A-3753 + CCUGAUGAGUAUGUCUGG 18 7602 SCNN1A-3754 + CCCUGAUGAGUAUGUCUGG 19 7603 SCNN1A-3755 + CCCCUGAUGAGUAUGUCUGG 20 7604 SCNN1A-3756 + ACCCCUGAUGAGUAUGUCUGG 21 7605 SCNN1A-3757 + CACCCCUGAUGAGUAUGUCUGG 22 7606 SCNN1A-3758 + CCACCCCUGAUGAGUAUGUCUGG 23 7607 SCNN1A-3759 + UCCACCCCUGAUGAGUAUGUCUGG 24 7608 SCNN1A-3760 + CCCCCAGAGGACAGGUGG 18 7609 SCNN1A-3761 + CCCCCCAGAGGACAGGUGG 19 7610 SCNN1A-1200 + CCCCCCCAGAGGACAGGUGG 20 5049 SCNN1A-3762 + GCCCCCCCAGAGGACAGGUGG 21 7611 SCNN1A-3763 + GGCCCCCCCAGAGGACAGGUGG 22 7612 SCNN1A-3764 + GGGCCCCCCCAGAGGACAGGUGG 23 7613 SCNN1A-3765 + AGGGCCCCCCCAGAGGACAGGUGG 24 7614 SCNN1A-3766 + UUUCCAUACAUCGGGUGG 18 7615 SCNN1A-3767 + GUUUCCAUACAUCGGGUGG 19 7616 SCNN1A-1202 + AGUUUCCAUACAUCGGGUGG 20 5051 SCNN1A-3768 + CAGUUUCCAUACAUCGGGUGG 21 7617 SCNN1A-3769 + GCAGUUUCCAUACAUCGGGUGG 22 7618 SCNN1A-3770 + AGCAGUUUCCAUACAUCGGGUGG 23 7619 SCNN1A-3771 + UAGCAGUUUCCAUACAUCGGGUGG 24 7620 SCNN1A-3772 + AACCUUCGGAGCAGCAUG 18 7621 SCNN1A-3773 + GAACCUUCGGAGCAGCAUG 19 7622 SCNN1A-1209 + GGAACCUUCGGAGCAGCAUG 20 5058 SCNN1A-3774 + CGGAACCUUCGGAGCAGCAUG 21 7623 SCNN1A-3775 + UCGGAACCUUCGGAGCAGCAUG 22 7624 SCNN1A-3776 + UUCGGAACCUUCGGAGCAGCAUG 23 7625 SCNN1A-3777 + CUUCGGAACCUUCGGAGCAGCAUG 24 7626 SCNN1A-3778 + CUGGUCACGCUGGGGAUG 18 7627 SCNN1A-3779 + GCUGGUCACGCUGGGGAUG 19 7628 SCNN1A-3780 + AGCUGGUCACGCUGGGGAUG 20 7629 SCNN1A-3781 + UAGCUGGUCACGCUGGGGAUG 21 7630 SCNN1A-3782 + GUAGCUGGUCACGCUGGGGAUG 22 7631 SCNN1A-3783 + GGUAGCUGGUCACGCUGGGGAUG 23 7632 SCNN1A-3784 + UGGUAGCUGGUCACGCUGGGGAUG 24 7633 SCNN1A-3785 + UUAAUUUCCGGGUACCUG 18 7634 SCNN1A-3786 + UUUAAUUUCCGGGUACCUG 19 7635 SCNN1A-3787 + CUUUAAUUUCCGGGUACCUG 20 7636 SCNN1A-3788 + UCUUUAAUUUCCGGGUACCUG 21 7637 SCNN1A-3789 + CUCUUUAAUUUCCGGGUACCUG 22 7638 SCNN1A-3790 + CCUCUUUAAUUUCCGGGUACCUG 23 7639 SCNN1A-3791 + UCCUCUUUAAUUUCCGGGUACCUG 24 7640 SCNN1A-3792 + UGGAGGAACUGGCCCCUG 18 7641 SCNN1A-3793 + GUGGAGGAACUGGCCCCUG 19 7642 SCNN1A-3794 + GGUGGAGGAACUGGCCCCUG 20 7643 SCNN1A-3795 + AGGUGGAGGAACUGGCCCCUG 21 7644 SCNN1A-3796 + CAGGUGGAGGAACUGGCCCCUG 22 7645 SCNN1A-3797 + ACAGGUGGAGGAACUGGCCCCUG 23 7646 SCNN1A-3798 + GACAGGUGGAGGAACUGGCCCCUG 24 7647 SCNN1A-3799 + GAGGGGCUGUCAAGGCUG 18 7648 SCNN1A-3800 + GGAGGGGCUGUCAAGGCUG 19 7649 SCNN1A-3801 + GGGAGGGGCUGUCAAGGCUG 20 7650 SCNN1A-3802 + GGGGAGGGGCUGUCAAGGCUG 21 7651 SCNN1A-3803 + GGGGGAGGGGCUGUCAAGGCUG 22 7652 SCNN1A-3804 + AGGGGGAGGGGCUGUCAAGGCUG 23 7653 SCNN1A-3805 + CAGGGGGAGGGGCUGUCAAGGCUG 24 7654 SCNN1A-3806 + CGCAGGUCGCGACGGCUG 18 7655 SCNN1A-3807 + CCGCAGGUCGCGACGGCUG 19 7656 SCNN1A-1223 + CCCGCAGGUCGCGACGGCUG 20 5072 SCNN1A-3808 + CCCCGCAGGUCGCGACGGCUG 21 7657 SCNN1A-3809 + CCCCCGCAGGUCGCGACGGCUG 22 7658 SCNN1A-3810 + UCCCCCGCAGGUCGCGACGGCUG 23 7659 SCNN1A-3811 + GUCCCCCGCAGGUCGCGACGGCUG 24 7660 SCNN1A-3812 + CUUGCCUUCCUCAUGCUG 18 7661 SCNN1A-3813 + CCUUGCCUUCCUCAUGCUG 19 7662 SCNN1A-3814 + UCCUUGCCUUCCUCAUGCUG 20 7663 SCNN1A-3815 + AUCCUUGCCUUCCUCAUGCUG 21 7664 SCNN1A-3816 + CAUCCUUGCCUUCCUCAUGCUG 22 7665 SCNN1A-3817 + GCAUCCUUGCCUUCCUCAUGCUG 23 7666 SCNN1A-3818 + AGCAUCCUUGCCUUCCUCAUGCUG 24 7667 SCNN1A-3819 + AACAGCCCAGGUGGUCUG 18 7668 SCNN1A-3820 + AAACAGCCCAGGUGGUCUG 19 7669 SCNN1A-1225 + GAAACAGCCCAGGUGGUCUG 20 5074 SCNN1A-3821 + UGAAACAGCCCAGGUGGUCUG 21 7670 SCNN1A-3822 + GUGAAACAGCCCAGGUGGUCUG 22 7671 SCNN1A-3823 + GGUGAAACAGCCCAGGUGGUCUG 23 7672 SCNN1A-3824 + UGGUGAAACAGCCCAGGUGGUCUG 24 7673 SCNN1A-3825 + GAGCCGGCCACGAGAGUG 18 7674 SCNN1A-3826 + GGAGCCGGCCACGAGAGUG 19 7675 SCNN1A-3827 + GGGAGCCGGCCACGAGAGUG 20 7676 SCNN1A-3828 + CGGGAGCCGGCCACGAGAGUG 21 7677 SCNN1A-3829 + GCGGGAGCCGGCCACGAGAGUG 22 7678 SCNN1A-3830 + UGCGGGAGCCGGCCACGAGAGUG 23 7679 SCNN1A-3831 + CUGCGGGAGCCGGCCACGAGAGUG 24 7680 SCNN1A-3832 + CCCCCCAGAGGACAGGUG 18 7681 SCNN1A-3833 + CCCCCCCAGAGGACAGGUG 19 7682 SCNN1A-3834 + GCCCCCCCAGAGGACAGGUG 20 7683 SCNN1A-3835 + GGCCCCCCCAGAGGACAGGUG 21 7684 SCNN1A-3836 + GGGCCCCCCCAGAGGACAGGUG 22 7685 SCNN1A-3837 + AGGGCCCCCCCAGAGGACAGGUG 23 7686 SCNN1A-3838 + CAGGGCCCCCCCAGAGGACAGGUG 24 7687 SCNN1A-3839 + CACUCCAUUUCUUAGGUG 18 7688 SCNN1A-3840 + CCACUCCAUUUCUUAGGUG 19 7689 SCNN1A-1232 + GCCACUCCAUUUCUUAGGUG 20 5081 SCNN1A-3841 + GGCCACUCCAUUUCUUAGGUG 21 7690 SCNN1A-3842 + UGGCCACUCCAUUUCUUAGGUG 22 7691 SCNN1A-3843 + UUGGCCACUCCAUUUCUUAGGUG 23 7692 SCNN1A-3844 + UUUGGCCACUCCAUUUCUUAGGUG 24 7693 SCNN1A-3845 + CUGGAAGGGAGGAGGGUG 18 7694 SCNN1A-3846 + CCUGGAAGGGAGGAGGGUG 19 7695 SCNN1A-3847 + ACCUGGAAGGGAGGAGGGUG 20 7696 SCNN1A-3848 + CACCUGGAAGGGAGGAGGGUG 21 7697 SCNN1A-3849 + ACACCUGGAAGGGAGGAGGGUG 22 7698 SCNN1A-3850 + CACACCUGGAAGGGAGGAGGGUG 23 7699 SCNN1A-3851 + ACACACCUGGAAGGGAGGAGGGUG 24 7700 SCNN1A-3852 + GUUUCCAUACAUCGGGUG 18 7701 SCNN1A-3853 + AGUUUCCAUACAUCGGGUG 19 7702 SCNN1A-3854 + CAGUUUCCAUACAUCGGGUG 20 7703 SCNN1A-3855 + GCAGUUUCCAUACAUCGGGUG 21 7704 SCNN1A-3856 + AGCAGUUUCCAUACAUCGGGUG 22 7705 SCNN1A-3857 + UAGCAGUUUCCAUACAUCGGGUG 23 7706 SCNN1A-3858 + AUAGCAGUUUCCAUACAUCGGGUG 24 7707 SCNN1A-3859 + GGGACAGACCUAGGGGUG 18 7708 SCNN1A-3860 + AGGGACAGACCUAGGGGUG 19 7709 SCNN1A-3861 + CAGGGACAGACCUAGGGGUG 20 7710 SCNN1A-3862 + UCAGGGACAGACCUAGGGGUG 21 7711 SCNN1A-3863 + AUCAGGGACAGACCUAGGGGUG 22 7712 SCNN1A-3864 + CAUCAGGGACAGACCUAGGGGUG 23 7713 SCNN1A-3865 + GCAUCAGGGACAGACCUAGGGGUG 24 7714 SCNN1A-3866 + CCGGCCACGAGAGUGGUG 18 7715 SCNN1A-3867 + GCCGGCCACGAGAGUGGUG 19 7716 SCNN1A-3868 + AGCCGGCCACGAGAGUGGUG 20 7717 SCNN1A-3869 + GAGCCGGCCACGAGAGUGGUG 21 7718 SCNN1A-3870 + GGAGCCGGCCACGAGAGUGGUG 22 7719 SCNN1A-3871 + GGGAGCCGGCCACGAGAGUGGUG 23 7720 SCNN1A-3872 + CGGGAGCCGGCCACGAGAGUGGUG 24 7721 SCNN1A-3873 + CAUGGCUUCCGGCACUUG 18 7722 SCNN1A-3874 + GCAUGGCUUCCGGCACUUG 19 7723 SCNN1A-3875 + UGCAUGGCUUCCGGCACUUG 20 7724 SCNN1A-3876 + CUGCAUGGCUUCCGGCACUUG 21 7725 SCNN1A-3877 + CCUGCAUGGCUUCCGGCACUUG 22 7726 SCNN1A-3878 + ACCUGCAUGGCUUCCGGCACUUG 23 7727 SCNN1A-3879 + AACCUGCAUGGCUUCCGGCACUUG 24 7728 SCNN1A-3880 + UUGUAGUUCAGCUCCUUG 18 7729 SCNN1A-3881 + UUUGUAGUUCAGCUCCUUG 19 7730 SCNN1A-3882 + UUUUGUAGUUCAGCUCCUUG 20 7731 SCNN1A-3883 + GUUUUGUAGUUCAGCUCCUUG 21 7732 SCNN1A-3884 + GGUUUUGUAGUUCAGCUCCUUG 22 7733 SCNN1A-3885 + UGGUUUUGUAGUUCAGCUCCUUG 23 7734 SCNN1A-3886 + UUGGUUUUGUAGUUCAGCUCCUUG 24 7735 SCNN1A-3887 + CUGACUCACGCCUGGUUG 18 7736 SCNN1A-3888 + ACUGACUCACGCCUGGUUG 19 7737 SCNN1A-3889 + GACUGACUCACGCCUGGUUG 20 7738 SCNN1A-3890 + GGACUGACUCACGCCUGGUUG 21 7739 SCNN1A-3891 + AGGACUGACUCACGCCUGGUUG 22 7740 SCNN1A-3892 + CAGGACUGACUCACGCCUGGUUG 23 7741 SCNN1A-3893 + GCAGGACUGACUCACGCCUGGUUG 24 7742 SCNN1A-3894 + GAACCUUCGGAGCAGCAU 18 7743 SCNN1A-3895 + GGAACCUUCGGAGCAGCAU 19 7744 SCNN1A-3896 + CGGAACCUUCGGAGCAGCAU 20 7745 SCNN1A-3897 + UCGGAACCUUCGGAGCAGCAU 21 7746 SCNN1A-3898 + UUCGGAACCUUCGGAGCAGCAU 22 7747 SCNN1A-3899 + CUUCGGAACCUUCGGAGCAGCAU 23 7748 SCNN1A-3900 + GCUUCGGAACCUUCGGAGCAGCAU 24 7749 SCNN1A-3901 + CUGCUCUGCGCGCAGCAU 18 7750 SCNN1A-3902 + UCUGCUCUGCGCGCAGCAU 19 7751 SCNN1A-3903 + UUCUGCUCUGCGCGCAGCAU 20 7752 SCNN1A-3904 + AUUCUGCUCUGCGCGCAGCAU 21 7753 SCNN1A-3905 + CAUUCUGCUCUGCGCGCAGCAU 22 7754 SCNN1A-3906 + UCAUUCUGCUCUGCGCGCAGCAU 23 7755 SCNN1A-3907 + GUCAUUCUGCUCUGCGCGCAGCAU 24 7756 SCNN1A-3908 + GUUCUGUCGCGAUAGCAU 18 7757 SCNN1A-3909 + UGUUCUGUCGCGAUAGCAU 19 7758 SCNN1A-3910 + UUGUUCUGUCGCGAUAGCAU 20 7759 SCNN1A-3911 + AUUGUUCUGUCGCGAUAGCAU 21 7760 SCNN1A-3912 + AAUUGUUCUGUCGCGAUAGCAU 22 7761 SCNN1A-3913 + UAAUUGUUCUGUCGCGAUAGCAU 23 7762 SCNN1A-3914 + GUAAUUGUUCUGUCGCGAUAGCAU 24 7763 SCNN1A-3915 + GUGAGAGUAAUUCCUUAU 18 7764 SCNN1A-3916 + AGUGAGAGUAAUUCCUUAU 19 7765 SCNN1A-3917 + AAGUGAGAGUAAUUCCUUAU 20 7766 SCNN1A-3918 + GAAGUGAGAGUAAUUCCUUAU 21 7767 SCNN1A-3919 + GGAAGUGAGAGUAAUUCCUUAU 22 7768 SCNN1A-3920 + UGGAAGUGAGAGUAAUUCCUUAU 23 7769 SCNN1A-3921 + GUGGAAGUGAGAGUAAUUCCUUAU 24 7770 SCNN1A-3922 + ACCCGGGCCCCAGUCACU 18 7771 SCNN1A-3923 + UACCCGGGCCCCAGUCACU 19 7772 SCNN1A-3924 + UUACCCGGGCCCCAGUCACU 20 7773 SCNN1A-3925 + AUUACCCGGGCCCCAGUCACU 21 7774 SCNN1A-3926 + CAUUACCCGGGCCCCAGUCACU 22 7775 SCNN1A-3927 + CCAUUACCCGGGCCCCAGUCACU 23 7776 SCNN1A-3928 + ACCAUUACCCGGGCCCCAGUCACU 24 7777 SCNN1A-3929 + UCACCUGCUGUGUGUACU 18 7778 SCNN1A-3930 + CUCACCUGCUGUGUGUACU 19 7779 SCNN1A-3931 + CCUCACCUGCUGUGUGUACU 20 7780 SCNN1A-3932 + GCCUCACCUGCUGUGUGUACU 21 7781 SCNN1A-3933 + GGCCUCACCUGCUGUGUGUACU 22 7782 SCNN1A-3934 + GGGCCUCACCUGCUGUGUGUACU 23 7783 SCNN1A-3935 + UGGGCCUCACCUGCUGUGUGUACU 24 7784 SCNN1A-3936 + GUAUCGGCUUCGGAACCU 18 7785 SCNN1A-3937 + AGUAUCGGCUUCGGAACCU 19 7786 SCNN1A-3938 + CAGUAUCGGCUUCGGAACCU 20 7787 SCNN1A-3939 + CCAGUAUCGGCUUCGGAACCU 21 7788 SCNN1A-3940 + ACCAGUAUCGGCUUCGGAACCU 22 7789 SCNN1A-3941 + GACCAGUAUCGGCUUCGGAACCU 23 7790 SCNN1A-3942 + AGACCAGUAUCGGCUUCGGAACCU 24 7791 SCNN1A-3943 + UCUGGAAGACCCAUUCCU 18 7792 SCNN1A-3944 + AUCUGGAAGACCCAUUCCU 19 7793 SCNN1A-1270 + CAUCUGGAAGACCCAUUCCU 20 5119 SCNN1A-3945 + GCAUCUGGAAGACCCAUUCCU 21 7794 SCNN1A-3946 + AGCAUCUGGAAGACCCAUUCCU 22 7795 SCNN1A-3947 + UAGCAUCUGGAAGACCCAUUCCU 23 7796 SCNN1A-3948 + AUAGCAUCUGGAAGACCCAUUCCU 24 7797 SCNN1A-3949 + GUCUGUCCAGGGUUUCCU 18 7798 SCNN1A-3950 + AGUCUGUCCAGGGUUUCCU 19 7799 SCNN1A-3951 + AAGUCUGUCCAGGGUUUCCU 20 7800 SCNN1A-3952 + CAAGUCUGUCCAGGGUUUCCU 21 7801 SCNN1A-3953 + CCAAGUCUGUCCAGGGUUUCCU 22 7802 SCNN1A-3954 + CCCAAGUCUGUCCAGGGUUUCCU 23 7803 SCNN1A-3955 + CCCCAAGUCUGUCCAGGGUUUCCU 24 7804 SCNN1A-3956 + CAAGCUGGAGGCCACGCU 18 7805 SCNN1A-3957 + GCAAGCUGGAGGCCACGCU 19 7806 SCNN1A-3958 + CGCAAGCUGGAGGCCACGCU 20 7807 SCNN1A-3959 + CCGCAAGCUGGAGGCCACGCU 21 7808 SCNN1A-3960 + CCCGCAAGCUGGAGGCCACGCU 22 7809 SCNN1A-3961 + UCCCGCAAGCUGGAGGCCACGCU 23 7810 SCNN1A-3962 + GUCCCGCAAGCUGGAGGCCACGCU 24 7811 SCNN1A-3963 + CCGCAGGUCGCGACGGCU 18 7812 SCNN1A-3964 + CCCGCAGGUCGCGACGGCU 19 7813 SCNN1A-3965 + CCCCGCAGGUCGCGACGGCU 20 7814 SCNN1A-3966 + CCCCCGCAGGUCGCGACGGCU 21 7815 SCNN1A-3967 + UCCCCCGCAGGUCGCGACGGCU 22 7816 SCNN1A-3968 + GUCCCCCGCAGGUCGCGACGGCU 23 7817 SCNN1A-3969 + AGUCCCCCGCAGGUCGCGACGGCU 24 7818 SCNN1A-3970 + UGGAGACCAGUAUCGGCU 18 7819 SCNN1A-3971 + CUGGAGACCAGUAUCGGCU 19 7820 SCNN1A-3972 + CCUGGAGACCAGUAUCGGCU 20 7821 SCNN1A-3973 + GCCUGGAGACCAGUAUCGGCU 21 7822 SCNN1A-3974 + GGCCUGGAGACCAGUAUCGGCU 22 7823 SCNN1A-3975 + CGGCCUGGAGACCAGUAUCGGCU 23 7824 SCNN1A-3976 + UCGGCCUGGAGACCAGUAUCGGCU 24 7825 SCNN1A-3977 + ACAGGAGGGUGACCAUCU 18 7826 SCNN1A-3978 + GACAGGAGGGUGACCAUCU 19 7827 SCNN1A-3979 + GGACAGGAGGGUGACCAUCU 20 7828 SCNN1A-3980 + UGGACAGGAGGGUGACCAUCU 21 7829 SCNN1A-3981 + UUGGACAGGAGGGUGACCAUCU 22 7830 SCNN1A-3982 + GUUGGACAGGAGGGUGACCAUCU 23 7831 SCNN1A-3983 + GGUUGGACAGGAGGGUGACCAUCU 24 7832 SCNN1A-3984 + AAACCUCUCCUUCCCUCU 18 7833 SCNN1A-3985 + GAAACCUCUCCUUCCCUCU 19 7834 SCNN1A-3986 + AGAAACCUCUCCUUCCCUCU 20 7835 SCNN1A-3987 + GAGAAACCUCUCCUUCCCUCU 21 7836 SCNN1A-3988 + UGAGAAACCUCUCCUUCCCUCU 22 7837 SCNN1A-3989 + GUGAGAAACCUCUCCUUCCCUCU 23 7838 SCNN1A-3990 + UGUGAGAAACCUCUCCUUCCCUCU 24 7839 SCNN1A-3991 + AAACAGCCCAGGUGGUCU 18 7840 SCNN1A-3992 + GAAACAGCCCAGGUGGUCU 19 7841 SCNN1A-3993 + UGAAACAGCCCAGGUGGUCU 20 7842 SCNN1A-3994 + GUGAAACAGCCCAGGUGGUCU 21 7843 SCNN1A-3995 + GGUGAAACAGCCCAGGUGGUCU 22 7844 SCNN1A-3996 + UGGUGAAACAGCCCAGGUGGUCU 23 7845 SCNN1A-3997 + UUGGUGAAACAGCCCAGGUGGUCU 24 7846 SCNN1A-3998 + UGGGGUGGGGGCAGAAGU 18 7847 SCNN1A-3999 + AUGGGGUGGGGGCAGAAGU 19 7848 SCNN1A-1279 + CAUGGGGUGGGGGCAGAAGU 20 5128 SCNN1A-4000 + ACAUGGGGUGGGGGCAGAAGU 21 7849 SCNN1A-4001 + GACAUGGGGUGGGGGCAGAAGU 22 7850 SCNN1A-4002 + AGACAUGGGGUGGGGGCAGAAGU 23 7851 SCNN1A-4003 + GAGACAUGGGGUGGGGGCAGAAGU 24 7852 SCNN1A-4004 + GGACACAGAGACUAGAGU 18 7853 SCNN1A-4005 + UGGACACAGAGACUAGAGU 19 7854 SCNN1A-4006 + CUGGACACAGAGACUAGAGU 20 7855 SCNN1A-4007 + ACUGGACACAGAGACUAGAGU 21 7856 SCNN1A-4008 + CACUGGACACAGAGACUAGAGU 22 7857 SCNN1A-4009 + GCACUGGACACAGAGACUAGAGU 23 7858 SCNN1A-4010 + UGCACUGGACACAGAGACUAGAGU 24 7859 SCNN1A-4011 + CCACUCCAUUUCUUAGGU 18 7860 SCNN1A-4012 + GCCACUCCAUUUCUUAGGU 19 7861 SCNN1A-4013 + GGCCACUCCAUUUCUUAGGU 20 7862 SCNN1A-4014 + UGGCCACUCCAUUUCUUAGGU 21 7863 SCNN1A-4015 + UUGGCCACUCCAUUUCUUAGGU 22 7864 SCNN1A-4016 + UUUGGCCACUCCAUUUCUUAGGU 23 7865 SCNN1A-4017 + CUUUGGCCACUCCAUUUCUUAGGU 24 7866 SCNN1A-4018 + AGGUGUGGGGCAGAGGGU 18 7867 SCNN1A-4019 + UAGGUGUGGGGCAGAGGGU 19 7868 SCNN1A-1286 + UUAGGUGUGGGGCAGAGGGU 20 5135 SCNN1A-4020 + CUUAGGUGUGGGGCAGAGGGU 21 7869 SCNN1A-4021 + UCUUAGGUGUGGGGCAGAGGGU 22 7870 SCNN1A-4022 + UUCUUAGGUGUGGGGCAGAGGGU 23 7871 SCNN1A-4023 + UUUCUUAGGUGUGGGGCAGAGGGU 24 7872 SCNN1A-4024 + GGAAAGAGAGAGUAGGGU 18 7873 SCNN1A-4025 + AGGAAAGAGAGAGUAGGGU 19 7874 SCNN1A-4026 + CAGGAAAGAGAGAGUAGGGU 20 7875 SCNN1A-4027 + UCAGGAAAGAGAGAGUAGGGU 21 7876 SCNN1A-4028 + AUCAGGAAAGAGAGAGUAGGGU 22 7877 SCNN1A-4029 + UAUCAGGAAAGAGAGAGUAGGGU 23 7878 SCNN1A-4030 + UUAUCAGGAAAGAGAGAGUAGGGU 24 7879 SCNN1A-4031 + AGGACAGAGACAUGGGGU 18 7880 SCNN1A-4032 + AAGGACAGAGACAUGGGGU 19 7881 SCNN1A-1287 + CAAGGACAGAGACAUGGGGU 20 5136 SCNN1A-4033 + ACAAGGACAGAGACAUGGGGU 21 7882 SCNN1A-4034 + GACAAGGACAGAGACAUGGGGU 22 7883 SCNN1A-4035 + GGACAAGGACAGAGACAUGGGGU 23 7884 SCNN1A-4036 + GGGACAAGGACAGAGACAUGGGGU 24 7885 SCNN1A-4037 + UGAAACAGCCCAGGUGGU 18 7886 SCNN1A-4038 + GUGAAACAGCCCAGGUGGU 19 7887 SCNN1A-4039 + GGUGAAACAGCCCAGGUGGU 20 7888 SCNN1A-4040 + UGGUGAAACAGCCCAGGUGGU 21 7889 SCNN1A-4041 + UUGGUGAAACAGCCCAGGUGGU 22 7890 SCNN1A-4042 + CUUGGUGAAACAGCCCAGGUGGU 23 7891 SCNN1A-4043 + ACUUGGUGAAACAGCCCAGGUGGU 24 7892 SCNN1A-4044 + AGGAGGGUGACCAUCUGU 18 7893 SCNN1A-4045 + CAGGAGGGUGACCAUCUGU 19 7894 SCNN1A-4046 + ACAGGAGGGUGACCAUCUGU 20 7895 SCNN1A-4047 + GACAGGAGGGUGACCAUCUGU 21 7896 SCNN1A-4048 + GGACAGGAGGGUGACCAUCUGU 22 7897 SCNN1A-4049 + UGGACAGGAGGGUGACCAUCUGU 23 7898 SCNN1A-4050 + UUGGACAGGAGGGUGACCAUCUGU 24 7899 SCNN1A-4051 + UAUCGGCUUCGGAACCUU 18 7900 SCNN1A-4052 + GUAUCGGCUUCGGAACCUU 19 7901 SCNN1A-1297 + AGUAUCGGCUUCGGAACCUU 20 5146 SCNN1A-4053 + CAGUAUCGGCUUCGGAACCUU 21 7902 SCNN1A-4054 + CCAGUAUCGGCUUCGGAACCUU 22 7903 SCNN1A-4055 + ACCAGUAUCGGCUUCGGAACCUU 23 7904 SCNN1A-4056 + GACCAGUAUCGGCUUCGGAACCUU 24 7905 SCNN1A-4057 + GGAGACCAGUAUCGGCUU 18 7906 SCNN1A-4058 + UGGAGACCAGUAUCGGCUU 19 7907 SCNN1A-1298 + CUGGAGACCAGUAUCGGCUU 20 5147 SCNN1A-4059 + CCUGGAGACCAGUAUCGGCUU 21 7908 SCNN1A-4060 + GCCUGGAGACCAGUAUCGGCUU 22 7909 SCNN1A-4061 + GGCCUGGAGACCAGUAUCGGCUU 23 7910 SCNN1A-4062 + CGGCCUGGAGACCAGUAUCGGCUU 24 7911 SCNN1A-4063 + GUCACAGUACUCCACGUU 18 7912 SCNN1A-4064 + AGUCACAGUACUCCACGUU 19 7913 SCNN1A-4065 + UAGUCACAGUACUCCACGUU 20 7914 SCNN1A-4066 + GUAGUCACAGUACUCCACGUU 21 7915 SCNN1A-4067 + UGUAGUCACAGUACUCCACGUU 22 7916 SCNN1A-4068 + CUGUAGUCACAGUACUCCACGUU 23 7917 SCNN1A-4069 + UCUGUAGUCACAGUACUCCACGUU 24 7918 SCNN1A-4070 CAGUGCAACCAGAACAAA 18 7919 SCNN1A-4071 CCAGUGCAACCAGAACAAA 19 7920 SCNN1A-4072 UCCAGUGCAACCAGAACAAA 20 7921 SCNN1A-4073 GUCCAGUGCAACCAGAACAAA 21 7922 SCNN1A-4074 UGUCCAGUGCAACCAGAACAAA 22 7923 SCNN1A-4075 GUGUCCAGUGCAACCAGAACAAA 23 7924 SCNN1A-4076 UGUGUCCAGUGCAACCAGAACAAA 24 7925 SCNN1A-4077 AGGUACCCGGAAAUUAAA 18 7926 SCNN1A-4078 CAGGUACCCGGAAAUUAAA 19 7927 SCNN1A-4079 UCAGGUACCCGGAAAUUAAA 20 7928 SCNN1A-4080 UUCAGGUACCCGGAAAUUAAA 21 7929 SCNN1A-4081 CUUCAGGUACCCGGAAAUUAAA 22 7930 SCNN1A-4082 CCUUCAGGUACCCGGAAAUUAAA 23 7931 SCNN1A-4083 CCCUUCAGGUACCCGGAAAUUAAA 24 7932 SCNN1A-4084 CUGCCCCACACCUAAGAA 18 7933 SCNN1A-4085 UCUGCCCCACACCUAAGAA 19 7934 SCNN1A-4086 CUCUGCCCCACACCUAAGAA 20 7935 SCNN1A-4087 CCUCUGCCCCACACCUAAGAA 21 7936 SCNN1A-4088 CCCUCUGCCCCACACCUAAGAA 22 7937 SCNN1A-4089 ACCCUCUGCCCCACACCUAAGAA 23 7938 SCNN1A-4090 CACCCUCUGCCCCACACCUAAGAA 24 7939 SCNN1A-4091 GUCCAACCUGGGCAGCCA 18 7940 SCNN1A-4092 UGUCCAACCUGGGCAGCCA 19 7941 SCNN1A-4093 CUGUCCAACCUGGGCAGCCA 20 7942 SCNN1A-4094 CCUGUCCAACCUGGGCAGCCA 21 7943 SCNN1A-4095 UCCUGUCCAACCUGGGCAGCCA 22 7944 SCNN1A-4096 CUCCUGUCCAACCUGGGCAGCCA 23 7945 SCNN1A-4097 CCUCCUGUCCAACCUGGGCAGCCA 24 7946 SCNN1A-4098 UCCUGGGGUGAGACUCCA 18 7947 SCNN1A-4099 UUCCUGGGGUGAGACUCCA 19 7948 SCNN1A-904 GUUCCUGGGGUGAGACUCCA 20 4753 SCNN1A-4100 AGUUCCUGGGGUGAGACUCCA 21 7949 SCNN1A-4101 CAGUUCCUGGGGUGAGACUCCA 22 7950 SCNN1A-4102 ACAGUUCCUGGGGUGAGACUCCA 23 7951 SCNN1A-4103 CACAGUUCCUGGGGUGAGACUCCA 24 7952 SCNN1A-4104 GGCCCCCGCCCAUCUCCA 18 7953 SCNN1A-4105 GGGCCCCCGCCCAUCUCCA 19 7954 SCNN1A-907 UGGGCCCCCGCCCAUCUCCA 20 4756 SCNN1A-4106 CUGGGCCCCCGCCCAUCUCCA 21 7955 SCNN1A-4107 CCUGGGCCCCCGCCCAUCUCCA 22 7956 SCNN1A-4108 CCCUGGGCCCCCGCCCAUCUCCA 23 7957 SCNN1A-4109 ACCCUGGGCCCCCGCCCAUCUCCA 24 7958 SCNN1A-4110 AGGAGCUGGACCGCAUCA 18 7959 SCNN1A-4111 GAGGAGCUGGACCGCAUCA 19 7960 SCNN1A-4112 GGAGGAGCUGGACCGCAUCA 20 7961 SCNN1A-4113 UGGAGGAGCUGGACCGCAUCA 21 7962 SCNN1A-4114 CUGGAGGAGCUGGACCGCAUCA 22 7963 SCNN1A-4115 GCUGGAGGAGCUGGACCGCAUCA 23 7964 SCNN1A-4116 AGCUGGAGGAGCUGGACCGCAUCA 24 7965 SCNN1A-4117 GGUCCCGCCCCCGCCUCA 18 7966 SCNN1A-4118 GGGUCCCGCCCCCGCCUCA 19 7967 SCNN1A-924 AGGGUCCCGCCCCCGCCUCA 20 4773 SCNN1A-4119 GAGGGUCCCGCCCCCGCCUCA 21 7968 SCNN1A-4120 UGAGGGUCCCGCCCCCGCCUCA 22 7969 SCNN1A-4121 CUGAGGGUCCCGCCCCCGCCUCA 23 7970 SCNN1A-4122 CCUGAGGGUCCCGCCCCCGCCUCA 24 7971 SCNN1A-4123 AAGUCAACAUCUUCUUCA 18 7972 SCNN1A-4124 AAAGUCAACAUCUUCUUCA 19 7973 SCNN1A-928 CAAAGUCAACAUCUUCUUCA 20 4777 SCNN1A-4125 CCAAAGUCAACAUCUUCUUCA 21 7974 SCNN1A-4126 GCCAAAGUCAACAUCUUCUUCA 22 7975 SCNN1A-4127 GGCCAAAGUCAACAUCUUCUUCA 23 7976 SCNN1A-4128 UGGCCAAAGUCAACAUCUUCUUCA 24 7977 SCNN1A-4129 UUGGUGUAUGUGGGUUCA 18 7978 SCNN1A-4130 CUUGGUGUAUGUGGGUUCA 19 7979 SCNN1A-4131 UCUUGGUGUAUGUGGGUUCA 20 7980 SCNN1A-4132 CUCUUGGUGUAUGUGGGUUCA 21 7981 SCNN1A-4133 UCUCUUGGUGUAUGUGGGUUCA 22 7982 SCNN1A-4134 AUCUCUUGGUGUAUGUGGGUUCA 23 7983 SCNN1A-4135 GAUCUCUUGGUGUAUGUGGGUUCA 24 7984 SCNN1A-4136 UCUGGGGGGGCCCUGAGA 18 7985 SCNN1A-4137 CUCUGGGGGGGCCCUGAGA 19 7986 SCNN1A-938 CCUCUGGGGGGGCCCUGAGA 20 4787 SCNN1A-4138 UCCUCUGGGGGGGCCCUGAGA 21 7987 SCNN1A-4139 GUCCUCUGGGGGGGCCCUGAGA 22 7988 SCNN1A-4140 UGUCCUCUGGGGGGGCCCUGAGA 23 7989 SCNN1A-4141 CUGUCCUCUGGGGGGGCCCUGAGA 24 7990 SCNN1A-4142 UACUGGUCUCCAGGCCGA 18 7991 SCNN1A-4143 AUACUGGUCUCCAGGCCGA 19 7992 SCNN1A-943 GAUACUGGUCUCCAGGCCGA 20 4792 SCNN1A-4144 CGAUACUGGUCUCCAGGCCGA 21 7993 SCNN1A-4145 CCGAUACUGGUCUCCAGGCCGA 22 7994 SCNN1A-4146 GCCGAUACUGGUCUCCAGGCCGA 23 7995 SCNN1A-4147 AGCCGAUACUGGUCUCCAGGCCGA 24 7996 SCNN1A-4148 UUCCAGAUGCUAUCGCGA 18 7997 SCNN1A-4149 CUUCCAGAUGCUAUCGCGA 19 7998 SCNN1A-4150 UCUUCCAGAUGCUAUCGCGA 20 7999 SCNN1A-4151 GUCUUCCAGAUGCUAUCGCGA 21 8000 SCNN1A-4152 GGUCUUCCAGAUGCUAUCGCGA 22 8001 SCNN1A-4153 GGGUCUUCCAGAUGCUAUCGCGA 23 8002 SCNN1A-4154 UGGGUCUUCCAGAUGCUAUCGCGA 24 8003 SCNN1A-4155 CCAGGUGGACUGGAAGGA 18 8004 SCNN1A-4156 CCCAGGUGGACUGGAAGGA 19 8005 SCNN1A-4157 CCCCAGGUGGACUGGAAGGA 20 8006 SCNN1A-4158 CCCCCAGGUGGACUGGAAGGA 21 8007 SCNN1A-4159 ACCCCCAGGUGGACUGGAAGGA 22 8008 SCNN1A-4160 AACCCCCAGGUGGACUGGAAGGA 23 8009 SCNN1A-4161 CAACCCCCAGGUGGACUGGAAGGA 24 8010 SCNN1A-4162 GGGGGGCCCUGAGAGGGA 18 8011 SCNN1A-4163 GGGGGGGCCCUGAGAGGGA 19 8012 SCNN1A-954 UGGGGGGGCCCUGAGAGGGA 20 4803 SCNN1A-4164 CUGGGGGGGCCCUGAGAGGGA 21 8013 SCNN1A-4165 UCUGGGGGGGCCCUGAGAGGGA 22 8014 SCNN1A-4166 CUCUGGGGGGGCCCUGAGAGGGA 23 8015 SCNN1A-4167 CCUCUGGGGGGGCCCUGAGAGGGA 24 8016 SCNN1A-4168 CGGUAGGUCGUGCCUGGA 18 8017 SCNN1A-4169 ACGGUAGGUCGUGCCUGGA 19 8018 SCNN1A-962 CACGGUAGGUCGUGCCUGGA 20 4811 SCNN1A-4170 UCACGGUAGGUCGUGCCUGGA 21 8019 SCNN1A-4171 GUCACGGUAGGUCGUGCCUGGA 22 8020 SCNN1A-4172 UGUCACGGUAGGUCGUGCCUGGA 23 8021 SCNN1A-4173 CUGUCACGGUAGGUCGUGCCUGGA 24 8022 SCNN1A-4174 CAACAACCCCCAGGUGGA 18 8023 SCNN1A-4175 ACAACAACCCCCAGGUGGA 19 8024 SCNN1A-4176 GACAACAACCCCCAGGUGGA 20 8025 SCNN1A-4177 GGACAACAACCCCCAGGUGGA 21 8026 SCNN1A-4178 GGGACAACAACCCCCAGGUGGA 22 8027 SCNN1A-4179 CGGGACAACAACCCCCAGGUGGA 23 8028 SCNN1A-4180 GCGGGACAACAACCCCCAGGUGGA 24 8029 SCNN1A-4181 CCUCUGGGGGGGCCCUGA 18 8030 SCNN1A-4182 UCCUCUGGGGGGGCCCUGA 19 8031 SCNN1A-4183 GUCCUCUGGGGGGGCCCUGA 20 8032 SCNN1A-4184 UGUCCUCUGGGGGGGCCCUGA 21 8033 SCNN1A-4185 CUGUCCUCUGGGGGGGCCCUGA 22 8034 SCNN1A-4186 CCUGUCCUCUGGGGGGGCCCUGA 23 8035 SCNN1A-4187 ACCUGUCCUCUGGGGGGGCCCUGA 24 8036 SCNN1A-4188 GGAAGGCAAGGAUGCUGA 18 8037 SCNN1A-4189 AGGAAGGCAAGGAUGCUGA 19 8038 SCNN1A-4190 GAGGAAGGCAAGGAUGCUGA 20 8039 SCNN1A-4191 UGAGGAAGGCAAGGAUGCUGA 21 8040 SCNN1A-4192 AUGAGGAAGGCAAGGAUGCUGA 22 8041 SCNN1A-4193 CAUGAGGAAGGCAAGGAUGCUGA 23 8042 SCNN1A-4194 GCAUGAGGAAGGCAAGGAUGCUGA 24 8043 SCNN1A-4195 CCCUGCUGUCCACAGUGA 18 8044 SCNN1A-4196 CCCCUGCUGUCCACAGUGA 19 8045 SCNN1A-4197 UCCCCUGCUGUCCACAGUGA 20 8046 SCNN1A-4198 UUCCCCUGCUGUCCACAGUGA 21 8047 SCNN1A-4199 AUUCCCCUGCUGUCCACAGUGA 22 8048 SCNN1A-4200 CAUUCCCCUGCUGUCCACAGUGA 23 8049 SCNN1A-4201 UCAUUCCCCUGCUGUCCACAGUGA 24 8050 SCNN1A-4202 CGUGGAGUACUGUGACUA 18 8051 SCNN1A-4203 ACGUGGAGUACUGUGACUA 19 8052 SCNN1A-4204 AACGUGGAGUACUGUGACUA 20 8053 SCNN1A-4205 GAACGUGGAGUACUGUGACUA 21 8054 SCNN1A-4206 AGAACGUGGAGUACUGUGACUA 22 8055 SCNN1A-4207 CAGAACGUGGAGUACUGUGACUA 23 8056 SCNN1A-4208 CCAGAACGUGGAGUACUGUGACUA 24 8057 SCNN1A-4209 CUUCCACCACCCGAUGUA 18 8058 SCNN1A-4210 ACUUCCACCACCCGAUGUA 19 8059 SCNN1A-975 CACUUCCACCACCCGAUGUA 20 4824 SCNN1A-4211 UCACUUCCACCACCCGAUGUA 21 8060 SCNN1A-4212 CUCACUUCCACCACCCGAUGUA 22 8061 SCNN1A-4213 UCUCACUUCCACCACCCGAUGUA 23 8062 SCNN1A-4214 CUCUCACUUCCACCACCCGAUGUA 24 8063 SCNN1A-4215 UCAGGUACCCGGAAAUUA 18 8064 SCNN1A-4216 UUCAGGUACCCGGAAAUUA 19 8065 SCNN1A-4217 CUUCAGGUACCCGGAAAUUA 20 8066 SCNN1A-4218 CCUUCAGGUACCCGGAAAUUA 21 8067 SCNN1A-4219 CCCUUCAGGUACCCGGAAAUUA 22 8068 SCNN1A-4220 CCCCUUCAGGUACCCGGAAAUUA 23 8069 SCNN1A-4221 GCCCCUUCAGGUACCCGGAAAUUA 24 8070 SCNN1A-4222 AAUUACACCGUCAACAAC 18 8071 SCNN1A-4223 CAAUUACACCGUCAACAAC 19 8072 SCNN1A-4224 ACAAUUACACCGUCAACAAC 20 8073 SCNN1A-4225 AACAAUUACACCGUCAACAAC 21 8074 SCNN1A-4226 GAACAAUUACACCGUCAACAAC 22 8075 SCNN1A-4227 AGAACAAUUACACCGUCAACAAC 23 8076 SCNN1A-4228 CAGAACAAUUACACCGUCAACAAC 24 8077 SCNN1A-4229 GUCACCCUCCUGUCCAAC 18 8078 SCNN1A-4230 GGUCACCCUCCUGUCCAAC 19 8079 SCNN1A-4231 UGGUCACCCUCCUGUCCAAC 20 8080 SCNN1A-4232 AUGGUCACCCUCCUGUCCAAC 21 8081 SCNN1A-4233 GAUGGUCACCCUCCUGUCCAAC 22 8082 SCNN1A-4234 AGAUGGUCACCCUCCUGUCCAAC 23 8083 SCNN1A-4235 CAGAUGGUCACCCUCCUGUCCAAC 24 8084 SCNN1A-4236 CUCUGUGUCCAGUGCAAC 18 8085 SCNN1A-4237 UCUCUGUGUCCAGUGCAAC 19 8086 SCNN1A-4238 GUCUCUGUGUCCAGUGCAAC 20 8087 SCNN1A-4239 AGUCUCUGUGUCCAGUGCAAC 21 8088 SCNN1A-4240 UAGUCUCUGUGUCCAGUGCAAC 22 8089 SCNN1A-4241 CUAGUCUCUGUGUCCAGUGCAAC 23 8090 SCNN1A-4242 UCUAGUCUCUGUGUCCAGUGCAAC 24 8091 SCNN1A-4243 UAUCCGCGGCCCCAGAAC 18 8092 SCNN1A-4244 CUAUCCGCGGCCCCAGAAC 19 8093 SCNN1A-4245 UCUAUCCGCGGCCCCAGAAC 20 8094 SCNN1A-4246 UUCUAUCCGCGGCCCCAGAAC 21 8095 SCNN1A-4247 CUUCUAUCCGCGGCCCCAGAAC 22 8096 SCNN1A-4248 UCUUCUAUCCGCGGCCCCAGAAC 23 8097 SCNN1A-4249 AUCUUCUAUCCGCGGCCCCAGAAC 24 8098 SCNN1A-4250 GACUUCUCCUCAGACCAC 18 8099 SCNN1A-4251 UGACUUCUCCUCAGACCAC 19 8100 SCNN1A-4252 UUGACUUCUCCUCAGACCAC 20 8101 SCNN1A-4253 GUUGACUUCUCCUCAGACCAC 21 8102 SCNN1A-4254 GGUUGACUUCUCCUCAGACCAC 22 8103 SCNN1A-4255 AGGUUGACUUCUCCUCAGACCAC 23 8104 SCNN1A-4256 CAGGUUGACUUCUCCUCAGACCAC 24 8105 SCNN1A-4257 AGGAAACCCUGGACAGAC 18 8106 SCNN1A-4258 UAGGAAACCCUGGACAGAC 19 8107 SCNN1A-4259 AUAGGAAACCCUGGACAGAC 20 8108 SCNN1A-4260 CAUAGGAAACCCUGGACAGAC 21 8109 SCNN1A-4261 UCAUAGGAAACCCUGGACAGAC 22 8110 SCNN1A-4262 UUCAUAGGAAACCCUGGACAGAC 23 8111 SCNN1A-4263 GUUCAUAGGAAACCCUGGACAGAC 24 8112 SCNN1A-4264 CAGGUGGACUGGAAGGAC 18 8113 SCNN1A-4265 CCAGGUGGACUGGAAGGAC 19 8114 SCNN1A-988 CCCAGGUGGACUGGAAGGAC 20 4837 SCNN1A-4266 CCCCAGGUGGACUGGAAGGAC 21 8115 SCNN1A-4267 CCCCCAGGUGGACUGGAAGGAC 22 8116 SCNN1A-4268 ACCCCCAGGUGGACUGGAAGGAC 23 8117 SCNN1A-4269 AACCCCCAGGUGGACUGGAAGGAC 24 8118 SCNN1A-4270 AACAACCCCCAGGUGGAC 18 8119 SCNN1A-4271 CAACAACCCCCAGGUGGAC 19 8120 SCNN1A-990 ACAACAACCCCCAGGUGGAC 20 4839 SCNN1A-4272 GACAACAACCCCCAGGUGGAC 21 8121 SCNN1A-4273 GGACAACAACCCCCAGGUGGAC 22 8122 SCNN1A-4274 GGGACAACAACCCCCAGGUGGAC 23 8123 SCNN1A-4275 CGGGACAACAACCCCCAGGUGGAC 24 8124 SCNN1A-4276 UGCUAUACUUUCAAUGAC 18 8125 SCNN1A-4277 CUGCUAUACUUUCAAUGAC 19 8126 SCNN1A-4278 ACUGCUAUACUUUCAAUGAC 20 8127 SCNN1A-4279 AACUGCUAUACUUUCAAUGAC 21 8128 SCNN1A-4280 AAACUGCUAUACUUUCAAUGAC 22 8129 SCNN1A-4281 GAAACUGCUAUACUUUCAAUGAC 23 8130 SCNN1A-4282 GGAAACUGCUAUACUUUCAAUGAC 24 8131 SCNN1A-4283 GAAGGCAAGGAUGCUGAC 18 8132 SCNN1A-4284 GGAAGGCAAGGAUGCUGAC 19 8133 SCNN1A-992 AGGAAGGCAAGGAUGCUGAC 20 4841 SCNN1A-4285 GAGGAAGGCAAGGAUGCUGAC 21 8134 SCNN1A-4286 UGAGGAAGGCAAGGAUGCUGAC 22 8135 SCNN1A-4287 AUGAGGAAGGCAAGGAUGCUGAC 23 8136 SCNN1A-4288 CAUGAGGAAGGCAAGGAUGCUGAC 24 8137 SCNN1A-4289 CCUGCUGUCCACAGUGAC 18 8138 SCNN1A-4290 CCCUGCUGUCCACAGUGAC 19 8139 SCNN1A-993 CCCCUGCUGUCCACAGUGAC 20 4842 SCNN1A-4291 UCCCCUGCUGUCCACAGUGAC 21 8140 SCNN1A-4292 UUCCCCUGCUGUCCACAGUGAC 22 8141 SCNN1A-4293 AUUCCCCUGCUGUCCACAGUGAC 23 8142 SCNN1A-4294 CAUUCCCCUGCUGUCCACAGUGAC 24 8143 SCNN1A-4295 CCUCGCCCCUUCAGGUAC 18 8144 SCNN1A-4296 CCCUCGCCCCUUCAGGUAC 19 8145 SCNN1A-4297 CCCCUCGCCCCUUCAGGUAC 20 8146 SCNN1A-4298 UCCCCUCGCCCCUUCAGGUAC 21 8147 SCNN1A-4299 UUCCCCUCGCCCCUUCAGGUAC 22 8148 SCNN1A-4300 CUUCCCCUCGCCCCUUCAGGUAC 23 8149 SCNN1A-4301 UCUUCCCCUCGCCCCUUCAGGUAC 24 8150 SCNN1A-4302 GUGGGUUCAUAGGAAACC 18 8151 SCNN1A-4303 UGUGGGUUCAUAGGAAACC 19 8152 SCNN1A-4304 AUGUGGGUUCAUAGGAAACC 20 8153 SCNN1A-4305 UAUGUGGGUUCAUAGGAAACC 21 8154 SCNN1A-4306 GUAUGUGGGUUCAUAGGAAACC 22 8155 SCNN1A-4307 UGUAUGUGGGUUCAUAGGAAACC 23 8156 SCNN1A-4308 GUGUAUGUGGGUUCAUAGGAAACC 24 8157 SCNN1A-4309 CCCCCUGCCUAUGCCACC 18 8158 SCNN1A-4310 UCCCCCUGCCUAUGCCACC 19 8159 SCNN1A-4311 CUCCCCCUGCCUAUGCCACC 20 8160 SCNN1A-4312 CCUCCCCCUGCCUAUGCCACC 21 8161 SCNN1A-4313 CCCUCCCCCUGCCUAUGCCACC 22 8162 SCNN1A-4314 CCCCUCCCCCUGCCUAUGCCACC 23 8163 SCNN1A-4315 GCCCCUCCCCCUGCCUAUGCCACC 24 8164 SCNN1A-4316 CUCGCCCCUUCAGGUACC 18 8165 SCNN1A-4317 CCUCGCCCCUUCAGGUACC 19 8166 SCNN1A-1007 CCCUCGCCCCUUCAGGUACC 20 4856 SCNN1A-4318 CCCCUCGCCCCUUCAGGUACC 21 8167 SCNN1A-4319 UCCCCUCGCCCCUUCAGGUACC 22 8168 SCNN1A-4320 UUCCCCUCGCCCCUUCAGGUACC 23 8169 SCNN1A-4321 CUUCCCCUCGCCCCUUCAGGUACC 24 8170 SCNN1A-4322 AUCUUCUAUCCGCGGCCC 18 8171 SCNN1A-4323 CAUCUUCUAUCCGCGGCCC 19 8172 SCNN1A-4324 ACAUCUUCUAUCCGCGGCCC 20 8173 SCNN1A-4325 UACAUCUUCUAUCCGCGGCCC 21 8174 SCNN1A-4326 CUACAUCUUCUAUCCGCGGCCC 22 8175 SCNN1A-4327 CCUACAUCUUCUAUCCGCGGCCC 23 8176 SCNN1A-4328 GCCUACAUCUUCUAUCCGCGGCCC 24 8177 SCNN1A-4329 CAGAGACUCUGCCAUCCC 18 8178 SCNN1A-4330 CCAGAGACUCUGCCAUCCC 19 8179 SCNN1A-1023 GCCAGAGACUCUGCCAUCCC 20 4872 SCNN1A-4331 UGCCAGAGACUCUGCCAUCCC 21 8180 SCNN1A-4332 CUGCCAGAGACUCUGCCAUCCC 22 8181 SCNN1A-4333 GCUGCCAGAGACUCUGCCAUCCC 23 8182 SCNN1A-4334 GGCUGCCAGAGACUCUGCCAUCCC 24 8183 SCNN1A-4335 GGUGAGGCCCGCAGCGCC 18 8184 SCNN1A-4336 UGGUGAGGCCCGCAGCGCC 19 8185 SCNN1A-4337 CUGGUGAGGCCCGCAGCGCC 20 8186 SCNN1A-4338 GCUGGUGAGGCCCGCAGCGCC 21 8187 SCNN1A-4339 AGCUGGUGAGGCCCGCAGCGCC 22 8188 SCNN1A-4340 CAGCUGGUGAGGCCCGCAGCGCC 23 8189 SCNN1A-4341 CCAGCUGGUGAGGCCCGCAGCGCC 24 8190 SCNN1A-4342 GAUACUGGUCUCCAGGCC 18 8191 SCNN1A-4343 CGAUACUGGUCUCCAGGCC 19 8192 SCNN1A-4344 CCGAUACUGGUCUCCAGGCC 20 8193 SCNN1A-4345 GCCGAUACUGGUCUCCAGGCC 21 8194 SCNN1A-4346 AGCCGAUACUGGUCUCCAGGCC 22 8195 SCNN1A-4347 AAGCCGAUACUGGUCUCCAGGCC 23 8196 SCNN1A-4348 GAAGCCGAUACUGGUCUCCAGGCC 24 8197 SCNN1A-4349 GAUGCUGACUGGGAGGCC 18 8198 SCNN1A-4350 GGAUGCUGACUGGGAGGCC 19 8199 SCNN1A-1028 AGGAUGCUGACUGGGAGGCC 20 4877 SCNN1A-4351 AAGGAUGCUGACUGGGAGGCC 21 8200 SCNN1A-4352 CAAGGAUGCUGACUGGGAGGCC 22 8201 SCNN1A-4353 GCAAGGAUGCUGACUGGGAGGCC 23 8202 SCNN1A-4354 GGCAAGGAUGCUGACUGGGAGGCC 24 8203 SCNN1A-4355 CUGUCCUCUGGGGGGGCC 18 8204 SCNN1A-4356 CCUGUCCUCUGGGGGGGCC 19 8205 SCNN1A-4357 ACCUGUCCUCUGGGGGGGCC 20 8206 SCNN1A-4358 CACCUGUCCUCUGGGGGGGCC 21 8207 SCNN1A-4359 CCACCUGUCCUCUGGGGGGGCC 22 8208 SCNN1A-4360 UCCACCUGUCCUCUGGGGGGGCC 23 8209 SCNN1A-4361 CUCCACCUGUCCUCUGGGGGGGCC 24 8210 SCNN1A-4362 CCAGAGACUCUGCCAUCC 18 8211 SCNN1A-4363 GCCAGAGACUCUGCCAUCC 19 8212 SCNN1A-4364 UGCCAGAGACUCUGCCAUCC 20 8213 SCNN1A-4365 CUGCCAGAGACUCUGCCAUCC 21 8214 SCNN1A-4366 GCUGCCAGAGACUCUGCCAUCC 22 8215 SCNN1A-4367 GGCUGCCAGAGACUCUGCCAUCC 23 8216 SCNN1A-4368 AGGCUGCCAGAGACUCUGCCAUCC 24 8217 SCNN1A-4369 UUCCUGGGGUGAGACUCC 18 8218 SCNN1A-4370 GUUCCUGGGGUGAGACUCC 19 8219 SCNN1A-1037 AGUUCCUGGGGUGAGACUCC 20 4886 SCNN1A-4371 CAGUUCCUGGGGUGAGACUCC 21 8220 SCNN1A-4372 ACAGUUCCUGGGGUGAGACUCC 22 8221 SCNN1A-4373 CACAGUUCCUGGGGUGAGACUCC 23 8222 SCNN1A-4374 GCACAGUUCCUGGGGUGAGACUCC 24 8223 SCNN1A-4375 GGGCCCCCGCCCAUCUCC 18 8224 SCNN1A-4376 UGGGCCCCCGCCCAUCUCC 19 8225 SCNN1A-1040 CUGGGCCCCCGCCCAUCUCC 20 4889 SCNN1A-4377 CCUGGGCCCCCGCCCAUCUCC 21 8226 SCNN1A-4378 CCCUGGGCCCCCGCCCAUCUCC 22 8227 SCNN1A-4379 ACCCUGGGCCCCCGCCCAUCUCC 23 8228 SCNN1A-4380 CACCCUGGGCCCCCGCCCAUCUCC 24 8229 SCNN1A-4381 GUAUUCACUCCUGCUUCC 18 8230 SCNN1A-4382 UGUAUUCACUCCUGCUUCC 19 8231 SCNN1A-1046 GUGUAUUCACUCCUGCUUCC 20 4895 SCNN1A-4383 UGUGUAUUCACUCCUGCUUCC 21 8232 SCNN1A-4384 GUGUGUAUUCACUCCUGCUUCC 22 8233 SCNN1A-4385 GGUGUGUAUUCACUCCUGCUUCC 23 8234 SCNN1A-4386 AGGUGUGUAUUCACUCCUGCUUCC 24 8235 SCNN1A-4387 GACACCCCCAUUCUUUCC 18 8236 SCNN1A-4388 UGACACCCCCAUUCUUUCC 19 8237 SCNN1A-4389 AUGACACCCCCAUUCUUUCC 20 8238 SCNN1A-4390 GAUGACACCCCCAUUCUUUCC 21 8239 SCNN1A-4391 UGAUGACACCCCCAUUCUUUCC 22 8240 SCNN1A-4392 UUGAUGACACCCCCAUUCUUUCC 23 8241 SCNN1A-4393 CUUGAUGACACCCCCAUUCUUUCC 24 8242 SCNN1A-4394 GUGGAGACCUCCAUCAGC 18 8243 SCNN1A-4395 CGUGGAGACCUCCAUCAGC 19 8244 SCNN1A-4396 GCGUGGAGACCUCCAUCAGC 20 8245 SCNN1A-4397 GGCGUGGAGACCUCCAUCAGC 21 8246 SCNN1A-4398 UGGCGUGGAGACCUCCAUCAGC 22 8247 SCNN1A-4399 CUGGCGUGGAGACCUCCAUCAGC 23 8248 SCNN1A-4400 CCUGGCGUGGAGACCUCCAUCAGC 24 8249 SCNN1A-4401 CGGAAAUUAAAGAGGAGC 18 8250 SCNN1A-4402 CCGGAAAUUAAAGAGGAGC 19 8251 SCNN1A-1058 CCCGGAAAUUAAAGAGGAGC 20 4907 SCNN1A-4403 ACCCGGAAAUUAAAGAGGAGC 21 8252 SCNN1A-4404 UACCCGGAAAUUAAAGAGGAGC 22 8253 SCNN1A-4405 GUACCCGGAAAUUAAAGAGGAGC 23 8254 SCNN1A-4406 GGUACCCGGAAAUUAAAGAGGAGC 24 8255 SCNN1A-4407 CCGCACCCCUUGCAGCGC 18 8256 SCNN1A-4408 GCCGCACCCCUUGCAGCGC 19 8257 SCNN1A-4409 UGCCGCACCCCUUGCAGCGC 20 8258 SCNN1A-4410 CUGCCGCACCCCUUGCAGCGC 21 8259 SCNN1A-4411 UCUGCCGCACCCCUUGCAGCGC 22 8260 SCNN1A-4412 CUCUGCCGCACCCCUUGCAGCGC 23 8261 SCNN1A-4413 ACUCUGCCGCACCCCUUGCAGCGC 24 8262 SCNN1A-4414 GGAUGCUGACUGGGAGGC 18 8263 SCNN1A-4415 AGGAUGCUGACUGGGAGGC 19 8264 SCNN1A-4416 AAGGAUGCUGACUGGGAGGC 20 8265 SCNN1A-4417 CAAGGAUGCUGACUGGGAGGC 21 8266 SCNN1A-4418 GCAAGGAUGCUGACUGGGAGGC 22 8267 SCNN1A-4419 GGCAAGGAUGCUGACUGGGAGGC 23 8268 SCNN1A-4420 AGGCAAGGAUGCUGACUGGGAGGC 24 8269 SCNN1A-4421 UUUAACUUGCGGCCUGGC 18 8270 SCNN1A-4422 CUUUAACUUGCGGCCUGGC 19 8271 SCNN1A-4423 GCUUUAACUUGCGGCCUGGC 20 8272 SCNN1A-4424 GGCUUUAACUUGCGGCCUGGC 21 8273 SCNN1A-4425 UGGCUUUAACUUGCGGCCUGGC 22 8274 SCNN1A-4426 GUGGCUUUAACUUGCGGCCUGGC 23 8275 SCNN1A-4427 GGUGGCUUUAACUUGCGGCCUGGC 24 8276 SCNN1A-4428 UCUGGAUGUCUUCCAUGC 18 8277 SCNN1A-4429 CUCUGGAUGUCUUCCAUGC 19 8278 SCNN1A-4430 CCUCUGGAUGUCUUCCAUGC 20 8279 SCNN1A-4431 ACCUCUGGAUGUCUUCCAUGC 21 8280 SCNN1A-4432 AACCUCUGGAUGUCUUCCAUGC 22 8281 SCNN1A-4433 CAACCUCUGGAUGUCUUCCAUGC 23 8282 SCNN1A-4434 CCAACCUCUGGAUGUCUUCCAUGC 24 8283 SCNN1A-4435 GCAGCCGUCGCGACCUGC 18 8284 SCNN1A-4436 CGCAGCCGUCGCGACCUGC 19 8285 SCNN1A-1079 CCGCAGCCGUCGCGACCUGC 20 4928 SCNN1A-4437 CCCGCAGCCGUCGCGACCUGC 21 8286 SCNN1A-4438 UCCCGCAGCCGUCGCGACCUGC 22 8287 SCNN1A-4439 CUCCCGCAGCCGUCGCGACCUGC 23 8288 SCNN1A-4440 GCUCCCGCAGCCGUCGCGACCUGC 24 8289 SCNN1A-4441 ACAUCCUGUCGAGGCUGC 18 8290 SCNN1A-4442 AACAUCCUGUCGAGGCUGC 19 8291 SCNN1A-4443 CAACAUCCUGUCGAGGCUGC 20 8292 SCNN1A-4444 UCAACAUCCUGUCGAGGCUGC 21 8293 SCNN1A-4445 AUCAACAUCCUGUCGAGGCUGC 22 8294 SCNN1A-4446 CAUCAACAUCCUGUCGAGGCUGC 23 8295 SCNN1A-4447 ACAUCAACAUCCUGUCGAGGCUGC 24 8296 SCNN1A-4448 AUCUCCAGGGGGCUCUGC 18 8297 SCNN1A-4449 CAUCUCCAGGGGGCUCUGC 19 8298 SCNN1A-1083 CCAUCUCCAGGGGGCUCUGC 20 4932 SCNN1A-4450 CCCAUCUCCAGGGGGCUCUGC 21 8299 SCNN1A-4451 GCCCAUCUCCAGGGGGCUCUGC 22 8300 SCNN1A-4452 CGCCCAUCUCCAGGGGGCUCUGC 23 8301 SCNN1A-4453 CCGCCCAUCUCCAGGGGGCUCUGC 24 8302 SCNN1A-4454 GGCUGUUUCACCAAGUGC 18 8303 SCNN1A-4455 GGGCUGUUUCACCAAGUGC 19 8304 SCNN1A-1085 UGGGCUGUUUCACCAAGUGC 20 4934 SCNN1A-4456 CUGGGCUGUUUCACCAAGUGC 21 8305 SCNN1A-4457 CCUGGGCUGUUUCACCAAGUGC 22 8306 SCNN1A-4458 ACCUGGGCUGUUUCACCAAGUGC 23 8307 SCNN1A-4459 CACCUGGGCUGUUUCACCAAGUGC 24 8308 SCNN1A-4460 GGGCCCGGGUAAUGGUGC 18 8309 SCNN1A-4461 GGGGCCCGGGUAAUGGUGC 19 8310 SCNN1A-4462 UGGGGCCCGGGUAAUGGUGC 20 8311 SCNN1A-4463 CUGGGGCCCGGGUAAUGGUGC 21 8312 SCNN1A-4464 ACUGGGGCCCGGGUAAUGGUGC 22 8313 SCNN1A-4465 GACUGGGGCCCGGGUAAUGGUGC 23 8314 SCNN1A-4466 UGACUGGGGCCCGGGUAAUGGUGC 24 8315 SCNN1A-4467 UUCCAGGAGAGCAUGAUC 18 8316 SCNN1A-4468 CUUCCAGGAGAGCAUGAUC 19 8317 SCNN1A-4469 GCUUCCAGGAGAGCAUGAUC 20 8318 SCNN1A-4470 UGCUUCCAGGAGAGCAUGAUC 21 8319 SCNN1A-4471 CUGCUUCCAGGAGAGCAUGAUC 22 8320 SCNN1A-4472 CCUGCUUCCAGGAGAGCAUGAUC 23 8321 SCNN1A-4473 UCCUGCUUCCAGGAGAGCAUGAUC 24 8322 SCNN1A-4474 GUUCCUGGGGUGAGACUC 18 8323 SCNN1A-4475 AGUUCCUGGGGUGAGACUC 19 8324 SCNN1A-4476 CAGUUCCUGGGGUGAGACUC 20 8325 SCNN1A-4477 ACAGUUCCUGGGGUGAGACUC 21 8326 SCNN1A-4478 CACAGUUCCUGGGGUGAGACUC 22 8327 SCNN1A-4479 GCACAGUUCCUGGGGUGAGACUC 23 8328 SCNN1A-4480 AGCACAGUUCCUGGGGUGAGACUC 24 8329 SCNN1A-4481 GGGUCCCGCCCCCGCCUC 18 8330 SCNN1A-4482 AGGGUCCCGCCCCCGCCUC 19 8331 SCNN1A-4483 GAGGGUCCCGCCCCCGCCUC 20 8332 SCNN1A-4484 UGAGGGUCCCGCCCCCGCCUC 21 8333 SCNN1A-4485 CUGAGGGUCCCGCCCCCGCCUC 22 8334 SCNN1A-4486 CCUGAGGGUCCCGCCCCCGCCUC 23 8335 SCNN1A-4487 GCCUGAGGGUCCCGCCCCCGCCUC 24 8336 SCNN1A-4488 GUUCCUCCACCUGUCCUC 18 8337 SCNN1A-4489 AGUUCCUCCACCUGUCCUC 19 8338 SCNN1A-1095 CAGUUCCUCCACCUGUCCUC 20 4944 SCNN1A-4490 CCAGUUCCUCCACCUGUCCUC 21 8339 SCNN1A-4491 GCCAGUUCCUCCACCUGUCCUC 22 8340 SCNN1A-4492 GGCCAGUUCCUCCACCUGUCCUC 23 8341 SCNN1A-4493 GGGCCAGUUCCUCCACCUGUCCUC 24 8342 SCNN1A-4494 GAGGGGGCAGGGGUGCUC 18 8343 SCNN1A-4495 CGAGGGGGCAGGGGUGCUC 19 8344 SCNN1A-1096 CCGAGGGGGCAGGGGUGCUC 20 4945 SCNN1A-4496 GCCGAGGGGGCAGGGGUGCUC 21 8345 SCNN1A-4497 GGCCGAGGGGGCAGGGGUGCUC 22 8346 SCNN1A-4498 AGGCCGAGGGGGCAGGGGUGCUC 23 8347 SCNN1A-4499 CAGGCCGAGGGGGCAGGGGUGCUC 24 8348 SCNN1A-4500 UGGGCCCCCGCCCAUCUC 18 8349 SCNN1A-4501 CUGGGCCCCCGCCCAUCUC 19 8350 SCNN1A-4502 CCUGGGCCCCCGCCCAUCUC 20 8351 SCNN1A-4503 CCCUGGGCCCCCGCCCAUCUC 21 8352 SCNN1A-4504 ACCCUGGGCCCCCGCCCAUCUC 22 8353 SCNN1A-4505 CACCCUGGGCCCCCGCCCAUCUC 23 8354 SCNN1A-4506 CCACCCUGGGCCCCCGCCCAUCUC 24 8355 SCNN1A-4507 UGUAUUCACUCCUGCUUC 18 8356 SCNN1A-4508 GUGUAUUCACUCCUGCUUC 19 8357 SCNN1A-4509 UGUGUAUUCACUCCUGCUUC 20 8358 SCNN1A-4510 GUGUGUAUUCACUCCUGCUUC 21 8359 SCNN1A-4511 GGUGUGUAUUCACUCCUGCUUC 22 8360 SCNN1A-4512 AGGUGUGUAUUCACUCCUGCUUC 23 8361 SCNN1A-4513 CAGGUGUGUAUUCACUCCUGCUUC 24 8362 SCNN1A-4514 AAAGUCAACAUCUUCUUC 18 8363 SCNN1A-4515 CAAAGUCAACAUCUUCUUC 19 8364 SCNN1A-4516 CCAAAGUCAACAUCUUCUUC 20 8365 SCNN1A-4517 GCCAAAGUCAACAUCUUCUUC 21 8366 SCNN1A-4518 GGCCAAAGUCAACAUCUUCUUC 22 8367 SCNN1A-4519 UGGCCAAAGUCAACAUCUUCUUC 23 8368 SCNN1A-4520 GUGGCCAAAGUCAACAUCUUCUUC 24 8369 SCNN1A-4521 CUACAGAAAGCACAGUUC 18 8370 SCNN1A-4522 ACUACAGAAAGCACAGUUC 19 8371 SCNN1A-4523 GACUACAGAAAGCACAGUUC 20 8372 SCNN1A-4524 UGACUACAGAAAGCACAGUUC 21 8373 SCNN1A-4525 GUGACUACAGAAAGCACAGUUC 22 8374 SCNN1A-4526 UGUGACUACAGAAAGCACAGUUC 23 8375 SCNN1A-4527 CUGUGACUACAGAAAGCACAGUUC 24 8376 SCNN1A-4528 GGUACCCGGAAAUUAAAG 18 8377 SCNN1A-4529 AGGUACCCGGAAAUUAAAG 19 8378 SCNN1A-1106 CAGGUACCCGGAAAUUAAAG 20 4955 SCNN1A-4530 UCAGGUACCCGGAAAUUAAAG 21 8379 SCNN1A-4531 UUCAGGUACCCGGAAAUUAAAG 22 8380 SCNN1A-4532 CUUCAGGUACCCGGAAAUUAAAG 23 8381 SCNN1A-4533 CCUUCAGGUACCCGGAAAUUAAAG 24 8382 SCNN1A-4534 GGGGCCCUGAGAGGGAAG 18 8383 SCNN1A-4535 GGGGGCCCUGAGAGGGAAG 19 8384 SCNN1A-4536 GGGGGGCCCUGAGAGGGAAG 20 8385 SCNN1A-4537 GGGGGGGCCCUGAGAGGGAAG 21 8386 SCNN1A-4538 UGGGGGGGCCCUGAGAGGGAAG 22 8387 SCNN1A-4539 CUGGGGGGGCCCUGAGAGGGAAG 23 8388 SCNN1A-4540 UCUGGGGGGGCCCUGAGAGGGAAG 24 8389 SCNN1A-4541 CGGGACAACAACCCCCAG 18 8390 SCNN1A-4542 GCGGGACAACAACCCCCAG 19 8391 SCNN1A-4543 UGCGGGACAACAACCCCCAG 20 8392 SCNN1A-4544 UUGCGGGACAACAACCCCCAG 21 8393 SCNN1A-4545 CUUGCGGGACAACAACCCCCAG 22 8394 SCNN1A-4546 GCUUGCGGGACAACAACCCCCAG 23 8395 SCNN1A-4547 AGCUUGCGGGACAACAACCCCCAG 24 8396 SCNN1A-4548 UCCAACCUGGGCAGCCAG 18 8397 SCNN1A-4549 GUCCAACCUGGGCAGCCAG 19 8398 SCNN1A-1116 UGUCCAACCUGGGCAGCCAG 20 4965 SCNN1A-4550 CUGUCCAACCUGGGCAGCCAG 21 8399 SCNN1A-4551 CCUGUCCAACCUGGGCAGCCAG 22 8400 SCNN1A-4552 UCCUGUCCAACCUGGGCAGCCAG 23 8401 SCNN1A-4553 CUCCUGUCCAACCUGGGCAGCCAG 24 8402 SCNN1A-4554 AUUCACUCCUGCUUCCAG 18 8403 SCNN1A-4555 UAUUCACUCCUGCUUCCAG 19 8404 SCNN1A-4556 GUAUUCACUCCUGCUUCCAG 20 8405 SCNN1A-4557 UGUAUUCACUCCUGCUUCCAG 21 8406 SCNN1A-4558 GUGUAUUCACUCCUGCUUCCAG 22 8407 SCNN1A-4559 UGUGUAUUCACUCCUGCUUCCAG 23 8408 SCNN1A-4560 GUGUGUAUUCACUCCUGCUUCCAG 24 8409 SCNN1A-4561 UCAAAGUACACACAGCAG 18 8410 SCNN1A-4562 UUCAAAGUACACACAGCAG 19 8411 SCNN1A-4563 CUUCAAAGUACACACAGCAG 20 8412 SCNN1A-4564 CCUUCAAAGUACACACAGCAG 21 8413 SCNN1A-4565 CCCUUCAAAGUACACACAGCAG 22 8414 SCNN1A-4566 ACCCUUCAAAGUACACACAGCAG 23 8415 SCNN1A-4567 UACCCUUCAAAGUACACACAGCAG 24 8416 SCNN1A-4568 AACAUCUUCUUCAAGGAG 18 8417 SCNN1A-4569 CAACAUCUUCUUCAAGGAG 19 8418 SCNN1A-4570 UCAACAUCUUCUUCAAGGAG 20 8419 SCNN1A-4571 GUCAACAUCUUCUUCAAGGAG 21 8420 SCNN1A-4572 AGUCAACAUCUUCUUCAAGGAG 22 8421 SCNN1A-4573 AAGUCAACAUCUUCUUCAAGGAG 23 8422 SCNN1A-4574 AAAGUCAACAUCUUCUUCAAGGAG 24 8423 SCNN1A-4575 CCGGAAAUUAAAGAGGAG 18 8424 SCNN1A-4576 CCCGGAAAUUAAAGAGGAG 19 8425 SCNN1A-4577 ACCCGGAAAUUAAAGAGGAG 20 8426 SCNN1A-4578 UACCCGGAAAUUAAAGAGGAG 21 8427 SCNN1A-4579 GUACCCGGAAAUUAAAGAGGAG 22 8428 SCNN1A-4580 GGUACCCGGAAAUUAAAGAGGAG 23 8429 SCNN1A-4581 AGGUACCCGGAAAUUAAAGAGGAG 24 8430 SCNN1A-4582 AAAGAGGAGCUGGAGGAG 18 8431 SCNN1A-4583 UAAAGAGGAGCUGGAGGAG 19 8432 SCNN1A-4584 UUAAAGAGGAGCUGGAGGAG 20 8433 SCNN1A-4585 AUUAAAGAGGAGCUGGAGGAG 21 8434 SCNN1A-4586 AAUUAAAGAGGAGCUGGAGGAG 22 8435 SCNN1A-4587 AAAUUAAAGAGGAGCUGGAGGAG 23 8436 SCNN1A-4588 GAAAUUAAAGAGGAGCUGGAGGAG 24 8437 SCNN1A-4589 ACUCUGCCAUCCCUGGAG 18 8438 SCNN1A-4590 GACUCUGCCAUCCCUGGAG 19 8439 SCNN1A-4591 AGACUCUGCCAUCCCUGGAG 20 8440 SCNN1A-4592 GAGACUCUGCCAUCCCUGGAG 21 8441 SCNN1A-4593 AGAGACUCUGCCAUCCCUGGAG 22 8442 SCNN1A-4594 CAGAGACUCUGCCAUCCCUGGAG 23 8443 SCNN1A-4595 CCAGAGACUCUGCCAUCCCUGGAG 24 8444 SCNN1A-4596 CUCUGGGGGGGCCCUGAG 18 8445 SCNN1A-4597 CCUCUGGGGGGGCCCUGAG 19 8446 SCNN1A-1140 UCCUCUGGGGGGGCCCUGAG 20 4989 SCNN1A-4598 GUCCUCUGGGGGGGCCCUGAG 21 8447 SCNN1A-4599 UGUCCUCUGGGGGGGCCCUGAG 22 8448 SCNN1A-4600 CUGUCCUCUGGGGGGGCCCUGAG 23 8449 SCNN1A-4601 CCUGUCCUCUGGGGGGGCCCUGAG 24 8450 SCNN1A-4602 UGCCUGGAAUCAACAACG 18 8451 SCNN1A-4603 AUGCCUGGAAUCAACAACG 19 8452 SCNN1A-4604 CAUGCCUGGAAUCAACAACG 20 8453 SCNN1A-4605 CCAUGCCUGGAAUCAACAACG 21 8454 SCNN1A-4606 UCCAUGCCUGGAAUCAACAACG 22 8455 SCNN1A-4607 UUCCAUGCCUGGAAUCAACAACG 23 8456 SCNN1A-4608 CUUCCAUGCCUGGAAUCAACAACG 24 8457 SCNN1A-4609 UCCCUGGAGGAGGACACG 18 8458 SCNN1A-4610 AUCCCUGGAGGAGGACACG 19 8459 SCNN1A-4611 CAUCCCUGGAGGAGGACACG 20 8460 SCNN1A-4612 CCAUCCCUGGAGGAGGACACG 21 8461 SCNN1A-4613 GCCAUCCCUGGAGGAGGACACG 22 8462 SCNN1A-4614 UGCCAUCCCUGGAGGAGGACACG 23 8463 SCNN1A-4615 CUGCCAUCCCUGGAGGAGGACACG 24 8464 SCNN1A-4616 CCCGCCUCACGGGGCCCG 18 8465 SCNN1A-4617 CCCCGCCUCACGGGGCCCG 19 8466 SCNN1A-4618 CCCCCGCCUCACGGGGCCCG 20 8467 SCNN1A-4619 GCCCCCGCCUCACGGGGCCCG 21 8468 SCNN1A-4620 CGCCCCCGCCUCACGGGGCCCG 22 8469 SCNN1A-4621 CCGCCCCCGCCUCACGGGGCCCG 23 8470 SCNN1A-4622 CCCGCCCCCGCCUCACGGGGCCCG 24 8471 SCNN1A-4623 GUGAGGCCCGCAGCGCCG 18 8472 SCNN1A-4624 GGUGAGGCCCGCAGCGCCG 19 8473 SCNN1A-1148 UGGUGAGGCCCGCAGCGCCG 20 4997 SCNN1A-4625 CUGGUGAGGCCCGCAGCGCCG 21 8474 SCNN1A-4626 GCUGGUGAGGCCCGCAGCGCCG 22 8475 SCNN1A-4627 AGCUGGUGAGGCCCGCAGCGCCG 23 8476 SCNN1A-4628 CAGCUGGUGAGGCCCGCAGCGCCG 24 8477 SCNN1A-4629 AUACUGGUCUCCAGGCCG 18 8478 SCNN1A-4630 GAUACUGGUCUCCAGGCCG 19 8479 SCNN1A-1149 CGAUACUGGUCUCCAGGCCG 20 4998 SCNN1A-4631 CCGAUACUGGUCUCCAGGCCG 21 8480 SCNN1A-4632 GCCGAUACUGGUCUCCAGGCCG 22 8481 SCNN1A-4633 AGCCGAUACUGGUCUCCAGGCCG 23 8482 SCNN1A-4634 AAGCCGAUACUGGUCUCCAGGCCG 24 8483 SCNN1A-4635 CUGGUGAGGCCCGCAGCG 18 8484 SCNN1A-4636 GCUGGUGAGGCCCGCAGCG 19 8485 SCNN1A-4637 AGCUGGUGAGGCCCGCAGCG 20 8486 SCNN1A-4638 CAGCUGGUGAGGCCCGCAGCG 21 8487 SCNN1A-4639 CCAGCUGGUGAGGCCCGCAGCG 22 8488 SCNN1A-4640 UCCAGCUGGUGAGGCCCGCAGCG 23 8489 SCNN1A-4641 UUCCAGCUGGUGAGGCCCGCAGCG 24 8490 SCNN1A-4642 UGUCCCUGAUGCUGCGCG 18 8491 SCNN1A-4643 CUGUCCCUGAUGCUGCGCG 19 8492 SCNN1A-4644 UCUGUCCCUGAUGCUGCGCG 20 8493 SCNN1A-4645 GUCUGUCCCUGAUGCUGCGCG 21 8494 SCNN1A-4646 GGUCUGUCCCUGAUGCUGCGCG 22 8495 SCNN1A-4647 AGGUCUGUCCCUGAUGCUGCGCG 23 8496 SCNN1A-4648 UAGGUCUGUCCCUGAUGCUGCGCG 24 8497 SCNN1A-4649 UUAACUUGCGGCCUGGCG 18 8498 SCNN1A-4650 UUUAACUUGCGGCCUGGCG 19 8499 SCNN1A-1157 CUUUAACUUGCGGCCUGGCG 20 5006 SCNN1A-4651 GCUUUAACUUGCGGCCUGGCG 21 8500 SCNN1A-4652 GGCUUUAACUUGCGGCCUGGCG 22 8501 SCNN1A-4653 UGGCUUUAACUUGCGGCCUGGCG 23 8502 SCNN1A-4654 GUGGCUUUAACUUGCGGCCUGGCG 24 8503 SCNN1A-4655 UCAUCAGGGGUGGAUGCG 18 8504 SCNN1A-4656 CUCAUCAGGGGUGGAUGCG 19 8505 SCNN1A-4657 ACUCAUCAGGGGUGGAUGCG 20 8506 SCNN1A-4658 UACUCAUCAGGGGUGGAUGCG 21 8507 SCNN1A-4659 AUACUCAUCAGGGGUGGAUGCG 22 8508 SCNN1A-4660 CAUACUCAUCAGGGGUGGAUGCG 23 8509 SCNN1A-4661 ACAUACUCAUCAGGGGUGGAUGCG 24 8510 SCNN1A-4662 CAGCCGUCGCGACCUGCG 18 8511 SCNN1A-4663 GCAGCCGUCGCGACCUGCG 19 8512 SCNN1A-1158 CGCAGCCGUCGCGACCUGCG 20 5007 SCNN1A-4664 CCGCAGCCGUCGCGACCUGCG 21 8513 SCNN1A-4665 CCCGCAGCCGUCGCGACCUGCG 22 8514 SCNN1A-4666 UCCCGCAGCCGUCGCGACCUGCG 23 8515 SCNN1A-4667 CUCCCGCAGCCGUCGCGACCUGCG 24 8516 SCNN1A-4668 CCGAUACUGGUCUCCAGG 18 8517 SCNN1A-4669 GCCGAUACUGGUCUCCAGG 19 8518 SCNN1A-4670 AGCCGAUACUGGUCUCCAGG 20 8519 SCNN1A-4671 AAGCCGAUACUGGUCUCCAGG 21 8520 SCNN1A-4672 GAAGCCGAUACUGGUCUCCAGG 22 8521 SCNN1A-4673 CGAAGCCGAUACUGGUCUCCAGG 23 8522 SCNN1A-4674 CCGAAGCCGAUACUGGUCUCCAGG 24 8523 SCNN1A-4675 UAAUGGUGCACGGGCAGG 18 8524 SCNN1A-4676 GUAAUGGUGCACGGGCAGG 19 8525 SCNN1A-4677 GGUAAUGGUGCACGGGCAGG 20 8526 SCNN1A-4678 GGGUAAUGGUGCACGGGCAGG 21 8527 SCNN1A-4679 CGGGUAAUGGUGCACGGGCAGG 22 8528 SCNN1A-4680 CCGGGUAAUGGUGCACGGGCAGG 23 8529 SCNN1A-4681 CCCGGGUAAUGGUGCACGGGCAGG 24 8530 SCNN1A-4682 GGGGGGGCCCUGAGAGGG 18 8531 SCNN1A-4683 UGGGGGGGCCCUGAGAGGG 19 8532 SCNN1A-4684 CUGGGGGGGCCCUGAGAGGG 20 8533 SCNN1A-4685 UCUGGGGGGGCCCUGAGAGGG 21 8534 SCNN1A-4686 CUCUGGGGGGGCCCUGAGAGGG 22 8535 SCNN1A-4687 CCUCUGGGGGGGCCCUGAGAGGG 23 8536 SCNN1A-4688 UCCUCUGGGGGGGCCCUGAGAGGG 24 8537 SCNN1A-4689 GUCUCCAGGCCGAGGGGG 18 8538 SCNN1A-4690 GGUCUCCAGGCCGAGGGGG 19 8539 SCNN1A-4691 UGGUCUCCAGGCCGAGGGGG 20 8540 SCNN1A-4692 CUGGUCUCCAGGCCGAGGGGG 21 8541 SCNN1A-4693 ACUGGUCUCCAGGCCGAGGGGG 22 8542 SCNN1A-4694 UACUGGUCUCCAGGCCGAGGGGG 23 8543 SCNN1A-4695 AUACUGGUCUCCAGGCCGAGGGGG 24 8544 SCNN1A-4696 CCCAGGUAGAGUGUGGGG 18 8545 SCNN1A-4697 UCCCAGGUAGAGUGUGGGG 19 8546 SCNN1A-4698 AUCCCAGGUAGAGUGUGGGG 20 8547 SCNN1A-4699 CAUCCCAGGUAGAGUGUGGGG 21 8548 SCNN1A-4700 ACAUCCCAGGUAGAGUGUGGGG 22 8549 SCNN1A-4701 GACAUCCCAGGUAGAGUGUGGGG 23 8550 SCNN1A-4702 UGACAUCCCAGGUAGAGUGUGGGG 24 8551 SCNN1A-4703 GUGUGGGGAAGGGAUGGG 18 8552 SCNN1A-4704 AGUGUGGGGAAGGGAUGGG 19 8553 SCNN1A-1189 GAGUGUGGGGAAGGGAUGGG 20 5038 SCNN1A-4705 AGAGUGUGGGGAAGGGAUGGG 21 8554 SCNN1A-4706 UAGAGUGUGGGGAAGGGAUGGG 22 8555 SCNN1A-4707 GUAGAGUGUGGGGAAGGGAUGGG 23 8556 SCNN1A-4708 GGUAGAGUGUGGGGAAGGGAUGGG 24 8557 SCNN1A-4709 GAAAGCACAGUUCCUGGG 18 8558 SCNN1A-4710 AGAAAGCACAGUUCCUGGG 19 8559 SCNN1A-4711 CAGAAAGCACAGUUCCUGGG 20 8560 SCNN1A-4712 ACAGAAAGCACAGUUCCUGGG 21 8561 SCNN1A-4713 UACAGAAAGCACAGUUCCUGGG 22 8562 SCNN1A-4714 CUACAGAAAGCACAGUUCCUGGG 23 8563 SCNN1A-4715 ACUACAGAAAGCACAGUUCCUGGG 24 8564 SCNN1A-4716 UGUCUGUGGUGGAGAUGG 18 8565 SCNN1A-4717 UUGUCUGUGGUGGAGAUGG 19 8566 SCNN1A-4718 GUUGUCUGUGGUGGAGAUGG 20 8567 SCNN1A-4719 UGUUGUCUGUGGUGGAGAUGG 21 8568 SCNN1A-4720 GUGUUGUCUGUGGUGGAGAUGG 22 8569 SCNN1A-4721 GGUGUUGUCUGUGGUGGAGAUGG 23 8570 SCNN1A-4722 CGGUGUUGUCUGUGGUGGAGAUGG 24 8571 SCNN1A-4723 AGUGUGGGGAAGGGAUGG 18 8572 SCNN1A-4724 GAGUGUGGGGAAGGGAUGG 19 8573 SCNN1A-4725 AGAGUGUGGGGAAGGGAUGG 20 8574 SCNN1A-4726 UAGAGUGUGGGGAAGGGAUGG 21 8575 SCNN1A-4727 GUAGAGUGUGGGGAAGGGAUGG 22 8576 SCNN1A-4728 GGUAGAGUGUGGGGAAGGGAUGG 23 8577 SCNN1A-4729 AGGUAGAGUGUGGGGAAGGGAUGG 24 8578 SCNN1A-4730 AACCCCCAGGUGGACUGG 18 8579 SCNN1A-4731 CAACCCCCAGGUGGACUGG 19 8580 SCNN1A-4732 ACAACCCCCAGGUGGACUGG 20 8581 SCNN1A-4733 AACAACCCCCAGGUGGACUGG 21 8582 SCNN1A-4734 CAACAACCCCCAGGUGGACUGG 22 8583 SCNN1A-4735 ACAACAACCCCCAGGUGGACUGG 23 8584 SCNN1A-4736 GACAACAACCCCCAGGUGGACUGG 24 8585 SCNN1A-4737 AGACUCUGCCAUCCCUGG 18 8586 SCNN1A-4738 GAGACUCUGCCAUCCCUGG 19 8587 SCNN1A-1196 AGAGACUCUGCCAUCCCUGG 20 5045 SCNN1A-4739 CAGAGACUCUGCCAUCCCUGG 21 8588 SCNN1A-4740 CCAGAGACUCUGCCAUCCCUGG 22 8589 SCNN1A-4741 GCCAGAGACUCUGCCAUCCCUGG 23 8590 SCNN1A-4742 UGCCAGAGACUCUGCCAUCCCUGG 24 8591 SCNN1A-4743 ACGGUAGGUCGUGCCUGG 18 8592 SCNN1A-4744 CACGGUAGGUCGUGCCUGG 19 8593 SCNN1A-4745 UCACGGUAGGUCGUGCCUGG 20 8594 SCNN1A-4746 GUCACGGUAGGUCGUGCCUGG 21 8595 SCNN1A-4747 UGUCACGGUAGGUCGUGCCUGG 22 8596 SCNN1A-4748 CUGUCACGGUAGGUCGUGCCUGG 23 8597 SCNN1A-4749 UCUGUCACGGUAGGUCGUGCCUGG 24 8598 SCNN1A-4750 AAAUUAAAGAGGAGCUGG 18 8599 SCNN1A-4751 GAAAUUAAAGAGGAGCUGG 19 8600 SCNN1A-1198 GGAAAUUAAAGAGGAGCUGG 20 5047 SCNN1A-4752 CGGAAAUUAAAGAGGAGCUGG 21 8601 SCNN1A-4753 CCGGAAAUUAAAGAGGAGCUGG 22 8602 SCNN1A-4754 CCCGGAAAUUAAAGAGGAGCUGG 23 8603 SCNN1A-4755 ACCCGGAAAUUAAAGAGGAGCUGG 24 8604 SCNN1A-4756 CCUCCACCUGUCCUCUGG 18 8605 SCNN1A-4757 UCCUCCACCUGUCCUCUGG 19 8606 SCNN1A-1199 UUCCUCCACCUGUCCUCUGG 20 5048 SCNN1A-4758 GUUCCUCCACCUGUCCUCUGG 21 8607 SCNN1A-4759 AGUUCCUCCACCUGUCCUCUGG 22 8608 SCNN1A-4760 CAGUUCCUCCACCUGUCCUCUGG 23 8609 SCNN1A-4761 CCAGUUCCUCCACCUGUCCUCUGG 24 8610 SCNN1A-4762 CCUCGGUGUUGUCUGUGG 18 8611 SCNN1A-4763 UCCUCGGUGUUGUCUGUGG 19 8612 SCNN1A-1205 CUCCUCGGUGUUGUCUGUGG 20 5054 SCNN1A-4764 GCUCCUCGGUGUUGUCUGUGG 21 8613 SCNN1A-4765 GGCUCCUCGGUGUUGUCUGUGG 22 8614 SCNN1A-4766 CGGCUCCUCGGUGUUGUCUGUGG 23 8615 SCNN1A-4767 UCGGCUCCUCGGUGUUGUCUGUGG 24 8616 SCNN1A-4768 GAGACCUCCAUCAGCAUG 18 8617 SCNN1A-4769 GGAGACCUCCAUCAGCAUG 19 8618 SCNN1A-1210 UGGAGACCUCCAUCAGCAUG 20 5059 SCNN1A-4770 GUGGAGACCUCCAUCAGCAUG 21 8619 SCNN1A-4771 CGUGGAGACCUCCAUCAGCAUG 22 8620 SCNN1A-4772 GCGUGGAGACCUCCAUCAGCAUG 23 8621 SCNN1A-4773 GGCGUGGAGACCUCCAUCAGCAUG 24 8622 SCNN1A-4774 CGCAGCCGUCGCGACCUG 18 8623 SCNN1A-4775 CCGCAGCCGUCGCGACCUG 19 8624 SCNN1A-1216 CCCGCAGCCGUCGCGACCUG 20 5065 SCNN1A-4776 UCCCGCAGCCGUCGCGACCUG 21 8625 SCNN1A-4777 CUCCCGCAGCCGUCGCGACCUG 22 8626 SCNN1A-4778 GCUCCCGCAGCCGUCGCGACCUG 23 8627 SCNN1A-4779 GGCUCCCGCAGCCGUCGCGACCUG 24 8628 SCNN1A-4780 GAGACUCUGCCAUCCCUG 18 8629 SCNN1A-4781 AGAGACUCUGCCAUCCCUG 19 8630 SCNN1A-4782 CAGAGACUCUGCCAUCCCUG 20 8631 SCNN1A-4783 CCAGAGACUCUGCCAUCCCUG 21 8632 SCNN1A-4784 GCCAGAGACUCUGCCAUCCCUG 22 8633 SCNN1A-4785 UGCCAGAGACUCUGCCAUCCCUG 23 8634 SCNN1A-4786 CUGCCAGAGACUCUGCCAUCCCUG 24 8635 SCNN1A-4787 CACUACAUCAACAUCCUG 18 8636 SCNN1A-4788 CCACUACAUCAACAUCCUG 19 8637 SCNN1A-4789 UCCACUACAUCAACAUCCUG 20 8638 SCNN1A-4790 UUCCACUACAUCAACAUCCUG 21 8639 SCNN1A-4791 CUUCCACUACAUCAACAUCCUG 22 8640 SCNN1A-4792 GCUUCCACUACAUCAACAUCCUG 23 8641 SCNN1A-4793 CGCUUCCACUACAUCAACAUCCUG 24 8642 SCNN1A-4794 AUGGCAGUGAUGUUCCUG 18 8643 SCNN1A-4795 AAUGGCAGUGAUGUUCCUG 19 8644 SCNN1A-4796 GAAUGGCAGUGAUGUUCCUG 20 8645 SCNN1A-4797 AGAAUGGCAGUGAUGUUCCUG 21 8646 SCNN1A-4798 AAGAAUGGCAGUGAUGUUCCUG 22 8647 SCNN1A-4799 CAAGAAUGGCAGUGAUGUUCCUG 23 8648 SCNN1A-4800 CCAAGAAUGGCAGUGAUGUUCCUG 24 8649 SCNN1A-4801 AAGAUCGGCUUCCAGCUG 18 8650 SCNN1A-4802 GAAGAUCGGCUUCCAGCUG 19 8651 SCNN1A-4803 GGAAGAUCGGCUUCCAGCUG 20 8652 SCNN1A-4804 UGGAAGAUCGGCUUCCAGCUG 21 8653 SCNN1A-4805 CUGGAAGAUCGGCUUCCAGCUG 22 8654 SCNN1A-4806 ACUGGAAGAUCGGCUUCCAGCUG 23 8655 SCNN1A-4807 GACUGGAAGAUCGGCUUCCAGCUG 24 8656 SCNN1A-4808 GAAAUUAAAGAGGAGCUG 18 8657 SCNN1A-4809 GGAAAUUAAAGAGGAGCUG 19 8658 SCNN1A-4810 CGGAAAUUAAAGAGGAGCUG 20 8659 SCNN1A-4811 CCGGAAAUUAAAGAGGAGCUG 21 8660 SCNN1A-4812 CCCGGAAAUUAAAGAGGAGCUG 22 8661 SCNN1A-4813 ACCCGGAAAUUAAAGAGGAGCUG 23 8662 SCNN1A-4814 UACCCGGAAAUUAAAGAGGAGCUG 24 8663 SCNN1A-4815 UCCUCCACCUGUCCUCUG 18 8664 SCNN1A-4816 UUCCUCCACCUGUCCUCUG 19 8665 SCNN1A-1224 GUUCCUCCACCUGUCCUCUG 20 5073 SCNN1A-4817 AGUUCCUCCACCUGUCCUCUG 21 8666 SCNN1A-4818 CAGUUCCUCCACCUGUCCUCUG 22 8667 SCNN1A-4819 CCAGUUCCUCCACCUGUCCUCUG 23 8668 SCNN1A-4820 GCCAGUUCCUCCACCUGUCCUCUG 24 8669 SCNN1A-4821 CAUCUCCAGGGGGCUCUG 18 8670 SCNN1A-4822 CCAUCUCCAGGGGGCUCUG 19 8671 SCNN1A-4823 CCCAUCUCCAGGGGGCUCUG 20 8672 SCNN1A-4824 GCCCAUCUCCAGGGGGCUCUG 21 8673 SCNN1A-4825 CGCCCAUCUCCAGGGGGCUCUG 22 8674 SCNN1A-4826 CCGCCCAUCUCCAGGGGGCUCUG 23 8675 SCNN1A-4827 CCCGCCCAUCUCCAGGGGGCUCUG 24 8676 SCNN1A-4828 GGGCUGUUUCACCAAGUG 18 8677 SCNN1A-4829 UGGGCUGUUUCACCAAGUG 19 8678 SCNN1A-4830 CUGGGCUGUUUCACCAAGUG 20 8679 SCNN1A-4831 CCUGGGCUGUUUCACCAAGUG 21 8680 SCNN1A-4832 ACCUGGGCUGUUUCACCAAGUG 22 8681 SCNN1A-4833 CACCUGGGCUGUUUCACCAAGUG 23 8682 SCNN1A-4834 CCACCUGGGCUGUUUCACCAAGUG 24 8683 SCNN1A-4835 GACAUCCCAGGUAGAGUG 18 8684 SCNN1A-4836 UGACAUCCCAGGUAGAGUG 19 8685 SCNN1A-1228 GUGACAUCCCAGGUAGAGUG 20 5077 SCNN1A-4837 GGUGACAUCCCAGGUAGAGUG 21 8686 SCNN1A-4838 CGGUGACAUCCCAGGUAGAGUG 22 8687 SCNN1A-4839 UCGGUGACAUCCCAGGUAGAGUG 23 8688 SCNN1A-4840 CUCGGUGACAUCCCAGGUAGAGUG 24 8689 SCNN1A-4841 UCAGGGGUGGAUGCGGUG 18 8690 SCNN1A-4842 AUCAGGGGUGGAUGCGGUG 19 8691 SCNN1A-1233 CAUCAGGGGUGGAUGCGGUG 20 5082 SCNN1A-4843 UCAUCAGGGGUGGAUGCGGUG 21 8692 SCNN1A-4844 CUCAUCAGGGGUGGAUGCGGUG 22 8693 SCNN1A-4845 ACUCAUCAGGGGUGGAUGCGGUG 23 8694 SCNN1A-4846 UACUCAUCAGGGGUGGAUGCGGUG 24 8695 SCNN1A-4847 UCCUCGGUGUUGUCUGUG 18 8696 SCNN1A-4848 CUCCUCGGUGUUGUCUGUG 19 8697 SCNN1A-4849 GCUCCUCGGUGUUGUCUGUG 20 8698 SCNN1A-4850 GGCUCCUCGGUGUUGUCUGUG 21 8699 SCNN1A-4851 CGGCUCCUCGGUGUUGUCUGUG 22 8700 SCNN1A-4852 UCGGCUCCUCGGUGUUGUCUGUG 23 8701 SCNN1A-4853 UUCGGCUCCUCGGUGUUGUCUGUG 24 8702 SCNN1A-4854 CAUCCCAGGUAGAGUGUG 18 8703 SCNN1A-4855 ACAUCCCAGGUAGAGUGUG 19 8704 SCNN1A-1238 GACAUCCCAGGUAGAGUGUG 20 5087 SCNN1A-4856 UGACAUCCCAGGUAGAGUGUG 21 8705 SCNN1A-4857 GUGACAUCCCAGGUAGAGUGUG 22 8706 SCNN1A-4858 GGUGACAUCCCAGGUAGAGUGUG 23 8707 SCNN1A-4859 CGGUGACAUCCCAGGUAGAGUGUG 24 8708 SCNN1A-4860 AGCGUGGCCUCCAGCUUG 18 8709 SCNN1A-4861 UAGCGUGGCCUCCAGCUUG 19 8710 SCNN1A-1242 GUAGCGUGGCCUCCAGCUUG 20 5091 SCNN1A-4862 CGUAGCGUGGCCUCCAGCUUG 21 8711 SCNN1A-4863 CCGUAGCGUGGCCUCCAGCUUG 22 8712 SCNN1A-4864 CCCGUAGCGUGGCCUCCAGCUUG 23 8713 SCNN1A-4865 GCCCGUAGCGUGGCCUCCAGCUUG 24 8714 SCNN1A-4866 GGAGACCUCCAUCAGCAU 18 8715 SCNN1A-4867 UGGAGACCUCCAUCAGCAU 19 8716 SCNN1A-4868 GUGGAGACCUCCAUCAGCAU 20 8717 SCNN1A-4869 CGUGGAGACCUCCAUCAGCAU 21 8718 SCNN1A-4870 GCGUGGAGACCUCCAUCAGCAU 22 8719 SCNN1A-4871 GGCGUGGAGACCUCCAUCAGCAU 23 8720 SCNN1A-4872 UGGCGUGGAGACCUCCAUCAGCAU 24 8721 SCNN1A-4873 UCUACCAGACAUACUCAU 18 8722 SCNN1A-4874 UUCUACCAGACAUACUCAU 19 8723 SCNN1A-4875 CUUCUACCAGACAUACUCAU 20 8724 SCNN1A-4876 GCUUCUACCAGACAUACUCAU 21 8725 SCNN1A-4877 UGCUUCUACCAGACAUACUCAU 22 8726 SCNN1A-4878 CUGCUUCUACCAGACAUACUCAU 23 8727 SCNN1A-4879 ACUGCUUCUACCAGACAUACUCAU 24 8728 SCNN1A-4880 UGGUGUAUGUGGGUUCAU 18 8729 SCNN1A-4881 UUGGUGUAUGUGGGUUCAU 19 8730 SCNN1A-1250 CUUGGUGUAUGUGGGUUCAU 20 5099 SCNN1A-4882 UCUUGGUGUAUGUGGGUUCAU 21 8731 SCNN1A-4883 CUCUUGGUGUAUGUGGGUUCAU 22 8732 SCNN1A-4884 UCUCUUGGUGUAUGUGGGUUCAU 23 8733 SCNN1A-4885 AUCUCUUGGUGUAUGUGGGUUCAU 24 8734 SCNN1A-4886 UACUCUCUCUUUCCUGAU 18 8735 SCNN1A-4887 CUACUCUCUCUUUCCUGAU 19 8736 SCNN1A-4888 CCUACUCUCUCUUUCCUGAU 20 8737 SCNN1A-4889 CCCUACUCUCUCUUUCCUGAU 21 8738 SCNN1A-4890 ACCCUACUCUCUCUUUCCUGAU 22 8739 SCNN1A-4891 GACCCUACUCUCUCUUUCCUGAU 23 8740 SCNN1A-4892 UGACCCUACUCUCUCUUUCCUGAU 24 8741 SCNN1A-4893 GGAAACCCUGGACAGACU 18 8742 SCNN1A-4894 AGGAAACCCUGGACAGACU 19 8743 SCNN1A-1257 UAGGAAACCCUGGACAGACU 20 5106 SCNN1A-4895 AUAGGAAACCCUGGACAGACU 21 8744 SCNN1A-4896 CAUAGGAAACCCUGGACAGACU 22 8745 SCNN1A-4897 UCAUAGGAAACCCUGGACAGACU 23 8746 SCNN1A-4898 UUCAUAGGAAACCCUGGACAGACU 24 8747 SCNN1A-4899 AAGGCAAGGAUGCUGACU 18 8748 SCNN1A-4900 GAAGGCAAGGAUGCUGACU 19 8749 SCNN1A-1258 GGAAGGCAAGGAUGCUGACU 20 5107 SCNN1A-4901 AGGAAGGCAAGGAUGCUGACU 21 8750 SCNN1A-4902 GAGGAAGGCAAGGAUGCUGACU 22 8751 SCNN1A-4903 UGAGGAAGGCAAGGAUGCUGACU 23 8752 SCNN1A-4904 AUGAGGAAGGCAAGGAUGCUGACU 24 8753 SCNN1A-4905 ACCCUCUGCCCCACACCU 18 8754 SCNN1A-4906 CACCCUCUGCCCCACACCU 19 8755 SCNN1A-4907 CCACCCUCUGCCCCACACCU 20 8756 SCNN1A-4908 CCCACCCUCUGCCCCACACCU 21 8757 SCNN1A-4909 UCCCACCCUCUGCCCCACACCU 22 8758 SCNN1A-4910 UUCCCACCCUCUGCCCCACACCU 23 8759 SCNN1A-4911 CUUCCCACCCUCUGCCCCACACCU 24 8760 SCNN1A-4912 CCGCAGCCGUCGCGACCU 18 8761 SCNN1A-4913 CCCGCAGCCGUCGCGACCU 19 8762 SCNN1A-4914 UCCCGCAGCCGUCGCGACCU 20 8763 SCNN1A-4915 CUCCCGCAGCCGUCGCGACCU 21 8764 SCNN1A-4916 GCUCCCGCAGCCGUCGCGACCU 22 8765 SCNN1A-4917 GGCUCCCGCAGCCGUCGCGACCU 23 8766 SCNN1A-4918 CGGCUCCCGCAGCCGUCGCGACCU 24 8767 SCNN1A-4919 GUCCUCUGGGGGGGCCCU 18 8768 SCNN1A-4920 UGUCCUCUGGGGGGGCCCU 19 8769 SCNN1A-4921 CUGUCCUCUGGGGGGGCCCU 20 8770 SCNN1A-4922 CCUGUCCUCUGGGGGGGCCCU 21 8771 SCNN1A-4923 ACCUGUCCUCUGGGGGGGCCCU 22 8772 SCNN1A-4924 CACCUGUCCUCUGGGGGGGCCCU 23 8773 SCNN1A-4925 CCACCUGUCCUCUGGGGGGGCCCU 24 8774 SCNN1A-4926 AGUUCCUCCACCUGUCCU 18 8775 SCNN1A-4927 CAGUUCCUCCACCUGUCCU 19 8776 SCNN1A-4928 CCAGUUCCUCCACCUGUCCU 20 8777 SCNN1A-4929 GCCAGUUCCUCCACCUGUCCU 21 8778 SCNN1A-4930 GGCCAGUUCCUCCACCUGUCCU 22 8779 SCNN1A-4931 GGGCCAGUUCCUCCACCUGUCCU 23 8780 SCNN1A-4932 GGGGCCAGUUCCUCCACCUGUCCU 24 8781 SCNN1A-4933 CAUGUUCCUCAUGCUGCU 18 8782 SCNN1A-4934 UCAUGUUCCUCAUGCUGCU 19 8783 SCNN1A-4935 AUCAUGUUCCUCAUGCUGCU 20 8784 SCNN1A-4936 CAUCAUGUUCCUCAUGCUGCU 21 8785 SCNN1A-4937 UCAUCAUGUUCCUCAUGCUGCU 22 8786 SCNN1A-4938 GUCAUCAUGUUCCUCAUGCUGCU 23 8787 SCNN1A-4939 GGUCAUCAUGUUCCUCAUGCUGCU 24 8788 SCNN1A-4940 CGAGGGGGCAGGGGUGCU 18 8789 SCNN1A-4941 CCGAGGGGGCAGGGGUGCU 19 8790 SCNN1A-4942 GCCGAGGGGGCAGGGGUGCU 20 8791 SCNN1A-4943 GGCCGAGGGGGCAGGGGUGCU 21 8792 SCNN1A-4944 AGGCCGAGGGGGCAGGGGUGCU 22 8793 SCNN1A-4945 CAGGCCGAGGGGGCAGGGGUGCU 23 8794 SCNN1A-4946 CCAGGCCGAGGGGGCAGGGGUGCU 24 8795 SCNN1A-4947 UUCCUCCACCUGUCCUCU 18 8796 SCNN1A-4948 GUUCCUCCACCUGUCCUCU 19 8797 SCNN1A-1276 AGUUCCUCCACCUGUCCUCU 20 5125 SCNN1A-4949 CAGUUCCUCCACCUGUCCUCU 21 8798 SCNN1A-4950 CCAGUUCCUCCACCUGUCCUCU 22 8799 SCNN1A-4951 GCCAGUUCCUCCACCUGUCCUCU 23 8800 SCNN1A-4952 GGCCAGUUCCUCCACCUGUCCUCU 24 8801 SCNN1A-4953 UGACAUCCCAGGUAGAGU 18 8802 SCNN1A-4954 GUGACAUCCCAGGUAGAGU 19 8803 SCNN1A-4955 GGUGACAUCCCAGGUAGAGU 20 8804 SCNN1A-4956 CGGUGACAUCCCAGGUAGAGU 21 8805 SCNN1A-4957 UCGGUGACAUCCCAGGUAGAGU 22 8806 SCNN1A-4958 CUCGGUGACAUCCCAGGUAGAGU 23 8807 SCNN1A-4959 CCUCGGUGACAUCCCAGGUAGAGU 24 8808 SCNN1A-4960 CCUGGAAUCAACAACGGU 18 8809 SCNN1A-4961 GCCUGGAAUCAACAACGGU 19 8810 SCNN1A-4962 UGCCUGGAAUCAACAACGGU 20 8811 SCNN1A-4963 AUGCCUGGAAUCAACAACGGU 21 8812 SCNN1A-4964 CAUGCCUGGAAUCAACAACGGU 22 8813 SCNN1A-4965 CCAUGCCUGGAAUCAACAACGGU 23 8814 SCNN1A-4966 UCCAUGCCUGGAAUCAACAACGGU 24 8815 SCNN1A-4967 AUCAGGGGUGGAUGCGGU 18 8816 SCNN1A-4968 CAUCAGGGGUGGAUGCGGU 19 8817 SCNN1A-4969 UCAUCAGGGGUGGAUGCGGU 20 8818 SCNN1A-4970 CUCAUCAGGGGUGGAUGCGGU 21 8819 SCNN1A-4971 ACUCAUCAGGGGUGGAUGCGGU 22 8820 SCNN1A-4972 UACUCAUCAGGGGUGGAUGCGGU 23 8821 SCNN1A-4973 AUACUCAUCAGGGGUGGAUGCGGU 24 8822 SCNN1A-4974 UGUGGGGAAGGGAUGGGU 18 8823 SCNN1A-4975 GUGUGGGGAAGGGAUGGGU 19 8824 SCNN1A-1288 AGUGUGGGGAAGGGAUGGGU 20 5137 SCNN1A-4976 GAGUGUGGGGAAGGGAUGGGU 21 8825 SCNN1A-4977 AGAGUGUGGGGAAGGGAUGGGU 22 8826 SCNN1A-4978 UAGAGUGUGGGGAAGGGAUGGGU 23 8827 SCNN1A-4979 GUAGAGUGUGGGGAAGGGAUGGGU 24 8828 SCNN1A-4980 ACUUCCACCACCCGAUGU 18 8829 SCNN1A-4981 CACUUCCACCACCCGAUGU 19 8830 SCNN1A-4982 UCACUUCCACCACCCGAUGU 20 8831 SCNN1A-4983 CUCACUUCCACCACCCGAUGU 21 8832 SCNN1A-4984 UCUCACUUCCACCACCCGAUGU 22 8833 SCNN1A-4985 CUCUCACUUCCACCACCCGAUGU 23 8834 SCNN1A-4986 ACUCUCACUUCCACCACCCGAUGU 24 8835 SCNN1A-4987 ACAUCCCAGGUAGAGUGU 18 8836 SCNN1A-4988 GACAUCCCAGGUAGAGUGU 19 8837 SCNN1A-1293 UGACAUCCCAGGUAGAGUGU 20 5142 SCNN1A-4989 GUGACAUCCCAGGUAGAGUGU 21 8838 SCNN1A-4990 GGUGACAUCCCAGGUAGAGUGU 22 8839 SCNN1A-4991 CGGUGACAUCCCAGGUAGAGUGU 23 8840 SCNN1A-4992 UCGGUGACAUCCCAGGUAGAGUGU 24 8841 SCNN1A-4993 GAAACCCUGGACAGACUU 18 8842 SCNN1A-4994 GGAAACCCUGGACAGACUU 19 8843 SCNN1A-1295 AGGAAACCCUGGACAGACUU 20 5144 SCNN1A-4995 UAGGAAACCCUGGACAGACUU 21 8844 SCNN1A-4996 AUAGGAAACCCUGGACAGACUU 22 8845 SCNN1A-4997 CAUAGGAAACCCUGGACAGACUU 23 8846 SCNN1A-4998 UCAUAGGAAACCCUGGACAGACUU 24 8847 SCNN1A-4999 UAGCGUGGCCUCCAGCUU 18 8848 SCNN1A-5000 GUAGCGUGGCCUCCAGCUU 19 8849 SCNN1A-5001 CGUAGCGUGGCCUCCAGCUU 20 8850 SCNN1A-5002 CCGUAGCGUGGCCUCCAGCUU 21 8851 SCNN1A-5003 CCCGUAGCGUGGCCUCCAGCUU 22 8852 SCNN1A-5004 GCCCGUAGCGUGGCCUCCAGCUU 23 8853 SCNN1A-5005 AGCCCGUAGCGUGGCCUCCAGCUU 24 8854 SCNN1A-5006 CAUGCUGCUCCGAAGGUU 18 8855 SCNN1A-5007 UCAUGCUGCUCCGAAGGUU 19 8856 SCNN1A-5008 CUCAUGCUGCUCCGAAGGUU 20 8857 SCNN1A-5009 CCUCAUGCUGCUCCGAAGGUU 21 8858 SCNN1A-5010 UCCUCAUGCUGCUCCGAAGGUU 22 8859 SCNN1A-5011 UUCCUCAUGCUGCUCCGAAGGUU 23 8860 SCNN1A-5012 GUUCCUCAUGCUGCUCCGAAGGUU 24 8861 SCNN1A-5013 GGCAGUGAUGUUCCUGUU 18 8862 SCNN1A-5014 UGGCAGUGAUGUUCCUGUU 19 8863 SCNN1A-5015 AUGGCAGUGAUGUUCCUGUU 20 8864 SCNN1A-5016 AAUGGCAGUGAUGUUCCUGUU 21 8865 SCNN1A-5017 GAAUGGCAGUGAUGUUCCUGUU 22 8866 SCNN1A-5018 AGAAUGGCAGUGAUGUUCCUGUU 23 8867 SCNN1A-5019 AAGAAUGGCAGUGAUGUUCCUGUU 24 8868

Table 45A provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 45A 1st Tier  Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-5020 + GGCUAGAGUCCUGCUCC 17 8869 SCNN1A-5021 + GUCUAGGGUCCUGCUCC 17 8870 SCNN1A-5022 + GAUUCCAAACCAGGUUC 17 8871 SCNN1A-5023 GAUGUACUGGCAAUUCG 17 8872

Table 45B provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 45B  2nd Tier Target  DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-322 + UGGUCACUGCGGGGAAG 17  915 SCNN1A-5024 + CCCUUCAUGAGCCCCGG 17 8873 SCNN1A-5025 + AGGGACUAACCGACCUG 17 8874 SCNN1A-238 + AGAUGGUCACUGCGGGGAAG 20  858 SCNN1A-5026 CAUGAUGUACUGGCAAUUCG 20 8875 SCNN1A-5027 + UUCCCCUUCAUGAGCCCCGG 20 8876 SCNN1A-1657 + CAGAGGGACUAACCGACCUG 20 5506

Table 45C provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 45C  3rd Tier Target  DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-5028 + GGCCCAGCCCCUGCUCC 17 8877 SCNN1A-5029 + GAGGGCUAGAGUCCUGCUCC 20 8878 SCNN1A-5030 + GAGGUCUAGGGUCCUGCUCC 20 8879

Table 45D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within the first 500 bp of the coding sequence (e.g., with 500 bp downstream from the start codon). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 45D  4th Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-5031 + CGGGGCCCAGCCCCUGCUCC 20 8880 SCNN1A-5032 + CAGGAUUCCAAACCAGGUUC 20 8881

Table 45E provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fifth tier parameters. The targeting domains fall in the coding sequence of the gene, downstream of the first 500 bp of coding sequence (e.g., anywhere from +500 (relative to the start codon) to the stop codon of the gene). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. meningitidis Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 45E  5th Tier Target  DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-5033 + GAGUCUCACCCCAGGAA 17 8882 SCNN1A-5034 ACAGCAGGUGAGGCCCA 17 8883 SCNN1A-485 + GCGCCAUGGAGCAAGCA 17 4334 SCNN1A-5035 + UAUGUCUGGUAGAAGCA 17 8884 SCNN1A-5036 UCCAGGUGUGUAUUCAC 17 8885 SCNN1A-577 + CUGAGGAGAAGUCAACC 17 4426 SCNN1A-5037 GCUUGCUCCAUGGCGCC 17 8886 SCNN1A-5038 GCAACUUCAUCUUCGCC 17 8887 SCNN1A-5039 GAGCCCGUAGCGUGGCC 17 8888 SCNN1A-5040 ACUGGAAGGACUGGAAG 17 8889 SCNN1A-5041 GCAACCAGAACAAAUCG 17 8890 SCNN1A-5042 AUGCGGUGAGGGAGUGG 17 8891 SCNN1A-787 ACCCUGGACAGACUUGG 17 4636 SCNN1A-5043 + AAGGGGACACUAACCUG 17 8892 SCNN1A-5044 CUGCCUUUAUGGAUGAU 17 8893 SCNN1A-5045 AACAACGGUGAGAAGCU 17 8894 SCNN1A-5046 + UCGGCCUGGAGACCAGU 17 8895 SCNN1A-5047 + AGGGAGCUUCUCACCGU 17 8896 SCNN1A-5048 + CUGGAGUCUCACCCCAGGAA 20 8897 SCNN1A-5049 CACACAGCAGGUGAGGCCCA 20 8898 SCNN1A-909 + AGGGCGCCAUGGAGCAAGCA 20 4758 SCNN1A-5050 + GAGUAUGUCUGGUAGAAGCA 20 8899 SCNN1A-5051 CCUUCCAGGUGUGUAUUCAC 20 8900 SCNN1A-1000 + GGUCUGAGGAGAAGUCAACC 20 4849 SCNN1A-5052 CCUGCUUGCUCCAUGGCGCC 20 8901 SCNN1A-5053 UGGGCAACUUCAUCUUCGCC 20 8902 SCNN1A-5054 GUCGAGCCCGUAGCGUGGCC 20 8903 SCNN1A-5055 UGGACUGGAAGGACUGGAAG 20 8904 SCNN1A-5056 AGUGCAACCAGAACAAAUCG 20 8905 SCNN1A-5057 UGGAUGCGGUGAGGGAGUGG 20 8906 SCNN1A-1206 GAAACCCUGGACAGACUUGG 20 5055 SCNN1A-5058 + GGGAAGGGGACACUAACCUG 20 8907 SCNN1A-5059 AACCUGCCUUUAUGGAUGAU 20 8908 SCNN1A-5060 AUCAACAACGGUGAGAAGCU 20 8909 SCNN1A-5061 + CCCUCGGCCUGGAGACCAGU 20 8910 SCNN1A-5062 + AGCAGGGAGCUUCUCACCGU 20 8911

Table 46A provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN8A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 46A  1st Tier Tar-  get DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-5063 + GAGAAUCAGACCCAAAA 17 8912 SCNN1A-5064 GAGCUGGCAAAUAGAAA 17 8913 SCNN1A-5065 + GAAGGAGCCAGCACCAA 17 8914 SCNN1A-5066 + GGGCAACACAAGGAGAA 17 8915 SCNN1A-5067 + GCUGGGCUUCCCUAGAA 17 8916 SCNN1A-5068 GCCAGAUUCAACUGGAA 17 8917 SCNN1A-327 + GAUACCUCCCCUUGGAA 17 4176 SCNN1A-5069 + GCUAGGAGGGCAACACA 17 8918 SCNN1A-328 GGGCGCAGGGUGGGACA 17 4177 SCNN1A-5070 + GAAACUGACCCUUCCCA 17 8919 SCNN1A-5071 GAGAGCAGACGAAUCCA 17 8920 SCNN1A-329 GCCUCACUCGGGUUCCA 17 4178 SCNN1A-5072 + GUGCCAAGUGGUGAGCA 17 8921 SCNN1A-330 GGGAGAAUGUGGGCGCA 17 4179 SCNN1A-5073 + GGUCCUUACAUUGGGCA 17 8922 SCNN1A-5074 GAAAGGUGGCCCUAUCA 17 8923 SCNN1A-5075 + GCAGUACUCCAGGCUCA 17 8924 SCNN1A-80 GCCCAUACCAGGUCUCA 17  529 SCNN1A-5076 GACACAGCUCGAGGUCA 17 8925 SCNN1A-5077 + GAGUACUGGACCUGAGA 17 8926 SCNN1A-5078 GAGGGCCUAGAGUGAGA 17 8927 SCNN1A-5079 + GGAAGGAGGGCUCCCGA 17 8928 SCNN1A-5080 + GGGAGUUUUCCGAAGGA 17 8929 SCNN1A-5081 + GUUUUCCGAAGGAAGGA 17 8930 SCNN1A-5082 + GAACCGGGAGGACAGGA 17 8931 SCNN1A-5083 + GGAGUCUGUCUCCAGGA 17 8932 SCNN1A-5084 + GGAUGUGAAAGCCGGGA 17 8933 SCNN1A-5085 GUCUGCUGGCUUGUGGA 17 8934 SCNN1A-5086 GUCUGGACAAGGUUGGA 17 8935 SCNN1A-5087 GCUCUGUGUGGGAGUGA 17 8936 SCNN1A-5088 + GAGGAGAAAUUCGUUGA 17 8937 SCNN1A-5089 GAGGAGAGGCCGUUCUA 17 8938 SCNN1A-5090 GGAGACUGGAGUUUCUA 17 8939 SCNN1A-5091 GGACCAUGCCCAAUGUA 17 8940 SCNN1A-5092 GGAAUCCUGGUUGACAC 17 8941 SCNN1A-5093 + GGCUGCCGCUUCCUCAC 17 8942 SCNN1A-5094 + GGGCUUUAGACGCAGAC 17 8943 SCNN1A-5095 + GAAAGCCGGUGUCAACC 17 8944 SCNN1A-5096 + GAGCAUUGAUACACACC 17 8945 SCNN1A-5097 + GAUUCUGUCUCUGCCCC 17 8946 SCNN1A-5098 GGGCGGGCUCCCCAGCC 17 8947 SCNN1A-5099 GCUGAGCCUCUAGCUCC 17 8948 SCNN1A-5100 GGGCGAUUACACAUUCC 17 8949 SCNN1A-5101 + GUCCCAAGUGUGCUUCC 17 8950 SCNN1A-5102 GGUGGCGAGGAAUCAGC 17 8951 SCNN1A-5103 + GCCAAAAGUGCCGGAGC 17 8952 SCNN1A-5104 + GAGGAUGUGGCCAGCGC 17 8953 SCNN1A-5105 + GAAGCUGGGGGCUAGGC 17 8954 SCNN1A-5106 + GAAGGCGGACUCUGGGC 17 8955 SCNN1A-5107 + GGAGCCCGCCCGCUGGC 17 8956 SCNN1A-5108 + GCCUAGGGGCUCACUGC 17 8957 SCNN1A-5109 + GGAGCCAGCAGACCUGC 17 8958 SCNN1A-5110 GCUGGGCCUUUGUCUGC 17 8959 SCNN1A-5111 + GUUGGGGCCAAAAGUGC 17 8960 SCNN1A-5112 + GCAGGCACUGAAGGUGC 17 8961 SCNN1A-5113 + GUCUGCUCUCUGGGUGC 17 8962 SCNN1A-5114 GCUGAGCACCUUAUUGC 17 8963 SCNN1A-5115 GGGGCAGAGACAGAAUC 17 8964 SCNN1A-5116 + GUGGGAGCAGCGCACUC 17 8965 SCNN1A-333 GAUGGGAGAGGGCACUC 17 4182 SCNN1A-5117 GGCCCUCGCGCUGCCUC 17 8966 SCNN1A-5118 + GGCAGUACUCCAGGCUC 17 8967 SCNN1A-5119 GGUGUGUAUCAAUGCUC 17 8968 SCNN1A-5120 GAGUUUCUAGGGGUCUC 17 8969 SCNN1A-5121 GGACACAGCUCGAGGUC 17 8970 SCNN1A-5122 GCUAGUGGUUGGAUUUC 17 8971 SCNN1A-5123 + GCUAGAGGCUCAGCAAG 17 8972 SCNN1A-5124 + GGAAUGUGGGCAACCAG 17 8973 SCNN1A-334 GACAUGGGCAUGGCCAG 17 4183 SCNN1A-5125 + GGGCUAGGGGAGCCUAG 17 8974 SCNN1A-5126 + GUGCUUCCAGGAGCUAG 17 8975 SCNN1A-5127 GAGACUGGAGUUUCUAG 17 8976 SCNN1A-5128 + GGGCACUGAGUGAGUAG 17 8977 SCNN1A-5129 GUCCACAGUGUCCUGCG 17 8978 SCNN1A-5130 GGACAAAACUCGAAAGG 17 8979 SCNN1A-5131 + GACGCAGACAGGCAAGG 17 8980 SCNN1A-5132 + GGAACCGGGAGGACAGG 17 8981 SCNN1A-5133 + GGAGCAGCGCACUCAGG 17 8982 SCNN1A-5134 GUAGAUAGCCCCAGAGG 17 8983 SCNN1A-5135 GGGCCUAGAGUGAGAGG 17 8984 SCNN1A-5136 + GCAUUGAUACACACCGG 17 8985 SCNN1A-5137 + GCACUGAAGGUGCAGGG 17 8986 SCNN1A-5138 + GACCCAAAAAGGGCUGG 17 8987 SCNN1A-5139 GGUCUGGACAAGGUUGG 17 8988 SCNN1A-5140 GGGGUCUCUGGGAUAUG 17 8989 SCNN1A-5141 + GGCCACGCAGGACACUG 17 8990 SCNN1A-5142 + GUGCAGCGGCCUGGCUG 17 8991 SCNN1A-5143 + GGGUCCAACCUGGUCUG 17 8992 SCNN1A-5144 + GAUAAAUCAGUUUUCUG 17 8993 SCNN1A-5145 + GUGAGUAGAGGCAGGUG 17 8994 SCNN1A-5146 GCUGCACCUGUCAGGUG 17 8995 SCNN1A-5147 GGUCUCUGGGAUAUGUG 17 8996 SCNN1A-335 GGCGCAGGGUGGGACAU 17 4184 SCNN1A-5148 + GAGCCAGGUCCUUACAU 17 8997 SCNN1A-5149 + GCGAAGGACAGAGAGAU 17 8998 SCNN1A-5150 + GGGCUAGGCGGGGCCCU 17 8999 SCNN1A-5151 GAAAACUGAUUUAUCCU 17 9000 SCNN1A-5152 + GUGCUGGGUUAUCUCCU 17 9001 SCNN1A-5153 GUAUCAAUGCUCAGGCU 17 9002 SCNN1A-5154 + GGUGCAGCGGCCUGGCU 17 9003 SCNN1A-336 + GGUCAAGGCUGAGCUCU 17 4185 SCNN1A-5155 + GGAUUCGUCUGCUCUCU 17 9004 SCNN1A-5156 GAGAUGACACCUUCUCU 17 9005 SCNN1A-5157 GGGAGACUGGAGUUUCU 17 9006 SCNN1A-5158 GGGAUAUGUGGGGCAGU 17 9007 SCNN1A-5159 + GAGCAGCGCACUCAGGU 17 9008 SCNN1A-337 GAAUGUGGGCGCAGGGU 17 4186 SCNN1A-5160 GGGUCUCUGGGAUAUGU 17 9009 SCNN1A-5161 + GUUCUUUUUUACACUGU 17 9010 SCNN1A-5162 GGGUGAGGCUGACCUGU 17 9011 SCNN1A-5163 GUUGCCCUCCUAGCUGU 17 9012 SCNN1A-5164 GGGUCAGUUUCUUCAUU 17 9013 SCNN1A-339 + GAGCCCCGGAGUGGAUU 17 4188 SCNN1A-5165 GGGAGCCCUCCUUCCUU 17 9014 SCNN1A-5166 + GCAGACCUGCGGGAGUU 17 9015 SCNN1A-5167 + GCAAGUGGGCAGCCCUCCAA 20 9016 SCNN1A-5168 + GUCUCCAGGAAGGAGAGCAA 20 9017 SCNN1A-5169 + GCAAAUAGUUUUCAUAUCAA 20 9018 SCNN1A-5170 + GGAGGGCAACACAAGGAGAA 20 9019 SCNN1A-5171 + GGAGCUGGGCUUCCCUAGAA 20 9020 SCNN1A-5172 GUGCUAGGACAAAACUCGAA 20 9021 SCNN1A-5173 GCUGCCAGAUUCAACUGGAA 20 9022 SCNN1A-5174 + GGAUGUGGCCAGCGCUGGAA 20 9023 SCNN1A-5175 GCCCCUCCCGGGUCUGGACA 20 9024 SCNN1A-5176 + GAAGAAACUGACCCUUCCCA 20 9025 SCNN1A-5177 + GAGAUAAGACAUAAGAGCCA 20 9026 SCNN1A-5178 + GCCCGCCCGCUGGCCGGCCA 20 9027 SCNN1A-340 GUGGGACAUGGGCAUGGCCA 20 4189 SCNN1A-341 GCAGCCUCACUCGGGUUCCA 20 4190 SCNN1A-342 GAGCAGUAUCAAGGUAAGCA 20 4191 SCNN1A-5179 + GGAGUGCCAAGUGGUGAGCA 20 9028 SCNN1A-5180 GCUGGCAAAUAGAAAAGGCA 20 9029 SCNN1A-5181 + GCUUUAGACGCAGACAGGCA 20 9030 SCNN1A-5182 GCCUAGAGUGAGAGGGGGCA 20 9031 SCNN1A-5183 + GAGAAGGCGGACUCUGGGCA 20 9032 SCNN1A-5184 GUGCUGAGCACCUUAUUGCA 20 9033 SCNN1A-5185 + GGCAAAUAGUUUUCAUAUCA 20 9034 SCNN1A-343 GUGAUGGGAGAGGGCACUCA 20 4192 SCNN1A-5186 + GGAAGGCUGCCGCUUCCUCA 20 9035 SCNN1A-1 GCAGCCCAUACCAGGUCUCA 20  503 SCNN1A-5187 + GCCAGCGCUGGAAAGGAAGA 20 9036 SCNN1A-5188 GCUGAGGGCCUAGAGUGAGA 20 9037 SCNN1A-5189 + GGCAACCAGAGGCAGCGCGA 20 9038 SCNN1A-5190 + GCCGGGAGUUUUCCGAAGGA 20 9039 SCNN1A-5191 + GGAGUUUUCCGAAGGAAGGA 20 9040 SCNN1A-5192 + GCCCGCUGGCCGGCCAGGGA 20 9041 SCNN1A-5193 + GGCCCUGCACGCGGCAGGGA 20 9042 SCNN1A-76 + GCCCUGGAGUGGACUGUGGA 20  528 SCNN1A-5194 GACCUGUGGGUGCCCUUGGA 20 9043 SCNN1A-5195 + GAGGAGGAGAAAUUCGUUGA 20 9044 SCNN1A-5196 + GCAUGGUCCUCCCUGCAAUA 20 9045 SCNN1A-5197 + GCCUGCAAUACAAUAAGAUA 20 9046 SCNN1A-5198 + GACAUAAGAGCCAAGGGCUA 20 9047 SCNN1A-344 + GUAUGGGCUGCAGAGGUCUA 20 4193 SCNN1A-5199 GCAGAGGAGAGGCCGUUCUA 20 9048 SCNN1A-5200 GGAGGACCAUGCCCAAUGUA 20 9049 SCNN1A-5201 + GAAAUCCAACCACUAGCUUA 20 9050 SCNN1A-5202 GUUUGGCUGCCAGAUUCAAC 20 9051 SCNN1A-5203 + GCUCCCGAGGGCAGGUGAAC 20 9052 SCNN1A-5204 + GCCUGAGCAUUGAUACACAC 20 9053 SCNN1A-5205 + GAAGGCUGCCGCUUCCUCAC 20 9054 SCNN1A-5206 + GAGUGCAGGAAUGUGGUCAC 20 9055 SCNN1A-5207 GGACCUGGCUCAAGGGAGAC 20 9056 SCNN1A-5208 + GGCAUGGCACACGCCUAGAC 20 9057 SCNN1A-5209 + GGGUGGGGAACCGGGAGGAC 20 9058 SCNN1A-5210 + GGUUGCGGCUGGACUGGGAC 20 9059 SCNN1A-5211 + GGCAGGUGAACUGGGAGUAC 20 9060 SCNN1A-5212 + GUCAACCAGGAUUCCAAACC 20 9061 SCNN1A-5213 GUCCCAGUCCAGCCGCAACC 20 9062 SCNN1A-5214 + GAGGGCCUGGGUGGGGAACC 20 9063 SCNN1A-5215 + GAUCGGGGCUCAGGUGCACC 20 9064 SCNN1A-5216 GCCUAGCCCCCAGCUUCACC 20 9065 SCNN1A-5217 + GGACACUGUGGACACAGACC 20 9066 SCNN1A-5218 GUCCUCCCGGUUCCCCACCC 20 9067 SCNN1A-346 + GUGCCCUCUCCCAUCACCCC 20 4195 SCNN1A-5219 + GCACACGCCUAGACAGGCCC 20 9068 SCNN1A-5220 GCUUCACCUGGGCCCCUCCC 20 9069 SCNN1A-5221 + GCUGAGGAGGAGUCAGAGCC 20 9070 SCNN1A-347 GGUGGGACAUGGGCAUGGCC 20 4196 SCNN1A-5222 GCGAUUACACAUUCCUGGCC 20 9071 SCNN1A-5223 + GUGAGAAGAAUUGCAAUGCC 20 9072 SCNN1A-5224 GGGAACCUGGUUUGGAAUCC 20 9073 SCNN1A-5225 + GGGAUGCGUCUGCCUCCUCC 20 9074 SCNN1A-5226 + GGAGUCCCAAGUGUGCUUCC 20 9075 SCNN1A-348 GGCAGCCUCACUCGGGUUCC 20 4197 SCNN1A-5227 + GUGCACCUGGAUGUGAAAGC 20 9076 SCNN1A-176 GCUCAUGAAGGGGAACAAGC 20  811 SCNN1A-5228 GCAACCUGGGAGUGGGAAGC 20 9077 SCNN1A-5229 GGGGGUGGCGAGGAAUCAGC 20 9078 SCNN1A-5230 GCUGCUCCCACUUAGUGAGC 20 9079 SCNN1A-349 GAGUGGGAGAAUGUGGGCGC 20 4198 SCNN1A-5231 GUGUGUAUCAAUGCUCAGGC 20 9080 SCNN1A-5232 + GAAUCAGACCCAAAAAGGGC 20 9081 SCNN1A-5233 + GAAGGAGGGCUCCCGAGGGC 20 9082 SCNN1A-5234 + GACAGGUGCAGCGGCCUGGC 20 9083 SCNN1A-5235 + GGAGCCUAGGGGCUCACUGC 20 9084 SCNN1A-5236 + GGAGUUGGGGCCAAAAGUGC 20 9085 SCNN1A-5237 GGUGCUGAGCACCUUAUUGC 20 9086 SCNN1A-5238 + GGUUCCUUUCCAGUUGAAUC 20 9087 SCNN1A-350 GGUGAUGGGAGAGGGCACUC 20 4199 SCNN1A-351 GGCCAGGGGCAGCCUCACUC 20 4200 SCNN1A-5239 + GGGCUCACUGCAGGAGACUC 20 9088 SCNN1A-5240 + GGACCUGAGAAGGCGGACUC 20 9089 SCNN1A-5241 GUUCUAGGGAAGCCCAGCUC 20 9090 SCNN1A-5242 GCCCUCCUAGCUGUGGGCUC 20 9091 SCNN1A-352 + GAUUGGGGAGAGCAAGGGUC 20 4201 SCNN1A-5243 GCCAGGCCGCUGCACCUGUC 20 9092 SCNN1A-5244 GCGAGGAAUCAGCAGGAAAG 20 9093 SCNN1A-5245 + GGAGCUAGAGGCUCAGCAAG 20 9094 SCNN1A-5246 GUGAGAGGGGGCAAGGCAAG 20 9095 SCNN1A-5247 + GGCCAGCGCUGGAAAGGAAG 20 9096 SCNN1A-5248 + GCAGGAAUGUGGGCAACCAG 20 9097 SCNN1A-5249 GCAAGAGACUGCCGCAAGAG 20 9098 SCNN1A-5250 GAAACAGAAGGCAGAUAGAG 20 9099 SCNN1A-5251 GUCCAGCCGCAACCUGGGAG 20 9100 SCNN1A-5252 GGGUCUGGACAAGGUUGGAG 20 9101 SCNN1A-5253 GCCAUGCUGCCUUAAGCUAG 20 9102 SCNN1A-5254 + GAGGGGCACUGAGUGAGUAG 20 9103 SCNN1A-353 GCUCUCCCCAAUCCACUCCG 20 4202 SCNN1A-5255 + GGGCAACCAGAGGCAGCGCG 20 9104 SCNN1A-5256 + GUGAAGCUGGGGGCUAGGCG 20 9105 SCNN1A-5257 + GACAGACUCAUGGGGGAUCG 20 9106 SCNN1A-5258 + GAGUACUGGACCUGAGAAGG 20 9107 SCNN1A-5259 + GGGAGUUUUCCGAAGGAAGG 20 9108 SCNN1A-5260 + GUGGGAGCAGCGCACUCAGG 20 9109 SCNN1A-5261 GUAGAUAGCCCCAGAGGAGG 20 9110 SCNN1A-5262 GGUCUGGACAAGGUUGGAGG 20 9111 SCNN1A-354 GGGAGAAUGUGGGCGCAGGG 20 4203 SCNN1A-5263 GGCAAAUAGAAAAGGCAGGG 20 9112 SCNN1A-5264 + GGCCUGGGUGGGGAACCGGG 20 9113 SCNN1A-5265 + GCAUUGAUACACACCGGGGG 20 9114 SCNN1A-2 GCCCAUACCAGGUCUCAUGG 20  497 SCNN1A-5266 GCUGGCUCCAGGAAAGGUGG 20 9115 SCNN1A-5267 + GUCACAGAGUUGCAGGAAUG 20 9116 SCNN1A-5268 + GAGGGCCACGCAGGACACUG 20 9117 SCNN1A-5269 GCACUCUGGGCUGCCUCCUG 20 9118 SCNN1A-5270 GCCGCUGCACCUGUCAGGUG 20 9119 SCNN1A-5271 GGCCUUUGUCUGCUGGCUUG 20 9120 SCNN1A-355 GUGGGCGCAGGGUGGGACAU 20 4204 SCNN1A-5272 + GAGACAGACUCAUGGGGGAU 20 9121 SCNN1A-5273 GUCUCCUGCAGUGAGCCCCU 20 9122 SCNN1A-5274 GGCUGACCUGUGGGUGCCCU 20 9123 SCNN1A-5275 + GCCAAGGGCUAGGGGAGCCU 20 9124 SCNN1A-5276 + GCCUUGCCCCCUCUCACUCU 20 9125 SCNN1A-5277 + GACCUGAGAAGGCGGACUCU 20 9126 SCNN1A-356 + GGUAUGGGCUGCAGAGGUCU 20 4205 SCNN1A-5278 + GCCAGCAGACCUGCGGGAGU 20 9127 SCNN1A-5279 GAGGAAGCCACAGACCAGGU 20 9128 SCNN1A-357 GGAGAAUGUGGGCGCAGGGU 20 4206 SCNN1A-5280 + GCGCUGGAAAGGAAGAGGGU 20 9129 SCNN1A-5281 GUGCAGGGCCUGGGUUGUGU 20 9130 SCNN1A-5282 GAAGGGUCAGUUUCUUCAUU 20 9131 SCNN1A-5283 GAGUCUCCUCCAGCCCUUUU 20 9132

Table 46B provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 46B  2nd Tier Target  DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-5284 + AAGGAGCCAGCACCAAA 17 9133 SCNN1A-5285 + AAACUUAAUGCAGCAAA 17 9134 SCNN1A-5286 CUGUCUCAGGAAGUAAA 17 9135 SCNN1A-5287 + UAAGACAUAAGAGCCAA 17 9136 SCNN1A-5288 + AGUGGGCAGCCCUCCAA 17 9137 SCNN1A-358 CCAGCUGUCCCUUCCAA 17 4207 SCNN1A-359 AGUAUCAAGGUAAGCAA 17 4208 SCNN1A-5289 + UGGCUGUUUGAUCUCAA 17 9138 SCNN1A-5290 CUAGGACAAAACUCGAA 17 9139 SCNN1A-5291 UCUGCUGGCUCCAGGAA 17 9140 SCNN1A-5292 UGAUUUAUCCUUGGGAA 17 9141 SCNN1A-5293 + UGUGGCCAGCGCUGGAA 17 9142 SCNN1A-360 ACUCCGGGGCUCAUGAA 17 4209 SCNN1A-5294 + AUUAGCAUCUCAAUUAA 17 9143 SCNN1A-5295 CCUCCCGGGUCUGGACA 17 9144 SCNN1A-5296 UUGAGAUCAAACAGCCA 17 9145 SCNN1A-5297 + AUAAGACAUAAGAGCCA 17 9146 SCNN1A-5298 ACCUUUUCACAGAGCCA 17 9147 SCNN1A-5299 + CGCCCGCUGGCCGGCCA 17 9148 SCNN1A-88 CUCCACAGUCCACUCCA 17  609 SCNN1A-5300 + AAGUGGGCAGCCCUCCA 17 9149 SCNN1A-5301 + CUGAAUCUUGACAAGCA 17 9150 SCNN1A-361 CAGUAUCAAGGUAAGCA 17 4210 SCNN1A-5302 ACUCUGUGACCACAGCA 17 9151 SCNN1A-5303 + ACUAGCUUAAGGCAGCA 17 9152 SCNN1A-5304 + UCAAUUAAAGGUGAGCA 17 9153 SCNN1A-5305 UGAGAGGGGGCAAGGCA 17 9154 SCNN1A-5306 + UUAGACGCAGACAGGCA 17 9155 SCNN1A-5307 + AGGCCCUGCACGCGGCA 17 9156 SCNN1A-5308 CUUCCCUGCCGCGUGCA 17 9157 SCNN1A-5309 + CAGGCACUGAAGGUGCA 17 9158 SCNN1A-5310 CUGAGCACCUUAUUGCA 17 9159 SCNN1A-362 UAUCAUGAGCAGUAUCA 17 4211 SCNN1A-363 AUGGGAGAGGGCACUCA 17 4212 SCNN1A-5311 + UUCCUGAGACAGACUCA 17 9160 SCNN1A-5312 + AGGCUGCCGCUUCCUCA 17 9161 SCNN1A-5313 UGUAAGGACCUGGCUCA 17 9162 SCNN1A-5314 + AGCGCUGGAAAGGAAGA 17 9163 SCNN1A-5315 + AGGGCAACACAAGGAGA 17 9164 SCNN1A-5316 + UGGUGGGGGCAAAUAGA 17 9165 SCNN1A-5317 + AGCCGGGAGUUUUCCGA 17 9166 SCNN1A-5318 + AACCAGAGGCAGCGCGA 17 9167 SCNN1A-5319 + UGAGCCCACAGCUAGGA 17 9168 SCNN1A-5320 + CGCUGGCCGGCCAGGGA 17 9169 SCNN1A-5321 + CCUGCACGCGGCAGGGA 17 9170 SCNN1A-5322 + CUUGUCCAGACCCGGGA 17 9171 SCNN1A-5323 + UGAGCAGGGCGGGGGGA 17 9172 SCNN1A-5324 UGACACCUUCUCUGGGA 17 9173 SCNN1A-82 AUACCAGGUCUCAUGGA 17  501 SCNN1A-364 + UGAUACCUCCCCUUGGA 17 4213 SCNN1A-5325 CUGUGGGUGCCCUUGGA 17 9174 SCNN1A-365 CACUCCGGGGCUCAUGA 17 4214 SCNN1A-5326 CUGCACCUGUCAGGUGA 17 9175 SCNN1A-366 UCGGGUUCCAGGGGUGA 17 4215 SCNN1A-5327 + UGGUCCUCCCUGCAAUA 17 9176 SCNN1A-5328 + CGAAGGACAGAGAGAUA 17 9177 SCNN1A-5329 + AGGGCUAGGGGAGCCUA 17 9178 SCNN1A-5330 AAGAACAGAAUGUCCUA 17 9179 SCNN1A-5331 + AUAAGAGCCAAGGGCUA 17 9180 SCNN1A-157 + CUCCAUGAGACCUGGUA 17  502 SCNN1A-5332 + AUCCAACCACUAGCUUA 17 9181 SCNN1A-5333 UGGCUGCCAGAUUCAAC 17 9182 SCNN1A-5334 + CCCGAGGGCAGGUGAAC 17 9183 SCNN1A-5335 + UGAGCAUUGAUACACAC 17 9184 SCNN1A-5336 + CCUCCAAGGGCACCCAC 17 9185 SCNN1A-5337 + UUCCUCACGGGCCCCAC 17 9186 SCNN1A-5338 AGAGCAGACGAAUCCAC 17 9187 SCNN1A-5339 + UGCAGGAAUGUGGUCAC 17 9188 SCNN1A-5340 CCUGGCUCAAGGGAGAC 17 9189 SCNN1A-5341 + AUGGCACACGCCUAGAC 17 9190 SCNN1A-5342 + CCAGGGAUGGAAGCGAC 17 9191 SCNN1A-5343 + UGGGGAACCGGGAGGAC 17 9192 SCNN1A-5344 + UGCGGCUGGACUGGGAC 17 9193 SCNN1A-5345 + CCAGGUUGCGGCUGGAC 17 9194 SCNN1A-5346 + CCUCCCCCUCACCUGAC 17 9195 SCNN1A-5347 + AGGUGAACUGGGAGUAC 17 9196 SCNN1A-5348 + AGGCUCAGGGUCCAACC 17 9197 SCNN1A-5349 CCAGUCCAGCCGCAACC 17 9198 SCNN1A-5350 + CCAACCUUGUCCAGACC 17 9199 SCNN1A-156 + UUCCCCUCCAUGAGACC 17  653 SCNN1A-5351 UGCCCAAUGUAAGGACC 17 9200 SCNN1A-368 CCUCUGCAGCCCAUACC 17 4217 SCNN1A-5352 CUCCCGGUUCCCCACCC 17 9201 SCNN1A-5353 + UAAGGUGCUCAGCACCC 17 9202 SCNN1A-5354 + CAACCUUGUCCAGACCC 17 9203 SCNN1A-369 + CCGAGUGAGGCUGCCCC 17 4218 SCNN1A-5355 AGGCCUAUCUCCUCCCC 17 9204 SCNN1A-5356 + ACACAGACCCGGAGCCC 17 9205 SCNN1A-5357 + AGACCCGGGAGGGGCCC 17 9206 SCNN1A-5358 CCUGUCGCUUCCAUCCC 17 9207 SCNN1A-5359 AGGUUGGACCCUGAGCC 17 9208 SCNN1A-5360 + CCAGUCUCCCUUGAGCC 17 9209 SCNN1A-5361 + CCGCCCGCUGGCCGGCC 17 9210 SCNN1A-5362 + UGACAGGUGCAGCGGCC 17 9211 SCNN1A-5363 CUGCCGCGUGCAGGGCC 17 9212 SCNN1A-5364 + AGAAGAAUUGCAAUGCC 17 9213 SCNN1A-5365 + UUACACUGUUGGCUGCC 17 9214 SCNN1A-5366 UCCCGGCUUUCACAUCC 17 9215 SCNN1A-5367 AGCUGAGACACAGAUCC 17 9216 SCNN1A-5368 UUCCUUCGGAAAACUCC 17 9217 SCNN1A-370 UCUCCCCAAUCCACUCC 17 4219 SCNN1A-87 CCUCCACAGUCCACUCC 17  608 SCNN1A-5369 + AGAAAAGGCAGUACUCC 17 9218 SCNN1A-5370 UUCACCUGGGCCCCUCC 17 9219 SCNN1A-5371 + AUGCGUCUGCCUCCUCC 17 9220 SCNN1A-5372 + UUUGGUCUUCUUCCUCC 17 9221 SCNN1A-5373 + AAAGGGAGUCUGUCUCC 17 9222 SCNN1A-371 AGCCUCACUCGGGUUCC 17 4220 SCNN1A-5374 + CUUCUUAAAGUGAAAGC 17 9223 SCNN1A-5375 + CACCUGGAUGUGAAAGC 17 9224 SCNN1A-260 CAUGAAGGGGAACAAGC 17  868 SCNN1A-84 CAUGGAGGGGAACAAGC 17  607 SCNN1A-5376 + AGGGGCCCAGGUGAAGC 17 9225 SCNN1A-5377 AACUCUGUGACCACAGC 17 9226 SCNN1A-372 + CCCUUGGAAGGGACAGC 17 4221 SCNN1A-5378 AUCCCUGGCCGGCCAGC 17 9227 SCNN1A-5379 + CUCAAUUAAAGGUGAGC 17 9228 SCNN1A-5380 + CAAGCAAGGAGUUUAGC 17 9229 SCNN1A-5381 + CAGCGCGAGGGCCACGC 17 9230 SCNN1A-5382 + CUGGGGAGCCCGCCCGC 17 9231 SCNN1A-5383 UUGGCCCCAACUCCCGC 17 9232 SCNN1A-5384 CUCUUCCUUUCCAGCGC 17 9233 SCNN1A-373 UGGGAGAAUGUGGGCGC 17 4222 SCNN1A-5385 UGGCAAAUAGAAAAGGC 17 9234 SCNN1A-5386 UGUAUCAAUGCUCAGGC 17 9235 SCNN1A-5387 + ACUGAGUGAGUAGAGGC 17 9236 SCNN1A-5388 + CAGGCCCUGCACGCGGC 17 9237 SCNN1A-5389 + CACUCCCAGGUUGCGGC 17 9238 SCNN1A-5390 + UCAGACCCAAAAAGGGC 17 9239 SCNN1A-5391 + UUAAAGGUGAGCAGGGC 17 9240 SCNN1A-5392 CUGGCCGGCCAGCGGGC 17 9241 SCNN1A-5393 UCGCUUCCAUCCCUGGC 17 9242 SCNN1A-5394 + AGGUGCAGCGGCCUGGC 17 9243 SCNN1A-5395 + AGAGAAGAGGUCUCUGC 17 9244 SCNN1A-5396 AACUCCCGCAGGUCUGC 17 9245 SCNN1A-5397 CCUUCCCUGCCGCGUGC 17 9246 SCNN1A-5398 CAGACUCCCUUUGGUGC 17 9247 SCNN1A-5399 UUAUCUUAUUGUAUUGC 17 9248 SCNN1A-5400 + UGUGGUCACAGAGUUGC 17 9249 SCNN1A-5401 + UCCUUUCCAGUUGAAUC 17 9250 SCNN1A-5402 + CAGACUCAUGGGGGAUC 17 9251 SCNN1A-5403 CGAAAGGUGGCCCUAUC 17 9252 SCNN1A-374 CUCUCCCCAAUCCACUC 17 4223 SCNN1A-375 CAGGGGCAGCCUCACUC 17 4224 SCNN1A-5404 + CUCACUGCAGGAGACUC 17 9253 SCNN1A-5405 + CCUGAGAAGGCGGACUC 17 9254 SCNN1A-5406 + AGGUCAGCCUCACCCUC 17 9255 SCNN1A-5407 CCAGUUCACCUGCCCUC 17 9256 SCNN1A-5408 CUAGGGAAGCCCAGCUC 17 9257 SCNN1A-5409 + AUGGGGGAUCGGGGCUC 17 9258 SCNN1A-5410 CUCCUAGCUGUGGGCUC 17 9259 SCNN1A-5411 + UGGAUUCGUCUGCUCUC 17 9260 SCNN1A-5412 CCCCAUGAGUCUGUCUC 17 9261 SCNN1A-5413 AGAGAUGACACCUUCUC 17 9262 SCNN1A-5414 CCAGAGUCCGCCUUCUC 17 9263 SCNN1A-376 + UGGGGAGAGCAAGGGUC 17 4225 SCNN1A-5415 + AAUUGCAAUGCCUGGUC 17 9264 SCNN1A-5416 AGGCCGCUGCACCUGUC 17 9265 SCNN1A-5417 + AGGAGUGGAGUGCCAAG 17 9266 SCNN1A-377 CAGCUGUCCCUUCCAAG 17 4226 SCNN1A-5418 + CAGCGCUGGAAAGGAAG 17 9267 SCNN1A-5419 + ACCCGGAGCCCAGGAAG 17 9268 SCNN1A-5420 UGGGGCCCGUGAGGAAG 17 9269 SCNN1A-378 CUCCGGGGCUCAUGAAG 17 4227 SCNN1A-5421 + CCUCCCCGCUCACUAAG 17 9270 SCNN1A-5422 UAAGUAGAUAGCCCCAG 17 9271 SCNN1A-5423 CAUCCCUGGCCGGCCAG 17 9272 SCNN1A-5424 CUCGAGGUCAGGGCCAG 17 9273 SCNN1A-379 CCUCACUCGGGUUCCAG 17 4228 SCNN1A-5425 CCCUAUCAGGGAAGCAG 17 9274 SCNN1A-5426 CUCUGUGACCACAGCAG 17 9275 SCNN1A-5427 UGGGAUAUGUGGGGCAG 17 9276 SCNN1A-5428 + AGGCGGACUCUGGGCAG 17 9277 SCNN1A-380 + CCUGGUAUGGGCUGCAG 17 4229 SCNN1A-5429 + UCACCUGACAGGUGCAG 17 9278 SCNN1A-5430 AGAGACUGCCGCAAGAG 17 9279 SCNN1A-5431 AGGGCCUAGAGUGAGAG 17 9280 SCNN1A-381 + CUUCAUGAGCCCCGGAG 17 4230 SCNN1A-5432 + UUGUCCAGACCCGGGAG 17 9281 SCNN1A-5433 CAAGGCAAGGGGGGGAG 17 9282 SCNN1A-5434 CAGCCGCAACCUGGGAG 17 9283 SCNN1A-5435 UCUGGACAAGGUUGGAG 17 9284 SCNN1A-5436 UGAGGGCCUAGAGUGAG 17 9285 SCNN1A-5437 UGCUCCCACUUAGUGAG 17 9286 SCNN1A-5438 AUGCUGCCUUAAGCUAG 17 9287 SCNN1A-5439 + UAAGAGCCAAGGGCUAG 17 9288 SCNN1A-5440 + AACCCAGGCCCUGCACG 17 9289 SCNN1A-5441 + AGCAUUGAUACACACCG 17 9290 SCNN1A-5442 + CUCCCACACAGAGCCCG 17 9291 SCNN1A-5443 + AGGAAGGAGGGCUCCCG 17 9292 SCNN1A-382 CUCCCCAAUCCACUCCG 17 4231 SCNN1A-5444 CUCCCACUUAGUGAGCG 17 9293 SCNN1A-5445 + CAACCAGAGGCAGCGCG 17 9294 SCNN1A-5446 + UAAAGGUGAGCAGGGCG 17 9295 SCNN1A-5447 + AGACUCAUGGGGGAUCG 17 9296 SCNN1A-5448 AAUCAGGACACAGCUCG 17 9297 SCNN1A-5449 + AGUUUUCCGAAGGAAGG 17 9298 SCNN1A-5450 + CUCACGGGCCCCACAGG 17 9299 SCNN1A-5451 + AAAGGUGAGCAGGGCGG 17 9300 SCNN1A-5452 + AUUAAAGGUGAGCAGGG 17 9301 SCNN1A-383 AGAAUGUGGGCGCAGGG 17 4232 SCNN1A-5453 AGCACCUUAUUGCAGGG 17 9302 SCNN1A-5454 + CUGGGUGGGGAACCGGG 17 9303 SCNN1A-5455 + CCUUGUCCAGACCCGGG 17 9304 SCNN1A-5456 CCUGGCCGGCCAGCGGG 17 9305 SCNN1A-5457 + AAGGUGAGCAGGGCGGG 17 9306 SCNN1A-384 CUGUCCCUUCCAAGGGG 17 4233 SCNN1A-5458 CCACUUAGUGAGCGGGG 17 9307 SCNN1A-5459 + UUGAUACACACCGGGGG 17 9308 SCNN1A-5460 + CCUAGACAGGCCCUGGG 17 9309 SCNN1A-5461 + CUGAGACAGACUCAUGG 17 9310 SCNN1A-81 CAUACCAGGUCUCAUGG 17  605 SCNN1A-5462 UGAGACACAGAUCCUGG 17 9311 SCNN1A-5463 UGUCUGCUGGCUUGUGG 17 9312 SCNN1A-5464 CCUGUGGGUGCCCUUGG 17 9313 SCNN1A-5465 + ACAGAGUUGCAGGAAUG 17 9314 SCNN1A-5466 + CCUGAGACAGACUCAUG 17 9315 SCNN1A-5467 UGUUGCCCUCCUAGCUG 17 9316 SCNN1A-5468 + UGUAAUCGCCCCUGCUG 17 9317 SCNN1A-385 + CCCCUGGAACCCGAGUG 17 4234 SCNN1A-5469 CUCCUGUGGGGCCCGUG 17 9318 SCNN1A-5470 AAUCCACGGGCUCUGUG 17 9319 SCNN1A-387 + AGCCCCGGAGUGGAUUG 17 4236 SCNN1A-5471 + UGUGGCUUCCUCUCUUG 17 9320 SCNN1A-5472 + CAGACCUGCGGGAGUUG 17 9321 SCNN1A-5473 + UCCUGAGACAGACUCAU 17 9322 SCNN1A-5474 + ACACCGGGGGAGGAGAU 17 9323 SCNN1A-5475 + ACAGACUCAUGGGGGAU 17 9324 SCNN1A-388 + UGAGCCCCGGAGUGGAU 17 4237 SCNN1A-5476 + UCCUCUGCUUCCCUGAU 17 9325 SCNN1A-389 CGGGUUCCAGGGGUGAU 17 4238 SCNN1A-5477 + AGGAGAAAUUCGUUGAU 17 9326 SCNN1A-158 + UCCAUGAGACCUGGUAU 17  654 SCNN1A-5478 + CCGAGGGCAGGUGAACU 17 9327 SCNN1A-5479 UCUCCUUGCUCACCACU 17 9328 SCNN1A-5480 + CAGGUUGCGGCUGGACU 17 9329 SCNN1A-5481 CAGUCCAGCCGCAACCU 17 9330 SCNN1A-5482 AGCCCCCAGCUUCACCU 17 9331 SCNN1A-5483 UAGGCUCCCCUAGCCCU 17 9332 SCNN1A-5484 + ACGCCUAGACAGGCCCU 17 9333 SCNN1A-5485 UGACCUGUGGGUGCCCU 17 9334 SCNN1A-5486 + AAGGGCUAGGGGAGCCU 17 9335 SCNN1A-5487 UGCCGCGUGCAGGGCCU 17 9336 SCNN1A-5488 + AUCCUGAGCCCACAGCU 17 9337 SCNN1A-5489 + CCAAAAGUGCCGGAGCU 17 9338 SCNN1A-5490 + CAUAAGAGCCAAGGGCU 17 9339 SCNN1A-5491 CCACAUUCCUGCACUCU 17 9340 SCNN1A-5492 + UUGCCCCCUCUCACUCU 17 9341 SCNN1A-5493 + CUGAGAAGGCGGACUCU 17 9342 SCNN1A-5494 AGUUUCUAGGGGUCUCU 17 9343 SCNN1A-390 + AUGGGCUGCAGAGGUCU 17 4239 SCNN1A-5495 + AGGGCUCCAGGAGGUCU 17 9344 SCNN1A-5496 AGAGGAGAGGCCGUUCU 17 9345 SCNN1A-5497 + CUAGAGGCUCAGCAAGU 17 9346 SCNN1A-5498 + CUCCCCGCUCACUAAGU 17 9347 SCNN1A-5499 + AGCAGACCUGCGGGAGU 17 9348 SCNN1A-5500 AGCCGCAACCUGGGAGU 17 9349 SCNN1A-5501 CCGGGUCUGGACAAGGU 17 9350 SCNN1A-5502 + AGUGAGUAGAGGCAGGU 17 9351 SCNN1A-5503 UGCCUUAAGCUAGUGGU 17 9352 SCNN1A-5504 + CAGAGUUGCAGGAAUGU 17 9353 SCNN1A-5505 UCUGGGCUGCCUCCUGU 17 9354 SCNN1A-5506 AUCCACGGGCUCUGUGU 17 9355 SCNN1A-5507 + AGCCAGGUCCUUACAUU 17 9356 SCNN1A-5508 CUCCUGGAAGCACACUU 17 9357 SCNN1A-5509 UGGAGACAGACUCCCUU 17 9358 SCNN1A-5510 UUUUGCUGCAUUAAGUU 17 9359 SCNN1A-392 AGCAAGGGAACCUGGUU 17 4241 SCNN1A-5511 CCCAGCUCCGGCACUUU 17 9360 SCNN1A-5512 UCUCCUCCAGCCCUUUU 17 9361 SCNN1A-5513 CUCCUCCAGCCCUUUUU 17 9362 SCNN1A-5514 + UCAGAGAAUCAGACCCAAAA 20 9363 SCNN1A-5515 + UAGAAGGAGCCAGCACCAAA 20 9364 SCNN1A-5516 CAUGAGCUGGCAAAUAGAAA 20 9365 SCNN1A-5517 + AUCUCCUUGGCUCUGUGAAA 20 9366 SCNN1A-5518 + AUAGAAGGAGCCAGCACCAA 20 9367 SCNN1A-5519 UCCUGGAGGAAGAAGACCAA 20 9368 SCNN1A-5520 + AGAUAAGACAUAAGAGCCAA 20 9369 SCNN1A-5521 AAUCCAGCUGUCCCUUCCAA 20 9370 SCNN1A-393 AGCAGUAUCAAGGUAAGCAA 20 4242 SCNN1A-5522 AAUGUAAGGACCUGGCUCAA 20 9371 SCNN1A-5523 + CCCUGGCUGUUUGAUCUCAA 20 9372 SCNN1A-5524 AGGUCUGCUGGCUCCAGGAA 20 9373 SCNN1A-5525 AACUGAUUUAUCCUUGGGAA 20 9374 SCNN1A-394 + CAUGAUACCUCCCCUUGGAA 20 4243 SCNN1A-5526 + CUCAUUAGCAUCUCAAUUAA 20 9375 SCNN1A-5527 + ACAGCUAGGAGGGCAACACA 20 9376 SCNN1A-395 UGUGGGCGCAGGGUGGGACA 20 4244 SCNN1A-5528 CCUUUGAGAUCAAACAGCCA 20 9377 SCNN1A-5529 CCAGAGAGCAGACGAAUCCA 20 9378 SCNN1A-5530 + AGCAAGUGGGCAGCCCUCCA 20 9379 SCNN1A-5531 AAAUCCAGCUGUCCCUUCCA 20 9380 SCNN1A-5532 + CUGCUGAAUCUUGACAAGCA 20 9381 SCNN1A-5533 + UGUCUCCAGGAAGGAGAGCA 20 9382 SCNN1A-5534 + AUCUCAAUUAAAGGUGAGCA 20 9383 SCNN1A-396 AGUGGGAGAAUGUGGGCGCA 20 4245 SCNN1A-5535 + CCGGAGCCCAGGAAGAGGCA 20 9384 SCNN1A-5536 + CCCAGGCCCUGCACGCGGCA 20 9385 SCNN1A-5537 + CCAGGUCCUUACAUUGGGCA 20 9386 SCNN1A-5538 AGCCUUCCCUGCCGCGUGCA 20 9387 SCNN1A-5539 + AAGCAGGCACUGAAGGUGCA 20 9388 SCNN1A-5540 CUCGAAAGGUGGCCCUAUCA 20 9389 SCNN1A-397 AGGUAUCAUGAGCAGUAUCA 20 4246 SCNN1A-5541 + AAGGCAGUACUCCAGGCUCA 20 9390 SCNN1A-5542 CAAUGUAAGGACCUGGCUCA 20 9391 SCNN1A-398 + AUUGGGGAGAGCAAGGGUCA 20 4247 SCNN1A-5543 + UGGGAGUACUGGACCUGAGA 20 9392 SCNN1A-5544 + CAGAGCCGGGAGUUUUCCGA 20 9393 SCNN1A-5545 + ACAAUAGAGAGGGACAGCGA 20 9394 SCNN1A-5546 + AAGGGAGUCUGUCUCCAGGA 20 9395 SCNN1A-5547 + UCCUGAGCCCACAGCUAGGA 20 9396 SCNN1A-5548 + AACCUUGUCCAGACCCGGGA 20 9397 SCNN1A-5549 + CCUGGAUGUGAAAGCCGGGA 20 9398 SCNN1A-5550 AGAUGACACCUUCUCUGGGA 20 9399 SCNN1A-5551 AAACUGAUUUAUCCUUGGGA 20 9400 SCNN1A-3 CCCAUACCAGGUCUCAUGGA 20 556 SCNN1A-5552 UUUGUCUGCUGGCUUGUGGA 20 9401 SCNN1A-399 + UCAUGAUACCUCCCCUUGGA 20 4248 SCNN1A-5553 CGGGUCUGGACAAGGUUGGA 20 9402 SCNN1A-400 AUCCACUCCGGGGCUCAUGA 20 4249 SCNN1A-5554 CUCUUCUCUGCAGGGCCUGA 20 9403 SCNN1A-5555 CGGGCUCUGUGUGGGAGUGA 20 9404 SCNN1A-5556 CCGCUGCACCUGUCAGGUGA 20 9405 SCNN1A-401 CACUCGGGUUCCAGGGGUGA 20 4250 SCNN1A-5557 + UCUCCUCUGCUUCCCUGAUA 20 9406 SCNN1A-5558 AAGGGAGACUGGAGUUUCUA 20 9407 SCNN1A-78 + CCCCUCCAUGAGACCUGGUA 20  500 SCNN1A-5559 UUUGGAAUCCUGGUUGACAC 20 9408 SCNN1A-5560 + AGCCCUCCAAGGGCACCCAC 20 9409 SCNN1A-5561 + CGCUUCCUCACGGGCCCCAC 20 9410 SCNN1A-5562 CAGAGAGCAGACGAAUCCAC 20 9411 SCNN1A-5563 + CAGGGGCUUUAGACGCAGAC 20 9412 SCNN1A-5564 + CGGCCAGGGAUGGAAGCGAC 20 9413 SCNN1A-5565 + CUCCCAGGUUGCGGCUGGAC 20 9414 SCNN1A-5566 + UCCAGGCUCAGGGUCCAACC 20 9415 SCNN1A-5567 + AGUGAAAGCCGGUGUCAACC 20 9416 SCNN1A-404 UCAAGGUAAGCAAGGGAACC 20 4253 SCNN1A-5568 + CCUGAGCAUUGAUACACACC 20 9417 SCNN1A-5569 + CCUCCAACCUUGUCCAGACC 20 9418 SCNN1A-5570 CCAUGCCCAAUGUAAGGACC 20 9419 SCNN1A-5571 AGCAGGAAAGAGGAGGGACC 20 9420 SCNN1A-405 AGACCUCUGCAGCCCAUACC 20 4254 SCNN1A-5572 + CUCCAACCUUGUCCAGACCC 20 9421 SCNN1A-406 + AACCCGAGUGAGGCUGCCCC 20 4255 SCNN1A-5573 + CCUGAUUCUGUCUCUGCCCC 20 9422 SCNN1A-5574 UGCAGGCCUAUCUCCUCCCC 20 9423 SCNN1A-5575 + UGGACACAGACCCGGAGCCC 20 9424 SCNN1A-5576 AUUCCUGUCGCUUCCAUCCC 20 9425 SCNN1A-5577 AACGAAUUUCUCCUCCUCCC 20 9426 SCNN1A-5578 ACCUUUGAGAUCAAACAGCC 20 9427 SCNN1A-5579 AGCGGGCGGGCUCCCCAGCC 20 9428 SCNN1A-5580 + ACAAGGAGAAGGGGCCAGCC 20 9429 SCNN1A-5581 ACCAGGUUGGACCCUGAGCC 20 9430 SCNN1A-5582 + ACUCCAGUCUCCCUUGAGCC 20 9431 SCNN1A-5583 + ACACUGUUGGCUGCCAGGCC 20 9432 SCNN1A-5584 + ACCUGACAGGUGCAGCGGCC 20 9433 SCNN1A-5585 UCCCUGCCGCGUGCAGGGCC 20 9434 SCNN1A-5586 + UUUUUACACUGUUGGCUGCC 20 9435 SCNN1A-5587 CCUUCCCGGCUUUCACAUCC 20 9436 SCNN1A-5588 AGGAGCUGAGACACAGAUCC 20 9437 SCNN1A-5589 UCCUUCCUUCGGAAAACUCC 20 9438 SCNN1A-408 UGCUCUCCCCAAUCCACUCC 20 4257 SCNN1A-8 AGCCCUCCACAGUCCACUCC 20  559 SCNN1A-5590 + AAGAGAAAAGGCAGUACUCC 20 9439 SCNN1A-5591 UGGAGGCAGCCCAGACCUCC 20 9440 SCNN1A-5592 AGCUUCACCUGGGCCCCUCC 20 9441 SCNN1A-5593 UUUCUGCCCUCCUGUCCUCC 20 9442 SCNN1A-5594 CUUGCUGAGCCUCUAGCUCC 20 9443 SCNN1A-5595 CCCGCAGGUCUGCUGGCUCC 20 9444 SCNN1A-5596 + ACCAAAGGGAGUCUGUCUCC 20 9445 SCNN1A-5597 CAGGGGCGAUUACACAUUCC 20 9446 SCNN1A-5598 UCCCCCCUUGCUCUCCUUCC 20 9447 SCNN1A-5 UCUCAUGGAGGGGAACAAGC 20  557 SCNN1A-5599 UGCAACUCUGUGACCACAGC 20 9448 SCNN1A-409 + CUCCCCUUGGAAGGGACAGC 20 4258 SCNN1A-5600 UCCAUCCCUGGCCGGCCAGC 20 9449 SCNN1A-5601 + CAUCUCAAUUAAAGGUGAGC 20 9450 SCNN1A-5602 + UGACAAGCAAGGAGUUUAGC 20 9451 SCNN1A-5603 + AGGCAGCGCGAGGGCCACGC 20 9452 SCNN1A-5604 + UGGCUGGGGAGCCCGCCCGC 20 9453 SCNN1A-5605 CUUUUGGCCCCAACUCCCGC 20 9454 SCNN1A-5606 ACCCUCUUCCUUUCCAGCGC 20 9455 SCNN1A-5607 UCGAGGUCAGGGCCAGAGGC 20 9456 SCNN1A-5608 + ACGCAGACAGGCAAGGAGGC 20 9457 SCNN1A-5609 + ACCCAGGCCCUGCACGCGGC 20 9458 SCNN1A-5610 + UCCCACUCCCAGGUUGCGGC 20 9459 SCNN1A-5611 + CAAUUAAAGGUGAGCAGGGC 20 9460 SCNN1A-5612 UCCCUGGCCGGCCAGCGGGC 20 9461 SCNN1A-5613 + UGAGAAGGCGGACUCUGGGC 20 9462 SCNN1A-5614 CUGUCGCUUCCAUCCCUGGC 20 9463 SCNN1A-5615 + CCUGGAGCCAGCAGACCUGC 20 9464 SCNN1A-5616 + AAGAGAGAAGAGGUCUCUGC 20 9465 SCNN1A-5617 CCCAACUCCCGCAGGUCUGC 20 9466 SCNN1A-5618 CAGGCUGGGCCUUUGUCUGC 20 9467 SCNN1A-5619 CAGCCUUCCCUGCCGCGUGC 20 9468 SCNN1A-5620 + AAAGCAGGCACUGAAGGUGC 20 9469 SCNN1A-5621 + UUCGUCUGCUCUCUGGGUGC 20 9470 SCNN1A-5622 ACCUUAUCUUAUUGUAUUGC 20 9471 SCNN1A-5623 + UGCUGUGGUCACAGAGUUGC 20 9472 SCNN1A-5624 CCUGGGGCAGAGACAGAAUC 20 9473 SCNN1A-5625 + AGACAGACUCAUGGGGGAUC 20 9474 SCNN1A-5626 ACUCGAAAGGUGGCCCUAUC 20 9475 SCNN1A-410 UUGCUCUCCCCAAUCCACUC 20 4259 SCNN1A-5627 + UAAGUGGGAGCAGCGCACUC 20 9476 SCNN1A-5628 + AAAAGGGCUGGAGGAGACUC 20 9477 SCNN1A-5629 + CACAGGUCAGCCUCACCCUC 20 9478 SCNN1A-5630 CGUGGCCCUCGCGCUGCCUC 20 9479 SCNN1A-411 + UCAGGGUCAAGGCUGAGCUC 20 4260 SCNN1A-5631 + AAAGGCAGUACUCCAGGCUC 20 9480 SCNN1A-5632 + CUCAUGGGGGAUCGGGGCUC 20 9481 SCNN1A-5633 CCCGGUGUGUAUCAAUGCUC 20 9482 SCNN1A-5634 + CCGUGGAUUCGUCUGCUCUC 20 9483 SCNN1A-5635 CUGGAGUUUCUAGGGGUCUC 20 9484 SCNN1A-5636 AUCCCCCAUGAGUCUGUCUC 20 9485 SCNN1A-5637 AGCAGAGAUGACACCUUCUC 20 9486 SCNN1A-5638 UGCCCAGAGUCCGCCUUCUC 20 9487 SCNN1A-5639 UCAGGACACAGCUCGAGGUC 20 9488 SCNN1A-5640 + AAGAAUUGCAAUGCCUGGUC 20 9489 SCNN1A-5641 UAAGCUAGUGGUUGGAUUUC 20 9490 SCNN1A-5642 + AUAAGGAGUGGAGUGCCAAG 20 9491 SCNN1A-412 AUCCAGCUGUCCCUUCCAAG 20 4261 SCNN1A-5643 + CAGACCCGGAGCCCAGGAAG 20 9492 SCNN1A-5644 CUGUGGGGCCCGUGAGGAAG 20 9493 SCNN1A-5645 + UCUCCUCCCCGCUCACUAAG 20 9494 SCNN1A-5646 CGCUAAGUAGAUAGCCCCAG 20 9495 SCNN1A-5647 UUCCAUCCCUGGCCGGCCAG 20 9496 SCNN1A-5648 CAGCUCGAGGUCAGGGCCAG 20 9497 SCNN1A-413 UGGGACAUGGGCAUGGCCAG 20 4262 SCNN1A-414 CAGCCUCACUCGGGUUCCAG 20 4263 SCNN1A-5649 UGGCCCUAUCAGGGAAGCAG 20 9498 SCNN1A-5650 CAACUCUGUGACCACAGCAG 20 9499 SCNN1A-5651 CUCUGGGAUAUGUGGGGCAG 20 9500 SCNN1A-5652 + AGAAGGCGGACUCUGGGCAG 20 9501 SCNN1A-415 + AGACCUGGUAUGGGCUGCAG 20 4264 SCNN1A-5653 CUGAGGGCCUAGAGUGAGAG 20 9502 SCNN1A-5654 + UGCAGCAAAAGGAUAAGGAG 20 9503 SCNN1A-5655 + ACCUUGUCCAGACCCGGGAG 20 9504 SCNN1A-4 CCAUACCAGGUCUCAUGGAG 20  498 SCNN1A-5656 + AAGGGGCCAGCCAGGCUGAG 20 9505 SCNN1A-5657 AGCUGAGGGCCUAGAGUGAG 20 9506 SCNN1A-5658 CGCUGCUCCCACUUAGUGAG 20 9507 SCNN1A-5659 CGCUGCACCUGUCAGGUGAG 20 9508 SCNN1A-5660 + CAAGGGCUAGGGGAGCCUAG 20 9509 SCNN1A-5661 + AGUGUGCUUCCAGGAGCUAG 20 9510 SCNN1A-5662 + ACAUAAGAGCCAAGGGCUAG 20 9511 SCNN1A-5663 AGGGAGACUGGAGUUUCUAG 20 9512 SCNN1A-5664 + CACAACCCAGGCCCUGCACG 20 9513 SCNN1A-5665 + CUGAGCAUUGAUACACACCG 20 9514 SCNN1A-5666 + UCACUCCCACACAGAGCCCG 20 9515 SCNN1A-5667 + CGAAGGAAGGAGGGCUCCCG 20 9516 SCNN1A-5668 CUGCUCCCACUUAGUGAGCG 20 9517 SCNN1A-5669 + AAUUAAAGGUGAGCAGGGCG 20 9518 SCNN1A-5670 CAAGGUUGGAGGGGGUGGCG 20 9519 SCNN1A-5671 UGUGUCCACAGUGUCCUGCG 20 9520 SCNN1A-5672 CAGAAUCAGGACACAGCUCG 20 9521 SCNN1A-5673 CUAGGACAAAACUCGAAAGG 20 9522 SCNN1A-5674 + UUAGACGCAGACAGGCAAGG 20 9523 SCNN1A-5675 + UUCCUCACGGGCCCCACAGG 20 9524 SCNN1A-5676 + UGGGGAACCGGGAGGACAGG 20 9525 SCNN1A-5677 + ACUGAGUGAGUAGAGGCAGG 20 9526 SCNN1A-5678 UAAGUAGAUAGCCCCAGAGG 20 9527 SCNN1A-5679 UGAGGGCCUAGAGUGAGAGG 20 9528 SCNN1A-5680 + AUCCUGAGCCCACAGCUAGG 20 9529 SCNN1A-5681 + AGGUGAAGCUGGGGGCUAGG 20 9530 SCNN1A-5682 + UGAGCAUUGAUACACACCGG 20 9531 SCNN1A-5683 + AUUAAAGGUGAGCAGGGCGG 20 9532 SCNN1A-5684 + CAGGCACUGAAGGUGCAGGG 20 9533 SCNN1A-5685 CUGAGCACCUUAUUGCAGGG 20 9534 SCNN1A-5686 + CAACCUUGUCCAGACCCGGG 20 9535 SCNN1A-5687 AUCCCUGGCCGGCCAGCGGG 20 9536 SCNN1A-5688 + UUAAAGGUGAGCAGGGCGGG 20 9537 SCNN1A-416 CAGCUGUCCCUUCCAAGGGG 20 4265 SCNN1A-5689 CUCCCACUUAGUGAGCGGGG 20 9538 SCNN1A-5690 CUGGACAAGGUUGGAGGGGG 20 9539 SCNN1A-5691 + ACGCCUAGACAGGCCCUGGG 20 9540 SCNN1A-5692 + UUCCUGAGACAGACUCAUGG 20 9541 SCNN1A-5693 AGCUGAGACACAGAUCCUGG 20 9542 SCNN1A-5694 + UCAGACCCAAAAAGGGCUGG 20 9543 SCNN1A-75 + AGCCCUGGAGUGGACUGUGG 20  602 SCNN1A-5695 CUUUGUCUGCUGGCUUGUGG 20 9544 SCNN1A-5696 UGACCUGUGGGUGCCCUUGG 20 9545 SCNN1A-5697 CCGGGUCUGGACAAGGUUGG 20 9546 SCNN1A-5698 + CUUCCUGAGACAGACUCAUG 20 9547 SCNN1A-5699 + CUGAAGGUGCAGGGAGGAUG 20 9548 SCNN1A-5700 CUAGGGGUCUCUGGGAUAUG 20 9549 SCNN1A-5701 + UCCUGGAGCCAGCAGACCUG 20 9550 SCNN1A-5702 CUGAGGGUGAGGCUGACCUG 20 9551 SCNN1A-5703 UCUCUUCUCUGCAGGGCCUG 20 9552 SCNN1A-5704 UUGUGUUGCCCUCCUAGCUG 20 9553 SCNN1A-5705 + CAGGUGCAGCGGCCUGGCUG 20 9554 SCNN1A-5706 + AUGUGUAAUCGCCCCUGCUG 20 9555 SCNN1A-5707 + AGAAUUCUCCUCCUCCUCUG 20 9556 SCNN1A-5708 + UCAGGGUCCAACCUGGUCUG 20 9557 SCNN1A-5709 + AAGGAUAAAUCAGUUUUCUG 20 9558 SCNN1A-5710 CUGGGAUAUGUGGGGCAGUG 20 9559 SCNN1A-417 + UCACCCCUGGAACCCGAGUG 20 4266 SCNN1A-5711 ACGGGCUCUGUGUGGGAGUG 20 9560 SCNN1A-5712 UGCCUCCUGUGGGGCCCGUG 20 9561 SCNN1A-5713 + UGAGUGAGUAGAGGCAGGUG 20 9562 SCNN1A-5714 CUCUGCAGGGCCUGAGGGUG 20 9563 SCNN1A-5715 AGGGGUCUCUGGGAUAUGUG 20 9564 SCNN1A-5716 ACUCUGGGCUGCCUCCUGUG 20 9565 SCNN1A-5717 ACGAAUCCACGGGCUCUGUG 20 9566 SCNN1A-5718 CGUGCAGGGCCUGGGUUGUG 20 9567 SCNN1A-419 + AUGAGCCCCGGAGUGGAUUG 20 4268 SCNN1A-5719 + CAGCAGACCUGCGGGAGUUG 20 9568 SCNN1A-5720 + CUGAGGUUAGAAAACAAAAU 20 9569 SCNN1A-5721 + CUUGAGCCAGGUCCUUACAU 20 9570 SCNN1A-5722 + ACAGCGAAGGACAGAGAGAU 20 9571 SCNN1A-5723 + UACACACCGGGGGAGGAGAU 20 9572 SCNN1A-420 + UCAUGAGCCCCGGAGUGGAU 20 4269 SCNN1A-5724 + CUCUCCUCUGCUUCCCUGAU 20 9573 SCNN1A-421 ACUCGGGUUCCAGGGGUGAU 20 4270 SCNN1A-5725 + AGGAGGAGAAAUUCGUUGAU 20 9574 SCNN1A-79 + CCCUCCAUGAGACCUGGUAU 20  604 SCNN1A-5726 + CUCCCGAGGGCAGGUGAACU 20 9575 SCNN1A-5727 CUAGCUCCUGGAAGCACACU 20 9576 SCNN1A-5728 CUCUCUCCUUGCUCACCACU 20 9577 SCNN1A-5729 + AAAAAGGGCUGGAGGAGACU 20 9578 SCNN1A-5730 + UCCCAGGUUGCGGCUGGACU 20 9579 SCNN1A-5731 UCCCAGUCCAGCCGCAACCU 20 9580 SCNN1A-5732 CCUAGCCCCCAGCUUCACCU 20 9581 SCNN1A-5733 CCCUAGGCUCCCCUAGCCCU 20 9582 SCNN1A-5734 + CACACGCCUAGACAGGCCCU 20 9583 SCNN1A-5735 + UGGGGGCUAGGCGGGGCCCU 20 9584 SCNN1A-5736 ACUCCCAGUUCACCUGCCCU 20 9585 SCNN1A-5737 CCCUGCCGCGUGCAGGGCCU 20 9586 SCNN1A-5738 + UGGGUGCUGGGUUAUCUCCU 20 9587 SCNN1A-5739 UCCUGGAGCCCUGCAGUCCU 20 9588 SCNN1A-5740 + AGGAUCCUGAGCCCACAGCU 20 9589 SCNN1A-5741 UGUGUAUCAAUGCUCAGGCU 20 9590 SCNN1A-5742 + CGCAGACAGGCAAGGAGGCU 20 9591 SCNN1A-5743 + AGACAUAAGAGCCAAGGGCU 20 9592 SCNN1A-5744 + ACAGGUGCAGCGGCCUGGCU 20 9593 SCNN1A-5745 + UCGUCUGCUCUCUGGGUGCU 20 9594 SCNN1A-5746 UGACCACAUUCCUGCACUCU 20 9595 SCNN1A-422 + CAGGGUCAAGGCUGAGCUCU 20 4271 SCNN1A-5747 + CGUGGAUUCGUCUGCUCUCU 20 9596 SCNN1A-5748 UGGAGUUUCUAGGGGUCUCU 20 9597 SCNN1A-5749 + UGCAGGGCUCCAGGAGGUCU 20 9598 SCNN1A-5750 AGCAGAGGAGAGGCCGUUCU 20 9599 SCNN1A-5751 CAAGGGAGACUGGAGUUUCU 20 9600 SCNN1A-5752 + CUCCUCCCCGCUCACUAAGU 20 9601 SCNN1A-5753 UCUGGGAUAUGUGGGGCAGU 20 9602 SCNN1A-5754 UCCAGCCGCAACCUGGGAGU 20 9603 SCNN1A-5755 CUCCCGGGUCUGGACAAGGU 20 9604 SCNN1A-5756 + CUGAGUGAGUAGAGGCAGGU 20 9605 SCNN1A-5757 + UGGGAGCAGCGCACUCAGGU 20 9606 SCNN1A-5758 UGCUGCCUUAAGCUAGUGGU 20 9607 SCNN1A-5759 AGGGAGGAGUGGGAGAAUGU 20 9608 SCNN1A-5760 + UCACAGAGUUGCAGGAAUGU 20 9609 SCNN1A-5761 UAGGGGUCUCUGGGAUAUGU 20 9610 SCNN1A-5762 + UCUGUUCUUUUUUACACUGU 20 9611 SCNN1A-5763 UGAGGGUGAGGCUGACCUGU 20 9612 SCNN1A-5764 CACUCUGGGCUGCCUCCUGU 20 9613 SCNN1A-5765 UGUGUUGCCCUCCUAGCUGU 20 9614 SCNN1A-5766 CGAAUCCACGGGCUCUGUGU 20 9615 SCNN1A-5767 + UUGAGCCAGGUCCUUACAUU 20 9616 SCNN1A-425 + CAUGAGCCCCGGAGUGGAUU 20 4274 SCNN1A-5768 UAGCUCCUGGAAGCACACUU 20 9617 SCNN1A-5769 UCCUGGAGACAGACUCCCUU 20 9618 SCNN1A-5770 CUCGGGAGCCCUCCUUCCUU 20 9619 SCNN1A-5771 UCCUUUUGCUGCAUUAAGUU 20 9620 SCNN1A-5772 + CCAGCAGACCUGCGGGAGUU 20 9621 SCNN1A-5773 UUAAGUUUGGAAAGAGAUUU 20 9622 SCNN1A-5774 AAGCCCAGCUCCGGCACUUU 20 9623 SCNN1A-5775 AGUCUCCUCCAGCCCUUUUU 20 9624

Table 46C provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN9A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene

TABLE 46C 3rd Tier Target DNA Site Seq gRNA Name Strand Targeting Domain Length ID SCNN1A-5776 GGGGGCAGAGACAGAAA 17 9625 SCNN1A-5777 GAGAGGGGGCAAGGCAA 17 9626 SCNN1A-5778 GUAAGGACCUGGCUCAA 17 9627 SCNN1A-5779 GAAGAAGACCAAAGGAA 17 9628 SCNN1A-426 GGACAUGGGCAUGGCCA 17 4275 SCNN1A-427 + GUGGAUUGGGGAGAGCA 17 4276 SCNN1A-5780 GGCAAAUAGAAAAGGCA 17 9629 SCNN1A-5781 + GAGCCCAGGAAGAGGCA 17 9630 SCNN1A-428 + GGGGAGAGCAAGGGUCA 17 4277 SCNN1A-5782 + GGAAGCCUUCCCAGAGA 17 9631 SCNN1A-5783 + GAGGGAGACAAUAGAGA 17 9632 SCNN1A-5784 + GGCCAGCCAGGCUGAGA 17 9633 SCNN1A-5785 GGAAGAAGACCAAAGGA 17 9634 SCNN1A-5786 + GAGGCUGGGGGACAGGA 17 9635 SCNN1A-5787 + GAGAUAGGGAUGGAGGA 17 9636 SCNN1A-5788 GAAAGGUGGAGGAGGGA 17 9637 SCNN1A-5789 + GGACAGAGAGAUAGGGA 17 9638 SCNN1A-5790 + GGGAAAGCAGGCACUGA 17 9639 SCNN1A-5791 + GACAGGAUGGCAGGUGA 17 9640 SCNN1A-5792 + GGGCCUGGGUGGGGAAC 17 9641 SCNN1A-5793 + GGCCUGGGUGGGGAACC 17 9642 SCNN1A-5794 GAAUUUCUCCUCCUCCC 17 9643 SCNN1A-5795 + GAGGAGGAGUCAGAGCC 17 9644 SCNN1A-5796 + GCCAGGCUGAGAGGGCC 17 9645 SCNN1A-429 GGGACAUGGGCAUGGCC 17 4278 SCNN1A-5797 GCCUCUUCCUGGGCUCC 17 9646 SCNN1A-5798 GCAGGUCUGCUGGCUCC 17 9647 SCNN1A-5799 + GAAGAGGCAGGGAAAGC 17 9648 SCNN1A-5800 GCCAGAAAGAGGAGAGC 17 9649 SCNN1A-86 GAACAAGCUGGAGGAGC 17 531 SCNN1A-5801 GGAUUUCAGGCAUGAGC 17 9650 SCNN1A-5802 GCUCCCACUUAGUGAGC 17 9651 SCNN1A-5803 + GGAGCCCAGGAAGAGGC 17 9652 SCNN1A-5804 GGGAGAGGAAGAGAGGC 17 9653 SCNN1A-5805 GAGAGGGAGUGAGAGGC 17 9654 SCNN1A-5806 GAUUAGAGAGAGGAGGC 17 9655 SCNN1A-5807 GGCUUGUGGAGGGAGGC 17 9656 SCNN1A-5808 + GGAGGGCUCCCGAGGGC 17 9657 SCNN1A-5809 GGCCCUCUCAGCCUGGC 17 9658 SCNN1A-5810 + GAGGCAGCCCAGAGUGC 17 9659 SCNN1A-5811 + GAAUUCUCCUCCUCCUC 17 9660 SCNN1A-430 + GGGUCAAGGCUGAGCUC 17 4279 SCNN1A-5812 GGAGGCAGGCCAGAAAG 17 9661 SCNN1A-5813 + GACAGGAGGGCAGAAAG 17 9662 SCNN1A-5814 + GGCAACACAAGGAGAAG 17 9663 SCNN1A-5815 GGGGGGGAGAGGAAGAG 17 9664 SCNN1A-5816 + GGUGAGCAAGGAGAGAG 17 9665 SCNN1A-5817 GAGGCAGGAUUAGAGAG 17 9666 SCNN1A-5818 GAGGAGGGAGGGAGGAG 17 9667 SCNN1A-5819 + GAGCAGGGCGGGGGGAG 17 9668 SCNN1A-5820 + GGGCCAGCCAGGCUGAG 17 9669 SCNN1A-5821 GAUAGAGAGGGAGUGAG 17 9670 SCNN1A-5822 GGUUGGAGGGGGUGGCG 17 9671 SCNN1A-5823 GCUGGCUCCAGGAAAGG 17 9672 SCNN1A-5824 GAGGGGGCAAGGCAAGG 17 9673 SCNN1A-5825 + GACUGCAGGGCUCCAGG 17 9674 SCNN1A-5826 + GAGUGAGUAGAGGCAGG 17 9675 SCNN1A-5827 + GAGCAAGGAGAGAGAGG 17 9676 SCNN1A-5828 GCAGGAUUAGAGAGAGG 17 9677 SCNN1A-5829 GAGGAGGGACCAGGAGG 17 9678 SCNN1A-5830 GAUAGCCCCAGAGGAGG 17 9679 SCNN1A-5831 + GGGGGGAGGGGCUGAGG 17 9680 SCNN1A-5832 GCACCUGUCAGGUGAGG 17 9681 SCNN1A-5833 GGCAGAGACAGAAAGGG 17 9682 SCNN1A-5834 + GCUGGAAAGGAAGAGGG 17 9683 SCNN1A-5835 GGAAAGGUGGAGGAGGG 17 9684 SCNN1A-5836 GGGGGCAAGGCAAGGGG 17 9685 SCNN1A-5837 GACAAGGUUGGAGGGGG 17 9686 SCNN1A-5838 + GUGAGCAGGGCGGGGGG 17 9687 SCNN1A-5839 + GGCUGAGAGGGCCUGGG 17 9688 SCNN1A-5840 + GAGUAGAGGCAGGUGGG 17 9689 SCNN1A-5841 GGCCUGGGUUGUGUGGG 17 9690 SCNN1A-431 GAAGGGGAACAAGCUGG 17 4280 SCNN1A-85 GGAGGGGAACAAGCUGG 17 530 SCNN1A-5842 + GGCCCAGGUGAAGCUGG 17 9691 SCNN1A-5843 GGCUCCAGGAAAGGUGG 17 9692 SCNN1A-5844 + GUGGGGGGCAGUGGUGG 17 9693 SCNN1A-5845 GGAGGAGUGGGAGAAUG 17 9694 SCNN1A-5846 GGAGCCCUGCAGUCCUG 17 9695 SCNN1A-5847 + GGGCCCAGGUGAAGCUG 17 9696 SCNN1A-5848 GCCAGAGGCUGGAGCUG 17 9697 SCNN1A-5849 + GACAGGCAAGGAGGCUG 17 9698 SCNN1A-5850 + GGCGGGGGGAGGGGCUG 17 9699 SCNN1A-5851 GGAUAUGUGGGGCAGUG 17 9700 SCNN1A-5852 GGCUCUGUGUGGGAGUG 17 9701 SCNN1A-5853 + GGACAGGAUGGCAGGUG 17 9702 SCNN1A-5854 + GGUGGGGGGCAGUGGUG 17 9703 SCNN1A-5855 GCAGGGCCUGGGUUGUG 17 9704 SCNN1A-5856 GCUCCUGGAAGCACACU 17 9705 SCNN1A-5857 + GGGGCCCAGGUGAAGCU 17 9706 SCNN1A-5858 GAAGCCACAGACCAGGU 17 9707 SCNN1A-5859 + GCUGAGAGGGCCUGGGU 17 9708 SCNN1A-5860 GAGGAGUGGGAGAAUGU 17 9709 SCNN1A-5861 GAGGGGGAGGAGAGGUU 17 9710 SCNN1A-5862 + GCCUUCUGUUUCUCUUU 17 9711 SCNN1A-5863 GAAGGGGGCAGAGACAGAAA 20 9712 SCNN1A-432 + GAGUGGAUUGGGGAGAGCAA 20 4281 SCNN1A-5864 GGAAGGGGGCAGAGACAGAA 20 9713 SCNN1A-5865 GAGGAAGAAGACCAAAGGAA 20 9714 SCNN1A-5866 GAGACCUUUUCACAGAGCCA 20 9715 SCNN1A-9 GCCCUCCACAGUCCACUCCA 20 499 SCNN1A-5867 GCAACUCUGUGACCACAGCA 20 9716 SCNN1A-433 + GGAGUGGAUUGGGGAGAGCA 20 4282 SCNN1A-5868 GAGUGAGAGGGGGCAAGGCA 20 9717 SCNN1A-5869 + GGAAAGGAAGAGGGUGGGCA 20 9718 SCNN1A-5870 + GUCUCUGCCCCAGGACUGCA 20 9719 SCNN1A-434 + GAGAGCAAGGGUCAGGGUCA 20 4283 SCNN1A-5871 GAGACCCAAAGAGAAACAGA 20 9720 SCNN1A-435 GUUCCAGGGGUGAUGGGAGA 20 4284 SCNN1A-5872 + GAAGGAAGGAGGGCUCCCGA 20 9721 SCNN1A-5873 GGAGGAAGAAGACCAAAGGA 20 9722 SCNN1A-5874 + GGGGAACCGGGAGGACAGGA 20 9723 SCNN1A-5875 GGAAUCAGCAGGAAAGAGGA 20 9724 SCNN1A-5876 + GUGAGCAAGGAGAGAGAGGA 20 9725 SCNN1A-5877 GCUCCAGGAAAGGUGGAGGA 20 9726 SCNN1A-5878 + GAAGGACAGAGAGAUAGGGA 20 9727 SCNN1A-5879 + GCAGGGAAAGCAGGCACUGA 20 9728 SCNN1A-5880 GGGCCAGAGGCUGGAGCUGA 20 9729 SCNN1A-5881 + GGGGACAGGAUGGCAGGUGA 20 9730 SCNN1A-5882 + GAGAGCCACCCACACAACCC 20 9731 SCNN1A-5883 + GCCUCCAGCUUCCCACUCCC 20 9732 SCNN1A-5884 GGGAGUGAGGGAGGCCUUCC 20 9733 SCNN1A-5885 + GGGAGGGGCCCAGGUGAAGC 20 9734 SCNN1A-5886 + GGCUGAGGAGGAGUCAGAGC 20 9735 SCNN1A-7 GGGGAACAAGCUGGAGGAGC 20 504 SCNN1A-5887 + GGGGCCAAAAGUGCCGGAGC 20 9736 SCNN1A-5888 GUUGGAUUUCAGGCAUGAGC 20 9737 SCNN1A-5889 GGGGGGAGAGGAAGAGAGGC 20 9738 SCNN1A-5890 + GGCACUGAGUGAGUAGAGGC 20 9739 SCNN1A-5891 GCUGGCUUGUGGAGGGAGGC 20 9740 SCNN1A-5892 + GGUGAAGCUGGGGGCUAGGC 20 9741 SCNN1A-5893 GUGACCACAUUCCUGCACUC 20 9742 SCNN1A-5894 + GAGGACAGGAGGGCAGAAAG 20 9743 SCNN1A-5895 + GAGGGCAACACAAGGAGAAG 20 9744 SCNN1A-5896 + GAAAGAGGGAGACAAUAGAG 20 9745 SCNN1A-5897 GUGGAGGAGGGAGGGAGGAG 20 9746 SCNN1A-5898 + GAGAGAUAGGGAUGGAGGAG 20 9747 SCNN1A-5899 + GGUGAGCAGGGCGGGGGGAG 20 9748 SCNN1A-5900 GGGCAAGGCAAGGGGGGGAG 20 9749 SCNN1A-436 GGUUCCAGGGGUGAUGGGAG 20 4285 SCNN1A-5901 GCAGAUAGAGAGGGAGUGAG 20 9750 SCNN1A-5902 + GGGACAGGAUGGCAGGUGAG 20 9751 SCNN1A-5903 GGAAGAAGACCAAAGGAAGG 20 9752 SCNN1A-5904 + GGUGAGCAAGGAGAGAGAGG 20 9753 SCNN1A-5905 GAGGCAGGAUUAGAGAGAGG 20 9754 SCNN1A-5906 GGCUCCAGGAAAGGUGGAGG 20 9755 SCNN1A-5907 + GGCGGGGGGAGGGGCUGAGG 20 9756 SCNN1A-5908 GCUGCACCUGUCAGGUGAGG 20 9757 SCNN1A-5909 GGGGGCAGAGACAGAAAGGG 20 9758 SCNN1A-5910 GAGAGGGGGCAAGGCAAGGG 20 9759 SCNN1A-5911 GAAAGGUGGAGGAGGGAGGG 20 9760 SCNN1A-5912 GUCUGCUGGCUUGUGGAGGG 20 9761 SCNN1A-5913 GCUCUGUGUGGGAGUGAGGG 20 9762 SCNN1A-5914 GCACCUGUCAGGUGAGGGGG 20 9763 SCNN1A-5915 + GGACAGAGAGAUAGGGAUGG 20 9764 SCNN1A-5916 + GAGUGAGUAGAGGCAGGUGG 20 9765 SCNN1A-5917 GAGGGAGGAGUGGGAGAAUG 20 9766 SCNN1A-5918 + GAGGGGCCCAGGUGAAGCUG 20 9767 SCNN1A-5919 + GCAGACAGGCAAGGAGGCUG 20 9768 SCNN1A-5920 + GGGGGACAGGAUGGCAGGUG 20 9769 SCNN1A-5921 + GCAGGUGGGGGGCAGUGGUG 20 9770 SCNN1A-5922 + GUCUGUGGCUUCCUCUCUUG 20 9771 SCNN1A-5923 + GGAGGGGCCCAGGUGAAGCU 20 9772 SCNN1A-5924 + GGGCCAAAAGUGCCGGAGCU 20 9773 SCNN1A-5925 GAGACAGAAAGGGAGGUGCU 20 9774 SCNN1A-5926 GCAGAGAUGACACCUUCUCU 20 9775 SCNN1A-5927 + GAGCUAGAGGCUCAGCAAGU 20 9776 SCNN1A-5928 + GGCAGGUGGGGGGCAGUGGU 20 9777 SCNN1A-5929 GGUGAGGGGGAGGAGAGGUU 20 9778 SCNN1A-437 GUAAGCAAGGGAACCUGGUU 20 4286

Table 46D provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene

TABLE 46D 4th Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID SCNN1A-5930 + AGAAUCAGACCCAAAAA 17 9779 SCNN1A-5931 + AAAGAUUGUCUUUAAAA 17 9780 SCNN1A-5932 + CAGGCAAAGAAGAGAAA 17 9781 SCNN1A-5933 + UCCUUGGCUCUGUGAAA 17 9782 SCNN1A-5934 + CACAAGCCAGCAGACAA 17 9783 SCNN1A-5935 UGGAGGAAGAAGACCAA 17 9784 SCNN1A-5936 + UCCAGGAAGGAGAGCAA 17 9785 SCNN1A-438 + UGGAUUGGGGAGAGCAA 17 4287 SCNN1A-5937 + AAUAGUUUUCAUAUCAA 17 9786 SCNN1A-5938 AGGGGGCAGAGACAGAA 17 9787 SCNN1A-5939 AAUUUCUCCUCCUCCCA 17 9788 SCNN1A-439 UCCAGCUGUCCCUUCCA 17 4288 SCNN1A-5940 + CUCCAGGAAGGAGAGCA 17 9789 SCNN1A-5941 UAGAGUGAGAGGGGGCA 17 9790 SCNN1A-440 AGGGUGGGACAUGGGCA 17 4289 SCNN1A-5942 + AAGGCGGACUCUGGGCA 17 9791 SCNN1A-5943 + AAGGAAGAGGGUGGGCA 17 9792 SCNN1A-5944 + UCUGCCCCAGGACUGCA 17 9793 SCNN1A-5945 CUUCUCUCUUCUCUGCA 17 9794 SCNN1A-5946 + AAAUAGUUUUCAUAUCA 17 9795 SCNN1A-441 + AGCAAGGGUCAGGGUCA 17 4290 SCNN1A-5947 + ACAGGAGGGCAGAAAGA 17 9796 SCNN1A-5948 ACCCAAAGAGAAACAGA 17 9797 SCNN1A-5949 CAGAAGGCAGAUAGAGA 17 9798 SCNN1A-443 CCAGGGGUGAUGGGAGA 17 4292 SCNN1A-5950 + AGAUCUGAACAAGUAGA 17 9799 SCNN1A-5951 + AUAGAGAGGGACAGCGA 17 9800 SCNN1A-5952 AUCAGCAGGAAAGAGGA 17 9801 SCNN1A-5953 + AGCAAGGAGAGAGAGGA 17 9802 SCNN1A-5954 CCAGGAAAGGUGGAGGA 17 9803 SCNN1A-5955 CUGAUUUAUCCUUGGGA 17 9804 SCNN1A-155 + CUGGAGUGGACUGUGGA 17 652 SCNN1A-5956 UUCUCUGCAGGGCCUGA 17 9805 SCNN1A-5957 CCAGAGGCUGGAGCUGA 17 9806 SCNN1A-5958 + UGCAAUACAAUAAGAUA 17 9807 SCNN1A-5959 + AAUGCAGCAAAAGGAUA 17 9808 SCNN1A-5960 + CCUCUGCUUCCCUGAUA 17 9809 SCNN1A-444 + UGGGCUGCAGAGGUCUA 17 4293 SCNN1A-5961 + CAAGGAGGCUGGGGGAC 17 9810 SCNN1A-5962 + AACCAGGAUUCCAAACC 17 9811 SCNN1A-445 AGGUAAGCAAGGGAACC 17 4294 SCNN1A-5963 + CGGGGCUCAGGUGCACC 17 9812 SCNN1A-5964 UAGCCCCCAGCUUCACC 17 9813 SCNN1A-5965 + CACUGUGGACACAGACC 17 9814 SCNN1A-5966 AGAGGAAGCCACAGACC 17 9815 SCNN1A-5967 AGGAAAGAGGAGGGACC 17 9816 SCNN1A-5968 + AGCCACCCACACAACCC 17 9817 SCNN1A-446 + CCCUCUCCCAUCACCCC 17 4295 SCNN1A-151 + UUCCCCUUCAUGAGCCC 17 648 SCNN1A-5969 + CACGCCUAGACAGGCCC 17 9818 SCNN1A-5970 + UCCAGCUUCCCACUCCC 17 9819 SCNN1A-5971 UCACCUGGGCCCCUCCC 17 9820 SCNN1A-5972 + ACCUGGAUGUGAAAGCC 17 9821 SCNN1A-5973 UUUGAGAUCAAACAGCC 17 9822 SCNN1A-5974 + AGGAGAAGGGGCCAGCC 17 9823 SCNN1A-5975 CCCAGGCCCUCUCAGCC 17 9824 SCNN1A-5976 + CUGUUGGCUGCCAGGCC 17 9825 SCNN1A-5977 AUUACACAUUCCUGGCC 17 9826 SCNN1A-5978 AACCUGGUUUGGAAUCC 17 9827 SCNN1A-5979 AGGCAGCCCAGACCUCC 17 9828 SCNN1A-5980 CUGCCCUCCUGUCCUCC 17 9829 SCNN1A-5981 + CAGGACUGCAGGGCUCC 17 9830 SCNN1A-5982 CUGGAGCCCUGCAGUCC 17 9831 SCNN1A-5983 AGUGAGGGAGGCCUUCC 17 9832 SCNN1A-5984 CCCCUUGCUCUCCUUCC 17 9833 SCNN1A-5985 CUUUCCCUGCCUCUUCC 17 9834 SCNN1A-5986 + CCCUCCUCCACCUUUCC 17 9835 SCNN1A-5987 ACCUGGGAGUGGGAAGC 17 9836 SCNN1A-5988 + UGAGGAGGAGUCAGAGC 17 9837 SCNN1A-5989 AGGUCAGGGCCAGAGGC 17 9838 SCNN1A-5990 + CAGACAGGCAAGGAGGC 17 9839 SCNN1A-5991 + CUGGGGGACAGGAUGGC 17 9840 SCNN1A-5992 + CUCUGCCCCAGGACUGC 17 9841 SCNN1A-5993 UCUUCUCUCUUCUCUGC 17 9842 SCNN1A-5994 ACCACAUUCCUGCACUC 17 9843 SCNN1A-5995 + AGGGCUGGAGGAGACUC 17 9844 SCNN1A-5996 + CCCUCAGCUCCAGCCUC 17 9845 SCNN1A-5997 UGCCUCUUCCUGGGCUC 17 9846 SCNN1A-5998 + CAGGGCUCCAGGAGGUC 17 9847 SCNN1A-5999 UGGGCCCCUCCCGGGUC 17 9848 SCNN1A-6000 + UCCUGCUCUCCUCUUUC 17 9849 SCNN1A-6001 AGGAAUCAGCAGGAAAG 17 9850 SCNN1A-6002 + CCAGGAAGGAGAGCAAG 17 9851 SCNN1A-6003 AGAGGGGGCAAGGCAAG 17 9852 SCNN1A-6004 + UGCAGAGAAGAGAGAAG 17 9853 SCNN1A-6005 AAGAAGACCAAAGGAAG 17 9854 SCNN1A-6006 + AGGCAGGUGGGGGGCAG 17 9855 SCNN1A-6007 + AGAGGGAGACAAUAGAG 17 9856 SCNN1A-6008 ACAGAAGGCAGAUAGAG 17 9857 SCNN1A-6009 + AGCAAAAGGAUAAGGAG 17 9858 SCNN1A-6010 UCAGGGAAGCAGAGGAG 17 9859 SCNN1A-6011 CAGGUGAGGGGGAGGAG 17 9860 SCNN1A-6012 + AGAUAGGGAUGGAGGAG 17 9861 SCNN1A-448 UCCAGGGGUGAUGGGAG 17 4297 SCNN1A-83 UACCAGGUCUCAUGGAG 17 606 SCNN1A-6013 + ACAGGAUGGCAGGUGAG 17 9862 SCNN1A-6014 UGCACCUGUCAGGUGAG 17 9863 SCNN1A-6015 + AAGCUGGGGGCUAGGCG 17 9864 SCNN1A-6016 + CAGGAAGGAGAGCAAGG 17 9865 SCNN1A-6017 + UACUGGACCUGAGAAGG 17 9866 SCNN1A-6018 AGAAGACCAAAGGAAGG 17 9867 SCNN1A-6019 AAAGAGGAGGGACCAGG 17 9868 SCNN1A-6020 AAUCAGCAGGAAAGAGG 17 9869 SCNN1A-6021 + AGACAGGCCCUGGGAGG 17 9870 SCNN1A-6022 + AGAGAUAGGGAUGGAGG 17 9871 SCNN1A-6023 UCCAGGAAAGGUGGAGG 17 9872 SCNN1A-6024 CUGGACAAGGUUGGAGG 17 9873 SCNN1A-6025 + CUGAGCCCACAGCUAGG 17 9874 SCNN1A-6026 + UGAAGCUGGGGGCUAGG 17 9875 SCNN1A-6027 + AGGAAGGAGAGCAAGGG 17 9876 SCNN1A-6028 AGGGGGCAAGGCAAGGG 17 9877 SCNN1A-6029 AAAUAGAAAAGGCAGGG 17 9878 SCNN1A-6030 AGGUGGAGGAGGGAGGG 17 9879 SCNN1A-6031 UGCUGGCUUGUGGAGGG 17 9880 SCNN1A-6032 CUGUGUGGGAGUGAGGG 17 9881 SCNN1A-6033 CCUGUCAGGUGAGGGGG 17 9882 SCNN1A-6034 + CAGAGAGAUAGGGAUGG 17 9883 SCNN1A-6035 UGGGAGUGGGAAGCUGG 17 9884 SCNN1A-6036 + ACAGGCAAGGAGGCUGG 17 9885 SCNN1A-6037 + CAGGUGGGGGGCAGUGG 17 9886 SCNN1A-6038 + UGAGUAGAGGCAGGUGG 17 9887 SCNN1A-154 + CCUGGAGUGGACUGUGG 17 651 SCNN1A-6039 + CCCAGAGUGCAGGAAUG 17 9888 SCNN1A-6040 + AAGGUGCAGGGAGGAUG 17 9889 SCNN1A-153 + AGCCCUGGAGUGGACUG 17 650 SCNN1A-6041 + UGGAGCCAGCAGACCUG 17 9890 SCNN1A-6042 AGGGUGAGGCUGACCUG 17 9891 SCNN1A-6043 CUUCUCUGCAGGGCCUG 17 9892 SCNN1A-6044 CUCUGGGCUGCCUCCUG 17 9893 SCNN1A-6045 + AUUCUCCUCCUCCUCUG 17 9894 SCNN1A-6046 UGCAGGGCCUGAGGGUG 17 9895 SCNN1A-6047 + CUGAGAGGGCCUGGGUG 17 9896 SCNN1A-6048 CUGGGCUGCCUCCUGUG 17 9897 SCNN1A-6049 CUUUGUCUGCUGGCUUG 17 9898 SCNN1A-6050 + UUCCCACUCCCAGGUUG 17 9899 SCNN1A-6051 + AGGUUAGAAAACAAAAU 17 9900 SCNN1A-449 CCAGGGGCAGCCUCACU 17 4298 SCNN1A-6052 + AAGGGCUGGAGGAGACU 17 9901 SCNN1A-6053 UCCUGCAGUGAGCCCCU 17 9902 SCNN1A-450 + CUCAUGAUACCUCCCCU 17 4299 SCNN1A-6054 CCCAGUUCACCUGCCCU 17 9903 SCNN1A-6055 + CCAGGCUGAGAGGGCCU 17 9904 SCNN1A-6056 UGGAGCCCUGCAGUCCU 17 9905 SCNN1A-6057 AAAGAACAGAAUGUCCU 17 9906 SCNN1A-6058 UUUCCCUGCCUCUUCCU 17 9907 SCNN1A-6059 + AGACAGGCAAGGAGGCU 17 9908 SCNN1A-6060 + AGGUGAAGCUGGGGGCU 17 9909 SCNN1A-6061 ACAGAAAGGGAGGUGCU 17 9910 SCNN1A-6062 + UCUGCUCUCUGGGUGCU 17 9911 SCNN1A-6063 + AAUUCUCCUCCUCCUCU 17 9912 SCNN1A-6064 CCUCCCAGGGCCUGUCU 17 9913 SCNN1A-6065 AGGAGGGAGGGAGGAGU 17 9914 SCNN1A-6066 + CUGGAAAGGAAGAGGGU 17 9915 SCNN1A-6067 + AGGUGGGGGGCAGUGGU 17 9916 SCNN1A-6068 CAGGGCCUGGGUUGUGU 17 9917 SCNN1A-6069 AAAACUGAUUUAUCCUU 17 9918 SCNN1A-6070 + UCUCUGCCCCCUUCCUU 17 9919 SCNN1A-6071 + UGCCUUCUGUUUCUCUU 17 9920 SCNN1A-6072 AGUUUGGAAAGAGAUUU 17 9921 SCNN1A-6073 + CAGAGAAUCAGACCCAAAAA 20 9922 SCNN1A-6074 + UUAAAAGAUUGUCUUUAAAA 20 9923 SCNN1A-6075 + UCCAAACUUAAUGCAGCAAA 20 9924 SCNN1A-6076 + UAGCAGGCAAAGAAGAGAAA 20 9925 SCNN1A-6077 AGUCUGUCUCAGGAAGUAAA 20 9926 SCNN1A-6078 + CUCCACAAGCCAGCAGACAA 20 9927 SCNN1A-6079 AGUGAGAGGGGGCAAGGCAA 20 9928 SCNN1A-451 UCCACUCCGGGGCUCAUGAA 20 4300 SCNN1A-6080 ACGAAUUUCUCCUCCUCCCA 20 9929 SCNN1A-6081 + ACCACUAGCUUAAGGCAGCA 20 9930 SCNN1A-452 CGCAGGGUGGGACAUGGGCA 20 4301 SCNN1A-6082 CCUCUUCUCUCUUCUCUGCA 20 9931 SCNN1A-6083 + UACUUCCUGAGACAGACUCA 20 9932 SCNN1A-6084 CAGGACACAGCUCGAGGUCA 20 9933 SCNN1A-6085 + AGGACAGGAGGGCAGAAAGA 20 9934 SCNN1A-6086 + UCAGGAAGCCUUCCCAGAGA 20 9935 SCNN1A-6087 + AAAGAGGGAGACAAUAGAGA 20 9936 SCNN1A-6088 AAACAGAAGGCAGAUAGAGA 20 9937 SCNN1A-6089 + AGGAGGGCAACACAAGGAGA 20 9938 SCNN1A-6090 + AGGGGCCAGCCAGGCUGAGA 20 9939 SCNN1A-6091 + CAGUGGUGGGGGCAAAUAGA 20 9940 SCNN1A-6092 + CAAAGAUCUGAACAAGUAGA 20 9941 SCNN1A-6093 + AAGGAGGCUGGGGGACAGGA 20 9942 SCNN1A-6094 + AGAGAGAUAGGGAUGGAGGA 20 9943 SCNN1A-6095 CAGGAAAGGUGGAGGAGGGA 20 9944 SCNN1A-6096 + AGGUGAGCAGGGCGGGGGGA 20 9945 SCNN1A-6097 + CAGCGAAGGACAGAGAGAUA 20 9946 SCNN1A-6098 + CUUAAUGCAGCAAAAGGAUA 20 9947 SCNN1A-6099 + CCAAGGGCUAGGGGAGCCUA 20 9948 SCNN1A-6100 AAAAAGAACAGAAUGUCCUA 20 9949 SCNN1A-6101 + AGAGGGCCUGGGUGGGGAAC 20 9950 SCNN1A-6102 + AGGCAAGGAGGCUGGGGGAC 20 9951 SCNN1A-6103 + UCUCCUCCCCCUCACCUGAC 20 9952 SCNN1A-6104 AAGAGAGGAAGCCACAGACC 20 9953 SCNN1A-77 + UUGUUCCCCUCCAUGAGACC 20 603 SCNN1A-6105 + CAAUAAGGUGCUCAGCACCC 20 9954 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20 599 SCNN1A-6106 + UCCAGACCCGGGAGGGGCCC 20 9955 SCNN1A-6107 + UGCACCUGGAUGUGAAAGCC 20 9956 SCNN1A-6108 CCACCCAGGCCCUCUCAGCC 20 9957 SCNN1A-6109 + AGCCCGCCCGCUGGCCGGCC 20 9958 SCNN1A-6110 + CCAGCCAGGCUGAGAGGGCC 20 9959 SCNN1A-6111 + UCCUUUGGUCUUCUUCCUCC 20 9960 SCNN1A-6112 + CCCCAGGACUGCAGGGCUCC 20 9961 SCNN1A-6113 CCUGCCUCUUCCUGGGCUCC 20 9962 SCNN1A-6114 CUCCUGGAGCCCUGCAGUCC 20 9963 SCNN1A-6115 CUGCUUUCCCUGCCUCUUCC 20 9964 SCNN1A-6116 + CCUCCCUCCUCCACCUUUCC 20 9965 SCNN1A-6117 + CAGGAAGAGGCAGGGAAAGC 20 9966 SCNN1A-6118 + CGACUUCUUAAAGUGAAAGC 20 9967 SCNN1A-6119 CAGGCCAGAAAGAGGAGAGC 20 9968 SCNN1A-6120 + AGGGAGGAUGUGGCCAGCGC 20 9969 SCNN1A-6121 AGCUGGCAAAUAGAAAAGGC 20 9970 SCNN1A-6122 + CCCGGAGCCCAGGAAGAGGC 20 9971 SCNN1A-6123 AUAGAGAGGGAGUGAGAGGC 20 9972 SCNN1A-6124 CAGGAUUAGAGAGAGGAGGC 20 9973 SCNN1A-6125 + AGGCUGGGGGACAGGAUGGC 20 9974 SCNN1A-6126 CCAGGCCCUCUCAGCCUGGC 20 9975 SCNN1A-6127 + UGGGGAGCCCGCCCGCUGGC 20 9976 SCNN1A-6128 + UGUCUCUGCCCCAGGACUGC 20 9977 SCNN1A-6129 ACCUCUUCUCUCUUCUCUGC 20 9978 SCNN1A-6130 + CAGGAGGCAGCCCAGAGUGC 20 9979 SCNN1A-6131 AGACAGACUCCCUUUGGUGC 20 9980 SCNN1A-6132 CUCCCAGUUCACCUGCCCUC 20 9981 SCNN1A-6133 + AGGCCCUCAGCUCCAGCCUC 20 9982 SCNN1A-6134 + UCAGAAUUCUCCUCCUCCUC 20 9983 SCNN1A-6135 CCCUGCCUCUUCCUGGGCUC 20 9984 SCNN1A-6136 + CUGCAGGGCUCCAGGAGGUC 20 9985 SCNN1A-6137 ACCUGGGCCCCUCCCGGGUC 20 9986 SCNN1A-6138 + CUCUCCUGCUCUCCUCUUUC 20 9987 SCNN1A-6139 AGAGGAGGCAGGCCAGAAAG 20 9988 SCNN1A-6140 + UCUCCAGGAAGGAGAGCAAG 20 9989 SCNN1A-6141 + CCCUGCAGAGAAGAGAGAAG 20 9990 SCNN1A-6142 AGGAAGAAGACCAAAGGAAG 20 9991 SCNN1A-453 CCACUCCGGGGCUCAUGAAG 20 4302 SCNN1A-6143 + UAGAGGCAGGUGGGGGGCAG 20 9992 SCNN1A-6144 + CCCUCACCUGACAGGUGCAG 20 9993 SCNN1A-6145 CAAGGGGGGGAGAGGAAGAG 20 9994 SCNN1A-6146 + AGUGGUGAGCAAGGAGAGAG 20 9995 SCNN1A-6147 AGAGAGGCAGGAUUAGAGAG 20 9996 SCNN1A-6148 CUAUCAGGGAAGCAGAGGAG 20 9997 SCNN1A-6149 UGUCAGGUGAGGGGGAGGAG 20 9998 SCNN1A-454 + CCCCUUCAUGAGCCCCGGAG 20 4303 SCNN1A-6150 UCUGCUGGCUCCAGGAAAGG 20 9999 SCNN1A-6151 + CUCCAGGAAGGAGAGCAAGG 20 10000 SCNN1A-6152 UGAGAGGGGGCAAGGCAAGG 20 10001 SCNN1A-6153 AGGAAAGAGGAGGGACCAGG 20 10002 SCNN1A-6154 + CAGGACUGCAGGGCUCCAGG 20 10003 SCNN1A-6155 AGGAAUCAGCAGGAAAGAGG 20 10004 SCNN1A-6156 AAAGAGGAGGGACCAGGAGG 20 10005 SCNN1A-6157 + CCUAGACAGGCCCUGGGAGG 20 10006 SCNN1A-6158 + CAGAGAGAUAGGGAUGGAGG 20 10007 SCNN1A-6159 + UCCAGGAAGGAGAGCAAGGG 20 10008 SCNN1A-6160 + UCAAUUAAAGGUGAGCAGGG 20 10009 SCNN1A-6161 + AGCGCUGGAAAGGAAGAGGG 20 10010 SCNN1A-6162 CCAGGAAAGGUGGAGGAGGG 20 10011 SCNN1A-6163 AGAGGGGGCAAGGCAAGGGG 20 10012 SCNN1A-6164 + AAGGUGAGCAGGGCGGGGGG 20 10013 SCNN1A-6165 + CCAGGCUGAGAGGGCCUGGG 20 10014 SCNN1A-6166 + AGUGAGUAGAGGCAGGUGGG 20 10015 SCNN1A-6167 CAGGGCCUGGGUUGUGUGGG 20 10016 SCNN1A-455 CAUGAAGGGGAACAAGCUGG 20 4304 SCNN1A-6 CAUGGAGGGGAACAAGCUGG 20 558 SCNN1A-6168 ACCUGGGAGUGGGAAGCUGG 20 10017 SCNN1A-6169 + AGGGGCCCAGGUGAAGCUGG 20 10018 SCNN1A-6170 + CAGACAGGCAAGGAGGCUGG 20 10019 SCNN1A-6171 + AGGCAGGUGGGGGGCAGUGG 20 10020 SCNN1A-6172 + CAGGUGGGGGGCAGUGGUGG 20 10021 SCNN1A-6173 + CAGCCCAGAGUGCAGGAAUG 20 10022 SCNN1A-6174 CCUGGAGCCCUGCAGUCCUG 20 10023 SCNN1A-6175 AGGGCCAGAGGCUGGAGCUG 20 10024 SCNN1A-6176 + CAGGGCGGGGGGAGGGGCUG 20 10025 SCNN1A-6177 + AGGCUGAGAGGGCCUGGGUG 20 10026 SCNN1A-6178 + AGCUUCCCACUCCCAGGUUG 20 10027 SCNN1A-6179 + ACUUCCUGAGACAGACUCAU 20 10028 SCNN1A-456 UGGCCAGGGGCAGCCUCACU 20 4305 SCNN1A-457 + CUGCUCAUGAUACCUCCCCU 20 4306 SCNN1A-6180 + CAGCCAGGCUGAGAGGGCCU 20 10029 SCNN1A-6181 UCAGAAAACUGAUUUAUCCU 20 10030 SCNN1A-6182 AAAAAAGAACAGAAUGUCCU 20 10031 SCNN1A-6183 UGCUUUCCCUGCCUCUUCCU 20 10032 SCNN1A-6184 + CCCAGGUGAAGCUGGGGGCU 20 10033 SCNN1A-6185 + CAGAAUUCUCCUCCUCCUCU 20 10034 SCNN1A-6186 CCUCCUCCCAGGGCCUGUCU 20 10035 SCNN1A-6187 UGGAGGAGGGAGGGAGGAGU 20 10036 SCNN1A-6188 + CAGGCUGAGAGGGCCUGGGU 20 10037 SCNN1A-6189 CAGAAAACUGAUUUAUCCUU 20 10038 SCNN1A-6190 + CUGUCUCUGCCCCCUUCCUU 20 10039 SCNN1A-6191 + AUCUGCCUUCUGUUUCUCUU 20 10040 SCNN1A-6192 + UCUGCCUUCUGUUUCUCUUU 20 10041

Table 46E provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the fifth tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. pyogenes eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 46E 5th Tier Target Site gRNA Name DNA Strand Targeting Domain Length Seq ID SCNN1A-6193 GAAAAUAAAAGCAAAAA 17 10042 SCNN1A-6194 AAAGAUCAUCUUUAAAA 17 10043 SCNN1A-6195 + UCCUUUCCCUCCCCAAA 17 10044 SCNN1A-6196 + GUCUGGGCUGAGCCAAA 17 10045 SCNN1A-6197 + UUCCUUUCCCUCCCCAA 17 10046 SCNN1A-6198 + GGUCUGGGCUGAGCCAA 17 10047 SCNN1A-125 + CCAGUACAUCAUGCCAA 17 632 SCNN1A-6199 UUGGGGAGGGAAAGGAA 17 10048 SCNN1A-6200 + GCGCAGGCACCAGGGAA 17 10049 SCNN1A-6201 CCCCUUUGGGGAGGGAA 17 10050 SCNN1A-6202 GGUGCCUGCGCCUGGAA 17 10051 SCNN1A-90 ACUCCAGGGCUCAUGAA 17 611 SCNN1A-6203 UACAUGUAAGUUUAUAA 17 10052 SCNN1A-6204 GAAAGGAAGGGGACUAA 17 10053 SCNN1A-6205 + GAGCUCUACCUGGGACA 17 10054 SCNN1A-6206 + UCCAGGCGCAGGCACCA 17 10055 SCNN1A-99 GGCGCCCCAGCAGCCCA 17 536 SCNN1A-104 AACAACACCACCAUCCA 17 617 SCNN1A-88 CUCCACAGUCCACUCCA 17 609 SCNN1A-6207 CCUGGAAGGGUGGUCCA 17 10056 SCNN1A-94 AACAAGCGUGAGGAGCA 17 613 SCNN1A-6208 GAAACAUACCUAUAGCA 17 10057 SCNN1A-6209 CCCGGCAGGACGUGGCA 17 10058 SCNN1A-141 + GCGGUGGAACUCGAUCA 17 551 SCNN1A-106 GCACAACCGCAUGAAGA 17 540 SCNN1A-126 + CCACAGCACUGCCCAGA 17 633 SCNN1A-442 + ACCAGGGAAGGGGCAGA 17 4291 SCNN1A-115 + GGGAUUGAGGGUGCAGA 17 542 SCNN1A-6210 UUUGGGGAGGGAAAGGA 17 10059 SCNN1A-132 + GGAGCACACCAGGCGGA 17 547 SCNN1A-6211 + GGCGCAGGCACCAGGGA 17 10060 SCNN1A-6212 UGGCUCCCCUUUGGGGA 17 10061 SCNN1A-6213 UGGUGCCUGCGCCUGGA 17 10062 SCNN1A-134 + GCGGAUGGCGCCGUGGA 17 548 SCNN1A-155 + CUGGAGUGGACUGUGGA 17 652 SCNN1A-89 CACUCCAGGGCUCAUGA 17 610 SCNN1A-6214 CAGAGCCUCAGACCUGA 17 10063 SCNN1A-121 + GUUGAUGUUGAGGCUGA 17 545 SCNN1A-367 + CGACCUGUAGGGAUUGA 17 4216 SCNN1A-6215 GGAAAGGAAGGGGACUA 17 10064 SCNN1A-6216 + CCACGUCCUGCCGGGUA 17 10065 SCNN1A-331 + GGACUAACCGACCUGUA 17 4180 SCNN1A-6217 GACAGAUAUACAAAUUA 17 10066 SCNN1A-6218 + CUGGAGCGGGCUAGAAC 17 10067 SCNN1A-6219 GGUGCUGAGGUGCUCAC 17 10068 SCNN1A-6220 + UUAUUUAUCUUAGAGAC 17 10069 SCNN1A-6221 + UGAGCUCUACCUGGGAC 17 10070 SCNN1A-122 + UUGAUGUUGAGGCUGAC 17 629 SCNN1A-332 GCACCCUCAAUCCCUAC 17 4181 SCNN1A-111 CCUUUGGCAUGAUGUAC 17 622 SCNN1A-130 + UGUGCUGGGAGCACACC 17 637 SCNN1A-6222 + UUCCAGGCGCAGGCACC 17 10071 SCNN1A-6223 UUGGCUCAGCCCAGACC 17 10072 SCNN1A-6224 + AAUAGAAAUCUGAGACC 17 10073 SCNN1A-6225 + CUGCAGCAUUCUAGACC 17 10074 SCNN1A-6226 AUUGCCACUCCCAUACC 17 10075 SCNN1A-6227 + CAGCAGUGAGCUCUACC 17 10076 SCNN1A-6228 + UGAGCACCUCAGCACCC 17 10077 SCNN1A-151 + UUCCCCUUCAUGAGCCC 17 648 SCNN1A-6229 ACUGACACCCCUGUCCC 17 10078 SCNN1A-447 UCCCUCUGCCCCUUCCC 17 4296 SCNN1A-105 CCACGGCGCCAUCCGCC 17 618 SCNN1A-6230 UCCCUGGUGCCUGCGCC 17 10079 SCNN1A-5364 + AGAAGAAUUGCAAUGCC 17 9213 SCNN1A-6231 + CCCUGCCACGUCCUGCC 17 10080 SCNN1A-87 CCUCCACAGUCCACUCC 17 608 SCNN1A-6232 CUGUUCUAGCCCGCUCC 17 10081 SCNN1A-6233 ACUUCUGACCAAAGUCC 17 10082 SCNN1A-6234 GCCUGGAAGGGUGGUCC 17 10083 SCNN1A-6235 + CCCUGGACCACCCUUCC 17 10084 SCNN1A-124 + AGUACUCUCCGAAAAGC 17 631 SCNN1A-93 GAACAAGCGUGAGGAGC 17 533 SCNN1A-6236 + CAUUCUAGACCUGGAGC 17 10085 SCNN1A-147 + GGCUGCUGGGGCGCCGC 17 554 SCNN1A-6237 + ACCACCCUUCCAGGCGC 17 10086 SCNN1A-6238 + UGCACUAUCCUCUAGGC 17 10087 SCNN1A-6239 CCACUCCCAUACCCGGC 17 10088 SCNN1A-96 GCGUGAGGAGCAGGGGC 17 534 SCNN1A-6240 UGAGGUGCUCACUGGGC 17 10089 SCNN1A-6241 ACCCGGCAGGACGUGGC 17 10090 SCNN1A-6242 CAGGUAGAGCUCACUGC 17 10091 SCNN1A-117 + GUGCAGAUGGUCACUGC 17 544 SCNN1A-6243 + ACCCUGCCACGUCCUGC 17 10092 SCNN1A-144 + CCUCCGCCGUGGGCUGC 17 643 SCNN1A-128 + UCUUCAUGCGGUUGUGC 17 635 SCNN1A-140 + AGCGGUGGAACUCGAUC 17 642 SCNN1A-6244 + UGUCAGUUCCCACCCUC 17 10093 SCNN1A-5415 + AAUUGCAAUGCCUGGUC 17 9264 SCNN1A-107 GCAUGAAGACGGCCUUC 17 541 SCNN1A-149 + UGGGGCGCCGCAGGUUC 17 647 SCNN1A-6245 + CCUUUCCCUCCCCAAAG 17 10094 SCNN1A-6246 UGGGGAGGGAAAGGAAG 17 10095 SCNN1A-6247 + CGCAGGCACCAGGGAAG 17 10096 SCNN1A-91 CUCCAGGGCUCAUGAAG 17 612 SCNN1A-6248 + AGCUCUACCUGGGACAG 17 10097 SCNN1A-95 ACAAGCGUGAGGAGCAG 17 614 SCNN1A-6249 + CACCAGGGAAGGGGCAG 17 10098 SCNN1A-138 + AGAGCUCUCGGUAGGAG 17 641 SCNN1A-6250 + CCUGCCGGGUAUGGGAG 17 10099 SCNN1A-6251 + GCAUUCUAGACCUGGAG 17 10100 SCNN1A-152 + CUUCAUGAGCCCUGGAG 17 649 SCNN1A-6252 GCUGUACUCCAGCCUAG 17 10101 SCNN1A-6253 CCAUACCCGGCAGGACG 17 10102 SCNN1A-123 + UGAUGUUGAGGCUGACG 17 630 SCNN1A-142 + GGCCUCCUCCUCCGCCG 17 552 SCNN1A-133 + CCAGGCGGAUGGCGCCG 17 638 SCNN1A-118 + UGCAGAUGGUCACUGCG 17 626 SCNN1A-150 + GGGGCGCCGCAGGUUCG 17 555 SCNN1A-131 + GCUGGGAGCACACCAGG 17 546 SCNN1A-103 GCCCACGGCGGAGGAGG 17 539 SCNN1A-102 GCAGCCCACGGCGGAGG 17 538 SCNN1A-100 GCCCCAGCAGCCCACGG 17 537 SCNN1A-139 + GCUCUCGGUAGGAGCGG 17 550 SCNN1A-101 CCAGCAGCCCACGGCGG 17 616 SCNN1A-6254 + UGGGCUGAGCCAAAGGG 17 10103 SCNN1A-6255 GCCUGCGCCUGGAAGGG 17 10104 SCNN1A-6256 AGCCUCAGACCUGAGGG 17 10105 SCNN1A-6257 GUGGCUCCCCUUUGGGG 17 10106 SCNN1A-135 + GAUGGCGCCGUGGAUGG 17 549 SCNN1A-6258 AGAUAUACAAAUUAUGG 17 10107 SCNN1A-154 + CCUGGAGUGGACUGUGG 17 651 SCNN1A-127 + AGAAGGCCGUCUUCAUG 17 634 SCNN1A-116 + GGUGCAGAUGGUCACUG 17 543 SCNN1A-153 + AGCCCUGGAGUGGACUG 17 650 SCNN1A-98 GCUGGGCCCCGAACCUG 17 535 SCNN1A-6259 GCAGAGCCUCAGACCUG 17 10108 SCNN1A-146 + UCCGCCGUGGGCUGCUG 17 645 SCNN1A-109 CCUUCUGGGCAGUGCUG 17 620 SCNN1A-6260 GGUGGUCCAGGGUGCUG 17 10109 SCNN1A-6261 + UCCCACCCUCAGGUCUG 17 10110 SCNN1A-92 GAAGGGGAACAAGCGUG 17 532 SCNN1A-6262 + ACAGGCUUGGUGUUGUG 17 10111 SCNN1A-386 + CCGACCUGUAGGGAUUG 17 4235 SCNN1A-119 + CGAGCUUGUCCGAGUUG 17 627 SCNN1A-120 + AGUUGAGGUUGAUGUUG 17 628 SCNN1A-6263 AUGGUGGCUCCCCUUUG 17 10112 SCNN1A-6264 + GACAGAGACCAUGCUAU 17 10113 SCNN1A-6265 + CACGUCCUGCCGGGUAU 17 10114 SCNN1A-114 CAACAUCAACCUCAACU 17 625 SCNN1A-6266 UAGAAUGCUGCAGCACU 17 10115 SCNN1A-6267 GUGCUGAGGUGCUCACU 17 10116 SCNN1A-6268 + AGCAGUGAGCUCUACCU 17 10117 SCNN1A-6269 + GCGGGCUAGAACAGGCU 17 10118 SCNN1A-97 CGUGAGGAGCAGGGGCU 17 615 SCNN1A-145 + CUCCGCCGUGGGCUGCU 17 644 SCNN1A-129 + CUUCAUGCGGUUGUGCU 17 636 SCNN1A-6270 + AUCAUGCACUAUCCUCU 17 10119 SCNN1A-136 + AGAACUCGAAGAGCUCU 17 639 SCNN1A-6271 + AUUGCAAUGCCUGGUCU 17 10120 SCNN1A-108 CAUGAAGACGGCCUUCU 17 619 SCNN1A-143 + GCCUCCUCCUCCGCCGU 17 553 SCNN1A-391 CCUCAAUCCCUACAGGU 17 4240 SCNN1A-137 + CUCGAAGAGCUCUCGGU 17 640 SCNN1A-6272 GCCUCAGACCUGAGGGU 17 10121 SCNN1A-338 + GGGACUAACCGACCUGU 17 4187 SCNN1A-112 AUGAUGUACUGGCAAUU 17 623 SCNN1A-6273 + AUCUGAGACCUGGACUU 17 10122 SCNN1A-110 CUGUGGCUCUGCACCUU 17 621 SCNN1A-6274 GCAGGGUCACCACCCUU 17 10123 SCNN1A-6275 UUAUGGUGGCUCCCCUU 17 10124 SCNN1A-148 + CUGGGGCGCCGCAGGUU 17 646 SCNN1A-6276 UAUGGUGGCUCCCCUUU 17 10125 SCNN1A-113 CAAUUCGGCCUGCUUUU 17 624 SCNN1A-6277 UAAGAAAAUAAAAGCAAAAA 20 10126 SCNN1A-6278 UUAAAAGAUCAUCUUUAAAA 20 10127 SCNN1A-6279 + CCUUCCUUUCCCUCCCCAAA 20 10128 SCNN1A-6280 + CUGGUCUGGGCUGAGCCAAA 20 10129 SCNN1A-6281 + CCCUUCCUUUCCCUCCCCAA 20 10130 SCNN1A-6282 + CCUGGUCUGGGCUGAGCCAA 20 10131 SCNN1A-46 + UUGCCAGUACAUCAUGCCAA 20 580 SCNN1A-6283 CCUUUGGGGAGGGAAAGGAA 20 10132 SCNN1A-6284 + CAGGCGCAGGCACCAGGGAA 20 10133 SCNN1A-6285 GCUCCCCUUUGGGGAGGGAA 20 10134 SCNN1A-6286 CCUGGUGCCUGCGCCUGGAA 20 10135 SCNN1A-11 UCCACUCCAGGGCUCAUGAA 20 560 SCNN1A-6287 AAAUACAUGUAAGUUUAUAA 20 10136 SCNN1A-6288 AGGGAAAGGAAGGGGACUAA 20 10137 SCNN1A-6289 + AGUGAGCUCUACCUGGGACA 20 10138 SCNN1A-6290 + CCUUCCAGGCGCAGGCACCA 20 10139 SCNN1A-20 UGCGGCGCCCCAGCAGCCCA 20 565 SCNN1A-25 UGCAACAACACCACCAUCCA 20 567 SCNN1A-9 GCCCUCCACAGUCCACUCCA 20 499 SCNN1A-6291 GCGCCUGGAAGGGUGGUCCA 20 10140 SCNN1A-15 GGGAACAAGCGUGAGGAGCA 20 507 SCNN1A-6292 GUAGAAACAUACCUAUAGCA 20 10141 SCNN1A-6293 AUACCCGGCAGGACGUGGCA 20 10142 SCNN1A-62 + GGAGCGGUGGAACUCGAUCA 20 525 SCNN1A-27 CCAGCACAACCGCAUGAAGA 20 569 SCNN1A-47 + GAGCCACAGCACUGCCCAGA 20 521 SCNN1A-6294 + GGCACCAGGGAAGGGGCAGA 20 10143 SCNN1A-36 + GUAGGGAUUGAGGGUGCAGA 20 516 SCNN1A-6295 CCCUUUGGGGAGGGAAAGGA 20 10144 SCNN1A-53 + CUGGGAGCACACCAGGCGGA 20 585 SCNN1A-6296 + CCAGGCGCAGGCACCAGGGA 20 10145 SCNN1A-6297 UGGUGGCUCCCCUUUGGGGA 20 10146 SCNN1A-6298 CCCUGGUGCCUGCGCCUGGA 20 10147 SCNN1A-55 + CAGGCGGAUGGCGCCGUGGA 20 587 SCNN1A-76 + GCCCUGGAGUGGACUGUGGA 20 528 SCNN1A-10 GUCCACUCCAGGGCUCAUGA 20 505 SCNN1A-6299 AGGCAGAGCCUCAGACCUGA 20 10148 SCNN1A-42 + GAGGUUGAUGUUGAGGCUGA 20 519 SCNN1A-402 + AACCGACCUGUAGGGAUUGA 20 4251 SCNN1A-6300 GAGGGAAAGGAAGGGGACUA 20 10149 SCNN1A-6301 + CUGCCACGUCCUGCCGGGUA 20 10150 SCNN1A-345 + GAGGGACUAACCGACCUGUA 20 4194 SCNN1A-6302 AUAGACAGAUAUACAAAUUA 20 10151 SCNN1A-6303 + GACCUGGAGCGGGCUAGAAC 20 10152 SCNN1A-6304 CAGGGUGCUGAGGUGCUCAC 20 10153 SCNN1A-6305 + UUCUUAUUUAUCUUAGAGAC 20 10154 SCNN1A-6306 + CAGUGAGCUCUACCUGGGAC 20 10155 SCNN1A-43 + AGGUUGAUGUUGAGGCUGAC 20 578 SCNN1A-403 UCUGCACCCUCAAUCCCUAC 20 4252 SCNN1A-32 GCACCUUUGGCAUGAUGUAC 20 514 SCNN1A-51 + GGUUGUGCUGGGAGCACACC 20 522 SCNN1A-6307 + CCCUUCCAGGCGCAGGCACC 20 10156 SCNN1A-6308 CCUUUGGCUCAGCCCAGACC 20 10157 SCNN1A-6309 + GAAAAUAGAAAUCUGAGACC 20 10158 SCNN1A-6310 + GUGCUGCAGCAUUCUAGACC 20 10159 SCNN1A-6311 CGCAUUGCCACUCCCAUACC 20 10160 SCNN1A-6312 + UGCCAGCAGUGAGCUCUACC 20 10161 SCNN1A-6313 + CAGUGAGCACCUCAGCACCC 20 10162 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20 599 SCNN1A-6314 GGAACUGACACCCCUGUCCC 20 10163 SCNN1A-407 UAGUCCCUCUGCCCCUUCCC 20 4256 SCNN1A-26 CAUCCACGGCGCCAUCCGCC 20 568 SCNN1A-6315 CCUUCCCUGGUGCCUGCGCC 20 10164 SCNN1A-5223 + GUGAGAAGAAUUGCAAUGCC 20 9072 SCNN1A-6316 + UGACCCUGCCACGUCCUGCC 20 10165 SCNN1A-8 AGCCCUCCACAGUCCACUCC 20 559 SCNN1A-6317 AGCCUGUUCUAGCCCGCUCC 20 10166 SCNN1A-6318 UGGACUUCUGACCAAAGUCC 20 10167 SCNN1A-6319 UGCGCCUGGAAGGGUGGUCC 20 10168 SCNN1A-6320 + GCACCCUGGACCACCCUUCC 20 10169 SCNN1A-45 + UGAAGUACUCUCCGAAAAGC 20 579 SCNN1A-14 GGGGAACAAGCGUGAGGAGC 20 506 SCNN1A-6321 + CAGCAUUCUAGACCUGGAGC 20 10170 SCNN1A-68 + GUGGGCUGCUGGGGCGCCGC 20 526 SCNN1A-6322 + UGGACCACCCUUCCAGGCGC 20 10171 SCNN1A-6323 + UCAUGCACUAUCCUCUAGGC 20 10172 SCNN1A-6324 UUGCCACUCCCAUACCCGGC 20 10173 SCNN1A-17 CAAGCGUGAGGAGCAGGGGC 20 563 SCNN1A-6325 UGCUGAGGUGCUCACUGGGC 20 10174 SCNN1A-6326 CAUACCCGGCAGGACGUGGC 20 10175 SCNN1A-6327 UCCCAGGUAGAGCUCACUGC 20 10176 SCNN1A-38 + AGGGUGCAGAUGGUCACUGC 20 575 SCNN1A-6328 + GUGACCCUGCCACGUCCUGC 20 10177 SCNN1A-65 + CCUCCUCCGCCGUGGGCUGC 20 594 SCNN1A-49 + CCGUCUUCAUGCGGUUGUGC 20 582 SCNN1A-61 + AGGAGCGGUGGAACUCGAUC 20 591 SCNN1A-6329 + GGGUGUCAGUUCCCACCCUC 20 10178 SCNN1A-5640 + AAGAAUUGCAAUGCCUGGUC 20 9489 SCNN1A-28 ACCGCAUGAAGACGGCCUUC 20 570 SCNN1A-70 + UGCUGGGGCGCCGCAGGUUC 20 598 SCNN1A-6330 + CUUCCUUUCCCUCCCCAAAG 20 10179 SCNN1A-6331 CUUUGGGGAGGGAAAGGAAG 20 10180 SCNN1A-6332 + AGGCGCAGGCACCAGGGAAG 20 10181 SCNN1A-12 CCACUCCAGGGCUCAUGAAG 20 561 SCNN1A-6333 + GUGAGCUCUACCUGGGACAG 20 10182 SCNN1A-16 GGAACAAGCGUGAGGAGCAG 20 508 SCNN1A-6334 + AGGCACCAGGGAAGGGGCAG 20 10183 SCNN1A-59 + CGAAGAGCUCUCGGUAGGAG 20 589 SCNN1A-6335 + CGUCCUGCCGGGUAUGGGAG 20 10184 SCNN1A-6336 + GCAGCAUUCUAGACCUGGAG 20 10185 SCNN1A-73 + CCCCUUCAUGAGCCCUGGAG 20 600 SCNN1A-6337 GCUGCUGUACUCCAGCCUAG 20 10186 SCNN1A-6338 CUCCCAUACCCGGCAGGACG 20 10187 SCNN1A-44 + GGUUGAUGUUGAGGCUGACG 20 520 SCNN1A-63 + CAGGGCCUCCUCCUCCGCCG 20 592 SCNN1A-54 + ACACCAGGCGGAUGGCGCCG 20 586 SCNN1A-39 + GGGUGCAGAUGGUCACUGCG 20 518 SCNN1A-71 + GCUGGGGCGCCGCAGGUUCG 20 527 SCNN1A-52 + UGUGCUGGGAGCACACCAGG 20 584 SCNN1A-24 GCAGCCCACGGCGGAGGAGG 20 512 SCNN1A-23 CCAGCAGCCCACGGCGGAGG 20 566 SCNN1A-21 GGCGCCCCAGCAGCCCACGG 20 510 SCNN1A-60 + AGAGCUCUCGGUAGGAGCGG 20 590 SCNN1A-22 GCCCCAGCAGCCCACGGCGG 20 511 SCNN1A-6339 + GUCUGGGCUGAGCCAAAGGG 20 10188 SCNN1A-6340 GGUGCCUGCGCCUGGAAGGG 20 10189 SCNN1A-6341 CAGAGCCUCAGACCUGAGGG 20 10190 SCNN1A-6342 AUGGUGGCUCCCCUUUGGGG 20 10191 SCNN1A-56 + GCGGAUGGCGCCGUGGAUGG 20 523 SCNN1A-6343 GACAGAUAUACAAAUUAUGG 20 10192 SCNN1A-75 + AGCCCUGGAGUGGACUGUGG 20 602 SCNN1A-48 + CCCAGAAGGCCGUCUUCAUG 20 581 SCNN1A-37 + GAGGGUGCAGAUGGUCACUG 20 517 SCNN1A-74 + AUGAGCCCUGGAGUGGACUG 20 601 SCNN1A-19 GGGGCUGGGCCCCGAACCUG 20 509 SCNN1A-6344 CAGGCAGAGCCUCAGACCUG 20 10193 SCNN1A-67 + UCCUCCGCCGUGGGCUGCUG 20 596 SCNN1A-30 CGGCCUUCUGGGCAGUGCUG 20 572 SCNN1A-6345 AAGGGUGGUCCAGGGUGCUG 20 10194 SCNN1A-6346 + AGUUCCCACCCUCAGGUCUG 20 10195 SCNN1A-13 CAUGAAGGGGAACAAGCGUG 20 562 SCNN1A-6347 + AGAACAGGCUUGGUGUUGUG 20 10196 SCNN1A-418 + UAACCGACCUGUAGGGAUUG 20 4267 SCNN1A-40 + AGACGAGCUUGUCCGAGUUG 20 576 SCNN1A-41 + CCGAGUUGAGGUUGAUGUUG 20 577 SCNN1A-6348 AUUAUGGUGGCUCCCCUUUG 20 10197 SCNN1A-6349 + UAUGACAGAGACCAUGCUAU 20 10198 SCNN1A-6350 + UGCCACGUCCUGCCGGGUAU 20 10199 SCNN1A-35 CCUCAACAUCAACCUCAACU 20 574 SCNN1A-6351 GUCUAGAAUGCUGCAGCACU 20 10200 SCNN1A-6352 AGGGUGCUGAGGUGCUCACU 20 10201 SCNN1A-6353 + GCCAGCAGUGAGCUCUACCU 20 10202 SCNN1A-6354 + GGAGCGGGCUAGAACAGGCU 20 10203 SCNN1A-18 AAGCGUGAGGAGCAGGGGCU 20 564 SCNN1A-66 + CUCCUCCGCCGUGGGCUGCU 20 595 SCNN1A-50 + CGUCUUCAUGCGGUUGUGCU 20 583 SCNN1A-6355 + AGGAUCAUGCACUAUCCUCU 20 10204 SCNN1A-57 + AGAAGAACUCGAAGAGCUCU 20 588 SCNN1A-6356 + AGAAUUGCAAUGCCUGGUCU 20 10205 SCNN1A-29 CCGCAUGAAGACGGCCUUCU 20 571 SCNN1A-64 + AGGGCCUCCUCCUCCGCCGU 20 593 SCNN1A-423 CACCCUCAAUCCCUACAGGU 20 4272 SCNN1A-58 + GAACUCGAAGAGCUCUCGGU 20 524 SCNN1A-6357 AGAGCCUCAGACCUGAGGGU 20 10206 SCNN1A-424 + AGAGGGACUAACCGACCUGU 20 4273 SCNN1A-33 GGCAUGAUGUACUGGCAAUU 20 515 SCNN1A-6358 + GAAAUCUGAGACCUGGACUU 20 10207 SCNN1A-31 GUGCUGUGGCUCUGCACCUU 20 513 SCNN1A-6359 GUGGCAGGGUCACCACCCUU 20 10208 SCNN1A-6360 AAAUUAUGGUGGCUCCCCUU 20 10209 SCNN1A-69 + CUGCUGGGGCGCCGCAGGUU 20 597 SCNN1A-6361 AAUUAUGGUGGCUCCCCUUU 20 10210 SCNN1A-34 UGGCAAUUCGGCCUGCUUUU 20 573

Table 47A provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality, start with a 5′G, and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 47A 1st Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-6362 + GAAGGAGCCAGCACCAAA 18 10211 SCNN1A-6363 + GCCAGCGCUGGAAAGGAA 18 10212 SCNN1A-6364 + GGCCAGCGCUGGAAAGGAA 19 10213 SCNN1A-6365 + GUGGCCAGCGCUGGAAAGGAA 21 10214 SCNN1A-6366 + GAUGUGGCCAGCGCUGGAAAGGAA 24 10215 SCNN1A-6367 + GCUGAAUCUUGACAAGCA 18 10216 SCNN1A-6368 + GUAAUCGCCCCUGCUGUGGUCA 22 10217 SCNN1A-6369 + GUGUAAUCGCCCCUGCUGUGGUCA 24 10218 SCNN1A-6370 + GUGAAAGCCGGUGUCAAC 18 10219 SCNN1A-1304 + GCCCUCUCCCAUCACCCCUGGAAC 24 5153 SCNN1A-6371 + GAUCGGGGCUCAGGUGCAC 19 10220 SCNN1A-6372 + GGAUCGGGGCUCAGGUGCAC 20 10221 SCNN1A-6373 + GGGAUCGGGGCUCAGGUGCAC 21 10222 SCNN1A-6374 + GGGGAUCGGGGCUCAGGUGCAC 22 10223 SCNN1A-6375 + GGGGGAUCGGGGCUCAGGUGCAC 23 10224 SCNN1A-6376 + GCCAGGGAUGGAAGCGAC 18 10225 SCNN1A-6377 + GGCCAGGGAUGGAAGCGAC 19 10226 SCNN1A-6378 + GCCGGCCAGGGAUGGAAGCGAC 22 10227 SCNN1A-6379 + GGCCGGCCAGGGAUGGAAGCGAC 23 10228 SCNN1A-6380 + GAAGAAACUGACCCUUCCC 19 10229 SCNN1A-6381 + GCCCCACAGGAGGCAGCC 18 10230 SCNN1A-6382 + GGCCCCACAGGAGGCAGCC 19 10231 SCNN1A-6383 + GGGCCCCACAGGAGGCAGCC 20 10232 SCNN1A-5221 + GCUGAGGAGGAGUCAGAGCC 20 9070 SCNN1A-6384 + GCCCGCCCGCUGGCCGGCC 19 10233 SCNN1A-6385 + GAGCCCGCCCGCUGGCCGGCC 21 10234 SCNN1A-6386 + GGAGCCCGCCCGCUGGCCGGCC 22 10235 SCNN1A-6387 + GGGAGCCCGCCCGCUGGCCGGCC 23 10236 SCNN1A-6388 + GGGGAGCCCGCCCGCUGGCCGGCC 24 10237 SCNN1A-1305 + GUCAAGGCUGAGCUCUGGGCC 21 5154 SCNN1A-1306 + GGUCAAGGCUGAGCUCUGGGCC 22 5155 SCNN1A-1307 + GGGUCAAGGCUGAGCUCUGGGCC 23 5156 SCNN1A-1308 + GAGUGGAUUGGGGAGAGC 18 5157 SCNN1A-1309 + GGAGUGGAUUGGGGAGAGC 19 5158 SCNN1A-1310 + GCCCCGGAGUGGAUUGGGGAGAGC 24 5159 SCNN1A-1311 + GCCCUGGAGUGGACUGUGGAGGGC 24 5160 SCNN1A-6389 + GGAGGCAGCCCAGAGUGC 18 10238 SCNN1A-6390 + GCUGUGGUCACAGAGUUGC 19 10239 SCNN1A-1312 + GUAUGGGCUGCAGAGGUC 18 5161 SCNN1A-1313 + GGUAUGGGCUGCAGAGGUC 19 5162 SCNN1A-1314 + GACCUGGUAUGGGCUGCAGAGGUC 24 5163 SCNN1A-1315 + GAUACCUCCCCUUGGAAGGGACAG 24 5164 SCNN1A-6391 + GGACUGGUUCCUUUCCAG 18 10240 SCNN1A-6392 + GGGACUGGUUCCUUUCCAG 19 10241 SCNN1A-6393 + GACUGGGACUGGUUCCUUUCCAG 23 10242 SCNN1A-6394 + GGACUGGGACUGGUUCCUUUCCAG 24 10243 SCNN1A-6395 + GCAGCAAAAGGAUAAGGAG 19 10244 SCNN1A-6396 + GGCAAAGAUCUGAACAAGUAG 21 10245 SCNN1A-6397 + GGGCAAAGAUCUGAACAAGUAG 22 10246 SCNN1A-6398 + GGGGCAAAGAUCUGAACAAGUAG 23 10247 SCNN1A-6399 + GCAGGCACUGAAGGUGCAGG 20 10248 SCNN1A-6400 + GGGAGCAGCGCACUCAGG 18 10249 SCNN1A-5260 + GUGGGAGCAGCGCACUCAGG 20 9109 SCNN1A-6401 + GAUUCGUCUGCUCUCUGGGUG 21 10250 SCNN1A-6402 + GGAUUCGUCUGCUCUCUGGGUG 22 10251 SCNN1A-6403 + GUGGAUUCGUCUGCUCUCUGGGUG 24 10252 SCNN1A-6404 + GCCCGUGGAUUCGUCUGCUCU 21 10253 SCNN1A-6405 + GAGCCCGUGGAUUCGUCUGCUCU 23 10254 SCNN1A-1322 + GAUUGGGGAGAGCAAGGGU 19 5171 SCNN1A-1323 + GGAUUGGGGAGAGCAAGGGU 20 5172 SCNN1A-1324 + GUGGAUUGGGGAGAGCAAGGGU 22 5173 SCNN1A-1325 + GAGUGGAUUGGGGAGAGCAAGGGU 24 5174 SCNN1A-6406 + GCAGAGCUAUAAACAGAAUU 20 10255 SCNN1A-6407 + GAGCAGAGCUAUAAACAGAAUU 22 10256 SCNN1A-6408 + GGAGCAGAGCUAUAAACAGAAUU 23 10257 SCNN1A-6409 + GCUUCCCUGAUAGGGCCACCUU 22 10258 SCNN1A-6410 GCCAACAGUGUAAAAAAGAA 20 10259 SCNN1A-6411 GCAGCCAACAGUGUAAAAAAGAA 23 10260 SCNN1A-6412 GGCAGCCAACAGUGUAAAAAAGAA 24 10261 SCNN1A-6413 GAGAAAAUAUAGCCCAUCA 19 10262 SCNN1A-6414 GGAGAAAAUAUAGCCCAUCA 20 10263 SCNN1A-6415 GCAGUCCUGGGGCAGAGA 18 10264 SCNN1A-6416 GGUCUGGACAAGGUUGGA 18 10265 SCNN1A-6417 GGGUCUGGACAAGGUUGGA 19 10266 SCNN1A-6418 GAGGCAGACGCAUCCCAC 18 10267 SCNN1A-6419 GGAGGCAGACGCAUCCCAC 19 10268 SCNN1A-6420 GAGGAGGCAGACGCAUCCCAC 21 10269 SCNN1A-6421 GGAGGAGGCAGACGCAUCCCAC 22 10270 SCNN1A-1335 GGCCAGGGGCAGCCUCAC 18 5184 SCNN1A-6422 GACCUGGCUCAAGGGAGAC 19 10271 SCNN1A-5207 GGACCUGGCUCAAGGGAGAC 20 9056 SCNN1A-6423 GCACCUGAGCCCCGAUCCCCC 21 10272 SCNN1A-6424 GUGCACCUGAGCCCCGAUCCCCC 23 10273 SCNN1A-6425 GGUGCACCUGAGCCCCGAUCCCCC 24 10274 SCNN1A-6426 GACCAGGUUGGACCCUGAGCC 21 10275 SCNN1A-6427 GCGUCUAAAGCCCCUGCC 18 10276 SCNN1A-6428 GUCUGCGUCUAAAGCCCCUGCC 22 10277 SCNN1A-1336 GCAGCCUCACUCGGGUUCC 19 5185 SCNN1A-348 GGCAGCCUCACUCGGGUUCC 20 4197 SCNN1A-6429 GAACCUUUGAGAUCAAACAGC 21 10278 SCNN1A-6430 GCCUUCCCUGCCGCGUGCAGGGC 23 10279 SCNN1A-6431 GCUUCACCUGGGCCCCUC 18 10280 SCNN1A-6432 GUUGUGUGGGUGGCUCUC 18 10281 SCNN1A-6433 GGUUGUGUGGGUGGCUCUC 19 10282 SCNN1A-6434 GGGUUGUGUGGGUGGCUCUC 20 10283 SCNN1A-6435 GGAGUUUCUAGGGGUCUC 18 10284 SCNN1A-6436 GACUGGAGUUUCUAGGGGUCUC 22 10285 SCNN1A-6437 GAGACUGGAGUUUCUAGGGGUCUC 24 10286 SCNN1A-6438 GAUAACCCAGCACCCAGAGAGCAG 24 10287 SCNN1A-6439 GAUAGCCCCAGAGGAGGAG 19 10288 SCNN1A-6440 GUAGAUAGCCCCAGAGGAGGAG 22 10289 SCNN1A-6441 GAGUGGGAGAAUGUGGGCG 19 10290 SCNN1A-6442 GGAGUGGGAGAAUGUGGGCG 20 10291 SCNN1A-6443 GACAAGGUUGGAGGGGGUGGCG 22 10292 SCNN1A-6444 GGACAAGGUUGGAGGGGGUGGCG 23 10293 SCNN1A-6445 GCUGCCUUAAGCUAGUGG 18 10294 SCNN1A-6446 GCCAUGCUGCCUUAAGCUAGUGG 23 10295 SCNN1A-6447 GUCCCAGUCCAGCCGCAACCU 21 10296 SCNN1A-6448 GCCUGAGGGUGAGGCUGACCU 21 10297 SCNN1A-6449 GGCCUGAGGGUGAGGCUGACCU 22 10298 SCNN1A-6450 GGGCCUGAGGGUGAGGCUGACCU 23 10299 SCNN1A-6451 GCCCUCCUAGCUGUGGGCU 19 10300 SCNN1A-6452 GCUCAAGGGAGACUGGAGUUUCU 23 10301 SCNN1A-6453 GGCUCAAGGGAGACUGGAGUUUCU 24 10302 SCNN1A-6454 GAAUCCACGGGCUCUGUGU 19 10303 SCNN1A-6455 GACGAAUCCACGGGCUCUGUGU 22 10304 SCNN1A-6456 GUGCAGGGCCUGGGUUGU 18 10305 SCNN1A-6457 GCGUGCAGGGCCUGGGUUGU 20 10306 SCNN1A-6458 GCCGCGUGCAGGGCCUGGGUUGU 23 10307 SCNN1A-437 GUAAGCAAGGGAACCUGGUU 20 4286 SCNN1A-1339 GGUAAGCAAGGGAACCUGGUU 21 5188 SCNN1A-6459 GAGUCUCCUCCAGCCCUUU 19 10308

Table 47B provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 47B 2nd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-6460 + AGAAGGAGCCAGCACCAAA 19 10309 SCNN1A-5515 + UAGAAGGAGCCAGCACCAAA 20 9364 SCNN1A-6461 + UAGGAGCAGAGCUAUAAA 18 10310 SCNN1A-6462 + AUAGGAGCAGAGCUAUAAA 19 10311 SCNN1A-6463 + AAUAGGAGCAGAGCUAUAAA 20 10312 SCNN1A-6464 + AAAUAGGAGCAGAGCUAUAAA 21 10313 SCNN1A-6465 + AAAAUAGGAGCAGAGCUAUAAA 22 10314 SCNN1A-6466 + CAAAAUAGGAGCAGAGCUAUAAA 23 10315 SCNN1A-6467 + ACAAAAUAGGAGCAGAGCUAUAAA 24 10316 SCNN1A-6468 + UUUCCAAACUUAAUGCAGCAA 21 10317 SCNN1A-6469 + CUUUCCAAACUUAAUGCAGCAA 22 10318 SCNN1A-6470 + UCUUUCCAAACUUAAUGCAGCAA 23 10319 SCNN1A-6471 + CUCUUUCCAAACUUAAUGCAGCAA 24 10320 SCNN1A-6472 + UGGCCAGCGCUGGAAAGGAA 20 10321 SCNN1A-6473 + UGUGGCCAGCGCUGGAAAGGAA 22 10322 SCNN1A-6474 + AUGUGGCCAGCGCUGGAAAGGAA 23 10323 SCNN1A-6475 + UGCUGAAUCUUGACAAGCA 19 10324 SCNN1A-5532 + CUGCUGAAUCUUGACAAGCA 20 9381 SCNN1A-6476 + UCUGCUGAAUCUUGACAAGCA 21 10325 SCNN1A-6477 + CUCUGCUGAAUCUUGACAAGCA 22 10326 SCNN1A-6478 + UCUCUGCUGAAUCUUGACAAGCA 23 10327 SCNN1A-6479 + AUCUCUGCUGAAUCUUGACAAGCA 24 10328 SCNN1A-6480 + AGGGAUGGAGGAGGGGCA 18 10329 SCNN1A-6481 + UAGGGAUGGAGGAGGGGCA 19 10330 SCNN1A-6482 + AUAGGGAUGGAGGAGGGGCA 20 10331 SCNN1A-6483 + UCGCCCCUGCUGUGGUCA 18 10332 SCNN1A-6484 + AUCGCCCCUGCUGUGGUCA 19 10333 SCNN1A-6485 + AAUCGCCCCUGCUGUGGUCA 20 10334 SCNN1A-6486 + UAAUCGCCCCUGCUGUGGUCA 21 10335 SCNN1A-6487 + UGUAAUCGCCCCUGCUGUGGUCA 23 10336 SCNN1A-6488 + UAAUGCAGCAAAAGGAUA 18 10337 SCNN1A-6489 + UUAAUGCAGCAAAAGGAUA 19 10338 SCNN1A-6098 + CUUAAUGCAGCAAAAGGAUA 20 9947 SCNN1A-6490 + AGUGAAAGCCGGUGUCAAC 19 10339 SCNN1A-6491 + AAGUGAAAGCCGGUGUCAAC 20 10340 SCNN1A-6492 + AAAGUGAAAGCCGGUGUCAAC 21 10341 SCNN1A-6493 + UAAAGUGAAAGCCGGUGUCAAC 22 10342 SCNN1A-6494 + UUAAAGUGAAAGCCGGUGUCAAC 23 10343 SCNN1A-6495 + CUUAAAGUGAAAGCCGGUGUCAAC 24 10344 SCNN1A-1344 + UCCCAUCACCCCUGGAAC 18 5193 SCNN1A-1345 + CUCCCAUCACCCCUGGAAC 19 5194 SCNN1A-1346 + UCUCCCAUCACCCCUGGAAC 20 5195 SCNN1A-1347 + CUCUCCCAUCACCCCUGGAAC 21 5196 SCNN1A-1348 + CCUCUCCCAUCACCCCUGGAAC 22 5197 SCNN1A-1349 + CCCUCUCCCAUCACCCCUGGAAC 23 5198 SCNN1A-6496 + AUCGGGGCUCAGGUGCAC 18 10345 SCNN1A-6497 + UGGGGGAUCGGGGCUCAGGUGCAC 24 10346 SCNN1A-5564 + CGGCCAGGGAUGGAAGCGAC 20 9413 SCNN1A-6498 + CCGGCCAGGGAUGGAAGCGAC 21 10347 SCNN1A-6499 + UGGCCGGCCAGGGAUGGAAGCGAC 24 10348 SCNN1A-6500 + CACUCCCACACAGAGCCC 18 10349 SCNN1A-6501 + UCACUCCCACACAGAGCCC 19 10350 SCNN1A-6502 + CUCACUCCCACACAGAGCCC 20 10351 SCNN1A-6503 + AAGAAACUGACCCUUCCC 18 10352 SCNN1A-6504 + UGAAGAAACUGACCCUUCCC 20 10353 SCNN1A-6505 + AUGAAGAAACUGACCCUUCCC 21 10354 SCNN1A-6506 + AAUGAAGAAACUGACCCUUCCC 22 10355 SCNN1A-6507 + UAAUGAAGAAACUGACCCUUCCC 23 10356 SCNN1A-6508 + CUAAUGAAGAAACUGACCCUUCCC 24 10357 SCNN1A-6509 + CGGGCCCCACAGGAGGCAGCC 21 10358 SCNN1A-6510 + ACGGGCCCCACAGGAGGCAGCC 22 10359 SCNN1A-6511 + CACGGGCCCCACAGGAGGCAGCC 23 10360 SCNN1A-6512 + UCACGGGCCCCACAGGAGGCAGCC 24 10361 SCNN1A-6513 + UGAGGAGGAGUCAGAGCC 18 10362 SCNN1A-6514 + CUGAGGAGGAGUCAGAGCC 19 10363 SCNN1A-6515 + ACUGUUGGCUGCCAGGCC 18 10364 SCNN1A-6516 + CACUGUUGGCUGCCAGGCC 19 10365 SCNN1A-5583 + ACACUGUUGGCUGCCAGGCC 20 9432 SCNN1A-6517 + UACACUGUUGGCUGCCAGGCC 21 10366 SCNN1A-6518 + UUACACUGUUGGCUGCCAGGCC 22 10367 SCNN1A-6519 + UUUACACUGUUGGCUGCCAGGCC 23 10368 SCNN1A-6520 + UUUUACACUGUUGGCUGCCAGGCC 24 10369 SCNN1A-6521 + CCCGCCCGCUGGCCGGCC 18 10370 SCNN1A-6109 + AGCCCGCCCGCUGGCCGGCC 20 9958 SCNN1A-1350 + AAGGCUGAGCUCUGGGCC 18 5199 SCNN1A-1351 + CAAGGCUGAGCUCUGGGCC 19 5200 SCNN1A-1352 + UCAAGGCUGAGCUCUGGGCC 20 5201 SCNN1A-1353 + AGGGUCAAGGCUGAGCUCUGGGCC 24 5202 SCNN1A-1354 + CGGAGUGGAUUGGGGAGAGC 20 5203 SCNN1A-1355 + CCGGAGUGGAUUGGGGAGAGC 21 5204 SCNN1A-1356 + CCCGGAGUGGAUUGGGGAGAGC 22 5205 SCNN1A-1357 + CCCCGGAGUGGAUUGGGGAGAGC 23 5206 SCNN1A-1358 + CUGGAGUGGACUGUGGAGGGC 21 5207 SCNN1A-1359 + CCUGGAGUGGACUGUGGAGGGC 22 5208 SCNN1A-1360 + CCCUGGAGUGGACUGUGGAGGGC 23 5209 SCNN1A-6522 + UGGAGCCAGCAGACCUGC 18 10371 SCNN1A-6523 + CUGGAGCCAGCAGACCUGC 19 10372 SCNN1A-5615 + CCUGGAGCCAGCAGACCUGC 20 9464 SCNN1A-6524 + AGGAGGCAGCCCAGAGUGC 19 10373 SCNN1A-6130 + CAGGAGGCAGCCCAGAGUGC 20 9979 SCNN1A-6525 + ACAGGAGGCAGCCCAGAGUGC 21 10374 SCNN1A-6526 + CACAGGAGGCAGCCCAGAGUGC 22 10375 SCNN1A-6527 + CCACAGGAGGCAGCCCAGAGUGC 23 10376 SCNN1A-6528 + CCCACAGGAGGCAGCCCAGAGUGC 24 10377 SCNN1A-6529 + CUGUGGUCACAGAGUUGC 18 10378 SCNN1A-5623 + UGCUGUGGUCACAGAGUUGC 20 9472 SCNN1A-6530 + CUGCUGUGGUCACAGAGUUGC 21 10379 SCNN1A-6531 + CCUGCUGUGGUCACAGAGUUGC 22 10380 SCNN1A-6532 + CCCUGCUGUGGUCACAGAGUUGC 23 10381 SCNN1A-6533 + CCCCUGCUGUGGUCACAGAGUUGC 24 10382 SCNN1A-6534 + CCUUUGGUCUUCUUCCUC 18 10383 SCNN1A-6535 + UCCUUUGGUCUUCUUCCUC 19 10384 SCNN1A-6536 + UUCCUUUGGUCUUCUUCCUC 20 10385 SCNN1A-1361 + UGGUAUGGGCUGCAGAGGUC 20 5210 SCNN1A-1362 + CUGGUAUGGGCUGCAGAGGUC 21 5211 SCNN1A-1363 + CCUGGUAUGGGCUGCAGAGGUC 22 5212 SCNN1A-1364 + ACCUGGUAUGGGCUGCAGAGGUC 23 5213 SCNN1A-1365 + UCCCCUUGGAAGGGACAG 18 5214 SCNN1A-1366 + CUCCCCUUGGAAGGGACAG 19 5215 SCNN1A-1367 + CCUCCCCUUGGAAGGGACAG 20 5216 SCNN1A-1368 + ACCUCCCCUUGGAAGGGACAG 21 5217 SCNN1A-1369 + UACCUCCCCUUGGAAGGGACAG 22 5218 SCNN1A-1370 + AUACCUCCCCUUGGAAGGGACAG 23 5219 SCNN1A-6537 + UGGGACUGGUUCCUUUCCAG 20 10386 SCNN1A-6538 + CUGGGACUGGUUCCUUUCCAG 21 10387 SCNN1A-6539 + ACUGGGACUGGUUCCUUUCCAG 22 10388 SCNN1A-6540 + CAGCAAAAGGAUAAGGAG 18 10389 SCNN1A-5654 + UGCAGCAAAAGGAUAAGGAG 20 9503 SCNN1A-6541 + AUGCAGCAAAAGGAUAAGGAG 21 10390 SCNN1A-6542 + AAUGCAGCAAAAGGAUAAGGAG 22 10391 SCNN1A-6543 + UAAUGCAGCAAAAGGAUAAGGAG 23 10392 SCNN1A-6544 + UUAAUGCAGCAAAAGGAUAAGGAG 24 10393 SCNN1A-6545 + UAUCAAGGGCUCUGUGAG 18 10394 SCNN1A-6546 + AUAUCAAGGGCUCUGUGAG 19 10395 SCNN1A-6547 + CAUAUCAAGGGCUCUGUGAG 20 10396 SCNN1A-6548 + UCAUAUCAAGGGCUCUGUGAG 21 10397 SCNN1A-6549 + UUCAUAUCAAGGGCUCUGUGAG 22 10398 SCNN1A-6550 + UUUCAUAUCAAGGGCUCUGUGAG 23 10399 SCNN1A-6551 + UUUUCAUAUCAAGGGCUCUGUGAG 24 10400 SCNN1A-6552 + AGGGGCAAAGAUCUGAACAAGUAG 24 10401 SCNN1A-6553 + AGGCACUGAAGGUGCAGG 18 10402 SCNN1A-6554 + CAGGCACUGAAGGUGCAGG 19 10403 SCNN1A-6555 + UGGGAGCAGCGCACUCAGG 19 10404 SCNN1A-6556 + AGUGGGAGCAGCGCACUCAGG 21 10405 SCNN1A-6557 + AAGUGGGAGCAGCGCACUCAGG 22 10406 SCNN1A-6558 + UAAGUGGGAGCAGCGCACUCAGG 23 10407 SCNN1A-6559 + CUAAGUGGGAGCAGCGCACUCAGG 24 10408 SCNN1A-6560 + CAGGAAGGAGAGCAAGGG 18 10409 SCNN1A-6561 + CCAGGAAGGAGAGCAAGGG 19 10410 SCNN1A-6159 + UCCAGGAAGGAGAGCAAGGG 20 10008 SCNN1A-6562 + UCCUGAGACAGACUCAUG 18 10411 SCNN1A-6563 + UUCCUGAGACAGACUCAUG 19 10412 SCNN1A-5698 + CUUCCUGAGACAGACUCAUG 20 9547 SCNN1A-6564 + ACUUCCUGAGACAGACUCAUG 21 10413 SCNN1A-6565 + UACUUCCUGAGACAGACUCAUG 22 10414 SCNN1A-6566 + UUACUUCCUGAGACAGACUCAUG 23 10415 SCNN1A-6567 + UUUACUUCCUGAGACAGACUCAUG 24 10416 SCNN1A-6568 + UCGUCUGCUCUCUGGGUG 18 10417 SCNN1A-6569 + UUCGUCUGCUCUCUGGGUG 19 10418 SCNN1A-6570 + AUUCGUCUGCUCUCUGGGUG 20 10419 SCNN1A-6571 + UGGAUUCGUCUGCUCUCUGGGUG 23 10420 SCNN1A-6572 + AGCGAAGGACAGAGAGAU 18 10421 SCNN1A-6573 + CAGCGAAGGACAGAGAGAU 19 10422 SCNN1A-5722 + ACAGCGAAGGACAGAGAGAU 20 9571 SCNN1A-6574 + CCCGAGGGCAGGUGAACU 18 10423 SCNN1A-6575 + UCCCGAGGGCAGGUGAACU 19 10424 SCNN1A-5726 + CUCCCGAGGGCAGGUGAACU 20 9575 SCNN1A-6576 + AAGGCAGUACUCCAGGCU 18 10425 SCNN1A-6577 + AAAGGCAGUACUCCAGGCU 19 10426 SCNN1A-6578 + AAAAGGCAGUACUCCAGGCU 20 10427 SCNN1A-6579 + CGUGGAUUCGUCUGCUCU 18 10428 SCNN1A-6580 + CCGUGGAUUCGUCUGCUCU 19 10429 SCNN1A-6581 + CCCGUGGAUUCGUCUGCUCU 20 10430 SCNN1A-6582 + AGCCCGUGGAUUCGUCUGCUCU 22 10431 SCNN1A-6583 + AGAGCCCGUGGAUUCGUCUGCUCU 24 10432 SCNN1A-6584 + UCUGCCUUCUGUUUCUCU 18 10433 SCNN1A-6585 + AUCUGCCUUCUGUUUCUCU 19 10434 SCNN1A-6586 + UAUCUGCCUUCUGUUUCUCU 20 10435 SCNN1A-6587 + CUAUCUGCCUUCUGUUUCUCU 21 10436 SCNN1A-6588 + UCUAUCUGCCUUCUGUUUCUCU 22 10437 SCNN1A-6589 + CUCUAUCUGCCUUCUGUUUCUCU 23 10438 SCNN1A-6590 + UCUCUAUCUGCCUUCUGUUUCUCU 24 10439 SCNN1A-1377 + AUUGGGGAGAGCAAGGGU 18 5226 SCNN1A-1378 + UGGAUUGGGGAGAGCAAGGGU 21 5227 SCNN1A-1379 + AGUGGAUUGGGGAGAGCAAGGGU 23 5228 SCNN1A-6591 + AGAGCUAUAAACAGAAUU 18 10440 SCNN1A-6592 + CAGAGCUAUAAACAGAAUU 19 10441 SCNN1A-6593 + AGCAGAGCUAUAAACAGAAUU 21 10442 SCNN1A-6594 + AGGAGCAGAGCUAUAAACAGAAUU 24 10443 SCNN1A-6595 + CUUCCCUGAUAGGGCCACCUU 21 10444 SCNN1A-6596 + UGCUUCCCUGAUAGGGCCACCUU 23 10445 SCNN1A-6597 + CUGCUUCCCUGAUAGGGCCACCUU 24 10446 SCNN1A-6598 CAACAGUGUAAAAAAGAA 18 10447 SCNN1A-6599 CCAACAGUGUAAAAAAGAA 19 10448 SCNN1A-6600 AGCCAACAGUGUAAAAAAGAA 21 10449 SCNN1A-6601 CAGCCAACAGUGUAAAAAAGAA 22 10450 SCNN1A-6602 AGAAAAUAUAGCCCAUCA 18 10451 SCNN1A-6603 UGCAGUCCUGGGGCAGAGA 19 10452 SCNN1A-6604 CUGCAGUCCUGGGGCAGAGA 20 10453 SCNN1A-5553 CGGGUCUGGACAAGGUUGGA 20 9402 SCNN1A-6605 CCGGGUCUGGACAAGGUUGGA 21 10454 SCNN1A-6606 CCCGGGUCUGGACAAGGUUGGA 22 10455 SCNN1A-6607 UCCCGGGUCUGGACAAGGUUGGA 23 10456 SCNN1A-6608 CUCCCGGGUCUGGACAAGGUUGGA 24 10457 SCNN1A-6609 AGGAGGCAGACGCAUCCCAC 20 10458 SCNN1A-6610 AGGAGGAGGCAGACGCAUCCCAC 23 10459 SCNN1A-6611 CAGGAGGAGGCAGACGCAUCCCAC 24 10460 SCNN1A-1392 UGGCCAGGGGCAGCCUCAC 19 5241 SCNN1A-1393 AUGGCCAGGGGCAGCCUCAC 20 5242 SCNN1A-6612 ACCUGGCUCAAGGGAGAC 18 10461 SCNN1A-6613 CCUGAGCCCCGAUCCCCC 18 10462 SCNN1A-6614 ACCUGAGCCCCGAUCCCCC 19 10463 SCNN1A-6615 CACCUGAGCCCCGAUCCCCC 20 10464 SCNN1A-6616 UGCACCUGAGCCCCGAUCCCCC 22 10465 SCNN1A-6617 CAGGUUGGACCCUGAGCC 18 10466 SCNN1A-6618 CCAGGUUGGACCCUGAGCC 19 10467 SCNN1A-5581 ACCAGGUUGGACCCUGAGCC 20 9430 SCNN1A-6619 AGACCAGGUUGGACCCUGAGCC 22 10468 SCNN1A-6620 CAGACCAGGUUGGACCCUGAGCC 23 10469 SCNN1A-6621 ACAGACCAGGUUGGACCCUGAGCC 24 10470 SCNN1A-6622 UGCGUCUAAAGCCCCUGCC 19 10471 SCNN1A-6623 CUGCGUCUAAAGCCCCUGCC 20 10472 SCNN1A-6624 UCUGCGUCUAAAGCCCCUGCC 21 10473 SCNN1A-6625 UGUCUGCGUCUAAAGCCCCUGCC 23 10474 SCNN1A-6626 CUGUCUGCGUCUAAAGCCCCUGCC 24 10475 SCNN1A-1394 CAGCCUCACUCGGGUUCC 18 5243 SCNN1A-6627 CCUUUGAGAUCAAACAGC 18 10476 SCNN1A-6628 ACCUUUGAGAUCAAACAGC 19 10477 SCNN1A-6629 AACCUUUGAGAUCAAACAGC 20 10478 SCNN1A-6630 AGAACCUUUGAGAUCAAACAGC 22 10479 SCNN1A-6631 CAGAACCUUUGAGAUCAAACAGC 23 10480 SCNN1A-6632 UCAGAACCUUUGAGAUCAAACAGC 24 10481 SCNN1A-6633 CCCUGCCGCGUGCAGGGC 18 10482 SCNN1A-6634 UCCCUGCCGCGUGCAGGGC 19 10483 SCNN1A-6635 UUCCCUGCCGCGUGCAGGGC 20 10484 SCNN1A-6636 CUUCCCUGCCGCGUGCAGGGC 21 10485 SCNN1A-6637 CCUUCCCUGCCGCGUGCAGGGC 22 10486 SCNN1A-6638 AGCCUUCCCUGCCGCGUGCAGGGC 24 10487 SCNN1A-6639 AGCUUCACCUGGGCCCCUC 19 10488 SCNN1A-6640 CAGCUUCACCUGGGCCCCUC 20 10489 SCNN1A-6641 CCAGCUUCACCUGGGCCCCUC 21 10490 SCNN1A-6642 CCCAGCUUCACCUGGGCCCCUC 22 10491 SCNN1A-6643 CCCCAGCUUCACCUGGGCCCCUC 23 10492 SCNN1A-6644 CCCCCAGCUUCACCUGGGCCCCUC 24 10493 SCNN1A-6645 UGGAGUUUCUAGGGGUCUC 19 10494 SCNN1A-5635 CUGGAGUUUCUAGGGGUCUC 20 9484 SCNN1A-6646 ACUGGAGUUUCUAGGGGUCUC 21 10495 SCNN1A-6647 AGACUGGAGUUUCUAGGGGUCUC 23 10496 SCNN1A-6648 CCAGCACCCAGAGAGCAG 18 10497 SCNN1A-6649 CCCAGCACCCAGAGAGCAG 19 10498 SCNN1A-6650 ACCCAGCACCCAGAGAGCAG 20 10499 SCNN1A-6651 AACCCAGCACCCAGAGAGCAG 21 10500 SCNN1A-6652 UAACCCAGCACCCAGAGAGCAG 22 10501 SCNN1A-6653 AUAACCCAGCACCCAGAGAGCAG 23 10502 SCNN1A-6654 AUAGCCCCAGAGGAGGAG 18 10503 SCNN1A-6655 AGAUAGCCCCAGAGGAGGAG 20 10504 SCNN1A-6656 UAGAUAGCCCCAGAGGAGGAG 21 10505 SCNN1A-6657 AGUAGAUAGCCCCAGAGGAGGAG 23 10506 SCNN1A-6658 AAGUAGAUAGCCCCAGAGGAGGAG 24 10507 SCNN1A-6659 AGUGGGAGAAUGUGGGCG 18 10508 SCNN1A-6660 AGGUUGGAGGGGGUGGCG 18 10509 SCNN1A-6661 AAGGUUGGAGGGGGUGGCG 19 10510 SCNN1A-5670 CAAGGUUGGAGGGGGUGGCG 20 9519 SCNN1A-6662 ACAAGGUUGGAGGGGGUGGCG 21 10511 SCNN1A-6663 UGGACAAGGUUGGAGGGGGUGGCG 24 10512 SCNN1A-6664 AACUGAUUUAUCCUUGGG 18 10513 SCNN1A-6665 AAACUGAUUUAUCCUUGGG 19 10514 SCNN1A-6666 AAAACUGAUUUAUCCUUGGG 20 10515 SCNN1A-6667 UGCUGCCUUAAGCUAGUGG 19 10516 SCNN1A-6668 AUGCUGCCUUAAGCUAGUGG 20 10517 SCNN1A-6669 CAUGCUGCCUUAAGCUAGUGG 21 10518 SCNN1A-6670 CCAUGCUGCCUUAAGCUAGUGG 22 10519 SCNN1A-6671 UGCCAUGCUGCCUUAAGCUAGUGG 24 10520 SCNN1A-6672 CCAGUCCAGCCGCAACCU 18 10521 SCNN1A-6673 CCCAGUCCAGCCGCAACCU 19 10522 SCNN1A-5731 UCCCAGUCCAGCCGCAACCU 20 9580 SCNN1A-6674 AGUCCCAGUCCAGCCGCAACCU 22 10523 SCNN1A-6675 CAGUCCCAGUCCAGCCGCAACCU 23 10524 SCNN1A-6676 CCAGUCCCAGUCCAGCCGCAACCU 24 10525 SCNN1A-6677 UGAGGGUGAGGCUGACCU 18 10526 SCNN1A-6678 CUGAGGGUGAGGCUGACCU 19 10527 SCNN1A-6679 CCUGAGGGUGAGGCUGACCU 20 10528 SCNN1A-6680 AGGGCCUGAGGGUGAGGCUGACCU 24 10529 SCNN1A-6681 CUCUUCUCUGCAGGGCCU 18 10530 SCNN1A-6682 UCUCUUCUCUGCAGGGCCU 19 10531 SCNN1A-6683 CUCUCUUCUCUGCAGGGCCU 20 10532 SCNN1A-6684 UCUCUCUUCUCUGCAGGGCCU 21 10533 SCNN1A-6685 UUCUCUCUUCUCUGCAGGGCCU 22 10534 SCNN1A-6686 CUUCUCUCUUCUCUGCAGGGCCU 23 10535 SCNN1A-6687 UCUUCUCUCUUCUCUGCAGGGCCU 24 10536 SCNN1A-6688 CCUGCCUCUUCCUGGGCU 18 10537 SCNN1A-6689 CCCUGCCUCUUCCUGGGCU 19 10538 SCNN1A-6690 UCCCUGCCUCUUCCUGGGCU 20 10539 SCNN1A-6691 CCCUCCUAGCUGUGGGCU 18 10540 SCNN1A-6692 UGCCCUCCUAGCUGUGGGCU 20 10541 SCNN1A-6693 AGGGAGACUGGAGUUUCU 18 10542 SCNN1A-6694 AAGGGAGACUGGAGUUUCU 19 10543 SCNN1A-5751 CAAGGGAGACUGGAGUUUCU 20 9600 SCNN1A-6695 UCAAGGGAGACUGGAGUUUCU 21 10544 SCNN1A-6696 CUCAAGGGAGACUGGAGUUUCU 22 10545 SCNN1A-6697 AAUCCACGGGCUCUGUGU 18 10546 SCNN1A-5766 CGAAUCCACGGGCUCUGUGU 20 9615 SCNN1A-6698 ACGAAUCCACGGGCUCUGUGU 21 10547 SCNN1A-6699 AGACGAAUCCACGGGCUCUGUGU 23 10548 SCNN1A-6700 CAGACGAAUCCACGGGCUCUGUGU 24 10549 SCNN1A-6701 CGUGCAGGGCCUGGGUUGU 19 10550 SCNN1A-6702 CGCGUGCAGGGCCUGGGUUGU 21 10551 SCNN1A-6703 CCGCGUGCAGGGCCUGGGUUGU 22 10552 SCNN1A-6704 UGCCGCGUGCAGGGCCUGGGUUGU 24 10553 SCNN1A-1405 AAGCAAGGGAACCUGGUU 18 5254 SCNN1A-1406 UAAGCAAGGGAACCUGGUU 19 5255 SCNN1A-1407 AGGUAAGCAAGGGAACCUGGUU 22 5256 SCNN1A-1408 AAGGUAAGCAAGGGAACCUGGUU 23 5257 SCNN1A-1409 CAAGGUAAGCAAGGGAACCUGGUU 24 5258 SCNN1A-6705 AGUCUCCUCCAGCCCUUU 18 10554 SCNN1A-6706 CGAGUCUCCUCCAGCCCUUU 20 10555 SCNN1A-6707 CCGAGUCUCCUCCAGCCCUUU 21 10556 SCNN1A-6708 CCCGAGUCUCCUCCAGCCCUUU 22 10557 SCNN1A-6709 UCCCGAGUCUCCUCCAGCCCUUU 23 10558 SCNN1A-6710 CUCCCGAGUCUCCUCCAGCCCUUU 24 10559

Table 47C provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 47C 3rd Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-6711 + AUAGAAGGAGCCAGCACCAAA 21 10560 SCNN1A-6712 + AAUAGAAGGAGCCAGCACCAAA 22 10561 SCNN1A-6713 + AAAUAGAAGGAGCCAGCACCAAA 23 10562 SCNN1A-6714 + CAAAUAGAAGGAGCCAGCACCAAA 24 10563 SCNN1A-6715 + CCAAACUUAAUGCAGCAA 18 10564 SCNN1A-6716 + UCCAAACUUAAUGCAGCAA 19 10565 SCNN1A-6717 + UUCCAAACUUAAUGCAGCAA 20 10566 SCNN1A-6718 + GAUAGGGAUGGAGGAGGGGCA 21 10567 SCNN1A-6719 + AGAUAGGGAUGGAGGAGGGGCA 22 10568 SCNN1A-6720 + GAGAUAGGGAUGGAGGAGGGGCA 23 10569 SCNN1A-6721 + AGAGAUAGGGAUGGAGGAGGGGCA 24 10570 SCNN1A-6722 + GGAGAGAGAGGAGGGUCA 18 10571 SCNN1A-6723 + AGGAGAGAGAGGAGGGUCA 19 10572 SCNN1A-6724 + AAGGAGAGAGAGGAGGGUCA 20 10573 SCNN1A-6725 + CAAGGAGAGAGAGGAGGGUCA 21 10574 SCNN1A-6726 + GCAAGGAGAGAGAGGAGGGUCA 22 10575 SCNN1A-6727 + AGCAAGGAGAGAGAGGAGGGUCA 23 10576 SCNN1A-6728 + GAGCAAGGAGAGAGAGGAGGGUCA 24 10577 SCNN1A-1410 + CCCUUCAUGAGCCCCGGA 18 5259 SCNN1A-1411 + CCCCUUCAUGAGCCCCGGA 19 5260 SCNN1A-1412 + UCCCCUUCAUGAGCCCCGGA 20 5261 SCNN1A-1413 + UUCCCCUUCAUGAGCCCCGGA 21 5262 SCNN1A-1414 + GUUCCCCUUCAUGAGCCCCGGA 22 5263 SCNN1A-1415 + UGUUCCCCUUCAUGAGCCCCGGA 23 5264 SCNN1A-1416 + UUGUUCCCCUUCAUGAGCCCCGGA 24 5265 SCNN1A-6729 + GGCAAGGAGGCUGGGGGA 18 10578 SCNN1A-6730 + AGGCAAGGAGGCUGGGGGA 19 10579 SCNN1A-6731 + CAGGCAAGGAGGCUGGGGGA 20 10580 SCNN1A-6732 + ACAGGCAAGGAGGCUGGGGGA 21 10581 SCNN1A-6733 + GACAGGCAAGGAGGCUGGGGGA 22 10582 SCNN1A-6734 + AGACAGGCAAGGAGGCUGGGGGA 23 10583 SCNN1A-6735 + CAGACAGGCAAGGAGGCUGGGGGA 24 10584 SCNN1A-6736 + AUGGAGGAGGGGCACUGA 18 10585 SCNN1A-6737 + GAUGGAGGAGGGGCACUGA 19 10586 SCNN1A-6738 + GGAUGGAGGAGGGGCACUGA 20 10587 SCNN1A-6739 + GGGAUGGAGGAGGGGCACUGA 21 10588 SCNN1A-6740 + AGGGAUGGAGGAGGGGCACUGA 22 10589 SCNN1A-6741 + UAGGGAUGGAGGAGGGGCACUGA 23 10590 SCNN1A-6742 + AUAGGGAUGGAGGAGGGGCACUGA 24 10591 SCNN1A-6743 + ACUUAAUGCAGCAAAAGGAUA 21 10592 SCNN1A-6744 + AACUUAAUGCAGCAAAAGGAUA 22 10593 SCNN1A-6745 + AAACUUAAUGCAGCAAAAGGAUA 23 10594 SCNN1A-6746 + CAAACUUAAUGCAGCAAAAGGAUA 24 10595 SCNN1A-6747 + CCUCACUCCCACACAGAGCCC 21 10596 SCNN1A-6748 + CCCUCACUCCCACACAGAGCCC 22 10597 SCNN1A-6749 + UCCCUCACUCCCACACAGAGCCC 23 10598 SCNN1A-6750 + CUCCCUCACUCCCACACAGAGCCC 24 10599 SCNN1A-1417 + GUUCCCCUUCAUGAGCCC 18 5266 SCNN1A-1418 + UGUUCCCCUUCAUGAGCCC 19 5267 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20 599 SCNN1A-1419 + CUUGUUCCCCUUCAUGAGCCC 21 5268 SCNN1A-1420 + GCUUGUUCCCCUUCAUGAGCCC 22 5269 SCNN1A-1421 + AGCUUGUUCCCCUUCAUGAGCCC 23 5270 SCNN1A-1422 + CAGCUUGUUCCCCUUCAUGAGCCC 24 5271 SCNN1A-6751 + GGCUGAGGAGGAGUCAGAGCC 21 10600 SCNN1A-6752 + GGGCUGAGGAGGAGUCAGAGCC 22 10601 SCNN1A-6753 + GGGGCUGAGGAGGAGUCAGAGCC 23 10602 SCNN1A-6754 + AGGGGCUGAGGAGGAGUCAGAGCC 24 10603 SCNN1A-6755 + CAGCCAGGCUGAGAGGGC 18 10604 SCNN1A-6756 + CCAGCCAGGCUGAGAGGGC 19 10605 SCNN1A-6757 + GCCAGCCAGGCUGAGAGGGC 20 10606 SCNN1A-6758 + GGCCAGCCAGGCUGAGAGGGC 21 10607 SCNN1A-6759 + GGGCCAGCCAGGCUGAGAGGGC 22 10608 SCNN1A-6760 + GGGGCCAGCCAGGCUGAGAGGGC 23 10609 SCNN1A-6761 + AGGGGCCAGCCAGGCUGAGAGGGC 24 10610 SCNN1A-1431 + GAGUGGACUGUGGAGGGC 18 5280 SCNN1A-1432 + GGAGUGGACUGUGGAGGGC 19 5281 SCNN1A-201 + UGGAGUGGACUGUGGAGGGC 20 830 SCNN1A-6762 + UCCUGGAGCCAGCAGACCUGC 21 10611 SCNN1A-6763 + UUCCUGGAGCCAGCAGACCUGC 22 10612 SCNN1A-6764 + UUUCCUGGAGCCAGCAGACCUGC 23 10613 SCNN1A-6765 + CUUUCCUGGAGCCAGCAGACCUGC 24 10614 SCNN1A-6766 + CUUCCUUUGGUCUUCUUCCUC 21 10615 SCNN1A-6767 + CCUUCCUUUGGUCUUCUUCCUC 22 10616 SCNN1A-6768 + CCCUUCCUUUGGUCUUCUUCCUC 23 10617 SCNN1A-6769 + CCCCUUCCUUUGGUCUUCUUCCUC 24 10618 SCNN1A-6770 + GUGAGCAAGGAGAGAGAG 18 10619 SCNN1A-6771 + GGUGAGCAAGGAGAGAGAG 19 10620 SCNN1A-6772 + UGGUGAGCAAGGAGAGAGAG 20 10621 SCNN1A-6773 + GUGGUGAGCAAGGAGAGAGAG 21 10622 SCNN1A-6774 + AGUGGUGAGCAAGGAGAGAGAG 22 10623 SCNN1A-6775 + AAGUGGUGAGCAAGGAGAGAGAG 23 10624 SCNN1A-6776 + CAAGUGGUGAGCAAGGAGAGAGAG 24 10625 SCNN1A-6777 + AAAGAUCUGAACAAGUAG 18 10626 SCNN1A-6778 + CAAAGAUCUGAACAAGUAG 19 10627 SCNN1A-6779 + GCAAAGAUCUGAACAAGUAG 20 10628 SCNN1A-6780 + AGCAGGCACUGAAGGUGCAGG 21 10629 SCNN1A-6781 + AAGCAGGCACUGAAGGUGCAGG 22 10630 SCNN1A-6782 + AAAGCAGGCACUGAAGGUGCAGG 23 10631 SCNN1A-6783 + GAAAGCAGGCACUGAAGGUGCAGG 24 10632 SCNN1A-6784 + CGGGGGGAGGGGCUGAGG 18 10633 SCNN1A-6785 + GCGGGGGGAGGGGCUGAGG 19 10634 SCNN1A-5907 + GGCGGGGGGAGGGGCUGAGG 20 9756 SCNN1A-6786 + GGGCGGGGGGAGGGGCUGAGG 21 10635 SCNN1A-6787 + AGGGCGGGGGGAGGGGCUGAGG 22 10636 SCNN1A-6788 + CAGGGCGGGGGGAGGGGCUGAGG 23 10637 SCNN1A-6789 + GCAGGGCGGGGGGAGGGGCUGAGG 24 10638 SCNN1A-6790 + CUCCAGGAAGGAGAGCAAGGG 21 10639 SCNN1A-6791 + UCUCCAGGAAGGAGAGCAAGGG 22 10640 SCNN1A-6792 + GUCUCCAGGAAGGAGAGCAAGGG 23 10641 SCNN1A-6793 + UGUCUCCAGGAAGGAGAGCAAGGG 24 10642 SCNN1A-6794 + GAGAAGGUGUCAUCUCUG 18 10643 SCNN1A-6795 + AGAGAAGGUGUCAUCUCUG 19 10644 SCNN1A-6796 + CAGAGAAGGUGUCAUCUCUG 20 10645 SCNN1A-6797 + CCAGAGAAGGUGUCAUCUCUG 21 10646 SCNN1A-6798 + CCCAGAGAAGGUGUCAUCUCUG 22 10647 SCNN1A-6799 + UCCCAGAGAAGGUGUCAUCUCUG 23 10648 SCNN1A-6800 + UUCCCAGAGAAGGUGUCAUCUCUG 24 10649 SCNN1A-6801 + GACAGCGAAGGACAGAGAGAU 21 10650 SCNN1A-6802 + GGACAGCGAAGGACAGAGAGAU 22 10651 SCNN1A-6803 + GGGACAGCGAAGGACAGAGAGAU 23 10652 SCNN1A-6804 + AGGGACAGCGAAGGACAGAGAGAU 24 10653 SCNN1A-6805 + GCUCCCGAGGGCAGGUGAACU 21 10654 SCNN1A-6806 + GGCUCCCGAGGGCAGGUGAACU 22 10655 SCNN1A-6807 + GGGCUCCCGAGGGCAGGUGAACU 23 10656 SCNN1A-6808 + AGGGCUCCCGAGGGCAGGUGAACU 24 10657 SCNN1A-6809 + GAAAAGGCAGUACUCCAGGCU 21 10658 SCNN1A-6810 + AGAAAAGGCAGUACUCCAGGCU 22 10659 SCNN1A-6811 + GAGAAAAGGCAGUACUCCAGGCU 23 10660 SCNN1A-6812 + AGAGAAAAGGCAGUACUCCAGGCU 24 10661 SCNN1A-6813 + CCCUGAUAGGGCCACCUU 18 10662 SCNN1A-6814 + UCCCUGAUAGGGCCACCUU 19 10663 SCNN1A-6815 + UUCCCUGAUAGGGCCACCUU 20 10664 SCNN1A-6816 UGGAGAAAAUAUAGCCCAUCA 21 10665 SCNN1A-6817 UUGGAGAAAAUAUAGCCCAUCA 22 10666 SCNN1A-6818 UUUGGAGAAAAUAUAGCCCAUCA 23 10667 SCNN1A-6819 UUUUGGAGAAAAUAUAGCCCAUCA 24 10668 SCNN1A-6820 CCUGCAGUCCUGGGGCAGAGA 21 10669 SCNN1A-6821 CCCUGCAGUCCUGGGGCAGAGA 22 10670 SCNN1A-6822 GCCCUGCAGUCCUGGGGCAGAGA 23 10671 SCNN1A-6823 AGCCCUGCAGUCCUGGGGCAGAGA 24 10672 SCNN1A-6824 ACAGAAGGCAGAUAGAGA 18 10673 SCNN1A-6825 AACAGAAGGCAGAUAGAGA 19 10674 SCNN1A-6088 AAACAGAAGGCAGAUAGAGA 20 9937 SCNN1A-6826 GAAACAGAAGGCAGAUAGAGA 21 10675 SCNN1A-6827 AGAAACAGAAGGCAGAUAGAGA 22 10676 SCNN1A-6828 GAGAAACAGAAGGCAGAUAGAGA 23 10677 SCNN1A-6829 AGAGAAACAGAAGGCAGAUAGAGA 24 10678 SCNN1A-1437 CAUGGCCAGGGGCAGCCUCAC 21 5286 SCNN1A-1438 GCAUGGCCAGGGGCAGCCUCAC 22 5287 SCNN1A-1439 GGCAUGGCCAGGGGCAGCCUCAC 23 5288 SCNN1A-1440 GGGCAUGGCCAGGGGCAGCCUCAC 24 5289 SCNN1A-6830 AGGACCUGGCUCAAGGGAGAC 21 10679 SCNN1A-6831 AAGGACCUGGCUCAAGGGAGAC 22 10680 SCNN1A-6832 UAAGGACCUGGCUCAAGGGAGAC 23 10681 SCNN1A-6833 GUAAGGACCUGGCUCAAGGGAGAC 24 10682 SCNN1A-6834 AGGCUGGAGCUGAGGGCC 18 10683 SCNN1A-6835 GAGGCUGGAGCUGAGGGCC 19 10684 SCNN1A-6836 AGAGGCUGGAGCUGAGGGCC 20 10685 SCNN1A-6837 CAGAGGCUGGAGCUGAGGGCC 21 10686 SCNN1A-6838 CCAGAGGCUGGAGCUGAGGGCC 22 10687 SCNN1A-6839 GCCAGAGGCUGGAGCUGAGGGCC 23 10688 SCNN1A-6840 GGCCAGAGGCUGGAGCUGAGGGCC 24 10689 SCNN1A-1441 GGGCAGCCUCACUCGGGUUCC 21 5290 SCNN1A-1442 GGGGCAGCCUCACUCGGGUUCC 22 5291 SCNN1A-1443 AGGGGCAGCCUCACUCGGGUUCC 23 5292 SCNN1A-1444 CAGGGGCAGCCUCACUCGGGUUCC 24 5293 SCNN1A-6841 UGGGUUGUGUGGGUGGCUCUC 21 10690 SCNN1A-6842 CUGGGUUGUGUGGGUGGCUCUC 22 10691 SCNN1A-6843 CCUGGGUUGUGUGGGUGGCUCUC 23 10692 SCNN1A-6844 GCCUGGGUUGUGUGGGUGGCUCUC 24 10693 SCNN1A-6845 CUUCUCUGGGAAGGCUUC 18 10694 SCNN1A-6846 CCUUCUCUGGGAAGGCUUC 19 10695 SCNN1A-6847 ACCUUCUCUGGGAAGGCUUC 20 10696 SCNN1A-6848 CACCUUCUCUGGGAAGGCUUC 21 10697 SCNN1A-6849 ACACCUUCUCUGGGAAGGCUUC 22 10698 SCNN1A-6850 GACACCUUCUCUGGGAAGGCUUC 23 10699 SCNN1A-6851 UGACACCUUCUCUGGGAAGGCUUC 24 10700 SCNN1A-6852 AGGAGUGGGAGAAUGUGGGCG 21 10701 SCNN1A-6853 GAGGAGUGGGAGAAUGUGGGCG 22 10702 SCNN1A-6854 GGAGGAGUGGGAGAAUGUGGGCG 23 10703 SCNN1A-6855 GGGAGGAGUGGGAGAAUGUGGGCG 24 10704 SCNN1A-6856 GGGGGAGAGGAAGAGAGG 18 10705 SCNN1A-6857 GGGGGGAGAGGAAGAGAGG 19 10706 SCNN1A-6858 GGGGGGGAGAGGAAGAGAGG 20 10707 SCNN1A-6859 AGGGGGGGAGAGGAAGAGAGG 21 10708 SCNN1A-6860 AAGGGGGGGAGAGGAAGAGAGG 22 10709 SCNN1A-6861 CAAGGGGGGGAGAGGAAGAGAGG 23 10710 SCNN1A-6862 GCAAGGGGGGGAGAGGAAGAGAGG 24 10711 SCNN1A-6863 AAGGUGGAGGAGGGAGGG 18 10712 SCNN1A-6864 AAAGGUGGAGGAGGGAGGG 19 10713 SCNN1A-5911 GAAAGGUGGAGGAGGGAGGG 20 9760 SCNN1A-6865 GGAAAGGUGGAGGAGGGAGGG 21 10714 SCNN1A-6866 AGGAAAGGUGGAGGAGGGAGGG 22 10715 SCNN1A-6867 CAGGAAAGGUGGAGGAGGGAGGG 23 10716 SCNN1A-6868 CCAGGAAAGGUGGAGGAGGGAGGG 24 10717 SCNN1A-6869 GAAAACUGAUUUAUCCUUGGG 21 10718 SCNN1A-6870 AGAAAACUGAUUUAUCCUUGGG 22 10719 SCNN1A-6871 CAGAAAACUGAUUUAUCCUUGGG 23 10720 SCNN1A-6872 UCAGAAAACUGAUUUAUCCUUGGG 24 10721 SCNN1A-6873 GGAGGGAGGGAGGAGUGG 18 10722 SCNN1A-6874 AGGAGGGAGGGAGGAGUGG 19 10723 SCNN1A-6875 GAGGAGGGAGGGAGGAGUGG 20 10724 SCNN1A-6876 GGAGGAGGGAGGGAGGAGUGG 21 10725 SCNN1A-6877 UGGAGGAGGGAGGGAGGAGUGG 22 10726 SCNN1A-6878 GUGGAGGAGGGAGGGAGGAGUGG 23 10727 SCNN1A-6879 GGUGGAGGAGGGAGGGAGGAGUGG 24 10728 SCNN1A-6880 UUCCCUGCCUCUUCCUGGGCU 21 10729 SCNN1A-6881 UUUCCCUGCCUCUUCCUGGGCU 22 10730 SCNN1A-6882 CUUUCCCUGCCUCUUCCUGGGCU 23 10731 SCNN1A-6883 GCUUUCCCUGCCUCUUCCUGGGCU 24 10732 SCNN1A-6884 UUGCCCUCCUAGCUGUGGGCU 21 10733 SCNN1A-6885 GUUGCCCUCCUAGCUGUGGGCU 22 10734 SCNN1A-6886 UGUUGCCCUCCUAGCUGUGGGCU 23 10735 SCNN1A-6887 GUGUUGCCCUCCUAGCUGUGGGCU 24 10736 SCNN1A-6888 CAGAGGAGGAGGAGAAUU 18 10737 SCNN1A-6889 CCAGAGGAGGAGGAGAAUU 19 10738 SCNN1A-6890 CCCAGAGGAGGAGGAGAAUU 20 10739 SCNN1A-6891 CCCCAGAGGAGGAGGAGAAUU 21 10740 SCNN1A-6892 GCCCCAGAGGAGGAGGAGAAUU 22 10741 SCNN1A-6893 AGCCCCAGAGGAGGAGGAGAAUU 23 10742 SCNN1A-6894 UAGCCCCAGAGGAGGAGGAGAAUU 24 10743

Table 47D provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 47D 4th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-6895 + UGAGGUUAGAAAACAAAA 18 10744 SCNN1A-6896 + CUGAGGUUAGAAAACAAAA 19 10745 SCNN1A-6897 + UCUGAGGUUAGAAAACAAAA 20 10746 SCNN1A-6898 + UUCUGAGGUUAGAAAACAAAA 21 10747 SCNN1A-6899 + UUUCUGAGGUUAGAAAACAAAA 22 10748 SCNN1A-6900 + UUUUCUGAGGUUAGAAAACAAAA 23 10749 SCNN1A-6901 + GUUUUCUGAGGUUAGAAAACAAAA 24 10750 SCNN1A-6902 + CAGAGAAUCAGACCCAAA 18 10751 SCNN1A-6903 + UCAGAGAAUCAGACCCAAA 19 10752 SCNN1A-6904 + GUCAGAGAAUCAGACCCAAA 20 10753 SCNN1A-6905 + GGUCAGAGAAUCAGACCCAAA 21 10754 SCNN1A-6906 + GGGUCAGAGAAUCAGACCCAAA 22 10755 SCNN1A-6907 + AGGGUCAGAGAAUCAGACCCAAA 23 10756 SCNN1A-6908 + GAGGGUCAGAGAAUCAGACCCAAA 24 10757 SCNN1A-6909 + GGCAGUGGUGGGGGCAAA 18 10758 SCNN1A-6910 + GGGCAGUGGUGGGGGCAAA 19 10759 SCNN1A-6911 + GGGGCAGUGGUGGGGGCAAA 20 10760 SCNN1A-6912 + GGGGGCAGUGGUGGGGGCAAA 21 10761 SCNN1A-6913 + GGGGGGCAGUGGUGGGGGCAAA 22 10762 SCNN1A-6914 + UGGGGGGCAGUGGUGGGGGCAAA 23 10763 SCNN1A-6915 + GUGGGGGGCAGUGGUGGGGGCAAA 24 10764 SCNN1A-6916 + AGGACAGGAGGGCAGAAA 18 10765 SCNN1A-6917 + GAGGACAGGAGGGCAGAAA 19 10766 SCNN1A-6918 + GGAGGACAGGAGGGCAGAAA 20 10767 SCNN1A-6919 + GGGAGGACAGGAGGGCAGAAA 21 10768 SCNN1A-6920 + CGGGAGGACAGGAGGGCAGAAA 22 10769 SCNN1A-6921 + CCGGGAGGACAGGAGGGCAGAAA 23 10770 SCNN1A-6922 + ACCGGGAGGACAGGAGGGCAGAAA 24 10771 SCNN1A-6923 + CUCUUGCGACUUCUUAAA 18 10772 SCNN1A-6924 + UCUCUUGCGACUUCUUAAA 19 10773 SCNN1A-6925 + GUCUCUUGCGACUUCUUAAA 20 10774 SCNN1A-6926 + AGUCUCUUGCGACUUCUUAAA 21 10775 SCNN1A-6927 + CAGUCUCUUGCGACUUCUUAAA 22 10776 SCNN1A-6928 + GCAGUCUCUUGCGACUUCUUAAA 23 10777 SCNN1A-6929 + GGCAGUCUCUUGCGACUUCUUAAA 24 10778 SCNN1A-6930 + UAAAAGAUUGUCUUUAAA 18 10779 SCNN1A-6931 + UUAAAAGAUUGUCUUUAAA 19 10780 SCNN1A-6932 + UUUAAAAGAUUGUCUUUAAA 20 10781 SCNN1A-6933 + CUUUAAAAGAUUGUCUUUAAA 21 10782 SCNN1A-6934 + ACUUUAAAAGAUUGUCUUUAAA 22 10783 SCNN1A-6935 + CACUUUAAAAGAUUGUCUUUAAA 23 10784 SCNN1A-6936 + ACACUUUAAAAGAUUGUCUUUAAA 24 10785 SCNN1A-6937 + GCAGAAAGAGGGAGACAA 18 10786 SCNN1A-6938 + GGCAGAAAGAGGGAGACAA 19 10787 SCNN1A-6939 + GGGCAGAAAGAGGGAGACAA 20 10788 SCNN1A-6940 + AGGGCAGAAAGAGGGAGACAA 21 10789 SCNN1A-6941 + GAGGGCAGAAAGAGGGAGACAA 22 10790 SCNN1A-6942 + GGAGGGCAGAAAGAGGGAGACAA 23 10791 SCNN1A-6943 + AGGAGGGCAGAAAGAGGGAGACAA 24 10792 SCNN1A-6944 + AGAAGGAGCCAGCACCAA 18 10793 SCNN1A-6945 + UAGAAGGAGCCAGCACCAA 19 10794 SCNN1A-5518 + AUAGAAGGAGCCAGCACCAA 20 9367 SCNN1A-6946 + AAUAGAAGGAGCCAGCACCAA 21 10795 SCNN1A-6947 + AAAUAGAAGGAGCCAGCACCAA 22 10796 SCNN1A-6948 + CAAAUAGAAGGAGCCAGCACCAA 23 10797 SCNN1A-6949 + GCAAAUAGAAGGAGCCAGCACCAA 24 10798 SCNN1A-6950 + GAGCUAGAGGCUCAGCAA 18 10799 SCNN1A-6951 + GGAGCUAGAGGCUCAGCAA 19 10800 SCNN1A-6952 + AGGAGCUAGAGGCUCAGCAA 20 10801 SCNN1A-6953 + CAGGAGCUAGAGGCUCAGCAA 21 10802 SCNN1A-6954 + CCAGGAGCUAGAGGCUCAGCAA 22 10803 SCNN1A-6955 + UCCAGGAGCUAGAGGCUCAGCAA 23 10804 SCNN1A-6956 + UUCCAGGAGCUAGAGGCUCAGCAA 24 10805 SCNN1A-6957 + CUCCAGGAAGGAGAGCAA 18 10806 SCNN1A-6958 + UCUCCAGGAAGGAGAGCAA 19 10807 SCNN1A-5168 + GUCUCCAGGAAGGAGAGCAA 20 9017 SCNN1A-6959 + UGUCUCCAGGAAGGAGAGCAA 21 10808 SCNN1A-6960 + CUGUCUCCAGGAAGGAGAGCAA 22 10809 SCNN1A-6961 + UCUGUCUCCAGGAAGGAGAGCAA 23 10810 SCNN1A-6962 + GUCUGUCUCCAGGAAGGAGAGCAA 24 10811 SCNN1A-6963 + AGUUUAGCAGGCAAAGAA 18 10812 SCNN1A-6964 + GAGUUUAGCAGGCAAAGAA 19 10813 SCNN1A-6965 + GGAGUUUAGCAGGCAAAGAA 20 10814 SCNN1A-6966 + AGGAGUUUAGCAGGCAAAGAA 21 10815 SCNN1A-6967 + AAGGAGUUUAGCAGGCAAAGAA 22 10816 SCNN1A-6968 + CAAGGAGUUUAGCAGGCAAAGAA 23 10817 SCNN1A-6969 + GCAAGGAGUUUAGCAGGCAAAGAA 24 10818 SCNN1A-6970 + CUCAGGCCCUGCAGAGAA 18 10819 SCNN1A-6971 + CCUCAGGCCCUGCAGAGAA 19 10820 SCNN1A-6972 + CCCUCAGGCCCUGCAGAGAA 20 10821 SCNN1A-6973 + ACCCUCAGGCCCUGCAGAGAA 21 10822 SCNN1A-6974 + CACCCUCAGGCCCUGCAGAGAA 22 10823 SCNN1A-6975 + UCACCCUCAGGCCCUGCAGAGAA 23 10824 SCNN1A-6976 + CUCACCCUCAGGCCCUGCAGAGAA 24 10825 SCNN1A-6977 + GAGGGCCUGGGUGGGGAA 18 10826 SCNN1A-6978 + AGAGGGCCUGGGUGGGGAA 19 10827 SCNN1A-6979 + GAGAGGGCCUGGGUGGGGAA 20 10828 SCNN1A-6980 + UGAGAGGGCCUGGGUGGGGAA 21 10829 SCNN1A-6981 + CUGAGAGGGCCUGGGUGGGGAA 22 10830 SCNN1A-6982 + GCUGAGAGGGCCUGGGUGGGGAA 23 10831 SCNN1A-6983 + GGCUGAGAGGGCCUGGGUGGGGAA 24 10832 SCNN1A-6984 + AUGUGGCCAGCGCUGGAA 18 10833 SCNN1A-6985 + GAUGUGGCCAGCGCUGGAA 19 10834 SCNN1A-5174 + GGAUGUGGCCAGCGCUGGAA 20 9023 SCNN1A-6986 + AGGAUGUGGCCAGCGCUGGAA 21 10835 SCNN1A-6987 + GAGGAUGUGGCCAGCGCUGGAA 22 10836 SCNN1A-6988 + GGAGGAUGUGGCCAGCGCUGGAA 23 10837 SCNN1A-6989 + GGGAGGAUGUGGCCAGCGCUGGAA 24 10838 SCNN1A-6990 + CUCCCGAGGGCAGGUGAA 18 10839 SCNN1A-6991 + GCUCCCGAGGGCAGGUGAA 19 10840 SCNN1A-6992 + GGCUCCCGAGGGCAGGUGAA 20 10841 SCNN1A-6993 + GGGCUCCCGAGGGCAGGUGAA 21 10842 SCNN1A-6994 + AGGGCUCCCGAGGGCAGGUGAA 22 10843 SCNN1A-6995 + GAGGGCUCCCGAGGGCAGGUGAA 23 10844 SCNN1A-6996 + GGAGGGCUCCCGAGGGCAGGUGAA 24 10845 SCNN1A-6997 + CUCCUCCCCGCUCACUAA 18 10846 SCNN1A-6998 + UCUCCUCCCCGCUCACUAA 19 10847 SCNN1A-6999 + GUCUCCUCCCCGCUCACUAA 20 10848 SCNN1A-7000 + GGUCUCCUCCCCGCUCACUAA 21 10849 SCNN1A-7001 + AGGUCUCCUCCCCGCUCACUAA 22 10850 SCNN1A-7002 + CAGGUCUCCUCCCCGCUCACUAA 23 10851 SCNN1A-7003 + GCAGGUCUCCUCCCCGCUCACUAA 24 10852 SCNN1A-7004 + AGCUAGGAGGGCAACACA 18 10853 SCNN1A-7005 + CAGCUAGGAGGGCAACACA 19 10854 SCNN1A-5527 + ACAGCUAGGAGGGCAACACA 20 9376 SCNN1A-7006 + CACAGCUAGGAGGGCAACACA 21 10855 SCNN1A-7007 + CCACAGCUAGGAGGGCAACACA 22 10856 SCNN1A-7008 + CCCACAGCUAGGAGGGCAACACA 23 10857 SCNN1A-7009 + GCCCACAGCUAGGAGGGCAACACA 24 10858 SCNN1A-7010 + CCUGAGCAUUGAUACACA 18 10859 SCNN1A-7011 + GCCUGAGCAUUGAUACACA 19 10860 SCNN1A-7012 + AGCCUGAGCAUUGAUACACA 20 10861 SCNN1A-7013 + CAGCCUGAGCAUUGAUACACA 21 10862 SCNN1A-7014 + CCAGCCUGAGCAUUGAUACACA 22 10863 SCNN1A-7015 + CCCAGCCUGAGCAUUGAUACACA 23 10864 SCNN1A-7016 + GCCCAGCCUGAGCAUUGAUACACA 24 10865 SCNN1A-7017 + GCCUCCCUCACUCCCACA 18 10866 SCNN1A-7018 + GGCCUCCCUCACUCCCACA 19 10867 SCNN1A-7019 + AGGCCUCCCUCACUCCCACA 20 10868 SCNN1A-7020 + AAGGCCUCCCUCACUCCCACA 21 10869 SCNN1A-7021 + GAAGGCCUCCCUCACUCCCACA 22 10870 SCNN1A-7022 + GGAAGGCCUCCCUCACUCCCACA 23 10871 SCNN1A-7023 + GGGAAGGCCUCCCUCACUCCCACA 24 10872 SCNN1A-7024 + GAGGGACAGCGAAGGACA 18 10873 SCNN1A-7025 + AGAGGGACAGCGAAGGACA 19 10874 SCNN1A-7026 + GAGAGGGACAGCGAAGGACA 20 10875 SCNN1A-7027 + AGAGAGGGACAGCGAAGGACA 21 10876 SCNN1A-7028 + UAGAGAGGGACAGCGAAGGACA 22 10877 SCNN1A-7029 + AUAGAGAGGGACAGCGAAGGACA 23 10878 SCNN1A-7030 + AAUAGAGAGGGACAGCGAAGGACA 24 10879 SCNN1A-7031 + AGACAAUAGAGAGGGACA 18 10880 SCNN1A-7032 + GAGACAAUAGAGAGGGACA 19 10881 SCNN1A-7033 + GGAGACAAUAGAGAGGGACA 20 10882 SCNN1A-7034 + GGGAGACAAUAGAGAGGGACA 21 10883 SCNN1A-7035 + AGGGAGACAAUAGAGAGGGACA 22 10884 SCNN1A-7036 + GAGGGAGACAAUAGAGAGGGACA 23 10885 SCNN1A-7037 + AGAGGGAGACAAUAGAGAGGGACA 24 10886 SCNN1A-7038 + UUGAGCCAGGUCCUUACA 18 10887 SCNN1A-7039 + CUUGAGCCAGGUCCUUACA 19 10888 SCNN1A-7040 + CCUUGAGCCAGGUCCUUACA 20 10889 SCNN1A-7041 + CCCUUGAGCCAGGUCCUUACA 21 10890 SCNN1A-7042 + UCCCUUGAGCCAGGUCCUUACA 22 10891 SCNN1A-7043 + CUCCCUUGAGCCAGGUCCUUACA 23 10892 SCNN1A-7044 + UCUCCCUUGAGCCAGGUCCUUACA 24 10893 SCNN1A-7045 + UAGAAGGAGCCAGCACCA 18 10894 SCNN1A-7046 + AUAGAAGGAGCCAGCACCA 19 10895 SCNN1A-7047 + AAUAGAAGGAGCCAGCACCA 20 10896 SCNN1A-7048 + AAAUAGAAGGAGCCAGCACCA 21 10897 SCNN1A-7049 + CAAAUAGAAGGAGCCAGCACCA 22 10898 SCNN1A-7050 + GCAAAUAGAAGGAGCCAGCACCA 23 10899 SCNN1A-7051 + GGCAAAUAGAAGGAGCCAGCACCA 24 10900 SCNN1A-7052 + GCUUCCUCACGGGCCCCA 18 10901 SCNN1A-7053 + CGCUUCCUCACGGGCCCCA 19 10902 SCNN1A-7054 + CCGCUUCCUCACGGGCCCCA 20 10903 SCNN1A-7055 + GCCGCUUCCUCACGGGCCCCA 21 10904 SCNN1A-7056 + UGCCGCUUCCUCACGGGCCCCA 22 10905 SCNN1A-7057 + CUGCCGCUUCCUCACGGGCCCCA 23 10906 SCNN1A-7058 + GCUGCCGCUUCCUCACGGGCCCCA 24 10907 SCNN1A-7059 + ACUCAGGAAGCCUUCCCA 18 10908 SCNN1A-7060 + GACUCAGGAAGCCUUCCCA 19 10909 SCNN1A-7061 + AGACUCAGGAAGCCUUCCCA 20 10910 SCNN1A-7062 + GAGACUCAGGAAGCCUUCCCA 21 10911 SCNN1A-7063 + GGAGACUCAGGAAGCCUUCCCA 22 10912 SCNN1A-7064 + AGGAGACUCAGGAAGCCUUCCCA 23 10913 SCNN1A-7065 + CAGGAGACUCAGGAAGCCUUCCCA 24 10914 SCNN1A-7066 + UCUCCAGGAAGGAGAGCA 18 10915 SCNN1A-7067 + GUCUCCAGGAAGGAGAGCA 19 10916 SCNN1A-5533 + UGUCUCCAGGAAGGAGAGCA 20 9382 SCNN1A-7068 + CUGUCUCCAGGAAGGAGAGCA 21 10917 SCNN1A-7069 + UCUGUCUCCAGGAAGGAGAGCA 22 10918 SCNN1A-7070 + GUCUGUCUCCAGGAAGGAGAGCA 23 10919 SCNN1A-7071 + AGUCUGUCUCCAGGAAGGAGAGCA 24 10920 SCNN1A-7072 + AGUGCCAAGUGGUGAGCA 18 10921 SCNN1A-7073 + GAGUGCCAAGUGGUGAGCA 19 10922 SCNN1A-5179 + GGAGUGCCAAGUGGUGAGCA 20 9028 SCNN1A-7074 + UGGAGUGCCAAGUGGUGAGCA 21 10923 SCNN1A-7075 + GUGGAGUGCCAAGUGGUGAGCA 22 10924 SCNN1A-7076 + AGUGGAGUGCCAAGUGGUGAGCA 23 10925 SCNN1A-7077 + GAGUGGAGUGCCAAGUGGUGAGCA 24 10926 SCNN1A-7078 + UUUAGACGCAGACAGGCA 18 10927 SCNN1A-7079 + CUUUAGACGCAGACAGGCA 19 10928 SCNN1A-5181 + GCUUUAGACGCAGACAGGCA 20 9030 SCNN1A-7080 + GGCUUUAGACGCAGACAGGCA 21 10929 SCNN1A-7081 + GGGCUUUAGACGCAGACAGGCA 22 10930 SCNN1A-7082 + GGGGCUUUAGACGCAGACAGGCA 23 10931 SCNN1A-7083 + AGGGGCUUUAGACGCAGACAGGCA 24 10932 SCNN1A-7084 + AGGCAGGGAAAGCAGGCA 18 10933 SCNN1A-7085 + GAGGCAGGGAAAGCAGGCA 19 10934 SCNN1A-7086 + AGAGGCAGGGAAAGCAGGCA 20 10935 SCNN1A-7087 + AAGAGGCAGGGAAAGCAGGCA 21 10936 SCNN1A-7088 + GAAGAGGCAGGGAAAGCAGGCA 22 10937 SCNN1A-7089 + GGAAGAGGCAGGGAAAGCAGGCA 23 10938 SCNN1A-7090 + AGGAAGAGGCAGGGAAAGCAGGCA 24 10939 SCNN1A-7091 + CAAGGAGUUUAGCAGGCA 18 10940 SCNN1A-7092 + GCAAGGAGUUUAGCAGGCA 19 10941 SCNN1A-7093 + AGCAAGGAGUUUAGCAGGCA 20 10942 SCNN1A-7094 + AAGCAAGGAGUUUAGCAGGCA 21 10943 SCNN1A-7095 + CAAGCAAGGAGUUUAGCAGGCA 22 10944 SCNN1A-7096 + ACAAGCAAGGAGUUUAGCAGGCA 23 10945 SCNN1A-7097 + GACAAGCAAGGAGUUUAGCAGGCA 24 10946 SCNN1A-7098 + GGAGCCCAGGAAGAGGCA 18 10947 SCNN1A-7099 + CGGAGCCCAGGAAGAGGCA 19 10948 SCNN1A-5535 + CCGGAGCCCAGGAAGAGGCA 20 9384 SCNN1A-7100 + CCCGGAGCCCAGGAAGAGGCA 21 10949 SCNN1A-7101 + ACCCGGAGCCCAGGAAGAGGCA 22 10950 SCNN1A-7102 + GACCCGGAGCCCAGGAAGAGGCA 23 10951 SCNN1A-7103 + AGACCCGGAGCCCAGGAAGAGGCA 24 10952 SCNN1A-7104 + CAGGCCCUGCACGCGGCA 18 10953 SCNN1A-7105 + CCAGGCCCUGCACGCGGCA 19 10954 SCNN1A-5536 + CCCAGGCCCUGCACGCGGCA 20 9385 SCNN1A-7106 + ACCCAGGCCCUGCACGCGGCA 21 10955 SCNN1A-7107 + AACCCAGGCCCUGCACGCGGCA 22 10956 SCNN1A-7108 + CAACCCAGGCCCUGCACGCGGCA 23 10957 SCNN1A-7109 + ACAACCCAGGCCCUGCACGCGGCA 24 10958 SCNN1A-7110 + UCACCCUCAGGCCCUGCA 18 10959 SCNN1A-7111 + CUCACCCUCAGGCCCUGCA 19 10960 SCNN1A-7112 + CCUCACCCUCAGGCCCUGCA 20 10961 SCNN1A-7113 + GCCUCACCCUCAGGCCCUGCA 21 10962 SCNN1A-7114 + AGCCUCACCCUCAGGCCCUGCA 22 10963 SCNN1A-7115 + CAGCCUCACCCUCAGGCCCUGCA 23 10964 SCNN1A-7116 + UCAGCCUCACCCUCAGGCCCUGCA 24 10965 SCNN1A-7117 + GCAGGCACUGAAGGUGCA 18 10966 SCNN1A-7118 + AGCAGGCACUGAAGGUGCA 19 10967 SCNN1A-5539 + AAGCAGGCACUGAAGGUGCA 20 9388 SCNN1A-7119 + AAAGCAGGCACUGAAGGUGCA 21 10968 SCNN1A-7120 + GAAAGCAGGCACUGAAGGUGCA 22 10969 SCNN1A-7121 + GGAAAGCAGGCACUGAAGGUGCA 23 10970 SCNN1A-7122 + GGGAAAGCAGGCACUGAAGGUGCA 24 10971 SCNN1A-7123 + CUUCCUGAGACAGACUCA 18 10972 SCNN1A-7124 + ACUUCCUGAGACAGACUCA 19 10973 SCNN1A-6083 + UACUUCCUGAGACAGACUCA 20 9932 SCNN1A-7125 + UUACUUCCUGAGACAGACUCA 21 10974 SCNN1A-7126 + UUUACUUCCUGAGACAGACUCA 22 10975 SCNN1A-7127 + AUUUACUUCCUGAGACAGACUCA 23 10976 SCNN1A-7128 + CAUUUACUUCCUGAGACAGACUCA 24 10977 SCNN1A-7129 + GACAGGAGGGCAGAAAGA 18 10978 SCNN1A-7130 + GGACAGGAGGGCAGAAAGA 19 10979 SCNN1A-6085 + AGGACAGGAGGGCAGAAAGA 20 9934 SCNN1A-7131 + GAGGACAGGAGGGCAGAAAGA 21 10980 SCNN1A-7132 + GGAGGACAGGAGGGCAGAAAGA 22 10981 SCNN1A-7133 + GGGAGGACAGGAGGGCAGAAAGA 23 10982 SCNN1A-7134 + CGGGAGGACAGGAGGGCAGAAAGA 24 10983 SCNN1A-7135 + CAGGCCCUGCAGAGAAGA 18 10984 SCNN1A-7136 + UCAGGCCCUGCAGAGAAGA 19 10985 SCNN1A-7137 + CUCAGGCCCUGCAGAGAAGA 20 10986 SCNN1A-7138 + CCUCAGGCCCUGCAGAGAAGA 21 10987 SCNN1A-7139 + CCCUCAGGCCCUGCAGAGAAGA 22 10988 SCNN1A-7140 + ACCCUCAGGCCCUGCAGAGAAGA 23 10989 SCNN1A-7141 + CACCCUCAGGCCCUGCAGAGAAGA 24 10990 SCNN1A-7142 + GGAGGACAGGAGGGCAGA 18 10991 SCNN1A-7143 + GGGAGGACAGGAGGGCAGA 19 10992 SCNN1A-7144 + CGGGAGGACAGGAGGGCAGA 20 10993 SCNN1A-7145 + CCGGGAGGACAGGAGGGCAGA 21 10994 SCNN1A-7146 + ACCGGGAGGACAGGAGGGCAGA 22 10995 SCNN1A-7147 + AACCGGGAGGACAGGAGGGCAGA 23 10996 SCNN1A-7148 + GAACCGGGAGGACAGGAGGGCAGA 24 10997 SCNN1A-7149 + CAGCGAAGGACAGAGAGA 18 10998 SCNN1A-7150 + ACAGCGAAGGACAGAGAGA 19 10999 SCNN1A-7151 + GACAGCGAAGGACAGAGAGA 20 11000 SCNN1A-7152 + GGACAGCGAAGGACAGAGAGA 21 11001 SCNN1A-7153 + GGGACAGCGAAGGACAGAGAGA 22 11002 SCNN1A-7154 + AGGGACAGCGAAGGACAGAGAGA 23 11003 SCNN1A-7155 + GAGGGACAGCGAAGGACAGAGAGA 24 11004 SCNN1A-7156 + GUGGUGAGCAAGGAGAGA 18 11005 SCNN1A-7157 + AGUGGUGAGCAAGGAGAGA 19 11006 SCNN1A-7158 + AAGUGGUGAGCAAGGAGAGA 20 11007 SCNN1A-7159 + CAAGUGGUGAGCAAGGAGAGA 21 11008 SCNN1A-7160 + CCAAGUGGUGAGCAAGGAGAGA 22 11009 SCNN1A-7161 + GCCAAGUGGUGAGCAAGGAGAGA 23 11010 SCNN1A-7162 + UGCCAAGUGGUGAGCAAGGAGAGA 24 11011 SCNN1A-7163 + GAGGGCAACACAAGGAGA 18 11012 SCNN1A-7164 + GGAGGGCAACACAAGGAGA 19 11013 SCNN1A-6089 + AGGAGGGCAACACAAGGAGA 20 9938 SCNN1A-7165 + UAGGAGGGCAACACAAGGAGA 21 11014 SCNN1A-7166 + CUAGGAGGGCAACACAAGGAGA 22 11015 SCNN1A-7167 + GCUAGGAGGGCAACACAAGGAGA 23 11016 SCNN1A-7168 + AGCUAGGAGGGCAACACAAGGAGA 24 11017 SCNN1A-7169 + AAGUGGUGAGCAAGGAGA 18 11018 SCNN1A-7170 + CAAGUGGUGAGCAAGGAGA 19 11019 SCNN1A-7171 + CCAAGUGGUGAGCAAGGAGA 20 11020 SCNN1A-7172 + GCCAAGUGGUGAGCAAGGAGA 21 11021 SCNN1A-7173 + UGCCAAGUGGUGAGCAAGGAGA 22 11022 SCNN1A-7174 + GUGCCAAGUGGUGAGCAAGGAGA 23 11023 SCNN1A-7175 + AGUGCCAAGUGGUGAGCAAGGAGA 24 11024 SCNN1A-7176 + GUGGUGGGGGCAAAUAGA 18 11025 SCNN1A-7177 + AGUGGUGGGGGCAAAUAGA 19 11026 SCNN1A-6091 + CAGUGGUGGGGGCAAAUAGA 20 9940 SCNN1A-7178 + GCAGUGGUGGGGGCAAAUAGA 21 11027 SCNN1A-7179 + GGCAGUGGUGGGGGCAAAUAGA 22 11028 SCNN1A-7180 + GGGCAGUGGUGGGGGCAAAUAGA 23 11029 SCNN1A-7181 + GGGGCAGUGGUGGGGGCAAAUAGA 24 11030 SCNN1A-7182 + AAAGAGGGAGACAAUAGA 18 11031 SCNN1A-7183 + GAAAGAGGGAGACAAUAGA 19 11032 SCNN1A-7184 + AGAAAGAGGGAGACAAUAGA 20 11033 SCNN1A-7185 + CAGAAAGAGGGAGACAAUAGA 21 11034 SCNN1A-7186 + GCAGAAAGAGGGAGACAAUAGA 22 11035 SCNN1A-7187 + GGCAGAAAGAGGGAGACAAUAGA 23 11036 SCNN1A-7188 + GGGCAGAAAGAGGGAGACAAUAGA 24 11037 SCNN1A-1445 + AUCACCCCUGGAACCCGA 18 5294 SCNN1A-1446 + CAUCACCCCUGGAACCCGA 19 5295 SCNN1A-1447 + CCAUCACCCCUGGAACCCGA 20 5296 SCNN1A-1448 + CCCAUCACCCCUGGAACCCGA 21 5297 SCNN1A-1449 + UCCCAUCACCCCUGGAACCCGA 22 5298 SCNN1A-1450 + CUCCCAUCACCCCUGGAACCCGA 23 5299 SCNN1A-1451 + UCUCCCAUCACCCCUGGAACCCGA 24 5300 SCNN1A-7189 + GAGCCGGGAGUUUUCCGA 18 11038 SCNN1A-7190 + AGAGCCGGGAGUUUUCCGA 19 11039 SCNN1A-5544 + CAGAGCCGGGAGUUUUCCGA 20 9393 SCNN1A-7191 + UCAGAGCCGGGAGUUUUCCGA 21 11040 SCNN1A-7192 + GUCAGAGCCGGGAGUUUUCCGA 22 11041 SCNN1A-7193 + AGUCAGAGCCGGGAGUUUUCCGA 23 11042 SCNN1A-7194 + GAGUCAGAGCCGGGAGUUUUCCGA 24 11043 SCNN1A-7195 + GGCCAGGGAUGGAAGCGA 18 11044 SCNN1A-7196 + CGGCCAGGGAUGGAAGCGA 19 11045 SCNN1A-7197 + CCGGCCAGGGAUGGAAGCGA 20 11046 SCNN1A-7198 + GCCGGCCAGGGAUGGAAGCGA 21 11047 SCNN1A-7199 + GGCCGGCCAGGGAUGGAAGCGA 22 11048 SCNN1A-7200 + UGGCCGGCCAGGGAUGGAAGCGA 23 11049 SCNN1A-7201 + CUGGCCGGCCAGGGAUGGAAGCGA 24 11050 SCNN1A-7202 + CCAAGUGGUGAGCAAGGA 18 11051 SCNN1A-7203 + GCCAAGUGGUGAGCAAGGA 19 11052 SCNN1A-7204 + UGCCAAGUGGUGAGCAAGGA 20 11053 SCNN1A-7205 + GUGCCAAGUGGUGAGCAAGGA 21 11054 SCNN1A-7206 + AGUGCCAAGUGGUGAGCAAGGA 22 11055 SCNN1A-7207 + GAGUGCCAAGUGGUGAGCAAGGA 23 11056 SCNN1A-7208 + GGAGUGCCAAGUGGUGAGCAAGGA 24 11057 SCNN1A-7209 + CGGGAGUUUUCCGAAGGA 18 11058 SCNN1A-7210 + CCGGGAGUUUUCCGAAGGA 19 11059 SCNN1A-5190 + GCCGGGAGUUUUCCGAAGGA 20 9039 SCNN1A-7211 + AGCCGGGAGUUUUCCGAAGGA 21 11060 SCNN1A-7212 + GAGCCGGGAGUUUUCCGAAGGA 22 11061 SCNN1A-7213 + AGAGCCGGGAGUUUUCCGAAGGA 23 11062 SCNN1A-7214 + CAGAGCCGGGAGUUUUCCGAAGGA 24 11063 SCNN1A-7215 + GAGAGGGACAGCGAAGGA 18 11064 SCNN1A-7216 + AGAGAGGGACAGCGAAGGA 19 11065 SCNN1A-7217 + UAGAGAGGGACAGCGAAGGA 20 11066 SCNN1A-7218 + AUAGAGAGGGACAGCGAAGGA 21 11067 SCNN1A-7219 + AAUAGAGAGGGACAGCGAAGGA 22 11068 SCNN1A-7220 + CAAUAGAGAGGGACAGCGAAGGA 23 11069 SCNN1A-7221 + ACAAUAGAGAGGGACAGCGAAGGA 24 11070 SCNN1A-7222 + GCAGCAAAAGGAUAAGGA 18 11071 SCNN1A-7223 + UGCAGCAAAAGGAUAAGGA 19 11072 SCNN1A-7224 + AUGCAGCAAAAGGAUAAGGA 20 11073 SCNN1A-7225 + AAUGCAGCAAAAGGAUAAGGA 21 11074 SCNN1A-7226 + UAAUGCAGCAAAAGGAUAAGGA 22 11075 SCNN1A-7227 + UUAAUGCAGCAAAAGGAUAAGGA 23 11076 SCNN1A-7228 + CUUAAUGCAGCAAAAGGAUAAGGA 24 11077 SCNN1A-7229 + GGGAGUCUGUCUCCAGGA 18 11078 SCNN1A-7230 + AGGGAGUCUGUCUCCAGGA 19 11079 SCNN1A-5546 + AAGGGAGUCUGUCUCCAGGA 20 9395 SCNN1A-7231 + AAAGGGAGUCUGUCUCCAGGA 21 11080 SCNN1A-7232 + CAAAGGGAGUCUGUCUCCAGGA 22 11081 SCNN1A-7233 + CCAAAGGGAGUCUGUCUCCAGGA 23 11082 SCNN1A-7234 + ACCAAAGGGAGUCUGUCUCCAGGA 24 11083 SCNN1A-7235 + GGUGGGGAACCGGGAGGA 18 11084 SCNN1A-7236 + GGGUGGGGAACCGGGAGGA 19 11085 SCNN1A-7237 + UGGGUGGGGAACCGGGAGGA 20 11086 SCNN1A-7238 + CUGGGUGGGGAACCGGGAGGA 21 11087 SCNN1A-7239 + CCUGGGUGGGGAACCGGGAGGA 22 11088 SCNN1A-7240 + GCCUGGGUGGGGAACCGGGAGGA 23 11089 SCNN1A-7241 + GGCCUGGGUGGGGAACCGGGAGGA 24 11090 SCNN1A-7242 + CCGCUGGCCGGCCAGGGA 18 11091 SCNN1A-7243 + CCCGCUGGCCGGCCAGGGA 19 11092 SCNN1A-5192 + GCCCGCUGGCCGGCCAGGGA 20 9041 SCNN1A-7244 + CGCCCGCUGGCCGGCCAGGGA 21 11093 SCNN1A-7245 + CCGCCCGCUGGCCGGCCAGGGA 22 11094 SCNN1A-7246 + CCCGCCCGCUGGCCGGCCAGGGA 23 11095 SCNN1A-7247 + GCCCGCCCGCUGGCCGGCCAGGGA 24 11096 SCNN1A-7248 + AGGACAGAGAGAUAGGGA 18 11097 SCNN1A-7249 + AAGGACAGAGAGAUAGGGA 19 11098 SCNN1A-5878 + GAAGGACAGAGAGAUAGGGA 20 9727 SCNN1A-7250 + CGAAGGACAGAGAGAUAGGGA 21 11099 SCNN1A-7251 + GCGAAGGACAGAGAGAUAGGGA 22 11100 SCNN1A-7252 + AGCGAAGGACAGAGAGAUAGGGA 23 11101 SCNN1A-7253 + CAGCGAAGGACAGAGAGAUAGGGA 24 11102 SCNN1A-7254 + AGACAGACUCAUGGGGGA 18 11103 SCNN1A-7255 + GAGACAGACUCAUGGGGGA 19 11104 SCNN1A-7256 + UGAGACAGACUCAUGGGGGA 20 11105 SCNN1A-7257 + CUGAGACAGACUCAUGGGGGA 21 11106 SCNN1A-7258 + CCUGAGACAGACUCAUGGGGGA 22 11107 SCNN1A-7259 + UCCUGAGACAGACUCAUGGGGGA 23 11108 SCNN1A-7260 + UUCCUGAGACAGACUCAUGGGGGA 24 11109 SCNN1A-7261 + GAUGUGGCCAGCGCUGGA 18 11110 SCNN1A-7262 + GGAUGUGGCCAGCGCUGGA 19 11111 SCNN1A-7263 + AGGAUGUGGCCAGCGCUGGA 20 11112 SCNN1A-7264 + GAGGAUGUGGCCAGCGCUGGA 21 11113 SCNN1A-7265 + GGAGGAUGUGGCCAGCGCUGGA 22 11114 SCNN1A-7266 + GGGAGGAUGUGGCCAGCGCUGGA 23 11115 SCNN1A-7267 + AGGGAGGAUGUGGCCAGCGCUGGA 24 11116 SCNN1A-7268 + UCCCAGGUUGCGGCUGGA 18 11117 SCNN1A-7269 + CUCCCAGGUUGCGGCUGGA 19 11118 SCNN1A-7270 + ACUCCCAGGUUGCGGCUGGA 20 11119 SCNN1A-7271 + CACUCCCAGGUUGCGGCUGGA 21 11120 SCNN1A-7272 + CCACUCCCAGGUUGCGGCUGGA 22 11121 SCNN1A-7273 + CCCACUCCCAGGUUGCGGCUGGA 23 11122 SCNN1A-7274 + UCCCACUCCCAGGUUGCGGCUGGA 24 11123 SCNN1A-1465 + CAUGAGCCCCGGAGUGGA 18 5314 SCNN1A-1466 + UCAUGAGCCCCGGAGUGGA 19 5315 SCNN1A-1467 + UUCAUGAGCCCCGGAGUGGA 20 5316 SCNN1A-1468 + CUUCAUGAGCCCCGGAGUGGA 21 5317 SCNN1A-1469 + CCUUCAUGAGCCCCGGAGUGGA 22 5318 SCNN1A-1470 + CCCUUCAUGAGCCCCGGAGUGGA 23 5319 SCNN1A-1471 + CCCCUUCAUGAGCCCCGGAGUGGA 24 5320 SCNN1A-1472 + AUGAUACCUCCCCUUGGA 18 5321 SCNN1A-1473 + CAUGAUACCUCCCCUUGGA 19 5322 SCNN1A-399 + UCAUGAUACCUCCCCUUGGA 20 4248 SCNN1A-1474 + CUCAUGAUACCUCCCCUUGGA 21 5323 SCNN1A-1475 + GCUCAUGAUACCUCCCCUUGGA 22 5324 SCNN1A-1476 + UGCUCAUGAUACCUCCCCUUGGA 23 5325 SCNN1A-1477 + CUGCUCAUGAUACCUCCCCUUGGA 24 5326 SCNN1A-7275 + UCUCCUCUGCUUCCCUGA 18 11124 SCNN1A-7276 + CUCUCCUCUGCUUCCCUGA 19 11125 SCNN1A-7277 + CCUCUCCUCUGCUUCCCUGA 20 11126 SCNN1A-7278 + GCCUCUCCUCUGCUUCCCUGA 21 11127 SCNN1A-7279 + GGCCUCUCCUCUGCUUCCCUGA 22 11128 SCNN1A-7280 + CGGCCUCUCCUCUGCUUCCCUGA 23 11129 SCNN1A-7281 + ACGGCCUCUCCUCUGCUUCCCUGA 24 11130 SCNN1A-7282 + AGGGGCCAGCCAGGCUGA 18 11131 SCNN1A-7283 + AAGGGGCCAGCCAGGCUGA 19 11132 SCNN1A-7284 + GAAGGGGCCAGCCAGGCUGA 20 11133 SCNN1A-7285 + AGAAGGGGCCAGCCAGGCUGA 21 11134 SCNN1A-7286 + GAGAAGGGGCCAGCCAGGCUGA 22 11135 SCNN1A-7287 + GGAGAAGGGGCCAGCCAGGCUGA 23 11136 SCNN1A-7288 + AGGAGAAGGGGCCAGCCAGGCUGA 24 11137 SCNN1A-7289 + AGAAAGAGGGAGACAAUA 18 11138 SCNN1A-7290 + CAGAAAGAGGGAGACAAUA 19 11139 SCNN1A-7291 + GCAGAAAGAGGGAGACAAUA 20 11140 SCNN1A-7292 + GGCAGAAAGAGGGAGACAAUA 21 11141 SCNN1A-7293 + GGGCAGAAAGAGGGAGACAAUA 22 11142 SCNN1A-7294 + AGGGCAGAAAGAGGGAGACAAUA 23 11143 SCNN1A-7295 + GAGGGCAGAAAGAGGGAGACAAUA 24 11144 SCNN1A-7296 + UUUUUCUUCAUUGUCCUA 18 11145 SCNN1A-7297 + AUUUUUCUUCAUUGUCCUA 19 11146 SCNN1A-7298 + GAUUUUUCUUCAUUGUCCUA 20 11147 SCNN1A-7299 + GGAUUUUUCUUCAUUGUCCUA 21 11148 SCNN1A-7300 + UGGAUUUUUCUUCAUUGUCCUA 22 11149 SCNN1A-7301 + CUGGAUUUUUCUUCAUUGUCCUA 23 11150 SCNN1A-7302 + GCUGGAUUUUUCUUCAUUGUCCUA 24 11151 SCNN1A-7303 + CAUAAGAGCCAAGGGCUA 18 11152 SCNN1A-7304 + ACAUAAGAGCCAAGGGCUA 19 11153 SCNN1A-5198 + GACAUAAGAGCCAAGGGCUA 20 9047 SCNN1A-7305 + AGACAUAAGAGCCAAGGGCUA 21 11154 SCNN1A-7306 + AAGACAUAAGAGCCAAGGGCUA 22 11155 SCNN1A-7307 + UAAGACAUAAGAGCCAAGGGCUA 23 11156 SCNN1A-7308 + AUAAGACAUAAGAGCCAAGGGCUA 24 11157 SCNN1A-7309 + GCAGGUGAACUGGGAGUA 18 11158 SCNN1A-7310 + GGCAGGUGAACUGGGAGUA 19 11159 SCNN1A-7311 + GGGCAGGUGAACUGGGAGUA 20 11160 SCNN1A-7312 + AGGGCAGGUGAACUGGGAGUA 21 11161 SCNN1A-7313 + GAGGGCAGGUGAACUGGGAGUA 22 11162 SCNN1A-7314 + CGAGGGCAGGUGAACUGGGAGUA 23 11163 SCNN1A-7315 + CCGAGGGCAGGUGAACUGGGAGUA 24 11164 SCNN1A-7316 + UGCAGGAAUGUGGGCAAC 18 11165 SCNN1A-7317 + UUGCAGGAAUGUGGGCAAC 19 11166 SCNN1A-7318 + GUUGCAGGAAUGUGGGCAAC 20 11167 SCNN1A-7319 + AGUUGCAGGAAUGUGGGCAAC 21 11168 SCNN1A-7320 + GAGUUGCAGGAAUGUGGGCAAC 22 11169 SCNN1A-7321 + AGAGUUGCAGGAAUGUGGGCAAC 23 11170 SCNN1A-7322 + CAGAGUUGCAGGAAUGUGGGCAAC 24 11171 SCNN1A-7323 + AGGGCCUGGGUGGGGAAC 18 11172 SCNN1A-7324 + GAGGGCCUGGGUGGGGAAC 19 11173 SCNN1A-6101 + AGAGGGCCUGGGUGGGGAAC 20 9950 SCNN1A-7325 + GAGAGGGCCUGGGUGGGGAAC 21 11174 SCNN1A-7326 + UGAGAGGGCCUGGGUGGGGAAC 22 11175 SCNN1A-7327 + CUGAGAGGGCCUGGGUGGGGAAC 23 11176 SCNN1A-7328 + GCUGAGAGGGCCUGGGUGGGGAAC 24 11177 SCNN1A-7329 + UCCCGAGGGCAGGUGAAC 18 11178 SCNN1A-7330 + CUCCCGAGGGCAGGUGAAC 19 11179 SCNN1A-5203 + GCUCCCGAGGGCAGGUGAAC 20 9052 SCNN1A-7331 + GGCUCCCGAGGGCAGGUGAAC 21 11180 SCNN1A-7332 + GGGCUCCCGAGGGCAGGUGAAC 22 11181 SCNN1A-7333 + AGGGCUCCCGAGGGCAGGUGAAC 23 11182 SCNN1A-7334 + GAGGGCUCCCGAGGGCAGGUGAAC 24 11183 SCNN1A-7335 + CAGCUAGGAGGGCAACAC 18 11184 SCNN1A-7336 + ACAGCUAGGAGGGCAACAC 19 11185 SCNN1A-7337 + CACAGCUAGGAGGGCAACAC 20 11186 SCNN1A-7338 + CCACAGCUAGGAGGGCAACAC 21 11187 SCNN1A-7339 + CCCACAGCUAGGAGGGCAACAC 22 11188 SCNN1A-7340 + GCCCACAGCUAGGAGGGCAACAC 23 11189 SCNN1A-7341 + AGCCCACAGCUAGGAGGGCAACAC 24 11190 SCNN1A-7342 + CUGAGCAUUGAUACACAC 18 11191 SCNN1A-7343 + CCUGAGCAUUGAUACACAC 19 11192 SCNN1A-5204 + GCCUGAGCAUUGAUACACAC 20 9053 SCNN1A-7344 + AGCCUGAGCAUUGAUACACAC 21 11193 SCNN1A-7345 + CAGCCUGAGCAUUGAUACACAC 22 11194 SCNN1A-7346 + CCAGCCUGAGCAUUGAUACACAC 23 11195 SCNN1A-7347 + CCCAGCCUGAGCAUUGAUACACAC 24 11196 SCNN1A-7348 + CUUCCUCACGGGCCCCAC 18 11197 SCNN1A-7349 + GCUUCCUCACGGGCCCCAC 19 11198 SCNN1A-5561 + CGCUUCCUCACGGGCCCCAC 20 9410 SCNN1A-7350 + CCGCUUCCUCACGGGCCCCAC 21 11199 SCNN1A-7351 + GCCGCUUCCUCACGGGCCCCAC 22 11200 SCNN1A-7352 + UGCCGCUUCCUCACGGGCCCCAC 23 11201 SCNN1A-7353 + CUGCCGCUUCCUCACGGGCCCCAC 24 11202 SCNN1A-7354 + GACACUGUGGACACAGAC 18 11203 SCNN1A-7355 + GGACACUGUGGACACAGAC 19 11204 SCNN1A-7356 + AGGACACUGUGGACACAGAC 20 11205 SCNN1A-7357 + CAGGACACUGUGGACACAGAC 21 11206 SCNN1A-7358 + GCAGGACACUGUGGACACAGAC 22 11207 SCNN1A-7359 + CGCAGGACACUGUGGACACAGAC 23 11208 SCNN1A-7360 + ACGCAGGACACUGUGGACACAGAC 24 11209 SCNN1A-7361 + CUCCAACCUUGUCCAGAC 18 11210 SCNN1A-7362 + CCUCCAACCUUGUCCAGAC 19 11211 SCNN1A-7363 + CCCUCCAACCUUGUCCAGAC 20 11212 SCNN1A-7364 + CCCCUCCAACCUUGUCCAGAC 21 11213 SCNN1A-7365 + CCCCCUCCAACCUUGUCCAGAC 22 11214 SCNN1A-7366 + ACCCCCUCCAACCUUGUCCAGAC 23 11215 SCNN1A-7367 + CACCCCCUCCAACCUUGUCCAGAC 24 11216 SCNN1A-7368 + AAAAGGGCUGGAGGAGAC 18 11217 SCNN1A-7369 + AAAAAGGGCUGGAGGAGAC 19 11218 SCNN1A-7370 + CAAAAAGGGCUGGAGGAGAC 20 11219 SCNN1A-7371 + CCAAAAAGGGCUGGAGGAGAC 21 11220 SCNN1A-7372 + CCCAAAAAGGGCUGGAGGAGAC 22 11221 SCNN1A-7373 + ACCCAAAAAGGGCUGGAGGAGAC 23 11222 SCNN1A-7374 + GACCCAAAAAGGGCUGGAGGAGAC 24 11223 SCNN1A-7375 + GUGGGGAACCGGGAGGAC 18 11224 SCNN1A-7376 + GGUGGGGAACCGGGAGGAC 19 11225 SCNN1A-5209 + GGGUGGGGAACCGGGAGGAC 20 9058 SCNN1A-7377 + UGGGUGGGGAACCGGGAGGAC 21 11226 SCNN1A-7378 + CUGGGUGGGGAACCGGGAGGAC 22 11227 SCNN1A-7379 + CCUGGGUGGGGAACCGGGAGGAC 23 11228 SCNN1A-7380 + GCCUGGGUGGGGAACCGGGAGGAC 24 11229 SCNN1A-7381 + GAACUGGGAGUACUGGAC 18 11230 SCNN1A-7382 + UGAACUGGGAGUACUGGAC 19 11231 SCNN1A-7383 + GUGAACUGGGAGUACUGGAC 20 11232 SCNN1A-7384 + GGUGAACUGGGAGUACUGGAC 21 11233 SCNN1A-7385 + AGGUGAACUGGGAGUACUGGAC 22 11234 SCNN1A-7386 + CAGGUGAACUGGGAGUACUGGAC 23 11235 SCNN1A-7387 + GCAGGUGAACUGGGAGUACUGGAC 24 11236 SCNN1A-7388 + CCCAGGUUGCGGCUGGAC 18 11237 SCNN1A-7389 + UCCCAGGUUGCGGCUGGAC 19 11238 SCNN1A-5565 + CUCCCAGGUUGCGGCUGGAC 20 9414 SCNN1A-7390 + ACUCCCAGGUUGCGGCUGGAC 21 11239 SCNN1A-7391 + CACUCCCAGGUUGCGGCUGGAC 22 11240 SCNN1A-7392 + CCACUCCCAGGUUGCGGCUGGAC 23 11241 SCNN1A-7393 + CCCACUCCCAGGUUGCGGCUGGAC 24 11242 SCNN1A-7394 + GGGCCUGGGUGGGGAACC 18 11243 SCNN1A-7395 + AGGGCCUGGGUGGGGAACC 19 11244 SCNN1A-5214 + GAGGGCCUGGGUGGGGAACC 20 9063 SCNN1A-7396 + AGAGGGCCUGGGUGGGGAACC 21 11245 SCNN1A-7397 + GAGAGGGCCUGGGUGGGGAACC 22 11246 SCNN1A-7398 + UGAGAGGGCCUGGGUGGGGAACC 23 11247 SCNN1A-7399 + CUGAGAGGGCCUGGGUGGGGAACC 24 11248 SCNN1A-7400 + UGAGCAUUGAUACACACC 18 11249 SCNN1A-7401 + CUGAGCAUUGAUACACACC 19 11250 SCNN1A-5568 + CCUGAGCAUUGAUACACACC 20 9417 SCNN1A-7402 + GCCUGAGCAUUGAUACACACC 21 11251 SCNN1A-7403 + AGCCUGAGCAUUGAUACACACC 22 11252 SCNN1A-7404 + CAGCCUGAGCAUUGAUACACACC 23 11253 SCNN1A-7405 + CCAGCCUGAGCAUUGAUACACACC 24 11254 SCNN1A-7406 + ACACUGUGGACACAGACC 18 11255 SCNN1A-7407 + GACACUGUGGACACAGACC 19 11256 SCNN1A-5217 + GGACACUGUGGACACAGACC 20 9066 SCNN1A-7408 + AGGACACUGUGGACACAGACC 21 11257 SCNN1A-7409 + CAGGACACUGUGGACACAGACC 22 11258 SCNN1A-7410 + GCAGGACACUGUGGACACAGACC 23 11259 SCNN1A-7411 + CGCAGGACACUGUGGACACAGACC 24 11260 SCNN1A-7412 + UCCAACCUUGUCCAGACC 18 11261 SCNN1A-7413 + CUCCAACCUUGUCCAGACC 19 11262 SCNN1A-5569 + CCUCCAACCUUGUCCAGACC 20 9418 SCNN1A-7414 + CCCUCCAACCUUGUCCAGACC 21 11263 SCNN1A-7415 + CCCCUCCAACCUUGUCCAGACC 22 11264 SCNN1A-7416 + CCCCCUCCAACCUUGUCCAGACC 23 11265 SCNN1A-7417 + ACCCCCUCCAACCUUGUCCAGACC 24 11266 SCNN1A-7418 + CAGCCUCUGGCCCUGACC 18 11267 SCNN1A-7419 + CCAGCCUCUGGCCCUGACC 19 11268 SCNN1A-7420 + UCCAGCCUCUGGCCCUGACC 20 11269 SCNN1A-7421 + CUCCAGCCUCUGGCCCUGACC 21 11270 SCNN1A-7422 + GCUCCAGCCUCUGGCCCUGACC 22 11271 SCNN1A-7423 + AGCUCCAGCCUCUGGCCCUGACC 23 11272 SCNN1A-7424 + CAGCUCCAGCCUCUGGCCCUGACC 24 11273 SCNN1A-1484 + UGCCCUCUCCCAUCACCC 18 5333 SCNN1A-1485 + GUGCCCUCUCCCAUCACCC 19 5334 SCNN1A-1486 + AGUGCCCUCUCCCAUCACCC 20 5335 SCNN1A-1487 + GAGUGCCCUCUCCCAUCACCC 21 5336 SCNN1A-1488 + UGAGUGCCCUCUCCCAUCACCC 22 5337 SCNN1A-1489 + CUGAGUGCCCUCUCCCAUCACCC 23 5338 SCNN1A-1490 + CCUGAGUGCCCUCUCCCAUCACCC 24 5339 SCNN1A-7425 + CCAACCUUGUCCAGACCC 18 11274 SCNN1A-7426 + UCCAACCUUGUCCAGACCC 19 11275 SCNN1A-5572 + CUCCAACCUUGUCCAGACCC 20 9421 SCNN1A-7427 + CCUCCAACCUUGUCCAGACCC 21 11276 SCNN1A-7428 + CCCUCCAACCUUGUCCAGACCC 22 11277 SCNN1A-7429 + CCCCUCCAACCUUGUCCAGACCC 23 11278 SCNN1A-7430 + CCCCCUCCAACCUUGUCCAGACCC 24 11279 SCNN1A-1491 + GCCCUCUCCCAUCACCCC 18 5340 SCNN1A-1492 + UGCCCUCUCCCAUCACCCC 19 5341 SCNN1A-346 + GUGCCCUCUCCCAUCACCCC 20 4195 SCNN1A-1493 + AGUGCCCUCUCCCAUCACCCC 21 5342 SCNN1A-1494 + GAGUGCCCUCUCCCAUCACCCC 22 5343 SCNN1A-1495 + UGAGUGCCCUCUCCCAUCACCCC 23 5344 SCNN1A-1496 + CUGAGUGCCCUCUCCCAUCACCCC 24 5345 SCNN1A-7431 + ACAUAUCCCAGAGACCCC 18 11280 SCNN1A-7432 + CACAUAUCCCAGAGACCCC 19 11281 SCNN1A-7433 + CCACAUAUCCCAGAGACCCC 20 11282 SCNN1A-7434 + CCCACAUAUCCCAGAGACCCC 21 11283 SCNN1A-7435 + CCCCACAUAUCCCAGAGACCCC 22 11284 SCNN1A-7436 + GCCCCACAUAUCCCAGAGACCCC 23 11285 SCNN1A-7437 + UGCCCCACAUAUCCCAGAGACCCC 24 11286 SCNN1A-1497 + UGCUCAUGAUACCUCCCC 18 5346 SCNN1A-1498 + CUGCUCAUGAUACCUCCCC 19 5347 SCNN1A-1499 + ACUGCUCAUGAUACCUCCCC 20 5348 SCNN1A-1500 + UACUGCUCAUGAUACCUCCCC 21 5349 SCNN1A-1501 + AUACUGCUCAUGAUACCUCCCC 22 5350 SCNN1A-1502 + GAUACUGCUCAUGAUACCUCCCC 23 5351 SCNN1A-1503 + UGAUACUGCUCAUGAUACCUCCCC 24 5352 SCNN1A-7438 + GACACAGACCCGGAGCCC 18 11287 SCNN1A-7439 + GGACACAGACCCGGAGCCC 19 11288 SCNN1A-5575 + UGGACACAGACCCGGAGCCC 20 9424 SCNN1A-7440 + GUGGACACAGACCCGGAGCCC 21 11289 SCNN1A-7441 + UGUGGACACAGACCCGGAGCCC 22 11290 SCNN1A-7442 + CUGUGGACACAGACCCGGAGCCC 23 11291 SCNN1A-7443 + ACUGUGGACACAGACCCGGAGCCC 24 11292 SCNN1A-7444 + ACACGCCUAGACAGGCCC 18 11293 SCNN1A-7445 + CACACGCCUAGACAGGCCC 19 11294 SCNN1A-5219 + GCACACGCCUAGACAGGCCC 20 9068 SCNN1A-7446 + GGCACACGCCUAGACAGGCCC 21 11295 SCNN1A-7447 + UGGCACACGCCUAGACAGGCCC 22 11296 SCNN1A-7448 + AUGGCACACGCCUAGACAGGCCC 23 11297 SCNN1A-7449 + CAUGGCACACGCCUAGACAGGCCC 24 11298 SCNN1A-7450 + GGGGGCUAGGCGGGGCCC 18 11299 SCNN1A-7451 + UGGGGGCUAGGCGGGGCCC 19 11300 SCNN1A-7452 + CUGGGGGCUAGGCGGGGCCC 20 11301 SCNN1A-7453 + GCUGGGGGCUAGGCGGGGCCC 21 11302 SCNN1A-7454 + AGCUGGGGGCUAGGCGGGGCCC 22 11303 SCNN1A-7455 + AAGCUGGGGGCUAGGCGGGGCCC 23 11304 SCNN1A-7456 + GAAGCUGGGGGCUAGGCGGGGCCC 24 11305 SCNN1A-7457 + CUGAUUCUGUCUCUGCCC 18 11306 SCNN1A-7458 + CCUGAUUCUGUCUCUGCCC 19 11307 SCNN1A-7459 + UCCUGAUUCUGUCUCUGCCC 20 11308 SCNN1A-7460 + GUCCUGAUUCUGUCUCUGCCC 21 11309 SCNN1A-7461 + UGUCCUGAUUCUGUCUCUGCCC 22 11310 SCNN1A-7462 + GUGUCCUGAUUCUGUCUCUGCCC 23 11311 SCNN1A-7463 + UGUGUCCUGAUUCUGUCUCUGCCC 24 11312 SCNN1A-7464 + GAAGGAAGGAGGGCUCCC 18 11313 SCNN1A-7465 + CGAAGGAAGGAGGGCUCCC 19 11314 SCNN1A-7466 + CCGAAGGAAGGAGGGCUCCC 20 11315 SCNN1A-7467 + UCCGAAGGAAGGAGGGCUCCC 21 11316 SCNN1A-7468 + UUCCGAAGGAAGGAGGGCUCCC 22 11317 SCNN1A-7469 + UUUCCGAAGGAAGGAGGGCUCCC 23 11318 SCNN1A-7470 + UUUUCCGAAGGAAGGAGGGCUCCC 24 11319 SCNN1A-7471 + UAGAAACUCCAGUCUCCC 18 11320 SCNN1A-7472 + CUAGAAACUCCAGUCUCCC 19 11321 SCNN1A-7473 + CCUAGAAACUCCAGUCUCCC 20 11322 SCNN1A-7474 + CCCUAGAAACUCCAGUCUCCC 21 11323 SCNN1A-7475 + CCCCUAGAAACUCCAGUCUCCC 22 11324 SCNN1A-7476 + ACCCCUAGAAACUCCAGUCUCCC 23 11325 SCNN1A-7477 + GACCCCUAGAAACUCCAGUCUCCC 24 11326 SCNN1A-7478 + GCCGGAGCUGGGCUUCCC 18 11327 SCNN1A-7479 + UGCCGGAGCUGGGCUUCCC 19 11328 SCNN1A-7480 + GUGCCGGAGCUGGGCUUCCC 20 11329 SCNN1A-7481 + AGUGCCGGAGCUGGGCUUCCC 21 11330 SCNN1A-7482 + AAGUGCCGGAGCUGGGCUUCCC 22 11331 SCNN1A-7483 + AAAGUGCCGGAGCUGGGCUUCCC 23 11332 SCNN1A-7484 + AAAAGUGCCGGAGCUGGGCUUCCC 24 11333 SCNN1A-7485 + CACCUGGAUGUGAAAGCC 18 11334 SCNN1A-7486 + GCACCUGGAUGUGAAAGCC 19 11335 SCNN1A-6107 + UGCACCUGGAUGUGAAAGCC 20 9956 SCNN1A-7487 + GUGCACCUGGAUGUGAAAGCC 21 11336 SCNN1A-7488 + GGUGCACCUGGAUGUGAAAGCC 22 11337 SCNN1A-7489 + AGGUGCACCUGGAUGUGAAAGCC 23 11338 SCNN1A-7490 + CAGGUGCACCUGGAUGUGAAAGCC 24 11339 SCNN1A-7491 + AGAUAAGACAUAAGAGCC 18 11340 SCNN1A-7492 + GAGAUAAGACAUAAGAGCC 19 11341 SCNN1A-7493 + AGAGAUAAGACAUAAGAGCC 20 11342 SCNN1A-7494 + CAGAGAUAAGACAUAAGAGCC 21 11343 SCNN1A-7495 + UCAGAGAUAAGACAUAAGAGCC 22 11344 SCNN1A-7496 + CUCAGAGAUAAGACAUAAGAGCC 23 11345 SCNN1A-7497 + UCUCAGAGAUAAGACAUAAGAGCC 24 11346 SCNN1A-7498 + GGACACAGACCCGGAGCC 18 11347 SCNN1A-7499 + UGGACACAGACCCGGAGCC 19 11348 SCNN1A-7500 + GUGGACACAGACCCGGAGCC 20 11349 SCNN1A-7501 + UGUGGACACAGACCCGGAGCC 21 11350 SCNN1A-7502 + CUGUGGACACAGACCCGGAGCC 22 11351 SCNN1A-7503 + ACUGUGGACACAGACCCGGAGCC 23 11352 SCNN1A-7504 + CACUGUGGACACAGACCCGGAGCC 24 11353 SCNN1A-7505 + CCAAGGGCUAGGGGAGCC 18 11354 SCNN1A-7506 + GCCAAGGGCUAGGGGAGCC 19 11355 SCNN1A-7507 + AGCCAAGGGCUAGGGGAGCC 20 11356 SCNN1A-7508 + GAGCCAAGGGCUAGGGGAGCC 21 11357 SCNN1A-7509 + AGAGCCAAGGGCUAGGGGAGCC 22 11358 SCNN1A-7510 + AAGAGCCAAGGGCUAGGGGAGCC 23 11359 SCNN1A-7511 + UAAGAGCCAAGGGCUAGGGGAGCC 24 11360 SCNN1A-1504 + UGUUCCCCUUCAUGAGCC 18 5353 SCNN1A-1505 + UUGUUCCCCUUCAUGAGCC 19 5354 SCNN1A-207 + CUUGUUCCCCUUCAUGAGCC 20 834 SCNN1A-1506 + GCUUGUUCCCCUUCAUGAGCC 21 5355 SCNN1A-1507 + AGCUUGUUCCCCUUCAUGAGCC 22 5356 SCNN1A-1508 + CAGCUUGUUCCCCUUCAUGAGCC 23 5357 SCNN1A-1509 + CCAGCUUGUUCCCCUUCAUGAGCC 24 5358 SCNN1A-7512 + CACACGCCUAGACAGGCC 18 11361 SCNN1A-7513 + GCACACGCCUAGACAGGCC 19 11362 SCNN1A-7514 + GGCACACGCCUAGACAGGCC 20 11363 SCNN1A-7515 + UGGCACACGCCUAGACAGGCC 21 11364 SCNN1A-7516 + AUGGCACACGCCUAGACAGGCC 22 11365 SCNN1A-7517 + CAUGGCACACGCCUAGACAGGCC 23 11366 SCNN1A-7518 + GCAUGGCACACGCCUAGACAGGCC 24 11367 SCNN1A-7519 + CCACUGCCCCACAUAUCC 18 11368 SCNN1A-7520 + CCCACUGCCCCACAUAUCC 19 11369 SCNN1A-7521 + CCCCACUGCCCCACAUAUCC 20 11370 SCNN1A-7522 + UCCCCACUGCCCCACAUAUCC 21 11371 SCNN1A-7523 + GUCCCCACUGCCCCACAUAUCC 22 11372 SCNN1A-7524 + UGUCCCCACUGCCCCACAUAUCC 23 11373 SCNN1A-7525 + CUGUCCCCACUGCCCCACAUAUCC 24 11374 SCNN1A-1525 + UCCAGCUUGUUCCCCUCC 18 5374 SCNN1A-1526 + CUCCAGCUUGUUCCCCUCC 19 5375 SCNN1A-200 + CCUCCAGCUUGUUCCCCUCC 20 829 SCNN1A-1527 + UCCUCCAGCUUGUUCCCCUCC 21 5376 SCNN1A-1528 + CUCCUCCAGCUUGUUCCCCUCC 22 5377 SCNN1A-1529 + GCUCCUCCAGCUUGUUCCCCUCC 23 5378 SCNN1A-1530 + UGCUCCUCCAGCUUGUUCCCCUCC 24 5379 SCNN1A-7526 + GCAAGUGGGCAGCCCUCC 18 11375 SCNN1A-7527 + AGCAAGUGGGCAGCCCUCC 19 11376 SCNN1A-7528 + CAGCAAGUGGGCAGCCCUCC 20 11377 SCNN1A-7529 + UCAGCAAGUGGGCAGCCCUCC 21 11378 SCNN1A-7530 + CUCAGCAAGUGGGCAGCCCUCC 22 11379 SCNN1A-7531 + GCUCAGCAAGUGGGCAGCCCUCC 23 11380 SCNN1A-7532 + GGCUCAGCAAGUGGGCAGCCCUCC 24 11381 SCNN1A-7533 + CCAGGACUGCAGGGCUCC 18 11382 SCNN1A-7534 + CCCAGGACUGCAGGGCUCC 19 11383 SCNN1A-6112 + CCCCAGGACUGCAGGGCUCC 20 9961 SCNN1A-7535 + GCCCCAGGACUGCAGGGCUCC 21 11384 SCNN1A-7536 + UGCCCCAGGACUGCAGGGCUCC 22 11385 SCNN1A-7537 + CUGCCCCAGGACUGCAGGGCUCC 23 11386 SCNN1A-7538 + UCUGCCCCAGGACUGCAGGGCUCC 24 11387 SCNN1A-7539 + CAAAGGGAGUCUGUCUCC 18 11388 SCNN1A-7540 + CCAAAGGGAGUCUGUCUCC 19 11389 SCNN1A-5596 + ACCAAAGGGAGUCUGUCUCC 20 9445 SCNN1A-7541 + CACCAAAGGGAGUCUGUCUCC 21 11390 SCNN1A-7542 + GCACCAAAGGGAGUCUGUCUCC 22 11391 SCNN1A-7543 + AGCACCAAAGGGAGUCUGUCUCC 23 11392 SCNN1A-7544 + CAGCACCAAAGGGAGUCUGUCUCC 24 11393 SCNN1A-7545 + AGACUCAGGAAGCCUUCC 18 11394 SCNN1A-7546 + GAGACUCAGGAAGCCUUCC 19 11395 SCNN1A-7547 + GGAGACUCAGGAAGCCUUCC 20 11396 SCNN1A-7548 + AGGAGACUCAGGAAGCCUUCC 21 11397 SCNN1A-7549 + CAGGAGACUCAGGAAGCCUUCC 22 11398 SCNN1A-7550 + GCAGGAGACUCAGGAAGCCUUCC 23 11399 SCNN1A-7551 + UGCAGGAGACUCAGGAAGCCUUCC 24 11400 SCNN1A-7552 + AGUCCCAAGUGUGCUUCC 18 11401 SCNN1A-7553 + GAGUCCCAAGUGUGCUUCC 19 11402 SCNN1A-5226 + GGAGUCCCAAGUGUGCUUCC 20 9075 SCNN1A-7554 + GGGAGUCCCAAGUGUGCUUCC 21 11403 SCNN1A-7555 + GGGGAGUCCCAAGUGUGCUUCC 22 11404 SCNN1A-7556 + GGGGGAGUCCCAAGUGUGCUUCC 23 11405 SCNN1A-7557 + GGGGGGAGUCCCAAGUGUGCUUCC 24 11406 SCNN1A-7558 + UCCCUCCUCCACCUUUCC 18 11407 SCNN1A-7559 + CUCCCUCCUCCACCUUUCC 19 11408 SCNN1A-6116 + CCUCCCUCCUCCACCUUUCC 20 9965 SCNN1A-7560 + CCCUCCCUCCUCCACCUUUCC 21 11409 SCNN1A-7561 + UCCCUCCCUCCUCCACCUUUCC 22 11410 SCNN1A-7562 + CUCCCUCCCUCCUCCACCUUUCC 23 11411 SCNN1A-7563 + CCUCCCUCCCUCCUCCACCUUUCC 24 11412 SCNN1A-7564 + GCACCUGGAUGUGAAAGC 18 11413 SCNN1A-7565 + UGCACCUGGAUGUGAAAGC 19 11414 SCNN1A-5227 + GUGCACCUGGAUGUGAAAGC 20 9076 SCNN1A-7566 + GGUGCACCUGGAUGUGAAAGC 21 11415 SCNN1A-7567 + AGGUGCACCUGGAUGUGAAAGC 22 11416 SCNN1A-7568 + CAGGUGCACCUGGAUGUGAAAGC 23 11417 SCNN1A-7569 + UCAGGUGCACCUGGAUGUGAAAGC 24 11418 SCNN1A-7570 + UGCUGAAUCUUGACAAGC 18 11419 SCNN1A-7571 + CUGCUGAAUCUUGACAAGC 19 11420 SCNN1A-7572 + UCUGCUGAAUCUUGACAAGC 20 11421 SCNN1A-7573 + CUCUGCUGAAUCUUGACAAGC 21 11422 SCNN1A-7574 + UCUCUGCUGAAUCUUGACAAGC 22 11423 SCNN1A-7575 + AUCUCUGCUGAAUCUUGACAAGC 23 11424 SCNN1A-7576 + CAUCUCUGCUGAAUCUUGACAAGC 24 11425 SCNN1A-7577 + GAGGGGCCCAGGUGAAGC 18 11426 SCNN1A-7578 + GGAGGGGCCCAGGUGAAGC 19 11427 SCNN1A-5885 + GGGAGGGGCCCAGGUGAAGC 20 9734 SCNN1A-7579 + CGGGAGGGGCCCAGGUGAAGC 21 11428 SCNN1A-7580 + CCGGGAGGGGCCCAGGUGAAGC 22 11429 SCNN1A-7581 + CCCGGGAGGGGCCCAGGUGAAGC 23 11430 SCNN1A-7582 + ACCCGGGAGGGGCCCAGGUGAAGC 24 11431 SCNN1A-7583 + GGAUCCUGAGCCCACAGC 18 11432 SCNN1A-7584 + AGGAUCCUGAGCCCACAGC 19 11433 SCNN1A-7585 + AAGGAUCCUGAGCCCACAGC 20 11434 SCNN1A-7586 + GAAGGAUCCUGAGCCCACAGC 21 11435 SCNN1A-7587 + AGAAGGAUCCUGAGCCCACAGC 22 11436 SCNN1A-7588 + UAGAAGGAUCCUGAGCCCACAGC 23 11437 SCNN1A-7589 + GUAGAAGGAUCCUGAGCCCACAGC 24 11438 SCNN1A-7590 + AGCAGACAAAGGCCCAGC 18 11439 SCNN1A-7591 + CAGCAGACAAAGGCCCAGC 19 11440 SCNN1A-7592 + CCAGCAGACAAAGGCCCAGC 20 11441 SCNN1A-7593 + GCCAGCAGACAAAGGCCCAGC 21 11442 SCNN1A-7594 + AGCCAGCAGACAAAGGCCCAGC 22 11443 SCNN1A-7595 + AAGCCAGCAGACAAAGGCCCAGC 23 11444 SCNN1A-7596 + CAAGCCAGCAGACAAAGGCCCAGC 24 11445 SCNN1A-7597 + UGGGCAACCAGAGGCAGC 18 11446 SCNN1A-7598 + GUGGGCAACCAGAGGCAGC 19 11447 SCNN1A-7599 + UGUGGGCAACCAGAGGCAGC 20 11448 SCNN1A-7600 + AUGUGGGCAACCAGAGGCAGC 21 11449 SCNN1A-7601 + AAUGUGGGCAACCAGAGGCAGC 22 11450 SCNN1A-7602 + GAAUGUGGGCAACCAGAGGCAGC 23 11451 SCNN1A-7603 + GGAAUGUGGGCAACCAGAGGCAGC 24 11452 SCNN1A-7604 + CUGAGGAGGAGUCAGAGC 18 11453 SCNN1A-7605 + GCUGAGGAGGAGUCAGAGC 19 11454 SCNN1A-5886 + GGCUGAGGAGGAGUCAGAGC 20 9735 SCNN1A-7606 + GGGCUGAGGAGGAGUCAGAGC 21 11455 SCNN1A-7607 + GGGGCUGAGGAGGAGUCAGAGC 22 11456 SCNN1A-7608 + AGGGGCUGAGGAGGAGUCAGAGC 23 11457 SCNN1A-7609 + GAGGGGCUGAGGAGGAGUCAGAGC 24 11458 SCNN1A-7610 + GUCUCCAGGAAGGAGAGC 18 11459 SCNN1A-7611 + UGUCUCCAGGAAGGAGAGC 19 11460 SCNN1A-7612 + CUGUCUCCAGGAAGGAGAGC 20 11461 SCNN1A-7613 + UCUGUCUCCAGGAAGGAGAGC 21 11462 SCNN1A-7614 + GUCUGUCUCCAGGAAGGAGAGC 22 11463 SCNN1A-7615 + AGUCUGUCUCCAGGAAGGAGAGC 23 11464 SCNN1A-7616 + GAGUCUGUCUCCAGGAAGGAGAGC 24 11465 SCNN1A-7617 + AAGUGUGCUUCCAGGAGC 18 11466 SCNN1A-7618 + CAAGUGUGCUUCCAGGAGC 19 11467 SCNN1A-7619 + CCAAGUGUGCUUCCAGGAGC 20 11468 SCNN1A-7620 + CCCAAGUGUGCUUCCAGGAGC 21 11469 SCNN1A-7621 + UCCCAAGUGUGCUUCCAGGAGC 22 11470 SCNN1A-7622 + GUCCCAAGUGUGCUUCCAGGAGC 23 11471 SCNN1A-7623 + AGUCCCAAGUGUGCUUCCAGGAGC 24 11472 SCNN1A-7624 + GAGUGCCAAGUGGUGAGC 18 11473 SCNN1A-7625 + GGAGUGCCAAGUGGUGAGC 19 11474 SCNN1A-7626 + UGGAGUGCCAAGUGGUGAGC 20 11475 SCNN1A-7627 + GUGGAGUGCCAAGUGGUGAGC 21 11476 SCNN1A-7628 + AGUGGAGUGCCAAGUGGUGAGC 22 11477 SCNN1A-7629 + GAGUGGAGUGCCAAGUGGUGAGC 23 11478 SCNN1A-7630 + GGAGUGGAGUGCCAAGUGGUGAGC 24 11479 SCNN1A-7631 + GGAGGAUGUGGCCAGCGC 18 11480 SCNN1A-7632 + GGGAGGAUGUGGCCAGCGC 19 11481 SCNN1A-6120 + AGGGAGGAUGUGGCCAGCGC 20 9969 SCNN1A-7633 + CAGGGAGGAUGUGGCCAGCGC 21 11482 SCNN1A-7634 + GCAGGGAGGAUGUGGCCAGCGC 22 11483 SCNN1A-7635 + UGCAGGGAGGAUGUGGCCAGCGC 23 11484 SCNN1A-7636 + GUGCAGGGAGGAUGUGGCCAGCGC 24 11485 SCNN1A-7637 + GGCAACCAGAGGCAGCGC 18 11486 SCNN1A-7638 + GGGCAACCAGAGGCAGCGC 19 11487 SCNN1A-7639 + UGGGCAACCAGAGGCAGCGC 20 11488 SCNN1A-7640 + GUGGGCAACCAGAGGCAGCGC 21 11489 SCNN1A-7641 + UGUGGGCAACCAGAGGCAGCGC 22 11490 SCNN1A-7642 + AUGUGGGCAACCAGAGGCAGCGC 23 11491 SCNN1A-7643 + AAUGUGGGCAACCAGAGGCAGCGC 24 11492 SCNN1A-7644 + CUUUAGACGCAGACAGGC 18 11493 SCNN1A-7645 + GCUUUAGACGCAGACAGGC 19 11494 SCNN1A-7646 + GGCUUUAGACGCAGACAGGC 20 11495 SCNN1A-7647 + GGGCUUUAGACGCAGACAGGC 21 11496 SCNN1A-7648 + GGGGCUUUAGACGCAGACAGGC 22 11497 SCNN1A-7649 + AGGGGCUUUAGACGCAGACAGGC 23 11498 SCNN1A-7650 + CAGGGGCUUUAGACGCAGACAGGC 24 11499 SCNN1A-7651 + CACUGUUGGCUGCCAGGC 18 11500 SCNN1A-7652 + ACACUGUUGGCUGCCAGGC 19 11501 SCNN1A-7653 + UACACUGUUGGCUGCCAGGC 20 11502 SCNN1A-7654 + UUACACUGUUGGCUGCCAGGC 21 11503 SCNN1A-7655 + UUUACACUGUUGGCUGCCAGGC 22 11504 SCNN1A-7656 + UUUUACACUGUUGGCUGCCAGGC 23 11505 SCNN1A-7657 + UUUUUACACUGUUGGCUGCCAGGC 24 11506 SCNN1A-7658 + CGGAGCCCAGGAAGAGGC 18 11507 SCNN1A-7659 + CCGGAGCCCAGGAAGAGGC 19 11508 SCNN1A-6122 + CCCGGAGCCCAGGAAGAGGC 20 9971 SCNN1A-7660 + ACCCGGAGCCCAGGAAGAGGC 21 11509 SCNN1A-7661 + GACCCGGAGCCCAGGAAGAGGC 22 11510 SCNN1A-7662 + AGACCCGGAGCCCAGGAAGAGGC 23 11511 SCNN1A-7663 + CAGACCCGGAGCCCAGGAAGAGGC 24 11512 SCNN1A-7664 + GCAGACAGGCAAGGAGGC 18 11513 SCNN1A-7665 + CGCAGACAGGCAAGGAGGC 19 11514 SCNN1A-5608 + ACGCAGACAGGCAAGGAGGC 20 9457 SCNN1A-7666 + GACGCAGACAGGCAAGGAGGC 21 11515 SCNN1A-7667 + AGACGCAGACAGGCAAGGAGGC 22 11516 SCNN1A-7668 + UAGACGCAGACAGGCAAGGAGGC 23 11517 SCNN1A-7669 + UUAGACGCAGACAGGCAAGGAGGC 24 11518 SCNN1A-7670 + GCCCGCCCGCUGGCCGGC 18 11519 SCNN1A-7671 + AGCCCGCCCGCUGGCCGGC 19 11520 SCNN1A-7672 + GAGCCCGCCCGCUGGCCGGC 20 11521 SCNN1A-7673 + GGAGCCCGCCCGCUGGCCGGC 21 11522 SCNN1A-7674 + GGGAGCCCGCCCGCUGGCCGGC 22 11523 SCNN1A-7675 + GGGGAGCCCGCCCGCUGGCCGGC 23 11524 SCNN1A-7676 + UGGGGAGCCCGCCCGCUGGCCGGC 24 11525 SCNN1A-7677 + CCAGGCCCUGCACGCGGC 18 11526 SCNN1A-7678 + CCCAGGCCCUGCACGCGGC 19 11527 SCNN1A-5609 + ACCCAGGCCCUGCACGCGGC 20 9458 SCNN1A-7679 + AACCCAGGCCCUGCACGCGGC 21 11528 SCNN1A-7680 + CAACCCAGGCCCUGCACGCGGC 22 11529 SCNN1A-7681 + ACAACCCAGGCCCUGCACGCGGC 23 11530 SCNN1A-7682 + CACAACCCAGGCCCUGCACGCGGC 24 11531 SCNN1A-7683 + AUCAGACCCAAAAAGGGC 18 11532 SCNN1A-7684 + AAUCAGACCCAAAAAGGGC 19 11533 SCNN1A-5232 + GAAUCAGACCCAAAAAGGGC 20 9081 SCNN1A-7685 + AGAAUCAGACCCAAAAAGGGC 21 11534 SCNN1A-7686 + GAGAAUCAGACCCAAAAAGGGC 22 11535 SCNN1A-7687 + AGAGAAUCAGACCCAAAAAGGGC 23 11536 SCNN1A-7688 + CAGAGAAUCAGACCCAAAAAGGGC 24 11537 SCNN1A-7689 + GACAUAAGAGCCAAGGGC 18 11538 SCNN1A-7690 + AGACAUAAGAGCCAAGGGC 19 11539 SCNN1A-7691 + AAGACAUAAGAGCCAAGGGC 20 11540 SCNN1A-7692 + UAAGACAUAAGAGCCAAGGGC 21 11541 SCNN1A-7693 + AUAAGACAUAAGAGCCAAGGGC 22 11542 SCNN1A-7694 + GAUAAGACAUAAGAGCCAAGGGC 23 11543 SCNN1A-7695 + AGAUAAGACAUAAGAGCCAAGGGC 24 11544 SCNN1A-7696 + AUUAAAGGUGAGCAGGGC 18 11545 SCNN1A-7697 + AAUUAAAGGUGAGCAGGGC 19 11546 SCNN1A-5611 + CAAUUAAAGGUGAGCAGGGC 20 9460 SCNN1A-7698 + UCAAUUAAAGGUGAGCAGGGC 21 11547 SCNN1A-7699 + CUCAAUUAAAGGUGAGCAGGGC 22 11548 SCNN1A-7700 + UCUCAAUUAAAGGUGAGCAGGGC 23 11549 SCNN1A-7701 + AUCUCAAUUAAAGGUGAGCAGGGC 24 11550 SCNN1A-7702 + AGAAGGCGGACUCUGGGC 18 11551 SCNN1A-7703 + GAGAAGGCGGACUCUGGGC 19 11552 SCNN1A-5613 + UGAGAAGGCGGACUCUGGGC 20 9462 SCNN1A-7704 + CUGAGAAGGCGGACUCUGGGC 21 11553 SCNN1A-7705 + CCUGAGAAGGCGGACUCUGGGC 22 11554 SCNN1A-7706 + ACCUGAGAAGGCGGACUCUGGGC 23 11555 SCNN1A-7707 + GACCUGAGAAGGCGGACUCUGGGC 24 11556 SCNN1A-7708 + CAGGUGCAGCGGCCUGGC 18 11557 SCNN1A-7709 + ACAGGUGCAGCGGCCUGGC 19 11558 SCNN1A-5234 + GACAGGUGCAGCGGCCUGGC 20 9083 SCNN1A-7710 + UGACAGGUGCAGCGGCCUGGC 21 11559 SCNN1A-7711 + CUGACAGGUGCAGCGGCCUGGC 22 11560 SCNN1A-7712 + CCUGACAGGUGCAGCGGCCUGGC 23 11561 SCNN1A-7713 + ACCUGACAGGUGCAGCGGCCUGGC 24 11562 SCNN1A-7714 + CUAUUUGCCAGCUCAUGC 18 11563 SCNN1A-7715 + UCUAUUUGCCAGCUCAUGC 19 11564 SCNN1A-7716 + UUCUAUUUGCCAGCUCAUGC 20 11565 SCNN1A-7717 + UUUCUAUUUGCCAGCUCAUGC 21 11566 SCNN1A-7718 + UUUUCUAUUUGCCAGCUCAUGC 22 11567 SCNN1A-7719 + CUUUUCUAUUUGCCAGCUCAUGC 23 11568 SCNN1A-7720 + CCUUUUCUAUUUGCCAGCUCAUGC 24 11569 SCNN1A-7721 + AGCCUAGGGGCUCACUGC 18 11570 SCNN1A-7722 + GAGCCUAGGGGCUCACUGC 19 11571 SCNN1A-5235 + GGAGCCUAGGGGCUCACUGC 20 9084 SCNN1A-7723 + GGGAGCCUAGGGGCUCACUGC 21 11572 SCNN1A-7724 + GGGGAGCCUAGGGGCUCACUGC 22 11573 SCNN1A-7725 + AGGGGAGCCUAGGGGCUCACUGC 23 11574 SCNN1A-7726 + UAGGGGAGCCUAGGGGCUCACUGC 24 11575 SCNN1A-7727 + AGUUGGGGCCAAAAGUGC 18 11576 SCNN1A-7728 + GAGUUGGGGCCAAAAGUGC 19 11577 SCNN1A-5236 + GGAGUUGGGGCCAAAAGUGC 20 9085 SCNN1A-7729 + GGGAGUUGGGGCCAAAAGUGC 21 11578 SCNN1A-7730 + CGGGAGUUGGGGCCAAAAGUGC 22 11579 SCNN1A-7731 + GCGGGAGUUGGGGCCAAAAGUGC 23 11580 SCNN1A-7732 + UGCGGGAGUUGGGGCCAAAAGUGC 24 11581 SCNN1A-7733 + AGCAGGCACUGAAGGUGC 18 11582 SCNN1A-7734 + AAGCAGGCACUGAAGGUGC 19 11583 SCNN1A-5620 + AAAGCAGGCACUGAAGGUGC 20 9469 SCNN1A-7735 + GAAAGCAGGCACUGAAGGUGC 21 11584 SCNN1A-7736 + GGAAAGCAGGCACUGAAGGUGC 22 11585 SCNN1A-7737 + GGGAAAGCAGGCACUGAAGGUGC 23 11586 SCNN1A-7738 + AGGGAAAGCAGGCACUGAAGGUGC 24 11587 SCNN1A-7739 + UGAACAAGUAGAAGGAUC 18 11588 SCNN1A-7740 + CUGAACAAGUAGAAGGAUC 19 11589 SCNN1A-7741 + UCUGAACAAGUAGAAGGAUC 20 11590 SCNN1A-7742 + AUCUGAACAAGUAGAAGGAUC 21 11591 SCNN1A-7743 + GAUCUGAACAAGUAGAAGGAUC 22 11592 SCNN1A-7744 + AGAUCUGAACAAGUAGAAGGAUC 23 11593 SCNN1A-7745 + AAGAUCUGAACAAGUAGAAGGAUC 24 11594 SCNN1A-7746 + GCAAAUAGUUUUCAUAUC 18 11595 SCNN1A-7747 + GGCAAAUAGUUUUCAUAUC 19 11596 SCNN1A-7748 + UGGCAAAUAGUUUUCAUAUC 20 11597 SCNN1A-7749 + AUGGCAAAUAGUUUUCAUAUC 21 11598 SCNN1A-7750 + CAUGGCAAAUAGUUUUCAUAUC 22 11599 SCNN1A-7751 + GCAUGGCAAAUAGUUUUCAUAUC 23 11600 SCNN1A-7752 + AGCAUGGCAAAUAGUUUUCAUAUC 24 11601 SCNN1A-7753 + ACUUCCUGAGACAGACUC 18 11602 SCNN1A-7754 + UACUUCCUGAGACAGACUC 19 11603 SCNN1A-7755 + UUACUUCCUGAGACAGACUC 20 11604 SCNN1A-7756 + UUUACUUCCUGAGACAGACUC 21 11605 SCNN1A-7757 + AUUUACUUCCUGAGACAGACUC 22 11606 SCNN1A-7758 + CAUUUACUUCCUGAGACAGACUC 23 11607 SCNN1A-7759 + CCAUUUACUUCCUGAGACAGACUC 24 11608 SCNN1A-7760 + GCUCACUGCAGGAGACUC 18 11609 SCNN1A-7761 + GGCUCACUGCAGGAGACUC 19 11610 SCNN1A-5239 + GGGCUCACUGCAGGAGACUC 20 9088 SCNN1A-7762 + GGGGCUCACUGCAGGAGACUC 21 11611 SCNN1A-7763 + AGGGGCUCACUGCAGGAGACUC 22 11612 SCNN1A-7764 + UAGGGGCUCACUGCAGGAGACUC 23 11613 SCNN1A-7765 + CUAGGGGCUCACUGCAGGAGACUC 24 11614 SCNN1A-7766 + AAGGGCUGGAGGAGACUC 18 11615 SCNN1A-7767 + AAAGGGCUGGAGGAGACUC 19 11616 SCNN1A-5628 + AAAAGGGCUGGAGGAGACUC 20 9477 SCNN1A-7768 + AAAAAGGGCUGGAGGAGACUC 21 11617 SCNN1A-7769 + CAAAAAGGGCUGGAGGAGACUC 22 11618 SCNN1A-7770 + CCAAAAAGGGCUGGAGGAGACUC 23 11619 SCNN1A-7771 + CCCAAAAAGGGCUGGAGGAGACUC 24 11620 SCNN1A-7772 + AGAAUUCUCCUCCUCCUC 18 11621 SCNN1A-7773 + CAGAAUUCUCCUCCUCCUC 19 11622 SCNN1A-6134 + UCAGAAUUCUCCUCCUCCUC 20 9983 SCNN1A-7774 + UUCAGAAUUCUCCUCCUCCUC 21 11623 SCNN1A-7775 + AUUCAGAAUUCUCCUCCUCCUC 22 11624 SCNN1A-7776 + AAUUCAGAAUUCUCCUCCUCCUC 23 11625 SCNN1A-7777 + GAAUUCAGAAUUCUCCUCCUCCUC 24 11626 SCNN1A-7778 + GAAGGCUGCCGCUUCCUC 18 11627 SCNN1A-7779 + GGAAGGCUGCCGCUUCCUC 19 11628 SCNN1A-7780 + GGGAAGGCUGCCGCUUCCUC 20 11629 SCNN1A-7781 + AGGGAAGGCUGCCGCUUCCUC 21 11630 SCNN1A-7782 + CAGGGAAGGCUGCCGCUUCCUC 22 11631 SCNN1A-7783 + GCAGGGAAGGCUGCCGCUUCCUC 23 11632 SCNN1A-7784 + GGCAGGGAAGGCUGCCGCUUCCUC 24 11633 SCNN1A-7785 + CCCAGGACUGCAGGGCUC 18 11634 SCNN1A-7786 + CCCCAGGACUGCAGGGCUC 19 11635 SCNN1A-7787 + GCCCCAGGACUGCAGGGCUC 20 11636 SCNN1A-7788 + UGCCCCAGGACUGCAGGGCUC 21 11637 SCNN1A-7789 + CUGCCCCAGGACUGCAGGGCUC 22 11638 SCNN1A-7790 + UCUGCCCCAGGACUGCAGGGCUC 23 11639 SCNN1A-7791 + CUCUGCCCCAGGACUGCAGGGCUC 24 11640 SCNN1A-7792 + CCGAAGGAAGGAGGGCUC 18 11641 SCNN1A-7793 + UCCGAAGGAAGGAGGGCUC 19 11642 SCNN1A-7794 + UUCCGAAGGAAGGAGGGCUC 20 11643 SCNN1A-7795 + UUUCCGAAGGAAGGAGGGCUC 21 11644 SCNN1A-7796 + UUUUCCGAAGGAAGGAGGGCUC 22 11645 SCNN1A-7797 + GUUUUCCGAAGGAAGGAGGGCUC 23 11646 SCNN1A-7798 + AGUUUUCCGAAGGAAGGAGGGCUC 24 11647 SCNN1A-7799 + CCAAAGGGAGUCUGUCUC 18 11648 SCNN1A-7800 + ACCAAAGGGAGUCUGUCUC 19 11649 SCNN1A-7801 + CACCAAAGGGAGUCUGUCUC 20 11650 SCNN1A-7802 + GCACCAAAGGGAGUCUGUCUC 21 11651 SCNN1A-7803 + AGCACCAAAGGGAGUCUGUCUC 22 11652 SCNN1A-7804 + CAGCACCAAAGGGAGUCUGUCUC 23 11653 SCNN1A-7805 + CCAGCACCAAAGGGAGUCUGUCUC 24 11654 SCNN1A-7806 + GCUUUUGCCAUUUACUUC 18 11655 SCNN1A-7807 + CGCUUUUGCCAUUUACUUC 19 11656 SCNN1A-7808 + GCGCUUUUGCCAUUUACUUC 20 11657 SCNN1A-7809 + AGCGCUUUUGCCAUUUACUUC 21 11658 SCNN1A-7810 + UAGCGCUUUUGCCAUUUACUUC 22 11659 SCNN1A-7811 + UUAGCGCUUUUGCCAUUUACUUC 23 11660 SCNN1A-7812 + CUUAGCGCUUUUGCCAUUUACUUC 24 11661 SCNN1A-1549 + UCCAGCUUGUUCCCCUUC 18 5398 SCNN1A-1550 + CUCCAGCUUGUUCCCCUUC 19 5399 SCNN1A-1551 + CCUCCAGCUUGUUCCCCUUC 20 5400 SCNN1A-1552 + UCCUCCAGCUUGUUCCCCUUC 21 5401 SCNN1A-1553 + CUCCUCCAGCUUGUUCCCCUUC 22 5402 SCNN1A-1554 + GCUCCUCCAGCUUGUUCCCCUUC 23 5403 SCNN1A-1555 + UGCUCCUCCAGCUUGUUCCCCUUC 24 5404 SCNN1A-7813 + GAGUCCCAAGUGUGCUUC 18 11662 SCNN1A-7814 + GGAGUCCCAAGUGUGCUUC 19 11663 SCNN1A-7815 + GGGAGUCCCAAGUGUGCUUC 20 11664 SCNN1A-7816 + GGGGAGUCCCAAGUGUGCUUC 21 11665 SCNN1A-7817 + GGGGGAGUCCCAAGUGUGCUUC 22 11666 SCNN1A-7818 + GGGGGGAGUCCCAAGUGUGCUUC 23 11667 SCNN1A-7819 + AGGGGGGAGUCCCAAGUGUGCUUC 24 11668 SCNN1A-7820 + CUCCCUCCUCCACCUUUC 18 11669 SCNN1A-7821 + CCUCCCUCCUCCACCUUUC 19 11670 SCNN1A-7822 + CCCUCCCUCCUCCACCUUUC 20 11671 SCNN1A-7823 + UCCCUCCCUCCUCCACCUUUC 21 11672 SCNN1A-7824 + CUCCCUCCCUCCUCCACCUUUC 22 11673 SCNN1A-7825 + CCUCCCUCCCUCCUCCACCUUUC 23 11674 SCNN1A-7826 + UCCUCCCUCCCUCCUCCACCUUUC 24 11675 SCNN1A-7827 + GGAGUUUAGCAGGCAAAG 18 11676 SCNN1A-7828 + AGGAGUUUAGCAGGCAAAG 19 11677 SCNN1A-7829 + AAGGAGUUUAGCAGGCAAAG 20 11678 SCNN1A-7830 + CAAGGAGUUUAGCAGGCAAAG 21 11679 SCNN1A-7831 + GCAAGGAGUUUAGCAGGCAAAG 22 11680 SCNN1A-7832 + AGCAAGGAGUUUAGCAGGCAAAG 23 11681 SCNN1A-7833 + AAGCAAGGAGUUUAGCAGGCAAAG 24 11682 SCNN1A-7834 + GGACAGGAGGGCAGAAAG 18 11683 SCNN1A-7835 + AGGACAGGAGGGCAGAAAG 19 11684 SCNN1A-5894 + GAGGACAGGAGGGCAGAAAG 20 9743 SCNN1A-7836 + GGAGGACAGGAGGGCAGAAAG 21 11685 SCNN1A-7837 + GGGAGGACAGGAGGGCAGAAAG 22 11686 SCNN1A-7838 + CGGGAGGACAGGAGGGCAGAAAG 23 11687 SCNN1A-7839 + CCGGGAGGACAGGAGGGCAGAAAG 24 11688 SCNN1A-7840 + UGCACCUGGAUGUGAAAG 18 11689 SCNN1A-7841 + GUGCACCUGGAUGUGAAAG 19 11690 SCNN1A-7842 + GGUGCACCUGGAUGUGAAAG 20 11691 SCNN1A-7843 + AGGUGCACCUGGAUGUGAAAG 21 11692 SCNN1A-7844 + CAGGUGCACCUGGAUGUGAAAG 22 11693 SCNN1A-7845 + UCAGGUGCACCUGGAUGUGAAAG 23 11694 SCNN1A-7846 + CUCAGGUGCACCUGGAUGUGAAAG 24 11695 SCNN1A-7847 + UUAGCAUCUCAAUUAAAG 18 11696 SCNN1A-7848 + AUUAGCAUCUCAAUUAAAG 19 11697 SCNN1A-7849 + CAUUAGCAUCUCAAUUAAAG 20 11698 SCNN1A-7850 + UCAUUAGCAUCUCAAUUAAAG 21 11699 SCNN1A-7851 + CUCAUUAGCAUCUCAAUUAAAG 22 11700 SCNN1A-7852 + UCUCAUUAGCAUCUCAAUUAAAG 23 11701 SCNN1A-7853 + AUCUCAUUAGCAUCUCAAUUAAAG 24 11702 SCNN1A-7854 + GGCAAAGAUCUGAACAAG 18 11703 SCNN1A-7855 + GGGCAAAGAUCUGAACAAG 19 11704 SCNN1A-7856 + GGGGCAAAGAUCUGAACAAG 20 11705 SCNN1A-7857 + AGGGGCAAAGAUCUGAACAAG 21 11706 SCNN1A-7858 + GAGGGGCAAAGAUCUGAACAAG 22 11707 SCNN1A-7859 + UGAGGGGCAAAGAUCUGAACAAG 23 11708 SCNN1A-7860 + GUGAGGGGCAAAGAUCUGAACAAG 24 11709 SCNN1A-7861 + CUAGGAGGGCAACACAAG 18 11710 SCNN1A-7862 + GCUAGGAGGGCAACACAAG 19 11711 SCNN1A-7863 + AGCUAGGAGGGCAACACAAG 20 11712 SCNN1A-7864 + CAGCUAGGAGGGCAACACAAG 21 11713 SCNN1A-7865 + ACAGCUAGGAGGGCAACACAAG 22 11714 SCNN1A-7866 + CACAGCUAGGAGGGCAACACAAG 23 11715 SCNN1A-7867 + CCACAGCUAGGAGGGCAACACAAG 24 11716 SCNN1A-7868 + UCCAGGAAGGAGAGCAAG 18 11717 SCNN1A-7869 + CUCCAGGAAGGAGAGCAAG 19 11718 SCNN1A-6140 + UCUCCAGGAAGGAGAGCAAG 20 9989 SCNN1A-7870 + GUCUCCAGGAAGGAGAGCAAG 21 11719 SCNN1A-7871 + UGUCUCCAGGAAGGAGAGCAAG 22 11720 SCNN1A-7872 + CUGUCUCCAGGAAGGAGAGCAAG 23 11721 SCNN1A-7873 + UCUGUCUCCAGGAAGGAGAGCAAG 24 11722 SCNN1A-7874 + UGCCAAGUGGUGAGCAAG 18 11723 SCNN1A-7875 + GUGCCAAGUGGUGAGCAAG 19 11724 SCNN1A-7876 + AGUGCCAAGUGGUGAGCAAG 20 11725 SCNN1A-7877 + GAGUGCCAAGUGGUGAGCAAG 21 11726 SCNN1A-7878 + GGAGUGCCAAGUGGUGAGCAAG 22 11727 SCNN1A-7879 + UGGAGUGCCAAGUGGUGAGCAAG 23 11728 SCNN1A-7880 + GUGGAGUGCCAAGUGGUGAGCAAG 24 11729 SCNN1A-7881 + AGUACUGGACCUGAGAAG 18 11730 SCNN1A-7882 + GAGUACUGGACCUGAGAAG 19 11731 SCNN1A-7883 + GGAGUACUGGACCUGAGAAG 20 11732 SCNN1A-7884 + GGGAGUACUGGACCUGAGAAG 21 11733 SCNN1A-7885 + UGGGAGUACUGGACCUGAGAAG 22 11734 SCNN1A-7886 + CUGGGAGUACUGGACCUGAGAAG 23 11735 SCNN1A-7887 + ACUGGGAGUACUGGACCUGAGAAG 24 11736 SCNN1A-7888 + GGAGUUUUCCGAAGGAAG 18 11737 SCNN1A-7889 + GGGAGUUUUCCGAAGGAAG 19 11738 SCNN1A-7890 + CGGGAGUUUUCCGAAGGAAG 20 11739 SCNN1A-7891 + CCGGGAGUUUUCCGAAGGAAG 21 11740 SCNN1A-7892 + GCCGGGAGUUUUCCGAAGGAAG 22 11741 SCNN1A-7893 + AGCCGGGAGUUUUCCGAAGGAAG 23 11742 SCNN1A-7894 + GAGCCGGGAGUUUUCCGAAGGAAG 24 11743 SCNN1A-7895 + GAGUCUGUCUCCAGGAAG 18 11744 SCNN1A-7896 + GGAGUCUGUCUCCAGGAAG 19 11745 SCNN1A-7897 + GGGAGUCUGUCUCCAGGAAG 20 11746 SCNN1A-7898 + AGGGAGUCUGUCUCCAGGAAG 21 11747 SCNN1A-7899 + AAGGGAGUCUGUCUCCAGGAAG 22 11748 SCNN1A-7900 + AAAGGGAGUCUGUCUCCAGGAAG 23 11749 SCNN1A-7901 + CAAAGGGAGUCUGUCUCCAGGAAG 24 11750 SCNN1A-7902 + GGAGGGGCCCAGGUGAAG 18 11751 SCNN1A-7903 + GGGAGGGGCCCAGGUGAAG 19 11752 SCNN1A-7904 + CGGGAGGGGCCCAGGUGAAG 20 11753 SCNN1A-7905 + CCGGGAGGGGCCCAGGUGAAG 21 11754 SCNN1A-7906 + CCCGGGAGGGGCCCAGGUGAAG 22 11755 SCNN1A-7907 + ACCCGGGAGGGGCCCAGGUGAAG 23 11756 SCNN1A-7908 + GACCCGGGAGGGGCCCAGGUGAAG 24 11757 SCNN1A-7909 + UCCUCCCCGCUCACUAAG 18 11758 SCNN1A-7910 + CUCCUCCCCGCUCACUAAG 19 11759 SCNN1A-5645 + UCUCCUCCCCGCUCACUAAG 20 9494 SCNN1A-7911 + GUCUCCUCCCCGCUCACUAAG 21 11760 SCNN1A-7912 + GGUCUCCUCCCCGCUCACUAAG 22 11761 SCNN1A-7913 + AGGUCUCCUCCCCGCUCACUAAG 23 11762 SCNN1A-7914 + CAGGUCUCCUCCCCGCUCACUAAG 24 11763 SCNN1A-7915 + GGGGAACCGGGAGGACAG 18 11764 SCNN1A-7916 + UGGGGAACCGGGAGGACAG 19 11765 SCNN1A-7917 + GUGGGGAACCGGGAGGACAG 20 11766 SCNN1A-7918 + GGUGGGGAACCGGGAGGACAG 21 11767 SCNN1A-7919 + GGGUGGGGAACCGGGAGGACAG 22 11768 SCNN1A-7920 + UGGGUGGGGAACCGGGAGGACAG 23 11769 SCNN1A-7921 + CUGGGUGGGGAACCGGGAGGACAG 24 11770 SCNN1A-7922 + GACCCGGGAGGGGCCCAG 18 11771 SCNN1A-7923 + AGACCCGGGAGGGGCCCAG 19 11772 SCNN1A-7924 + CAGACCCGGGAGGGGCCCAG 20 11773 SCNN1A-7925 + CCAGACCCGGGAGGGGCCCAG 21 11774 SCNN1A-7926 + UCCAGACCCGGGAGGGGCCCAG 22 11775 SCNN1A-7927 + GUCCAGACCCGGGAGGGGCCCAG 23 11776 SCNN1A-7928 + UGUCCAGACCCGGGAGGGGCCCAG 24 11777 SCNN1A-7929 + CUGAGUGAGUAGAGGCAG 18 11778 SCNN1A-7930 + ACUGAGUGAGUAGAGGCAG 19 11779 SCNN1A-7931 + CACUGAGUGAGUAGAGGCAG 20 11780 SCNN1A-7932 + GCACUGAGUGAGUAGAGGCAG 21 11781 SCNN1A-7933 + GGCACUGAGUGAGUAGAGGCAG 22 11782 SCNN1A-7934 + GGGCACUGAGUGAGUAGAGGCAG 23 11783 SCNN1A-7935 + GGGGCACUGAGUGAGUAGAGGCAG 24 11784 SCNN1A-7936 + GAGGGCUCCCGAGGGCAG 18 11785 SCNN1A-7937 + GGAGGGCUCCCGAGGGCAG 19 11786 SCNN1A-7938 + AGGAGGGCUCCCGAGGGCAG 20 11787 SCNN1A-7939 + AAGGAGGGCUCCCGAGGGCAG 21 11788 SCNN1A-7940 + GAAGGAGGGCUCCCGAGGGCAG 22 11789 SCNN1A-7941 + GGAAGGAGGGCUCCCGAGGGCAG 23 11790 SCNN1A-7942 + AGGAAGGAGGGCUCCCGAGGGCAG 24 11791 SCNN1A-7943 + UGGGGGACAGGAUGGCAG 18 11792 SCNN1A-7944 + CUGGGGGACAGGAUGGCAG 19 11793 SCNN1A-7945 + GCUGGGGGACAGGAUGGCAG 20 11794 SCNN1A-7946 + GGCUGGGGGACAGGAUGGCAG 21 11795 SCNN1A-7947 + AGGCUGGGGGACAGGAUGGCAG 22 11796 SCNN1A-7948 + GAGGCUGGGGGACAGGAUGGCAG 23 11797 SCNN1A-7949 + GGAGGCUGGGGGACAGGAUGGCAG 24 11798 SCNN1A-7950 + UGGGAGCAGCGCACUCAG 18 11799 SCNN1A-7951 + GUGGGAGCAGCGCACUCAG 19 11800 SCNN1A-7952 + AGUGGGAGCAGCGCACUCAG 20 11801 SCNN1A-7953 + AAGUGGGAGCAGCGCACUCAG 21 11802 SCNN1A-7954 + UAAGUGGGAGCAGCGCACUCAG 22 11803 SCNN1A-7955 + CUAAGUGGGAGCAGCGCACUCAG 23 11804 SCNN1A-7956 + ACUAAGUGGGAGCAGCGCACUCAG 24 11805 SCNN1A-7957 + CCCUCAGGCCCUGCAGAG 18 11806 SCNN1A-7958 + ACCCUCAGGCCCUGCAGAG 19 11807 SCNN1A-7959 + CACCCUCAGGCCCUGCAGAG 20 11808 SCNN1A-7960 + UCACCCUCAGGCCCUGCAGAG 21 11809 SCNN1A-7961 + CUCACCCUCAGGCCCUGCAGAG 22 11810 SCNN1A-7962 + CCUCACCCUCAGGCCCUGCAGAG 23 11811 SCNN1A-7963 + GCCUCACCCUCAGGCCCUGCAGAG 24 11812 SCNN1A-7964 + GCUGAGGAGGAGUCAGAG 18 11813 SCNN1A-7965 + GGCUGAGGAGGAGUCAGAG 19 11814 SCNN1A-7966 + GGGCUGAGGAGGAGUCAGAG 20 11815 SCNN1A-7967 + GGGGCUGAGGAGGAGUCAGAG 21 11816 SCNN1A-7968 + AGGGGCUGAGGAGGAGUCAGAG 22 11817 SCNN1A-7969 + GAGGGGCUGAGGAGGAGUCAGAG 23 11818 SCNN1A-7970 + GGAGGGGCUGAGGAGGAGUCAGAG 24 11819 SCNN1A-7971 + GCCCUGCAGAGAAGAGAG 18 11820 SCNN1A-7972 + GGCCCUGCAGAGAAGAGAG 19 11821 SCNN1A-7973 + AGGCCCUGCAGAGAAGAGAG 20 11822 SCNN1A-7974 + CAGGCCCUGCAGAGAAGAGAG 21 11823 SCNN1A-7975 + UCAGGCCCUGCAGAGAAGAGAG 22 11824 SCNN1A-7976 + CUCAGGCCCUGCAGAGAAGAGAG 23 11825 SCNN1A-7977 + CCUCAGGCCCUGCAGAGAAGAGAG 24 11826 SCNN1A-7978 + UGGUGAGCAAGGAGAGAG 18 11827 SCNN1A-7979 + GUGGUGAGCAAGGAGAGAG 19 11828 SCNN1A-6146 + AGUGGUGAGCAAGGAGAGAG 20 9995 SCNN1A-7980 + AAGUGGUGAGCAAGGAGAGAG 21 11829 SCNN1A-7981 + CAAGUGGUGAGCAAGGAGAGAG 22 11830 SCNN1A-7982 + CCAAGUGGUGAGCAAGGAGAGAG 23 11831 SCNN1A-7983 + GCCAAGUGGUGAGCAAGGAGAGAG 24 11832 SCNN1A-7984 + AAGAGGGAGACAAUAGAG 18 11833 SCNN1A-7985 + AAAGAGGGAGACAAUAGAG 19 11834 SCNN1A-5896 + GAAAGAGGGAGACAAUAGAG 20 9745 SCNN1A-7986 + AGAAAGAGGGAGACAAUAGAG 21 11835 SCNN1A-7987 + CAGAAAGAGGGAGACAAUAGAG 22 11836 SCNN1A-7988 + GCAGAAAGAGGGAGACAAUAGAG 23 11837 SCNN1A-7989 + GGCAGAAAGAGGGAGACAAUAGAG 24 11838 SCNN1A-7990 + GGAGGGCAACACAAGGAG 18 11839 SCNN1A-7991 + AGGAGGGCAACACAAGGAG 19 11840 SCNN1A-7992 + UAGGAGGGCAACACAAGGAG 20 11841 SCNN1A-7993 + CUAGGAGGGCAACACAAGGAG 21 11842 SCNN1A-7994 + GCUAGGAGGGCAACACAAGGAG 22 11843 SCNN1A-7995 + AGCUAGGAGGGCAACACAAGGAG 23 11844 SCNN1A-7996 + CAGCUAGGAGGGCAACACAAGGAG 24 11845 SCNN1A-7997 + GACAGGCCCUGGGAGGAG 18 11846 SCNN1A-7998 + AGACAGGCCCUGGGAGGAG 19 11847 SCNN1A-7999 + UAGACAGGCCCUGGGAGGAG 20 11848 SCNN1A-8000 + CUAGACAGGCCCUGGGAGGAG 21 11849 SCNN1A-8001 + CCUAGACAGGCCCUGGGAGGAG 22 11850 SCNN1A-8002 + GCCUAGACAGGCCCUGGGAGGAG 23 11851 SCNN1A-8003 + CGCCUAGACAGGCCCUGGGAGGAG 24 11852 SCNN1A-8004 + UAGAAAACAAAAUAGGAG 18 11853 SCNN1A-8005 + UUAGAAAACAAAAUAGGAG 19 11854 SCNN1A-8006 + GUUAGAAAACAAAAUAGGAG 20 11855 SCNN1A-8007 + GGUUAGAAAACAAAAUAGGAG 21 11856 SCNN1A-8008 + AGGUUAGAAAACAAAAUAGGAG 22 11857 SCNN1A-8009 + GAGGUUAGAAAACAAAAUAGGAG 23 11858 SCNN1A-8010 + UGAGGUUAGAAAACAAAAUAGGAG 24 11859 SCNN1A-8011 + GGGCCAAAAGUGCCGGAG 18 11860 SCNN1A-8012 + GGGGCCAAAAGUGCCGGAG 19 11861 SCNN1A-8013 + UGGGGCCAAAAGUGCCGGAG 20 11862 SCNN1A-8014 + UUGGGGCCAAAAGUGCCGGAG 21 11863 SCNN1A-8015 + GUUGGGGCCAAAAGUGCCGGAG 22 11864 SCNN1A-8016 + AGUUGGGGCCAAAAGUGCCGGAG 23 11865 SCNN1A-8017 + GAGUUGGGGCCAAAAGUGCCGGAG 24 11866 SCNN1A-8018 + CCAGCAGACCUGCGGGAG 18 11867 SCNN1A-8019 + GCCAGCAGACCUGCGGGAG 19 11868 SCNN1A-8020 + AGCCAGCAGACCUGCGGGAG 20 11869 SCNN1A-8021 + GAGCCAGCAGACCUGCGGGAG 21 11870 SCNN1A-8022 + GGAGCCAGCAGACCUGCGGGAG 22 11871 SCNN1A-8023 + UGGAGCCAGCAGACCUGCGGGAG 23 11872 SCNN1A-8024 + CUGGAGCCAGCAGACCUGCGGGAG 24 11873 SCNN1A-8025 + CUAGACAGGCCCUGGGAG 18 11874 SCNN1A-8026 + CCUAGACAGGCCCUGGGAG 19 11875 SCNN1A-8027 + GCCUAGACAGGCCCUGGGAG 20 11876 SCNN1A-8028 + CGCCUAGACAGGCCCUGGGAG 21 11877 SCNN1A-8029 + ACGCCUAGACAGGCCCUGGGAG 22 11878 SCNN1A-8030 + CACGCCUAGACAGGCCCUGGGAG 23 11879 SCNN1A-8031 + ACACGCCUAGACAGGCCCUGGGAG 24 11880 SCNN1A-8032 + AGAGAGAUAGGGAUGGAG 18 11881 SCNN1A-8033 + CAGAGAGAUAGGGAUGGAG 19 11882 SCNN1A-8034 + ACAGAGAGAUAGGGAUGGAG 20 11883 SCNN1A-8035 + GACAGAGAGAUAGGGAUGGAG 21 11884 SCNN1A-8036 + GGACAGAGAGAUAGGGAUGGAG 22 11885 SCNN1A-8037 + AGGACAGAGAGAUAGGGAUGGAG 23 11886 SCNN1A-8038 + AAGGACAGAGAGAUAGGGAUGGAG 24 11887 SCNN1A-8039 + GCGGGGGGAGGGGCUGAG 18 11888 SCNN1A-8040 + GGCGGGGGGAGGGGCUGAG 19 11889 SCNN1A-8041 + GGGCGGGGGGAGGGGCUGAG 20 11890 SCNN1A-8042 + AGGGCGGGGGGAGGGGCUGAG 21 11891 SCNN1A-8043 + CAGGGCGGGGGGAGGGGCUGAG 22 11892 SCNN1A-8044 + GCAGGGCGGGGGGAGGGGCUGAG 23 11893 SCNN1A-8045 + AGCAGGGCGGGGGGAGGGGCUGAG 24 11894 SCNN1A-8046 + GGAGGGGCACUGAGUGAG 18 11895 SCNN1A-8047 + AGGAGGGGCACUGAGUGAG 19 11896 SCNN1A-8048 + GAGGAGGGGCACUGAGUGAG 20 11897 SCNN1A-8049 + GGAGGAGGGGCACUGAGUGAG 21 11898 SCNN1A-8050 + UGGAGGAGGGGCACUGAGUGAG 22 11899 SCNN1A-8051 + AUGGAGGAGGGGCACUGAGUGAG 23 11900 SCNN1A-8052 + GAUGGAGGAGGGGCACUGAGUGAG 24 11901 SCNN1A-8053 + AUCUCAAUUAAAGGUGAG 18 11902 SCNN1A-8054 + CAUCUCAAUUAAAGGUGAG 19 11903 SCNN1A-8055 + GCAUCUCAAUUAAAGGUGAG 20 11904 SCNN1A-8056 + AGCAUCUCAAUUAAAGGUGAG 21 11905 SCNN1A-8057 + UAGCAUCUCAAUUAAAGGUGAG 22 11906 SCNN1A-8058 + UUAGCAUCUCAAUUAAAGGUGAG 23 11907 SCNN1A-8059 + AUUAGCAUCUCAAUUAAAGGUGAG 24 11908 SCNN1A-8060 + AGUGGUGGGGGCAAAUAG 18 11909 SCNN1A-8061 + CAGUGGUGGGGGCAAAUAG 19 11910 SCNN1A-8062 + GCAGUGGUGGGGGCAAAUAG 20 11911 SCNN1A-8063 + GGCAGUGGUGGGGGCAAAUAG 21 11912 SCNN1A-8064 + GGGCAGUGGUGGGGGCAAAUAG 22 11913 SCNN1A-8065 + GGGGCAGUGGUGGGGGCAAAUAG 23 11914 SCNN1A-8066 + GGGGGCAGUGGUGGGGGCAAAUAG 24 11915 SCNN1A-8067 + UCCUGAGCCCACAGCUAG 18 11916 SCNN1A-8068 + AUCCUGAGCCCACAGCUAG 19 11917 SCNN1A-8069 + GAUCCUGAGCCCACAGCUAG 20 11918 SCNN1A-8070 + GGAUCCUGAGCCCACAGCUAG 21 11919 SCNN1A-8071 + AGGAUCCUGAGCCCACAGCUAG 22 11920 SCNN1A-8072 + AAGGAUCCUGAGCCCACAGCUAG 23 11921 SCNN1A-8073 + GAAGGAUCCUGAGCCCACAGCUAG 24 11922 SCNN1A-8074 + AUAAGAGCCAAGGGCUAG 18 11923 SCNN1A-8075 + CAUAAGAGCCAAGGGCUAG 19 11924 SCNN1A-5662 + ACAUAAGAGCCAAGGGCUAG 20 9511 SCNN1A-8076 + GACAUAAGAGCCAAGGGCUAG 21 11925 SCNN1A-8077 + AGACAUAAGAGCCAAGGGCUAG 22 11926 SCNN1A-8078 + AAGACAUAAGAGCCAAGGGCUAG 23 11927 SCNN1A-8079 + UAAGACAUAAGAGCCAAGGGCUAG 24 11928 SCNN1A-8080 + GGUGAAGCUGGGGGCUAG 18 11929 SCNN1A-8081 + AGGUGAAGCUGGGGGCUAG 19 11930 SCNN1A-8082 + CAGGUGAAGCUGGGGGCUAG 20 11931 SCNN1A-8083 + CCAGGUGAAGCUGGGGGCUAG 21 11932 SCNN1A-8084 + CCCAGGUGAAGCUGGGGGCUAG 22 11933 SCNN1A-8085 + GCCCAGGUGAAGCUGGGGGCUAG 23 11934 SCNN1A-8086 + GGCCCAGGUGAAGCUGGGGGCUAG 24 11935 SCNN1A-8087 + GGCAGCGCGAGGGCCACG 18 11936 SCNN1A-8088 + AGGCAGCGCGAGGGCCACG 19 11937 SCNN1A-8089 + GAGGCAGCGCGAGGGCCACG 20 11938 SCNN1A-8090 + AGAGGCAGCGCGAGGGCCACG 21 11939 SCNN1A-8091 + CAGAGGCAGCGCGAGGGCCACG 22 11940 SCNN1A-8092 + CCAGAGGCAGCGCGAGGGCCACG 23 11941 SCNN1A-8093 + ACCAGAGGCAGCGCGAGGGCCACG 24 11942 SCNN1A-8094 + GAGCAUUGAUACACACCG 18 11943 SCNN1A-8095 + UGAGCAUUGAUACACACCG 19 11944 SCNN1A-5665 + CUGAGCAUUGAUACACACCG 20 9514 SCNN1A-8096 + CCUGAGCAUUGAUACACACCG 21 11945 SCNN1A-8097 + GCCUGAGCAUUGAUACACACCG 22 11946 SCNN1A-8098 + AGCCUGAGCAUUGAUACACACCG 23 11947 SCNN1A-8099 + CAGCCUGAGCAUUGAUACACACCG 24 11948 SCNN1A-8100 + AGAGCCGGGAGUUUUCCG 18 11949 SCNN1A-8101 + CAGAGCCGGGAGUUUUCCG 19 11950 SCNN1A-8102 + UCAGAGCCGGGAGUUUUCCG 20 11951 SCNN1A-8103 + GUCAGAGCCGGGAGUUUUCCG 21 11952 SCNN1A-8104 + AGUCAGAGCCGGGAGUUUUCCG 22 11953 SCNN1A-8105 + GAGUCAGAGCCGGGAGUUUUCCG 23 11954 SCNN1A-8106 + GGAGUCAGAGCCGGGAGUUUUCCG 24 11955 SCNN1A-8107 + CAAUAGAGAGGGACAGCG 18 11956 SCNN1A-8108 + ACAAUAGAGAGGGACAGCG 19 11957 SCNN1A-8109 + GACAAUAGAGAGGGACAGCG 20 11958 SCNN1A-8110 + AGACAAUAGAGAGGGACAGCG 21 11959 SCNN1A-8111 + GAGACAAUAGAGAGGGACAGCG 22 11960 SCNN1A-8112 + GGAGACAAUAGAGAGGGACAGCG 23 11961 SCNN1A-8113 + GGGAGACAAUAGAGAGGGACAGCG 24 11962 SCNN1A-8114 + GGGAGGAUGUGGCCAGCG 18 11963 SCNN1A-8115 + AGGGAGGAUGUGGCCAGCG 19 11964 SCNN1A-8116 + CAGGGAGGAUGUGGCCAGCG 20 11965 SCNN1A-8117 + GCAGGGAGGAUGUGGCCAGCG 21 11966 SCNN1A-8118 + UGCAGGGAGGAUGUGGCCAGCG 22 11967 SCNN1A-8119 + GUGCAGGGAGGAUGUGGCCAGCG 23 11968 SCNN1A-8120 + GGUGCAGGGAGGAUGUGGCCAGCG 24 11969 SCNN1A-8121 + UUAAAGGUGAGCAGGGCG 18 11970 SCNN1A-8122 + AUUAAAGGUGAGCAGGGCG 19 11971 SCNN1A-5669 + AAUUAAAGGUGAGCAGGGCG 20 9518 SCNN1A-8123 + CAAUUAAAGGUGAGCAGGGCG 21 11972 SCNN1A-8124 + UCAAUUAAAGGUGAGCAGGGCG 22 11973 SCNN1A-8125 + CUCAAUUAAAGGUGAGCAGGGCG 23 11974 SCNN1A-8126 + UCUCAAUUAAAGGUGAGCAGGGCG 24 11975 SCNN1A-8127 + UGGCCAGCGCUGGAAAGG 18 11976 SCNN1A-8128 + GUGGCCAGCGCUGGAAAGG 19 11977 SCNN1A-8129 + UGUGGCCAGCGCUGGAAAGG 20 11978 SCNN1A-8130 + AUGUGGCCAGCGCUGGAAAGG 21 11979 SCNN1A-8131 + GAUGUGGCCAGCGCUGGAAAGG 22 11980 SCNN1A-8132 + GGAUGUGGCCAGCGCUGGAAAGG 23 11981 SCNN1A-8133 + AGGAUGUGGCCAGCGCUGGAAAGG 24 11982 SCNN1A-8134 + CCAGGAAGGAGAGCAAGG 18 11983 SCNN1A-8135 + UCCAGGAAGGAGAGCAAGG 19 11984 SCNN1A-6151 + CUCCAGGAAGGAGAGCAAGG 20 10000 SCNN1A-8136 + UCUCCAGGAAGGAGAGCAAGG 21 11985 SCNN1A-8137 + GUCUCCAGGAAGGAGAGCAAGG 22 11986 SCNN1A-8138 + UGUCUCCAGGAAGGAGAGCAAGG 23 11987 SCNN1A-8139 + CUGUCUCCAGGAAGGAGAGCAAGG 24 11988 SCNN1A-1604 + CAAGGGUCAGGGUCAAGG 18 5453 SCNN1A-1605 + GCAAGGGUCAGGGUCAAGG 19 5454 SCNN1A-1606 + AGCAAGGGUCAGGGUCAAGG 20 5455 SCNN1A-1607 + GAGCAAGGGUCAGGGUCAAGG 21 5456 SCNN1A-1608 + AGAGCAAGGGUCAGGGUCAAGG 22 5457 SCNN1A-1609 + GAGAGCAAGGGUCAGGGUCAAGG 23 5458 SCNN1A-1610 + GGAGAGCAAGGGUCAGGGUCAAGG 24 5459 SCNN1A-8140 + CCGGGAGUUUUCCGAAGG 18 11989 SCNN1A-8141 + GCCGGGAGUUUUCCGAAGG 19 11990 SCNN1A-8142 + AGCCGGGAGUUUUCCGAAGG 20 11991 SCNN1A-8143 + GAGCCGGGAGUUUUCCGAAGG 21 11992 SCNN1A-8144 + AGAGCCGGGAGUUUUCCGAAGG 22 11993 SCNN1A-8145 + CAGAGCCGGGAGUUUUCCGAAGG 23 11994 SCNN1A-8146 + UCAGAGCCGGGAGUUUUCCGAAGG 24 11995 SCNN1A-8147 + ACAGACCCGGAGCCCAGG 18 11996 SCNN1A-8148 + CACAGACCCGGAGCCCAGG 19 11997 SCNN1A-8149 + ACACAGACCCGGAGCCCAGG 20 11998 SCNN1A-8150 + GACACAGACCCGGAGCCCAGG 21 11999 SCNN1A-8151 + GGACACAGACCCGGAGCCCAGG 22 12000 SCNN1A-8152 + UGGACACAGACCCGGAGCCCAGG 23 12001 SCNN1A-8153 + GUGGACACAGACCCGGAGCCCAGG 24 12002 SCNN1A-8154 + GAGAAGGGGCCAGCCAGG 18 12003 SCNN1A-8155 + GGAGAAGGGGCCAGCCAGG 19 12004 SCNN1A-8156 + AGGAGAAGGGGCCAGCCAGG 20 12005 SCNN1A-8157 + AAGGAGAAGGGGCCAGCCAGG 21 12006 SCNN1A-8158 + CAAGGAGAAGGGGCCAGCCAGG 22 12007 SCNN1A-8159 + ACAAGGAGAAGGGGCCAGCCAGG 23 12008 SCNN1A-8160 + CACAAGGAGAAGGGGCCAGCCAGG 24 12009 SCNN1A-8161 + AGGGAGUCUGUCUCCAGG 18 12010 SCNN1A-8162 + AAGGGAGUCUGUCUCCAGG 19 12011 SCNN1A-8163 + AAAGGGAGUCUGUCUCCAGG 20 12012 SCNN1A-8164 + CAAAGGGAGUCUGUCUCCAGG 21 12013 SCNN1A-8165 + CCAAAGGGAGUCUGUCUCCAGG 22 12014 SCNN1A-8166 + ACCAAAGGGAGUCUGUCUCCAGG 23 12015 SCNN1A-8167 + CACCAAAGGGAGUCUGUCUCCAGG 24 12016 SCNN1A-8168 + CAAUUAAAGGUGAGCAGG 18 12017 SCNN1A-8169 + UCAAUUAAAGGUGAGCAGG 19 12018 SCNN1A-8170 + CUCAAUUAAAGGUGAGCAGG 20 12019 SCNN1A-8171 + UCUCAAUUAAAGGUGAGCAGG 21 12020 SCNN1A-8172 + AUCUCAAUUAAAGGUGAGCAGG 22 12021 SCNN1A-8173 + CAUCUCAAUUAAAGGUGAGCAGG 23 12022 SCNN1A-8174 + GCAUCUCAAUUAAAGGUGAGCAGG 24 12023 SCNN1A-8175 + UGAGUGAGUAGAGGCAGG 18 12024 SCNN1A-8176 + CUGAGUGAGUAGAGGCAGG 19 12025 SCNN1A-5677 + ACUGAGUGAGUAGAGGCAGG 20 9526 SCNN1A-8177 + CACUGAGUGAGUAGAGGCAGG 21 12026 SCNN1A-8178 + GCACUGAGUGAGUAGAGGCAGG 22 12027 SCNN1A-8179 + GGCACUGAGUGAGUAGAGGCAGG 23 12028 SCNN1A-8180 + GGGCACUGAGUGAGUAGAGGCAGG 24 12029 SCNN1A-8181 + GCGCUGGAAAGGAAGAGG 18 12030 SCNN1A-8182 + AGCGCUGGAAAGGAAGAGG 19 12031 SCNN1A-8183 + CAGCGCUGGAAAGGAAGAGG 20 12032 SCNN1A-8184 + CCAGCGCUGGAAAGGAAGAGG 21 12033 SCNN1A-8185 + GCCAGCGCUGGAAAGGAAGAGG 22 12034 SCNN1A-8186 + GGCCAGCGCUGGAAAGGAAGAGG 23 12035 SCNN1A-8187 + UGGCCAGCGCUGGAAAGGAAGAGG 24 12036 SCNN1A-8188 + CCGGAGCCCAGGAAGAGG 18 12037 SCNN1A-8189 + CCCGGAGCCCAGGAAGAGG 19 12038 SCNN1A-8190 + ACCCGGAGCCCAGGAAGAGG 20 12039 SCNN1A-8191 + GACCCGGAGCCCAGGAAGAGG 21 12040 SCNN1A-8192 + AGACCCGGAGCCCAGGAAGAGG 22 12041 SCNN1A-8193 + CAGACCCGGAGCCCAGGAAGAGG 23 12042 SCNN1A-8194 + ACAGACCCGGAGCCCAGGAAGAGG 24 12043 SCNN1A-8195 + CGCAGACAGGCAAGGAGG 18 12044 SCNN1A-8196 + ACGCAGACAGGCAAGGAGG 19 12045 SCNN1A-8197 + GACGCAGACAGGCAAGGAGG 20 12046 SCNN1A-8198 + AGACGCAGACAGGCAAGGAGG 21 12047 SCNN1A-8199 + UAGACGCAGACAGGCAAGGAGG 22 12048 SCNN1A-8200 + UUAGACGCAGACAGGCAAGGAGG 23 12049 SCNN1A-8201 + UUUAGACGCAGACAGGCAAGGAGG 24 12050 SCNN1A-8202 + UAGACAGGCCCUGGGAGG 18 12051 SCNN1A-8203 + CUAGACAGGCCCUGGGAGG 19 12052 SCNN1A-6157 + CCUAGACAGGCCCUGGGAGG 20 10006 SCNN1A-8204 + GCCUAGACAGGCCCUGGGAGG 21 12053 SCNN1A-8205 + CGCCUAGACAGGCCCUGGGAGG 22 12054 SCNN1A-8206 + ACGCCUAGACAGGCCCUGGGAGG 23 12055 SCNN1A-8207 + CACGCCUAGACAGGCCCUGGGAGG 24 12056 SCNN1A-8208 + GAGAGAUAGGGAUGGAGG 18 12057 SCNN1A-8209 + AGAGAGAUAGGGAUGGAGG 19 12058 SCNN1A-6158 + CAGAGAGAUAGGGAUGGAGG 20 10007 SCNN1A-8210 + ACAGAGAGAUAGGGAUGGAGG 21 12059 SCNN1A-8211 + GACAGAGAGAUAGGGAUGGAGG 22 12060 SCNN1A-8212 + GGACAGAGAGAUAGGGAUGGAGG 23 12061 SCNN1A-8213 + AGGACAGAGAGAUAGGGAUGGAGG 24 12062 SCNN1A-8214 + GUGAAGCUGGGGGCUAGG 18 12063 SCNN1A-8215 + GGUGAAGCUGGGGGCUAGG 19 12064 SCNN1A-5681 + AGGUGAAGCUGGGGGCUAGG 20 9530 SCNN1A-8216 + CAGGUGAAGCUGGGGGCUAGG 21 12065 SCNN1A-8217 + CCAGGUGAAGCUGGGGGCUAGG 22 12066 SCNN1A-8218 + CCCAGGUGAAGCUGGGGGCUAGG 23 12067 SCNN1A-8219 + GCCCAGGUGAAGCUGGGGGCUAGG 24 12068 SCNN1A-8220 + GCCUGGGUGGGGAACCGG 18 12069 SCNN1A-8221 + GGCCUGGGUGGGGAACCGG 19 12070 SCNN1A-8222 + GGGCCUGGGUGGGGAACCGG 20 12071 SCNN1A-8223 + AGGGCCUGGGUGGGGAACCGG 21 12072 SCNN1A-8224 + GAGGGCCUGGGUGGGGAACCGG 22 12073 SCNN1A-8225 + AGAGGGCCUGGGUGGGGAACCGG 23 12074 SCNN1A-8226 + GAGAGGGCCUGGGUGGGGAACCGG 24 12075 SCNN1A-8227 + AGCAUUGAUACACACCGG 18 12076 SCNN1A-8228 + GAGCAUUGAUACACACCGG 19 12077 SCNN1A-5682 + UGAGCAUUGAUACACACCGG 20 9531 SCNN1A-8229 + CUGAGCAUUGAUACACACCGG 21 12078 SCNN1A-8230 + CCUGAGCAUUGAUACACACCGG 22 12079 SCNN1A-8231 + GCCUGAGCAUUGAUACACACCGG 23 12080 SCNN1A-8232 + AGCCUGAGCAUUGAUACACACCGG 24 12081 SCNN1A-8233 + AACCUUGUCCAGACCCGG 18 12082 SCNN1A-8234 + CAACCUUGUCCAGACCCGG 19 12083 SCNN1A-8235 + CCAACCUUGUCCAGACCCGG 20 12084 SCNN1A-8236 + UCCAACCUUGUCCAGACCCGG 21 12085 SCNN1A-8237 + CUCCAACCUUGUCCAGACCCGG 22 12086 SCNN1A-8238 + CCUCCAACCUUGUCCAGACCCGG 23 12087 SCNN1A-8239 + CCCUCCAACCUUGUCCAGACCCGG 24 12088 SCNN1A-8240 + CCCAGGCCCUGCACGCGG 18 12089 SCNN1A-8241 + ACCCAGGCCCUGCACGCGG 19 12090 SCNN1A-8242 + AACCCAGGCCCUGCACGCGG 20 12091 SCNN1A-8243 + CAACCCAGGCCCUGCACGCGG 21 12092 SCNN1A-8244 + ACAACCCAGGCCCUGCACGCGG 22 12093 SCNN1A-8245 + CACAACCCAGGCCCUGCACGCGG 23 12094 SCNN1A-8246 + ACACAACCCAGGCCCUGCACGCGG 24 12095 SCNN1A-8247 + UAAAGGUGAGCAGGGCGG 18 12096 SCNN1A-8248 + UUAAAGGUGAGCAGGGCGG 19 12097 SCNN1A-5683 + AUUAAAGGUGAGCAGGGCGG 20 9532 SCNN1A-8249 + AAUUAAAGGUGAGCAGGGCGG 21 12098 SCNN1A-8250 + CAAUUAAAGGUGAGCAGGGCGG 22 12099 SCNN1A-8251 + UCAAUUAAAGGUGAGCAGGGCGG 23 12100 SCNN1A-8252 + CUCAAUUAAAGGUGAGCAGGGCGG 24 12101 SCNN1A-8253 + CCCACUCCCAGGUUGCGG 18 12102 SCNN1A-8254 + UCCCACUCCCAGGUUGCGG 19 12103 SCNN1A-8255 + UUCCCACUCCCAGGUUGCGG 20 12104 SCNN1A-8256 + CUUCCCACUCCCAGGUUGCGG 21 12105 SCNN1A-8257 + GCUUCCCACUCCCAGGUUGCGG 22 12106 SCNN1A-8258 + AGCUUCCCACUCCCAGGUUGCGG 23 12107 SCNN1A-8259 + CAGCUUCCCACUCCCAGGUUGCGG 24 12108 SCNN1A-8260 + GGGCUGGAGGAGACUCGG 18 12109 SCNN1A-8261 + AGGGCUGGAGGAGACUCGG 19 12110 SCNN1A-8262 + AAGGGCUGGAGGAGACUCGG 20 12111 SCNN1A-8263 + AAAGGGCUGGAGGAGACUCGG 21 12112 SCNN1A-8264 + AAAAGGGCUGGAGGAGACUCGG 22 12113 SCNN1A-8265 + AAAAAGGGCUGGAGGAGACUCGG 23 12114 SCNN1A-8266 + CAAAAAGGGCUGGAGGAGACUCGG 24 12115 SCNN1A-8267 + AAUCAGACCCAAAAAGGG 18 12116 SCNN1A-8268 + GAAUCAGACCCAAAAAGGG 19 12117 SCNN1A-8269 + AGAAUCAGACCCAAAAAGGG 20 12118 SCNN1A-8270 + GAGAAUCAGACCCAAAAAGGG 21 12119 SCNN1A-8271 + AGAGAAUCAGACCCAAAAAGGG 22 12120 SCNN1A-8272 + CAGAGAAUCAGACCCAAAAAGGG 23 12121 SCNN1A-8273 + UCAGAGAAUCAGACCCAAAAAGGG 24 12122 SCNN1A-8274 + CCCGCUGGCCGGCCAGGG 18 12123 SCNN1A-8275 + GCCCGCUGGCCGGCCAGGG 19 12124 SCNN1A-8276 + CGCCCGCUGGCCGGCCAGGG 20 12125 SCNN1A-8277 + CCGCCCGCUGGCCGGCCAGGG 21 12126 SCNN1A-8278 + CCCGCCCGCUGGCCGGCCAGGG 22 12127 SCNN1A-8279 + GCCCGCCCGCUGGCCGGCCAGGG 23 12128 SCNN1A-8280 + AGCCCGCCCGCUGGCCGGCCAGGG 24 12129 SCNN1A-8281 + AAUUAAAGGUGAGCAGGG 18 12130 SCNN1A-8282 + CAAUUAAAGGUGAGCAGGG 19 12131 SCNN1A-6160 + UCAAUUAAAGGUGAGCAGGG 20 10009 SCNN1A-8283 + CUCAAUUAAAGGUGAGCAGGG 21 12132 SCNN1A-8284 + UCUCAAUUAAAGGUGAGCAGGG 22 12133 SCNN1A-8285 + AUCUCAAUUAAAGGUGAGCAGGG 23 12134 SCNN1A-8286 + CAUCUCAAUUAAAGGUGAGCAGGG 24 12135 SCNN1A-8287 + ACCGGGAGGACAGGAGGG 18 12136 SCNN1A-8288 + AACCGGGAGGACAGGAGGG 19 12137 SCNN1A-8289 + GAACCGGGAGGACAGGAGGG 20 12138 SCNN1A-8290 + GGAACCGGGAGGACAGGAGGG 21 12139 SCNN1A-8291 + GGGAACCGGGAGGACAGGAGGG 22 12140 SCNN1A-8292 + GGGGAACCGGGAGGACAGGAGGG 23 12141 SCNN1A-8293 + UGGGGAACCGGGAGGACAGGAGGG 24 12142 SCNN1A-8294 + AAGGACAGAGAGAUAGGG 18 12143 SCNN1A-8295 + GAAGGACAGAGAGAUAGGG 19 12144 SCNN1A-8296 + CGAAGGACAGAGAGAUAGGG 20 12145 SCNN1A-8297 + GCGAAGGACAGAGAGAUAGGG 21 12146 SCNN1A-8298 + AGCGAAGGACAGAGAGAUAGGG 22 12147 SCNN1A-8299 + CAGCGAAGGACAGAGAGAUAGGG 23 12148 SCNN1A-8300 + ACAGCGAAGGACAGAGAGAUAGGG 24 12149 SCNN1A-8301 + ACCUUGUCCAGACCCGGG 18 12150 SCNN1A-8302 + AACCUUGUCCAGACCCGGG 19 12151 SCNN1A-5686 + CAACCUUGUCCAGACCCGGG 20 9535 SCNN1A-8303 + CCAACCUUGUCCAGACCCGGG 21 12152 SCNN1A-8304 + UCCAACCUUGUCCAGACCCGGG 22 12153 SCNN1A-8305 + CUCCAACCUUGUCCAGACCCGGG 23 12154 SCNN1A-8306 + CCUCCAACCUUGUCCAGACCCGGG 24 12155 SCNN1A-8307 + AAAGGUGAGCAGGGCGGG 18 12156 SCNN1A-8308 + UAAAGGUGAGCAGGGCGGG 19 12157 SCNN1A-5688 + UUAAAGGUGAGCAGGGCGGG 20 9537 SCNN1A-8309 + AUUAAAGGUGAGCAGGGCGGG 21 12158 SCNN1A-8310 + AAUUAAAGGUGAGCAGGGCGGG 22 12159 SCNN1A-8311 + CAAUUAAAGGUGAGCAGGGCGGG 23 12160 SCNN1A-8312 + UCAAUUAAAGGUGAGCAGGGCGGG 24 12161 SCNN1A-8313 + GCAGGGCGGGGGGAGGGG 18 12162 SCNN1A-8314 + AGCAGGGCGGGGGGAGGGG 19 12163 SCNN1A-8315 + GAGCAGGGCGGGGGGAGGGG 20 12164 SCNN1A-8316 + UGAGCAGGGCGGGGGGAGGGG 21 12165 SCNN1A-8317 + GUGAGCAGGGCGGGGGGAGGGG 22 12166 SCNN1A-8318 + GGUGAGCAGGGCGGGGGGAGGGG 23 12167 SCNN1A-8319 + AGGUGAGCAGGGCGGGGGGAGGGG 24 12168 SCNN1A-8320 + CAUUGAUACACACCGGGG 18 12169 SCNN1A-8321 + GCAUUGAUACACACCGGGG 19 12170 SCNN1A-8322 + AGCAUUGAUACACACCGGGG 20 12171 SCNN1A-8323 + GAGCAUUGAUACACACCGGGG 21 12172 SCNN1A-8324 + UGAGCAUUGAUACACACCGGGG 22 12173 SCNN1A-8325 + CUGAGCAUUGAUACACACCGGGG 23 12174 SCNN1A-8326 + CCUGAGCAUUGAUACACACCGGGG 24 12175 SCNN1A-8327 + AUUGAUACACACCGGGGG 18 12176 SCNN1A-8328 + CAUUGAUACACACCGGGGG 19 12177 SCNN1A-5265 + GCAUUGAUACACACCGGGGG 20 9114 SCNN1A-8329 + AGCAUUGAUACACACCGGGGG 21 12178 SCNN1A-8330 + GAGCAUUGAUACACACCGGGGG 22 12179 SCNN1A-8331 + UGAGCAUUGAUACACACCGGGGG 23 12180 SCNN1A-8332 + CUGAGCAUUGAUACACACCGGGGG 24 12181 SCNN1A-8333 + AGGUGAGCAGGGCGGGGG 18 12182 SCNN1A-8334 + AAGGUGAGCAGGGCGGGGG 19 12183 SCNN1A-8335 + AAAGGUGAGCAGGGCGGGGG 20 12184 SCNN1A-8336 + UAAAGGUGAGCAGGGCGGGGG 21 12185 SCNN1A-8337 + UUAAAGGUGAGCAGGGCGGGGG 22 12186 SCNN1A-8338 + AUUAAAGGUGAGCAGGGCGGGGG 23 12187 SCNN1A-8339 + AAUUAAAGGUGAGCAGGGCGGGGG 24 12188 SCNN1A-8340 + GGUGAGCAGGGCGGGGGG 18 12189 SCNN1A-8341 + AGGUGAGCAGGGCGGGGGG 19 12190 SCNN1A-6164 + AAGGUGAGCAGGGCGGGGGG 20 10013 SCNN1A-8342 + AAAGGUGAGCAGGGCGGGGGG 21 12191 SCNN1A-8343 + UAAAGGUGAGCAGGGCGGGGGG 22 12192 SCNN1A-8344 + UUAAAGGUGAGCAGGGCGGGGGG 23 12193 SCNN1A-8345 + AUUAAAGGUGAGCAGGGCGGGGGG 24 12194 SCNN1A-8346 + GCCUAGACAGGCCCUGGG 18 12195 SCNN1A-8347 + CGCCUAGACAGGCCCUGGG 19 12196 SCNN1A-5691 + ACGCCUAGACAGGCCCUGGG 20 9540 SCNN1A-8348 + CACGCCUAGACAGGCCCUGGG 21 12197 SCNN1A-8349 + ACACGCCUAGACAGGCCCUGGG 22 12198 SCNN1A-8350 + CACACGCCUAGACAGGCCCUGGG 23 12199 SCNN1A-8351 + GCACACGCCUAGACAGGCCCUGGG 24 12200 SCNN1A-8352 + AGGCUGAGAGGGCCUGGG 18 12201 SCNN1A-8353 + CAGGCUGAGAGGGCCUGGG 19 12202 SCNN1A-6165 + CCAGGCUGAGAGGGCCUGGG 20 10014 SCNN1A-8354 + GCCAGGCUGAGAGGGCCUGGG 21 12203 SCNN1A-8355 + AGCCAGGCUGAGAGGGCCUGGG 22 12204 SCNN1A-8356 + CAGCCAGGCUGAGAGGGCCUGGG 23 12205 SCNN1A-8357 + CCAGCCAGGCUGAGAGGGCCUGGG 24 12206 SCNN1A-8358 + GAGAAGGCGGACUCUGGG 18 12207 SCNN1A-8359 + UGAGAAGGCGGACUCUGGG 19 12208 SCNN1A-8360 + CUGAGAAGGCGGACUCUGGG 20 12209 SCNN1A-8361 + CCUGAGAAGGCGGACUCUGGG 21 12210 SCNN1A-8362 + ACCUGAGAAGGCGGACUCUGGG 22 12211 SCNN1A-8363 + GACCUGAGAAGGCGGACUCUGGG 23 12212 SCNN1A-8364 + GGACCUGAGAAGGCGGACUCUGGG 24 12213 SCNN1A-1623 + GCCCCGGAGUGGAUUGGG 18 5472 SCNN1A-1624 + AGCCCCGGAGUGGAUUGGG 19 5473 SCNN1A-1625 + GAGCCCCGGAGUGGAUUGGG 20 5474 SCNN1A-1626 + UGAGCCCCGGAGUGGAUUGGG 21 5475 SCNN1A-1627 + AUGAGCCCCGGAGUGGAUUGGG 22 5476 SCNN1A-1628 + CAUGAGCCCCGGAGUGGAUUGGG 23 5477 SCNN1A-1629 + UCAUGAGCCCCGGAGUGGAUUGGG 24 5478 SCNN1A-8365 + ACAGAGAGAUAGGGAUGG 18 12214 SCNN1A-8366 + GACAGAGAGAUAGGGAUGG 19 12215 SCNN1A-5915 + GGACAGAGAGAUAGGGAUGG 20 9764 SCNN1A-8367 + AGGACAGAGAGAUAGGGAUGG 21 12216 SCNN1A-8368 + AAGGACAGAGAGAUAGGGAUGG 22 12217 SCNN1A-8369 + GAAGGACAGAGAGAUAGGGAUGG 23 12218 SCNN1A-8370 + CGAAGGACAGAGAGAUAGGGAUGG 24 12219 SCNN1A-8371 + CGCCUAGACAGGCCCUGG 18 12220 SCNN1A-8372 + ACGCCUAGACAGGCCCUGG 19 12221 SCNN1A-8373 + CACGCCUAGACAGGCCCUGG 20 12222 SCNN1A-8374 + ACACGCCUAGACAGGCCCUGG 21 12223 SCNN1A-8375 + CACACGCCUAGACAGGCCCUGG 22 12224 SCNN1A-8376 + GCACACGCCUAGACAGGCCCUGG 23 12225 SCNN1A-8377 + GGCACACGCCUAGACAGGCCCUGG 24 12226 SCNN1A-8378 + ACAGGUGCAGCGGCCUGG 18 12227 SCNN1A-8379 + GACAGGUGCAGCGGCCUGG 19 12228 SCNN1A-8380 + UGACAGGUGCAGCGGCCUGG 20 12229 SCNN1A-8381 + CUGACAGGUGCAGCGGCCUGG 21 12230 SCNN1A-8382 + CCUGACAGGUGCAGCGGCCUGG 22 12231 SCNN1A-8383 + ACCUGACAGGUGCAGCGGCCUGG 23 12232 SCNN1A-8384 + CACCUGACAGGUGCAGCGGCCUGG 24 12233 SCNN1A-8385 + CAGGCUGAGAGGGCCUGG 18 12234 SCNN1A-8386 + CCAGGCUGAGAGGGCCUGG 19 12235 SCNN1A-8387 + GCCAGGCUGAGAGGGCCUGG 20 12236 SCNN1A-8388 + AGCCAGGCUGAGAGGGCCUGG 21 12237 SCNN1A-8389 + CAGCCAGGCUGAGAGGGCCUGG 22 12238 SCNN1A-8390 + CCAGCCAGGCUGAGAGGGCCUGG 23 12239 SCNN1A-8391 + GCCAGCCAGGCUGAGAGGGCCUGG 24 12240 SCNN1A-8392 + AGACCCAAAAAGGGCUGG 18 12241 SCNN1A-8393 + CAGACCCAAAAAGGGCUGG 19 12242 SCNN1A-5694 + UCAGACCCAAAAAGGGCUGG 20 9543 SCNN1A-8394 + AUCAGACCCAAAAAGGGCUGG 21 12243 SCNN1A-8395 + AAUCAGACCCAAAAAGGGCUGG 22 12244 SCNN1A-8396 + GAAUCAGACCCAAAAAGGGCUGG 23 12245 SCNN1A-8397 + AGAAUCAGACCCAAAAAGGGCUGG 24 12246 SCNN1A-8398 + GCAGGUGGGGGGCAGUGG 18 12247 SCNN1A-8399 + GGCAGGUGGGGGGCAGUGG 19 12248 SCNN1A-6171 + AGGCAGGUGGGGGGCAGUGG 20 10020 SCNN1A-8400 + GAGGCAGGUGGGGGGCAGUGG 21 12249 SCNN1A-8401 + AGAGGCAGGUGGGGGGCAGUGG 22 12250 SCNN1A-8402 + UAGAGGCAGGUGGGGGGCAGUGG 23 12251 SCNN1A-8403 + GUAGAGGCAGGUGGGGGGCAGUGG 24 12252 SCNN1A-1630 + CAUGAUACCUCCCCUUGG 18 5479 SCNN1A-1631 + UCAUGAUACCUCCCCUUGG 19 5480 SCNN1A-1632 + CUCAUGAUACCUCCCCUUGG 20 5481 SCNN1A-1633 + GCUCAUGAUACCUCCCCUUGG 21 5482 SCNN1A-1634 + UGCUCAUGAUACCUCCCCUUGG 22 5483 SCNN1A-1635 + CUGCUCAUGAUACCUCCCCUUGG 23 5484 SCNN1A-1636 + ACUGCUCAUGAUACCUCCCCUUGG 24 5485 SCNN1A-8404 + UUCUUCAUUGUCCUAAUG 18 12253 SCNN1A-8405 + UUUCUUCAUUGUCCUAAUG 19 12254 SCNN1A-8406 + UUUUCUUCAUUGUCCUAAUG 20 12255 SCNN1A-8407 + UUUUUCUUCAUUGUCCUAAUG 21 12256 SCNN1A-8408 + AUUUUUCUUCAUUGUCCUAAUG 22 12257 SCNN1A-8409 + GAUUUUUCUUCAUUGUCCUAAUG 23 12258 SCNN1A-8410 + GGAUUUUUCUUCAUUGUCCUAAUG 24 12259 SCNN1A-8411 + GACAGAGAGAUAGGGAUG 18 12260 SCNN1A-8412 + GGACAGAGAGAUAGGGAUG 19 12261 SCNN1A-8413 + AGGACAGAGAGAUAGGGAUG 20 12262 SCNN1A-8414 + AAGGACAGAGAGAUAGGGAUG 21 12263 SCNN1A-8415 + GAAGGACAGAGAGAUAGGGAUG 22 12264 SCNN1A-8416 + CGAAGGACAGAGAGAUAGGGAUG 23 12265 SCNN1A-8417 + GCGAAGGACAGAGAGAUAGGGAUG 24 12266 SCNN1A-8418 + GAGCCUAGGGGCUCACUG 18 12267 SCNN1A-8419 + GGAGCCUAGGGGCUCACUG 19 12268 SCNN1A-8420 + GGGAGCCUAGGGGCUCACUG 20 12269 SCNN1A-8421 + GGGGAGCCUAGGGGCUCACUG 21 12270 SCNN1A-8422 + AGGGGAGCCUAGGGGCUCACUG 22 12271 SCNN1A-8423 + UAGGGGAGCCUAGGGGCUCACUG 23 12272 SCNN1A-8424 + CUAGGGGAGCCUAGGGGCUCACUG 24 12273 SCNN1A-8425 + GUCUCUGCCCCAGGACUG 18 12274 SCNN1A-8426 + UGUCUCUGCCCCAGGACUG 19 12275 SCNN1A-8427 + CUGUCUCUGCCCCAGGACUG 20 12276 SCNN1A-8428 + UCUGUCUCUGCCCCAGGACUG 21 12277 SCNN1A-8429 + UUCUGUCUCUGCCCCAGGACUG 22 12278 SCNN1A-8430 + AUUCUGUCUCUGCCCCAGGACUG 23 12279 SCNN1A-8431 + GAUUCUGUCUCUGCCCCAGGACUG 24 12280 SCNN1A-8432 + CUGGAGCCAGCAGACCUG 18 12281 SCNN1A-8433 + CCUGGAGCCAGCAGACCUG 19 12282 SCNN1A-5701 + UCCUGGAGCCAGCAGACCUG 20 9550 SCNN1A-8434 + UUCCUGGAGCCAGCAGACCUG 21 12283 SCNN1A-8435 + UUUCCUGGAGCCAGCAGACCUG 22 12284 SCNN1A-8436 + CUUUCCUGGAGCCAGCAGACCUG 23 12285 SCNN1A-8437 + CCUUUCCUGGAGCCAGCAGACCUG 24 12286 SCNN1A-8438 + CCUCACCCUCAGGCCCUG 18 12287 SCNN1A-8439 + GCCUCACCCUCAGGCCCUG 19 12288 SCNN1A-8440 + AGCCUCACCCUCAGGCCCUG 20 12289 SCNN1A-8441 + CAGCCUCACCCUCAGGCCCUG 21 12290 SCNN1A-8442 + UCAGCCUCACCCUCAGGCCCUG 22 12291 SCNN1A-8443 + GUCAGCCUCACCCUCAGGCCCUG 23 12292 SCNN1A-8444 + GGUCAGCCUCACCCUCAGGCCCUG 24 12293 SCNN1A-8445 + AGACAGGCAAGGAGGCUG 18 12294 SCNN1A-8446 + CAGACAGGCAAGGAGGCUG 19 12295 SCNN1A-5919 + GCAGACAGGCAAGGAGGCUG 20 9768 SCNN1A-8447 + CGCAGACAGGCAAGGAGGCUG 21 12296 SCNN1A-8448 + ACGCAGACAGGCAAGGAGGCUG 22 12297 SCNN1A-8449 + GACGCAGACAGGCAAGGAGGCUG 23 12298 SCNN1A-8450 + AGACGCAGACAGGCAAGGAGGCUG 24 12299 SCNN1A-8451 + CAGACCCAAAAAGGGCUG 18 12300 SCNN1A-8452 + UCAGACCCAAAAAGGGCUG 19 12301 SCNN1A-8453 + AUCAGACCCAAAAAGGGCUG 20 12302 SCNN1A-8454 + AAUCAGACCCAAAAAGGGCUG 21 12303 SCNN1A-8455 + GAAUCAGACCCAAAAAGGGCUG 22 12304 SCNN1A-8456 + AGAAUCAGACCCAAAAAGGGCUG 23 12305 SCNN1A-8457 + GAGAAUCAGACCCAAAAAGGGCUG 24 12306 SCNN1A-8458 + GGGCGGGGGGAGGGGCUG 18 12307 SCNN1A-8459 + AGGGCGGGGGGAGGGGCUG 19 12308 SCNN1A-6176 + CAGGGCGGGGGGAGGGGCUG 20 10025 SCNN1A-8460 + GCAGGGCGGGGGGAGGGGCUG 21 12309 SCNN1A-8461 + AGCAGGGCGGGGGGAGGGGCUG 22 12310 SCNN1A-8462 + GAGCAGGGCGGGGGGAGGGGCUG 23 12311 SCNN1A-8463 + UGAGCAGGGCGGGGGGAGGGGCUG 24 12312 SCNN1A-1668 + GAGACCUGGUAUGGGCUG 18 5517 SCNN1A-1669 + UGAGACCUGGUAUGGGCUG 19 5518 SCNN1A-1670 + AUGAGACCUGGUAUGGGCUG 20 5519 SCNN1A-1671 + CAUGAGACCUGGUAUGGGCUG 21 5520 SCNN1A-1672 + CCAUGAGACCUGGUAUGGGCUG 22 5521 SCNN1A-1673 + UCCAUGAGACCUGGUAUGGGCUG 23 5522 SCNN1A-1674 + CUCCAUGAGACCUGGUAUGGGCUG 24 5523 SCNN1A-8464 + GGUGCAGCGGCCUGGCUG 18 12313 SCNN1A-8465 + AGGUGCAGCGGCCUGGCUG 19 12314 SCNN1A-5705 + CAGGUGCAGCGGCCUGGCUG 20 9554 SCNN1A-8466 + ACAGGUGCAGCGGCCUGGCUG 21 12315 SCNN1A-8467 + GACAGGUGCAGCGGCCUGGCUG 22 12316 SCNN1A-8468 + UGACAGGUGCAGCGGCCUGGCUG 23 12317 SCNN1A-8469 + CUGACAGGUGCAGCGGCCUGGCUG 24 12318 SCNN1A-8470 + GAGUUGGGGCCAAAAGUG 18 12319 SCNN1A-8471 + GGAGUUGGGGCCAAAAGUG 19 12320 SCNN1A-8472 + GGGAGUUGGGGCCAAAAGUG 20 12321 SCNN1A-8473 + CGGGAGUUGGGGCCAAAAGUG 21 12322 SCNN1A-8474 + GCGGGAGUUGGGGCCAAAAGUG 22 12323 SCNN1A-8475 + UGCGGGAGUUGGGGCCAAAAGUG 23 12324 SCNN1A-8476 + CUGCGGGAGUUGGGGCCAAAAGUG 24 12325 SCNN1A-8477 + GGAGUGGAGUGCCAAGUG 18 12326 SCNN1A-8478 + AGGAGUGGAGUGCCAAGUG 19 12327 SCNN1A-8479 + AAGGAGUGGAGUGCCAAGUG 20 12328 SCNN1A-8480 + UAAGGAGUGGAGUGCCAAGUG 21 12329 SCNN1A-8481 + AUAAGGAGUGGAGUGCCAAGUG 22 12330 SCNN1A-8482 + GAUAAGGAGUGGAGUGCCAAGUG 23 12331 SCNN1A-8483 + GGAUAAGGAGUGGAGUGCCAAGUG 24 12332 SCNN1A-8484 + GGCAGGUGGGGGGCAGUG 18 12333 SCNN1A-8485 + AGGCAGGUGGGGGGCAGUG 19 12334 SCNN1A-8486 + GAGGCAGGUGGGGGGCAGUG 20 12335 SCNN1A-8487 + AGAGGCAGGUGGGGGGCAGUG 21 12336 SCNN1A-8488 + UAGAGGCAGGUGGGGGGCAGUG 22 12337 SCNN1A-8489 + GUAGAGGCAGGUGGGGGGCAGUG 23 12338 SCNN1A-8490 + AGUAGAGGCAGGUGGGGGGCAGUG 24 12339 SCNN1A-8491 + AGGAGGCAGCCCAGAGUG 18 12340 SCNN1A-8492 + CAGGAGGCAGCCCAGAGUG 19 12341 SCNN1A-8493 + ACAGGAGGCAGCCCAGAGUG 20 12342 SCNN1A-8494 + CACAGGAGGCAGCCCAGAGUG 21 12343 SCNN1A-8495 + CCACAGGAGGCAGCCCAGAGUG 22 12344 SCNN1A-8496 + CCCACAGGAGGCAGCCCAGAGUG 23 12345 SCNN1A-8497 + CCCCACAGGAGGCAGCCCAGAGUG 24 12346 SCNN1A-8498 + AAGCAGGCACUGAAGGUG 18 12347 SCNN1A-8499 + AAAGCAGGCACUGAAGGUG 19 12348 SCNN1A-8500 + GAAAGCAGGCACUGAAGGUG 20 12349 SCNN1A-8501 + GGAAAGCAGGCACUGAAGGUG 21 12350 SCNN1A-8502 + GGGAAAGCAGGCACUGAAGGUG 22 12351 SCNN1A-8503 + AGGGAAAGCAGGCACUGAAGGUG 23 12352 SCNN1A-8504 + CAGGGAAAGCAGGCACUGAAGGUG 24 12353 SCNN1A-8505 + AGUGAGUAGAGGCAGGUG 18 12354 SCNN1A-8506 + GAGUGAGUAGAGGCAGGUG 19 12355 SCNN1A-5713 + UGAGUGAGUAGAGGCAGGUG 20 9562 SCNN1A-8507 + CUGAGUGAGUAGAGGCAGGUG 21 12356 SCNN1A-8508 + ACUGAGUGAGUAGAGGCAGGUG 22 12357 SCNN1A-8509 + CACUGAGUGAGUAGAGGCAGGUG 23 12358 SCNN1A-8510 + GCACUGAGUGAGUAGAGGCAGGUG 24 12359 SCNN1A-8511 + GGGACAGGAUGGCAGGUG 18 12360 SCNN1A-8512 + GGGGACAGGAUGGCAGGUG 19 12361 SCNN1A-5920 + GGGGGACAGGAUGGCAGGUG 20 9769 SCNN1A-8513 + UGGGGGACAGGAUGGCAGGUG 21 12362 SCNN1A-8514 + CUGGGGGACAGGAUGGCAGGUG 22 12363 SCNN1A-8515 + GCUGGGGGACAGGAUGGCAGGUG 23 12364 SCNN1A-8516 + GGCUGGGGGACAGGAUGGCAGGUG 24 12365 SCNN1A-8517 + GCUGAGAGGGCCUGGGUG 18 12366 SCNN1A-8518 + GGCUGAGAGGGCCUGGGUG 19 12367 SCNN1A-6177 + AGGCUGAGAGGGCCUGGGUG 20 10026 SCNN1A-8519 + CAGGCUGAGAGGGCCUGGGUG 21 12368 SCNN1A-8520 + CCAGGCUGAGAGGGCCUGGGUG 22 12369 SCNN1A-8521 + GCCAGGCUGAGAGGGCCUGGGUG 23 12370 SCNN1A-8522 + AGCCAGGCUGAGAGGGCCUGGGUG 24 12371 SCNN1A-1699 + GAGCCCCGGAGUGGAUUG 18 5548 SCNN1A-1700 + UGAGCCCCGGAGUGGAUUG 19 5549 SCNN1A-419 + AUGAGCCCCGGAGUGGAUUG 20 4268 SCNN1A-1701 + CAUGAGCCCCGGAGUGGAUUG 21 5550 SCNN1A-1702 + UCAUGAGCCCCGGAGUGGAUUG 22 5551 SCNN1A-1703 + UUCAUGAGCCCCGGAGUGGAUUG 23 5552 SCNN1A-1704 + CUUCAUGAGCCCCGGAGUGGAUUG 24 5553 SCNN1A-8523 + GCUGUGGUCACAGAGUUG 18 12372 SCNN1A-8524 + UGCUGUGGUCACAGAGUUG 19 12373 SCNN1A-8525 + CUGCUGUGGUCACAGAGUUG 20 12374 SCNN1A-8526 + CCUGCUGUGGUCACAGAGUUG 21 12375 SCNN1A-8527 + CCCUGCUGUGGUCACAGAGUUG 22 12376 SCNN1A-8528 + CCCCUGCUGUGGUCACAGAGUUG 23 12377 SCNN1A-8529 + GCCCCUGCUGUGGUCACAGAGUUG 24 12378 SCNN1A-8530 + AGGAGGAGAAAUUCGUUG 18 12379 SCNN1A-8531 + GAGGAGGAGAAAUUCGUUG 19 12380 SCNN1A-8532 + GGAGGAGGAGAAAUUCGUUG 20 12381 SCNN1A-8533 + GGGAGGAGGAGAAAUUCGUUG 21 12382 SCNN1A-8534 + UGGGAGGAGGAGAAAUUCGUUG 22 12383 SCNN1A-8535 + CUGGGAGGAGGAGAAAUUCGUUG 23 12384 SCNN1A-8536 + CCUGGGAGGAGGAGAAAUUCGUUG 24 12385 SCNN1A-8537 + GAGGUUAGAAAACAAAAU 18 12386 SCNN1A-8538 + UGAGGUUAGAAAACAAAAU 19 12387 SCNN1A-5720 + CUGAGGUUAGAAAACAAAAU 20 9569 SCNN1A-8539 + UCUGAGGUUAGAAAACAAAAU 21 12388 SCNN1A-8540 + UUCUGAGGUUAGAAAACAAAAU 22 12389 SCNN1A-8541 + UUUCUGAGGUUAGAAAACAAAAU 23 12390 SCNN1A-8542 + UUUUCUGAGGUUAGAAAACAAAAU 24 12391 SCNN1A-8543 + UCACAGAGUUGCAGGAAU 18 12392 SCNN1A-8544 + GUCACAGAGUUGCAGGAAU 19 12393 SCNN1A-8545 + GGUCACAGAGUUGCAGGAAU 20 12394 SCNN1A-8546 + UGGUCACAGAGUUGCAGGAAU 21 12395 SCNN1A-8547 + GUGGUCACAGAGUUGCAGGAAU 22 12396 SCNN1A-8548 + UGUGGUCACAGAGUUGCAGGAAU 23 12397 SCNN1A-8549 + CUGUGGUCACAGAGUUGCAGGAAU 24 12398 SCNN1A-8550 + UUCUCAGAGAUAAGACAU 18 12399 SCNN1A-8551 + UUUCUCAGAGAUAAGACAU 19 12400 SCNN1A-8552 + AUUUCUCAGAGAUAAGACAU 20 12401 SCNN1A-8553 + GAUUUCUCAGAGAUAAGACAU 21 12402 SCNN1A-8554 + AGAUUUCUCAGAGAUAAGACAU 22 12403 SCNN1A-8555 + CAGAUUUCUCAGAGAUAAGACAU 23 12404 SCNN1A-8556 + UCAGAUUUCUCAGAGAUAAGACAU 24 12405 SCNN1A-8557 + UUCCUGAGACAGACUCAU 18 12406 SCNN1A-8558 + CUUCCUGAGACAGACUCAU 19 12407 SCNN1A-6179 + ACUUCCUGAGACAGACUCAU 20 10028 SCNN1A-8559 + UACUUCCUGAGACAGACUCAU 21 12408 SCNN1A-8560 + UUACUUCCUGAGACAGACUCAU 22 12409 SCNN1A-8561 + UUUACUUCCUGAGACAGACUCAU 23 12410 SCNN1A-8562 + AUUUACUUCCUGAGACAGACUCAU 24 12411 SCNN1A-8563 + CAGGUGAGGGGCAAAGAU 18 12412 SCNN1A-8564 + GCAGGUGAGGGGCAAAGAU 19 12413 SCNN1A-8565 + GGCAGGUGAGGGGCAAAGAU 20 12414 SCNN1A-8566 + UGGCAGGUGAGGGGCAAAGAU 21 12415 SCNN1A-8567 + AUGGCAGGUGAGGGGCAAAGAU 22 12416 SCNN1A-8568 + GAUGGCAGGUGAGGGGCAAAGAU 23 12417 SCNN1A-8569 + GGAUGGCAGGUGAGGGGCAAAGAU 24 12418 SCNN1A-8570 + UUAAUGCAGCAAAAGGAU 18 12419 SCNN1A-8571 + CUUAAUGCAGCAAAAGGAU 19 12420 SCNN1A-8572 + ACUUAAUGCAGCAAAAGGAU 20 12421 SCNN1A-8573 + AACUUAAUGCAGCAAAAGGAU 21 12422 SCNN1A-8574 + AAACUUAAUGCAGCAAAAGGAU 22 12423 SCNN1A-8575 + CAAACUUAAUGCAGCAAAAGGAU 23 12424 SCNN1A-8576 + CCAAACUUAAUGCAGCAAAAGGAU 24 12425 SCNN1A-8577 + GACAGACUCAUGGGGGAU 18 12426 SCNN1A-8578 + AGACAGACUCAUGGGGGAU 19 12427 SCNN1A-5272 + GAGACAGACUCAUGGGGGAU 20 9121 SCNN1A-8579 + UGAGACAGACUCAUGGGGGAU 21 12428 SCNN1A-8580 + CUGAGACAGACUCAUGGGGGAU 22 12429 SCNN1A-8581 + CCUGAGACAGACUCAUGGGGGAU 23 12430 SCNN1A-8582 + UCCUGAGACAGACUCAUGGGGGAU 24 12431 SCNN1A-8583 + GCUCAGGUGCACCUGGAU 18 12432 SCNN1A-8584 + GGCUCAGGUGCACCUGGAU 19 12433 SCNN1A-8585 + GGGCUCAGGUGCACCUGGAU 20 12434 SCNN1A-8586 + GGGGCUCAGGUGCACCUGGAU 21 12435 SCNN1A-8587 + CGGGGCUCAGGUGCACCUGGAU 22 12436 SCNN1A-8588 + UCGGGGCUCAGGUGCACCUGGAU 23 12437 SCNN1A-8589 + AUCGGGGCUCAGGUGCACCUGGAU 24 12438 SCNN1A-1717 + AUGAGCCCCGGAGUGGAU 18 5566 SCNN1A-1718 + CAUGAGCCCCGGAGUGGAU 19 5567 SCNN1A-420 + UCAUGAGCCCCGGAGUGGAU 20 4269 SCNN1A-1719 + UUCAUGAGCCCCGGAGUGGAU 21 5568 SCNN1A-1720 + CUUCAUGAGCCCCGGAGUGGAU 22 5569 SCNN1A-1721 + CCUUCAUGAGCCCCGGAGUGGAU 23 5570 SCNN1A-1722 + CCCUUCAUGAGCCCCGGAGUGGAU 24 5571 SCNN1A-8590 + AGGGCCACGCAGGACACU 18 12439 SCNN1A-8591 + GAGGGCCACGCAGGACACU 19 12440 SCNN1A-8592 + CGAGGGCCACGCAGGACACU 20 12441 SCNN1A-8593 + GCGAGGGCCACGCAGGACACU 21 12442 SCNN1A-8594 + CGCGAGGGCCACGCAGGACACU 22 12443 SCNN1A-8595 + GCGCGAGGGCCACGCAGGACACU 23 12444 SCNN1A-8596 + AGCGCGAGGGCCACGCAGGACACU 24 12445 SCNN1A-8597 + GGCUCACUGCAGGAGACU 18 12446 SCNN1A-8598 + GGGCUCACUGCAGGAGACU 19 12447 SCNN1A-8599 + GGGGCUCACUGCAGGAGACU 20 12448 SCNN1A-8600 + AGGGGCUCACUGCAGGAGACU 21 12449 SCNN1A-8601 + UAGGGGCUCACUGCAGGAGACU 22 12450 SCNN1A-8602 + CUAGGGGCUCACUGCAGGAGACU 23 12451 SCNN1A-8603 + CCUAGGGGCUCACUGCAGGAGACU 24 12452 SCNN1A-8604 + AAAGGGCUGGAGGAGACU 18 12453 SCNN1A-8605 + AAAAGGGCUGGAGGAGACU 19 12454 SCNN1A-5729 + AAAAAGGGCUGGAGGAGACU 20 9578 SCNN1A-8606 + CAAAAAGGGCUGGAGGAGACU 21 12455 SCNN1A-8607 + CCAAAAAGGGCUGGAGGAGACU 22 12456 SCNN1A-8608 + CCCAAAAAGGGCUGGAGGAGACU 23 12457 SCNN1A-8609 + ACCCAAAAAGGGCUGGAGGAGACU 24 12458 SCNN1A-8610 + GACCUGAGAAGGCGGACU 18 12459 SCNN1A-8611 + GGACCUGAGAAGGCGGACU 19 12460 SCNN1A-8612 + UGGACCUGAGAAGGCGGACU 20 12461 SCNN1A-8613 + CUGGACCUGAGAAGGCGGACU 21 12462 SCNN1A-8614 + ACUGGACCUGAGAAGGCGGACU 22 12463 SCNN1A-8615 + UACUGGACCUGAGAAGGCGGACU 23 12464 SCNN1A-8616 + GUACUGGACCUGAGAAGGCGGACU 24 12465 SCNN1A-8617 + CCUGGAGCCAGCAGACCU 18 12466 SCNN1A-8618 + UCCUGGAGCCAGCAGACCU 19 12467 SCNN1A-8619 + UUCCUGGAGCCAGCAGACCU 20 12468 SCNN1A-8620 + UUUCCUGGAGCCAGCAGACCU 21 12469 SCNN1A-8621 + CUUUCCUGGAGCCAGCAGACCU 22 12470 SCNN1A-8622 + CCUUUCCUGGAGCCAGCAGACCU 23 12471 SCNN1A-8623 + ACCUUUCCUGGAGCCAGCAGACCU 24 12472 SCNN1A-8624 + ACUGGGAGUACUGGACCU 18 12473 SCNN1A-8625 + AACUGGGAGUACUGGACCU 19 12474 SCNN1A-8626 + GAACUGGGAGUACUGGACCU 20 12475 SCNN1A-8627 + UGAACUGGGAGUACUGGACCU 21 12476 SCNN1A-8628 + GUGAACUGGGAGUACUGGACCU 22 12477 SCNN1A-8629 + GGUGAACUGGGAGUACUGGACCU 23 12478 SCNN1A-8630 + AGGUGAACUGGGAGUACUGGACCU 24 12479 SCNN1A-1735 + GCUCAUGAUACCUCCCCU 18 5584 SCNN1A-1736 + UGCUCAUGAUACCUCCCCU 19 5585 SCNN1A-457 + CUGCUCAUGAUACCUCCCCU 20 4306 SCNN1A-1737 + ACUGCUCAUGAUACCUCCCCU 21 5586 SCNN1A-1738 + UACUGCUCAUGAUACCUCCCCU 22 5587 SCNN1A-1739 + AUACUGCUCAUGAUACCUCCCCU 23 5588 SCNN1A-1740 + GAUACUGCUCAUGAUACCUCCCCU 24 5589 SCNN1A-8631 + CACGCCUAGACAGGCCCU 18 12480 SCNN1A-8632 + ACACGCCUAGACAGGCCCU 19 12481 SCNN1A-5734 + CACACGCCUAGACAGGCCCU 20 9583 SCNN1A-8633 + GCACACGCCUAGACAGGCCCU 21 12482 SCNN1A-8634 + GGCACACGCCUAGACAGGCCCU 22 12483 SCNN1A-8635 + UGGCACACGCCUAGACAGGCCCU 23 12484 SCNN1A-8636 + AUGGCACACGCCUAGACAGGCCCU 24 12485 SCNN1A-8637 + CAAGGGCUAGGGGAGCCU 18 12486 SCNN1A-8638 + CCAAGGGCUAGGGGAGCCU 19 12487 SCNN1A-5275 + GCCAAGGGCUAGGGGAGCCU 20 9124 SCNN1A-8639 + AGCCAAGGGCUAGGGGAGCCU 21 12488 SCNN1A-8640 + GAGCCAAGGGCUAGGGGAGCCU 22 12489 SCNN1A-8641 + AGAGCCAAGGGCUAGGGGAGCCU 23 12490 SCNN1A-8642 + AAGAGCCAAGGGCUAGGGGAGCCU 24 12491 SCNN1A-8643 + CAGAAUUCUCCUCCUCCU 18 12492 SCNN1A-8644 + UCAGAAUUCUCCUCCUCCU 19 12493 SCNN1A-8645 + UUCAGAAUUCUCCUCCUCCU 20 12494 SCNN1A-8646 + AUUCAGAAUUCUCCUCCUCCU 21 12495 SCNN1A-8647 + AAUUCAGAAUUCUCCUCCUCCU 22 12496 SCNN1A-8648 + GAAUUCAGAAUUCUCCUCCUCCU 23 12497 SCNN1A-8649 + AGAAUUCAGAAUUCUCCUCCUCCU 24 12498 SCNN1A-8650 + AGGGGCCCAGGUGAAGCU 18 12499 SCNN1A-8651 + GAGGGGCCCAGGUGAAGCU 19 12500 SCNN1A-5923 + GGAGGGGCCCAGGUGAAGCU 20 9772 SCNN1A-8652 + GGGAGGGGCCCAGGUGAAGCU 21 12501 SCNN1A-8653 + CGGGAGGGGCCCAGGUGAAGCU 22 12502 SCNN1A-8654 + CCGGGAGGGGCCCAGGUGAAGCU 23 12503 SCNN1A-8655 + CCCGGGAGGGGCCCAGGUGAAGCU 24 12504 SCNN1A-8656 + GAUCCUGAGCCCACAGCU 18 12505 SCNN1A-8657 + GGAUCCUGAGCCCACAGCU 19 12506 SCNN1A-5740 + AGGAUCCUGAGCCCACAGCU 20 9589 SCNN1A-8658 + AAGGAUCCUGAGCCCACAGCU 21 12507 SCNN1A-8659 + GAAGGAUCCUGAGCCCACAGCU 22 12508 SCNN1A-8660 + AGAAGGAUCCUGAGCCCACAGCU 23 12509 SCNN1A-8661 + UAGAAGGAUCCUGAGCCCACAGCU 24 12510 SCNN1A-1741 + CAGGGUCAAGGCUGAGCU 18 5590 SCNN1A-1742 + UCAGGGUCAAGGCUGAGCU 19 5591 SCNN1A-1743 + GUCAGGGUCAAGGCUGAGCU 20 5592 SCNN1A-1744 + GGUCAGGGUCAAGGCUGAGCU 21 5593 SCNN1A-1745 + GGGUCAGGGUCAAGGCUGAGCU 22 5594 SCNN1A-1746 + AGGGUCAGGGUCAAGGCUGAGCU 23 5595 SCNN1A-1747 + AAGGGUCAGGGUCAAGGCUGAGCU 24 5596 SCNN1A-8662 + GAAGGGGCCAGCCAGGCU 18 12511 SCNN1A-8663 + AGAAGGGGCCAGCCAGGCU 19 12512 SCNN1A-8664 + GAGAAGGGGCCAGCCAGGCU 20 12513 SCNN1A-8665 + GGAGAAGGGGCCAGCCAGGCU 21 12514 SCNN1A-8666 + AGGAGAAGGGGCCAGCCAGGCU 22 12515 SCNN1A-8667 + AAGGAGAAGGGGCCAGCCAGGCU 23 12516 SCNN1A-8668 + CAAGGAGAAGGGGCCAGCCAGGCU 24 12517 SCNN1A-8669 + CAGACAGGCAAGGAGGCU 18 12518 SCNN1A-8670 + GCAGACAGGCAAGGAGGCU 19 12519 SCNN1A-5742 + CGCAGACAGGCAAGGAGGCU 20 9591 SCNN1A-8671 + ACGCAGACAGGCAAGGAGGCU 21 12520 SCNN1A-8672 + GACGCAGACAGGCAAGGAGGCU 22 12521 SCNN1A-8673 + AGACGCAGACAGGCAAGGAGGCU 23 12522 SCNN1A-8674 + UAGACGCAGACAGGCAAGGAGGCU 24 12523 SCNN1A-8675 + ACAUAAGAGCCAAGGGCU 18 12524 SCNN1A-8676 + GACAUAAGAGCCAAGGGCU 19 12525 SCNN1A-5743 + AGACAUAAGAGCCAAGGGCU 20 9592 SCNN1A-8677 + AAGACAUAAGAGCCAAGGGCU 21 12526 SCNN1A-8678 + UAAGACAUAAGAGCCAAGGGCU 22 12527 SCNN1A-8679 + AUAAGACAUAAGAGCCAAGGGCU 23 12528 SCNN1A-8680 + GAUAAGACAUAAGAGCCAAGGGCU 24 12529 SCNN1A-8681 + AGGGCGGGGGGAGGGGCU 18 12530 SCNN1A-8682 + CAGGGCGGGGGGAGGGGCU 19 12531 SCNN1A-8683 + GCAGGGCGGGGGGAGGGGCU 20 12532 SCNN1A-8684 + AGCAGGGCGGGGGGAGGGGCU 21 12533 SCNN1A-8685 + GAGCAGGGCGGGGGGAGGGGCU 22 12534 SCNN1A-8686 + UGAGCAGGGCGGGGGGAGGGGCU 23 12535 SCNN1A-8687 + GUGAGCAGGGCGGGGGGAGGGGCU 24 12536 SCNN1A-8688 + AGGUGCAGCGGCCUGGCU 18 12537 SCNN1A-8689 + CAGGUGCAGCGGCCUGGCU 19 12538 SCNN1A-5744 + ACAGGUGCAGCGGCCUGGCU 20 9593 SCNN1A-8690 + GACAGGUGCAGCGGCCUGGCU 21 12539 SCNN1A-8691 + UGACAGGUGCAGCGGCCUGGCU 22 12540 SCNN1A-8692 + CUGACAGGUGCAGCGGCCUGGCU 23 12541 SCNN1A-8693 + CCUGACAGGUGCAGCGGCCUGGCU 24 12542 SCNN1A-8694 + UUUCAUAUCAAGGGCUCU 18 12543 SCNN1A-8695 + UUUUCAUAUCAAGGGCUCU 19 12544 SCNN1A-8696 + GUUUUCAUAUCAAGGGCUCU 20 12545 SCNN1A-8697 + AGUUUUCAUAUCAAGGGCUCU 21 12546 SCNN1A-8698 + UAGUUUUCAUAUCAAGGGCUCU 22 12547 SCNN1A-8699 + AUAGUUUUCAUAUCAAGGGCUCU 23 12548 SCNN1A-8700 + AAUAGUUUUCAUAUCAAGGGCUCU 24 12549 SCNN1A-8701 + GGUUAUCUCCUUGGCUCU 18 12550 SCNN1A-8702 + GGGUUAUCUCCUUGGCUCU 19 12551 SCNN1A-8703 + UGGGUUAUCUCCUUGGCUCU 20 12552 SCNN1A-8704 + CUGGGUUAUCUCCUUGGCUCU 21 12553 SCNN1A-8705 + GCUGGGUUAUCUCCUUGGCUCU 22 12554 SCNN1A-8706 + UGCUGGGUUAUCUCCUUGGCUCU 23 12555 SCNN1A-8707 + GUGCUGGGUUAUCUCCUUGGCUCU 24 12556 SCNN1A-8708 + UGCAGAUCUCAGAUUUCU 18 12557 SCNN1A-8709 + GUGCAGAUCUCAGAUUUCU 19 12558 SCNN1A-8710 + AGUGCAGAUCUCAGAUUUCU 20 12559 SCNN1A-8711 + AAGUGCAGAUCUCAGAUUUCU 21 12560 SCNN1A-8712 + AAAGUGCAGAUCUCAGAUUUCU 22 12561 SCNN1A-8713 + AAAAGUGCAGAUCUCAGAUUUCU 23 12562 SCNN1A-8714 + CAAAAGUGCAGAUCUCAGAUUUCU 24 12563 SCNN1A-8715 + CCUCCCCGCUCACUAAGU 18 12564 SCNN1A-8716 + UCCUCCCCGCUCACUAAGU 19 12565 SCNN1A-5752 + CUCCUCCCCGCUCACUAAGU 20 9601 SCNN1A-8717 + UCUCCUCCCCGCUCACUAAGU 21 12566 SCNN1A-8718 + GUCUCCUCCCCGCUCACUAAGU 22 12567 SCNN1A-8719 + GGUCUCCUCCCCGCUCACUAAGU 23 12568 SCNN1A-8720 + AGGUCUCCUCCCCGCUCACUAAGU 24 12569 SCNN1A-8721 + GAGGGGCUGAGGAGGAGU 18 12570 SCNN1A-8722 + GGAGGGGCUGAGGAGGAGU 19 12571 SCNN1A-8723 + GGGAGGGGCUGAGGAGGAGU 20 12572 SCNN1A-8724 + GGGGAGGGGCUGAGGAGGAGU 21 12573 SCNN1A-8725 + GGGGGAGGGGCUGAGGAGGAGU 22 12574 SCNN1A-8726 + GGGGGGAGGGGCUGAGGAGGAGU 23 12575 SCNN1A-8727 + CGGGGGGAGGGGCUGAGGAGGAGU 24 12576 SCNN1A-8728 + CAGCAGACCUGCGGGAGU 18 12577 SCNN1A-8729 + CCAGCAGACCUGCGGGAGU 19 12578 SCNN1A-5278 + GCCAGCAGACCUGCGGGAGU 20 9127 SCNN1A-8730 + AGCCAGCAGACCUGCGGGAGU 21 12579 SCNN1A-8731 + GAGCCAGCAGACCUGCGGGAGU 22 12580 SCNN1A-8732 + GGAGCCAGCAGACCUGCGGGAGU 23 12581 SCNN1A-8733 + UGGAGCCAGCAGACCUGCGGGAGU 24 12582 SCNN1A-8734 + GAGUGAGUAGAGGCAGGU 18 12583 SCNN1A-8735 + UGAGUGAGUAGAGGCAGGU 19 12584 SCNN1A-5756 + CUGAGUGAGUAGAGGCAGGU 20 9605 SCNN1A-8736 + ACUGAGUGAGUAGAGGCAGGU 21 12585 SCNN1A-8737 + CACUGAGUGAGUAGAGGCAGGU 22 12586 SCNN1A-8738 + GCACUGAGUGAGUAGAGGCAGGU 23 12587 SCNN1A-8739 + GGCACUGAGUGAGUAGAGGCAGGU 24 12588 SCNN1A-8740 + GGGGACAGGAUGGCAGGU 18 12589 SCNN1A-8741 + GGGGGACAGGAUGGCAGGU 19 12590 SCNN1A-8742 + UGGGGGACAGGAUGGCAGGU 20 12591 SCNN1A-8743 + CUGGGGGACAGGAUGGCAGGU 21 12592 SCNN1A-8744 + GCUGGGGGACAGGAUGGCAGGU 22 12593 SCNN1A-8745 + GGCUGGGGGACAGGAUGGCAGGU 23 12594 SCNN1A-8746 + AGGCUGGGGGACAGGAUGGCAGGU 24 12595 SCNN1A-8747 + UGCAGGGCUCCAGGAGGU 18 12596 SCNN1A-8748 + CUGCAGGGCUCCAGGAGGU 19 12597 SCNN1A-8749 + ACUGCAGGGCUCCAGGAGGU 20 12598 SCNN1A-8750 + GACUGCAGGGCUCCAGGAGGU 21 12599 SCNN1A-8751 + GGACUGCAGGGCUCCAGGAGGU 22 12600 SCNN1A-8752 + AGGACUGCAGGGCUCCAGGAGGU 23 12601 SCNN1A-8753 + CAGGACUGCAGGGCUCCAGGAGGU 24 12602 SCNN1A-8754 + AAAUCAGUUUUCUGAGGU 18 12603 SCNN1A-8755 + UAAAUCAGUUUUCUGAGGU 19 12604 SCNN1A-8756 + AUAAAUCAGUUUUCUGAGGU 20 12605 SCNN1A-8757 + GAUAAAUCAGUUUUCUGAGGU 21 12606 SCNN1A-8758 + GGAUAAAUCAGUUUUCUGAGGU 22 12607 SCNN1A-8759 + AGGAUAAAUCAGUUUUCUGAGGU 23 12608 SCNN1A-8760 + AAGGAUAAAUCAGUUUUCUGAGGU 24 12609 SCNN1A-8761 + AAGGAGAGAGAGGAGGGU 18 12610 SCNN1A-8762 + CAAGGAGAGAGAGGAGGGU 19 12611 SCNN1A-8763 + GCAAGGAGAGAGAGGAGGGU 20 12612 SCNN1A-8764 + AGCAAGGAGAGAGAGGAGGGU 21 12613 SCNN1A-8765 + GAGCAAGGAGAGAGAGGAGGGU 22 12614 SCNN1A-8766 + UGAGCAAGGAGAGAGAGGAGGGU 23 12615 SCNN1A-8767 + GUGAGCAAGGAGAGAGAGGAGGGU 24 12616 SCNN1A-8768 + GGCUGAGAGGGCCUGGGU 18 12617 SCNN1A-8769 + AGGCUGAGAGGGCCUGGGU 19 12618 SCNN1A-6188 + CAGGCUGAGAGGGCCUGGGU 20 10037 SCNN1A-8770 + CCAGGCUGAGAGGGCCUGGGU 21 12619 SCNN1A-8771 + GCCAGGCUGAGAGGGCCUGGGU 22 12620 SCNN1A-8772 + AGCCAGGCUGAGAGGGCCUGGGU 23 12621 SCNN1A-8773 + CAGCCAGGCUGAGAGGGCCUGGGU 24 12622 SCNN1A-1772 + CCCUCCAUGAGACCUGGU 18 5621 SCNN1A-1773 + CCCCUCCAUGAGACCUGGU 19 5622 SCNN1A-199 + UCCCCUCCAUGAGACCUGGU 20 828 SCNN1A-1774 + UUCCCCUCCAUGAGACCUGGU 21 5623 SCNN1A-1775 + GUUCCCCUCCAUGAGACCUGGU 22 5624 SCNN1A-1776 + UGUUCCCCUCCAUGAGACCUGGU 23 5625 SCNN1A-1777 + UUGUUCCCCUCCAUGAGACCUGGU 24 5626 SCNN1A-8774 + CAGGUGGGGGGCAGUGGU 18 12623 SCNN1A-8775 + GCAGGUGGGGGGCAGUGGU 19 12624 SCNN1A-5928 + GGCAGGUGGGGGGCAGUGGU 20 9777 SCNN1A-8776 + AGGCAGGUGGGGGGCAGUGGU 21 12625 SCNN1A-8777 + GAGGCAGGUGGGGGGCAGUGGU 22 12626 SCNN1A-8778 + AGAGGCAGGUGGGGGGCAGUGGU 23 12627 SCNN1A-8779 + UAGAGGCAGGUGGGGGGCAGUGGU 24 12628 SCNN1A-8780 + UCAUAUCAAGGGCUCUGU 18 12629 SCNN1A-8781 + UUCAUAUCAAGGGCUCUGU 19 12630 SCNN1A-8782 + UUUCAUAUCAAGGGCUCUGU 20 12631 SCNN1A-8783 + UUUUCAUAUCAAGGGCUCUGU 21 12632 SCNN1A-8784 + GUUUUCAUAUCAAGGGCUCUGU 22 12633 SCNN1A-8785 + AGUUUUCAUAUCAAGGGCUCUGU 23 12634 SCNN1A-8786 + UAGUUUUCAUAUCAAGGGCUCUGU 24 12635 SCNN1A-1778 + UGAGCCCCGGAGUGGAUU 18 5627 SCNN1A-1779 + AUGAGCCCCGGAGUGGAUU 19 5628 SCNN1A-425 + CAUGAGCCCCGGAGUGGAUU 20 4274 SCNN1A-1780 + UCAUGAGCCCCGGAGUGGAUU 21 5629 SCNN1A-1781 + UUCAUGAGCCCCGGAGUGGAUU 22 5630 SCNN1A-1782 + CUUCAUGAGCCCCGGAGUGGAUU 23 5631 SCNN1A-1783 + CCUUCAUGAGCCCCGGAGUGGAUU 24 5632 SCNN1A-8787 + UGUUUGAUCUCAAAGGUU 18 12636 SCNN1A-8788 + CUGUUUGAUCUCAAAGGUU 19 12637 SCNN1A-8789 + GCUGUUUGAUCUCAAAGGUU 20 12638 SCNN1A-8790 + GGCUGUUUGAUCUCAAAGGUU 21 12639 SCNN1A-8791 + UGGCUGUUUGAUCUCAAAGGUU 22 12640 SCNN1A-8792 + CUGGCUGUUUGAUCUCAAAGGUU 23 12641 SCNN1A-8793 + CCUGGCUGUUUGAUCUCAAAGGUU 24 12642 SCNN1A-8794 + CAAGGAUAAAUCAGUUUU 18 12643 SCNN1A-8795 + CCAAGGAUAAAUCAGUUUU 19 12644 SCNN1A-8796 + CCCAAGGAUAAAUCAGUUUU 20 12645 SCNN1A-8797 + UCCCAAGGAUAAAUCAGUUUU 21 12646 SCNN1A-8798 + UUCCCAAGGAUAAAUCAGUUUU 22 12647 SCNN1A-8799 + CUUCCCAAGGAUAAAUCAGUUUU 23 12648 SCNN1A-8800 + CCUUCCCAAGGAUAAAUCAGUUUU 24 12649 SCNN1A-8801 + GUCAGAGCCGGGAGUUUU 18 12650 SCNN1A-8802 + AGUCAGAGCCGGGAGUUUU 19 12651 SCNN1A-8803 + GAGUCAGAGCCGGGAGUUUU 20 12652 SCNN1A-8804 + GGAGUCAGAGCCGGGAGUUUU 21 12653 SCNN1A-8805 + AGGAGUCAGAGCCGGGAGUUUU 22 12654 SCNN1A-8806 + GAGGAGUCAGAGCCGGGAGUUUU 23 12655 SCNN1A-8807 + GGAGGAGUCAGAGCCGGGAGUUUU 24 12656 SCNN1A-8808 GCAGCCAACAGUGUAAAA 18 12657 SCNN1A-8809 GGCAGCCAACAGUGUAAAA 19 12658 SCNN1A-8810 UGGCAGCCAACAGUGUAAAA 20 12659 SCNN1A-8811 CUGGCAGCCAACAGUGUAAAA 21 12660 SCNN1A-8812 CCUGGCAGCCAACAGUGUAAAA 22 12661 SCNN1A-8813 GCCUGGCAGCCAACAGUGUAAAA 23 12662 SCNN1A-8814 GGCCUGGCAGCCAACAGUGUAAAA 24 12663 SCNN1A-8815 UCUUUUAAAGUGUACAAA 18 12664 SCNN1A-8816 AUCUUUUAAAGUGUACAAA 19 12665 SCNN1A-8817 AAUCUUUUAAAGUGUACAAA 20 12666 SCNN1A-8818 CAAUCUUUUAAAGUGUACAAA 21 12667 SCNN1A-8819 ACAAUCUUUUAAAGUGUACAAA 22 12668 SCNN1A-8820 GACAAUCUUUUAAAGUGUACAAA 23 12669 SCNN1A-8821 AGACAAUCUUUUAAAGUGUACAAA 24 12670 SCNN1A-8822 GAGCAGGAGAGACCCAAA 18 12671 SCNN1A-8823 AGAGCAGGAGAGACCCAAA 19 12672 SCNN1A-8824 GAGAGCAGGAGAGACCCAAA 20 12673 SCNN1A-8825 GGAGAGCAGGAGAGACCCAAA 21 12674 SCNN1A-8826 AGGAGAGCAGGAGAGACCCAAA 22 12675 SCNN1A-8827 GAGGAGAGCAGGAGAGACCCAAA 23 12676 SCNN1A-8828 AGAGGAGAGCAGGAGAGACCCAAA 24 12677 SCNN1A-8829 CAGGCAUGAGCUGGCAAA 18 12678 SCNN1A-8830 UCAGGCAUGAGCUGGCAAA 19 12679 SCNN1A-8831 UUCAGGCAUGAGCUGGCAAA 20 12680 SCNN1A-8832 UUUCAGGCAUGAGCUGGCAAA 21 12681 SCNN1A-8833 AUUUCAGGCAUGAGCUGGCAAA 22 12682 SCNN1A-8834 GAUUUCAGGCAUGAGCUGGCAAA 23 12683 SCNN1A-8835 GGAUUUCAGGCAUGAGCUGGCAAA 24 12684 SCNN1A-8836 AGGGGGCAGAGACAGAAA 18 12685 SCNN1A-8837 AAGGGGGCAGAGACAGAAA 19 12686 SCNN1A-5863 GAAGGGGGCAGAGACAGAAA 20 9712 SCNN1A-8838 GGAAGGGGGCAGAGACAGAAA 21 12687 SCNN1A-8839 AGGAAGGGGGCAGAGACAGAAA 22 12688 SCNN1A-8840 AAGGAAGGGGGCAGAGACAGAAA 23 12689 SCNN1A-8841 AAAGGAAGGGGGCAGAGACAGAAA 24 12690 SCNN1A-8842 GAGGAGGCAGGCCAGAAA 18 12691 SCNN1A-8843 AGAGGAGGCAGGCCAGAAA 19 12692 SCNN1A-8844 GAGAGGAGGCAGGCCAGAAA 20 12693 SCNN1A-8845 AGAGAGGAGGCAGGCCAGAAA 21 12694 SCNN1A-8846 GAGAGAGGAGGCAGGCCAGAAA 22 12695 SCNN1A-8847 AGAGAGAGGAGGCAGGCCAGAAA 23 12696 SCNN1A-8848 UAGAGAGAGGAGGCAGGCCAGAAA 24 12697 SCNN1A-8849 GAGAGACCCAAAGAGAAA 18 12698 SCNN1A-8850 GGAGAGACCCAAAGAGAAA 19 12699 SCNN1A-8851 AGGAGAGACCCAAAGAGAAA 20 12700 SCNN1A-8852 CAGGAGAGACCCAAAGAGAAA 21 12701 SCNN1A-8853 GCAGGAGAGACCCAAAGAGAAA 22 12702 SCNN1A-8854 AGCAGGAGAGACCCAAAGAGAAA 23 12703 SCNN1A-8855 GAGCAGGAGAGACCCAAAGAGAAA 24 12704 SCNN1A-8856 CGAGGAAUCAGCAGGAAA 18 12705 SCNN1A-8857 GCGAGGAAUCAGCAGGAAA 19 12706 SCNN1A-8858 GGCGAGGAAUCAGCAGGAAA 20 12707 SCNN1A-8859 UGGCGAGGAAUCAGCAGGAAA 21 12708 SCNN1A-8860 GUGGCGAGGAAUCAGCAGGAAA 22 12709 SCNN1A-8861 GGUGGCGAGGAAUCAGCAGGAAA 23 12710 SCNN1A-8862 GGGUGGCGAGGAAUCAGCAGGAAA 24 12711 SCNN1A-8863 CUGGAGGAAGAAGACCAA 18 12712 SCNN1A-8864 CCUGGAGGAAGAAGACCAA 19 12713 SCNN1A-5519 UCCUGGAGGAAGAAGACCAA 20 9368 SCNN1A-8865 AUCCUGGAGGAAGAAGACCAA 21 12714 SCNN1A-8866 GAUCCUGGAGGAAGAAGACCAA 22 12715 SCNN1A-8867 AGAUCCUGGAGGAAGAAGACCAA 23 12716 SCNN1A-8868 CAGAUCCUGGAGGAAGAAGACCAA 24 12717 SCNN1A-8869 UCCAGCUGUCCCUUCCAA 18 12718 SCNN1A-8870 AUCCAGCUGUCCCUUCCAA 19 12719 SCNN1A-5521 AAUCCAGCUGUCCCUUCCAA 20 9370 SCNN1A-8871 AAAUCCAGCUGUCCCUUCCAA 21 12720 SCNN1A-8872 AAAAUCCAGCUGUCCCUUCCAA 22 12721 SCNN1A-8873 AAAAAUCCAGCUGUCCCUUCCAA 23 12722 SCNN1A-8874 GAAAAAUCCAGCUGUCCCUUCCAA 24 12723 SCNN1A-1790 CAGUAUCAAGGUAAGCAA 18 5639 SCNN1A-1791 GCAGUAUCAAGGUAAGCAA 19 5640 SCNN1A-393 AGCAGUAUCAAGGUAAGCAA 20 4242 SCNN1A-1792 GAGCAGUAUCAAGGUAAGCAA 21 5641 SCNN1A-1793 UGAGCAGUAUCAAGGUAAGCAA 22 5642 SCNN1A-1794 AUGAGCAGUAUCAAGGUAAGCAA 23 5643 SCNN1A-1795 CAUGAGCAGUAUCAAGGUAAGCAA 24 5644 SCNN1A-8875 CGCAAGAGACUGCCGCAA 18 12724 SCNN1A-8876 UCGCAAGAGACUGCCGCAA 19 12725 SCNN1A-8877 GUCGCAAGAGACUGCCGCAA 20 12726 SCNN1A-8878 AGUCGCAAGAGACUGCCGCAA 21 12727 SCNN1A-8879 AAGUCGCAAGAGACUGCCGCAA 22 12728 SCNN1A-8880 GAAGUCGCAAGAGACUGCCGCAA 23 12729 SCNN1A-8881 AGAAGUCGCAAGAGACUGCCGCAA 24 12730 SCNN1A-8882 UGAGAGGGGGCAAGGCAA 18 12731 SCNN1A-8883 GUGAGAGGGGGCAAGGCAA 19 12732 SCNN1A-6079 AGUGAGAGGGGGCAAGGCAA 20 9928 SCNN1A-8884 GAGUGAGAGGGGGCAAGGCAA 21 12733 SCNN1A-8885 AGAGUGAGAGGGGGCAAGGCAA 22 12734 SCNN1A-8886 UAGAGUGAGAGGGGGCAAGGCAA 23 12735 SCNN1A-8887 CUAGAGUGAGAGGGGGCAAGGCAA 24 12736 SCNN1A-8888 UGUAAGGACCUGGCUCAA 18 12737 SCNN1A-8889 AUGUAAGGACCUGGCUCAA 19 12738 SCNN1A-5522 AAUGUAAGGACCUGGCUCAA 20 9371 SCNN1A-8890 CAAUGUAAGGACCUGGCUCAA 21 12739 SCNN1A-8891 CCAAUGUAAGGACCUGGCUCAA 22 12740 SCNN1A-8892 CCCAAUGUAAGGACCUGGCUCAA 23 12741 SCNN1A-8893 GCCCAAUGUAAGGACCUGGCUCAA 24 12742 SCNN1A-8894 UUUGGCUGCCAGAUUCAA 18 12743 SCNN1A-8895 GUUUGGCUGCCAGAUUCAA 19 12744 SCNN1A-8896 GGUUUGGCUGCCAGAUUCAA 20 12745 SCNN1A-8897 AGGUUUGGCUGCCAGAUUCAA 21 12746 SCNN1A-8898 GAGGUUUGGCUGCCAGAUUCAA 22 12747 SCNN1A-8899 AGAGGUUUGGCUGCCAGAUUCAA 23 12748 SCNN1A-8900 GAGAGGUUUGGCUGCCAGAUUCAA 24 12749 SCNN1A-8901 AAGGGGGCAGAGACAGAA 18 12750 SCNN1A-8902 GAAGGGGGCAGAGACAGAA 19 12751 SCNN1A-5864 GGAAGGGGGCAGAGACAGAA 20 9713 SCNN1A-8903 AGGAAGGGGGCAGAGACAGAA 21 12752 SCNN1A-8904 AAGGAAGGGGGCAGAGACAGAA 22 12753 SCNN1A-8905 AAAGGAAGGGGGCAGAGACAGAA 23 12754 SCNN1A-8906 CAAAGGAAGGGGGCAGAGACAGAA 24 12755 SCNN1A-8907 GGAAGAAGACCAAAGGAA 18 12756 SCNN1A-8908 AGGAAGAAGACCAAAGGAA 19 12757 SCNN1A-5865 GAGGAAGAAGACCAAAGGAA 20 9714 SCNN1A-8909 GGAGGAAGAAGACCAAAGGAA 21 12758 SCNN1A-8910 UGGAGGAAGAAGACCAAAGGAA 22 12759 SCNN1A-8911 CUGGAGGAAGAAGACCAAAGGAA 23 12760 SCNN1A-8912 CCUGGAGGAAGAAGACCAAAGGAA 24 12761 SCNN1A-8913 GCAAGGGGGGGAGAGGAA 18 12762 SCNN1A-8914 GGCAAGGGGGGGAGAGGAA 19 12763 SCNN1A-8915 AGGCAAGGGGGGGAGAGGAA 20 12764 SCNN1A-8916 AAGGCAAGGGGGGGAGAGGAA 21 12765 SCNN1A-8917 CAAGGCAAGGGGGGGAGAGGAA 22 12766 SCNN1A-8918 GCAAGGCAAGGGGGGGAGAGGAA 23 12767 SCNN1A-8919 GGCAAGGCAAGGGGGGGAGAGGAA 24 12768 SCNN1A-8920 UGCCAGAUUCAACUGGAA 18 12769 SCNN1A-8921 CUGCCAGAUUCAACUGGAA 19 12770 SCNN1A-5173 GCUGCCAGAUUCAACUGGAA 20 9022 SCNN1A-8922 GGCUGCCAGAUUCAACUGGAA 21 12771 SCNN1A-8923 UGGCUGCCAGAUUCAACUGGAA 22 12772 SCNN1A-8924 UUGGCUGCCAGAUUCAACUGGAA 23 12773 SCNN1A-8925 UUUGGCUGCCAGAUUCAACUGGAA 24 12774 SCNN1A-1802 CACUCCGGGGCUCAUGAA 18 5651 SCNN1A-1803 CCACUCCGGGGCUCAUGAA 19 5652 SCNN1A-451 UCCACUCCGGGGCUCAUGAA 20 4300 SCNN1A-1804 AUCCACUCCGGGGCUCAUGAA 21 5653 SCNN1A-1805 AAUCCACUCCGGGGCUCAUGAA 22 5654 SCNN1A-1806 CAAUCCACUCCGGGGCUCAUGAA 23 5655 SCNN1A-1807 CCAAUCCACUCCGGGGCUCAUGAA 24 5656 SCNN1A-8926 CGCCCUGCUCACCUUUAA 18 12775 SCNN1A-8927 CCGCCCUGCUCACCUUUAA 19 12776 SCNN1A-8928 CCCGCCCUGCUCACCUUUAA 20 12777 SCNN1A-8929 CCCCGCCCUGCUCACCUUUAA 21 12778 SCNN1A-8930 CCCCCGCCCUGCUCACCUUUAA 22 12779 SCNN1A-8931 CCCCCCGCCCUGCUCACCUUUAA 23 12780 SCNN1A-8932 UCCCCCCGCCCUGCUCACCUUUAA 24 12781 SCNN1A-8933 AGUUUCUUCAUUAGGACA 18 12782 SCNN1A-8934 CAGUUUCUUCAUUAGGACA 19 12783 SCNN1A-8935 UCAGUUUCUUCAUUAGGACA 20 12784 SCNN1A-8936 GUCAGUUUCUUCAUUAGGACA 21 12785 SCNN1A-8937 GGUCAGUUUCUUCAUUAGGACA 22 12786 SCNN1A-8938 GGGUCAGUUUCUUCAUUAGGACA 23 12787 SCNN1A-8939 AGGGUCAGUUUCUUCAUUAGGACA 24 12788 SCNN1A-8940 CCUGGAGGAAGAAGACCA 18 12789 SCNN1A-8941 UCCUGGAGGAAGAAGACCA 19 12790 SCNN1A-8942 AUCCUGGAGGAAGAAGACCA 20 12791 SCNN1A-8943 GAUCCUGGAGGAAGAAGACCA 21 12792 SCNN1A-8944 AGAUCCUGGAGGAAGAAGACCA 22 12793 SCNN1A-8945 CAGAUCCUGGAGGAAGAAGACCA 23 12794 SCNN1A-8946 ACAGAUCCUGGAGGAAGAAGACCA 24 12795 SCNN1A-8947 GAGAUAACCCAGCACCCA 18 12796 SCNN1A-8948 GGAGAUAACCCAGCACCCA 19 12797 SCNN1A-8949 AGGAGAUAACCCAGCACCCA 20 12798 SCNN1A-8950 AAGGAGAUAACCCAGCACCCA 21 12799 SCNN1A-8951 CAAGGAGAUAACCCAGCACCCA 22 12800 SCNN1A-8952 CCAAGGAGAUAACCCAGCACCCA 23 12801 SCNN1A-8953 GCCAAGGAGAUAACCCAGCACCCA 24 12802 SCNN1A-8954 GAGAGCAGGAGAGACCCA 18 12803 SCNN1A-8955 GGAGAGCAGGAGAGACCCA 19 12804 SCNN1A-8956 AGGAGAGCAGGAGAGACCCA 20 12805 SCNN1A-8957 GAGGAGAGCAGGAGAGACCCA 21 12806 SCNN1A-8958 AGAGGAGAGCAGGAGAGACCCA 22 12807 SCNN1A-8959 AAGAGGAGAGCAGGAGAGACCCA 23 12808 SCNN1A-8960 AAAGAGGAGAGCAGGAGAGACCCA 24 12809 SCNN1A-8961 GCUAAGUAGAUAGCCCCA 18 12810 SCNN1A-8962 CGCUAAGUAGAUAGCCCCA 19 12811 SCNN1A-8963 GCGCUAAGUAGAUAGCCCCA 20 12812 SCNN1A-8964 AGCGCUAAGUAGAUAGCCCCA 21 12813 SCNN1A-8965 AAGCGCUAAGUAGAUAGCCCCA 22 12814 SCNN1A-8966 AAAGCGCUAAGUAGAUAGCCCCA 23 12815 SCNN1A-8967 AAAAGCGCUAAGUAGAUAGCCCCA 24 12816 SCNN1A-8968 GACCUUUUCACAGAGCCA 18 12817 SCNN1A-8969 AGACCUUUUCACAGAGCCA 19 12818 SCNN1A-5866 GAGACCUUUUCACAGAGCCA 20 9715 SCNN1A-8970 AGAGACCUUUUCACAGAGCCA 21 12819 SCNN1A-8971 CAGAGACCUUUUCACAGAGCCA 22 12820 SCNN1A-8972 GCAGAGACCUUUUCACAGAGCCA 23 12821 SCNN1A-8973 UGCAGAGACCUUUUCACAGAGCCA 24 12822 SCNN1A-8974 UCCAUCCCUGGCCGGCCA 18 12823 SCNN1A-8975 UUCCAUCCCUGGCCGGCCA 19 12824 SCNN1A-8976 CUUCCAUCCCUGGCCGGCCA 20 12825 SCNN1A-8977 GCUUCCAUCCCUGGCCGGCCA 21 12826 SCNN1A-8978 CGCUUCCAUCCCUGGCCGGCCA 22 12827 SCNN1A-8979 UCGCUUCCAUCCCUGGCCGGCCA 23 12828 SCNN1A-8980 GUCGCUUCCAUCCCUGGCCGGCCA 24 12829 SCNN1A-8981 AUCCAGCUGUCCCUUCCA 18 12830 SCNN1A-8982 AAUCCAGCUGUCCCUUCCA 19 12831 SCNN1A-5531 AAAUCCAGCUGUCCCUUCCA 20 9380 SCNN1A-8983 AAAAUCCAGCUGUCCCUUCCA 21 12832 SCNN1A-8984 AAAAAUCCAGCUGUCCCUUCCA 22 12833 SCNN1A-8985 GAAAAAUCCAGCUGUCCCUUCCA 23 12834 SCNN1A-8986 AGAAAAAUCCAGCUGUCCCUUCCA 24 12835 SCNN1A-8987 GGCCCUAUCAGGGAAGCA 18 12836 SCNN1A-8988 UGGCCCUAUCAGGGAAGCA 19 12837 SCNN1A-8989 GUGGCCCUAUCAGGGAAGCA 20 12838 SCNN1A-8990 GGUGGCCCUAUCAGGGAAGCA 21 12839 SCNN1A-8991 AGGUGGCCCUAUCAGGGAAGCA 22 12840 SCNN1A-8992 AAGGUGGCCCUAUCAGGGAAGCA 23 12841 SCNN1A-8993 AAAGGUGGCCCUAUCAGGGAAGCA 24 12842 SCNN1A-1808 GCAGUAUCAAGGUAAGCA 18 5657 SCNN1A-1809 AGCAGUAUCAAGGUAAGCA 19 5658 SCNN1A-342 GAGCAGUAUCAAGGUAAGCA 20 4191 SCNN1A-1810 UGAGCAGUAUCAAGGUAAGCA 21 5659 SCNN1A-1811 AUGAGCAGUAUCAAGGUAAGCA 22 5660 SCNN1A-1812 CAUGAGCAGUAUCAAGGUAAGCA 23 5661 SCNN1A-1813 UCAUGAGCAGUAUCAAGGUAAGCA 24 5662 SCNN1A-8994 UGGCAAAUAGAAAAGGCA 18 12843 SCNN1A-8995 CUGGCAAAUAGAAAAGGCA 19 12844 SCNN1A-5180 GCUGGCAAAUAGAAAAGGCA 20 9029 SCNN1A-8996 AGCUGGCAAAUAGAAAAGGCA 21 12845 SCNN1A-8997 GAGCUGGCAAAUAGAAAAGGCA 22 12846 SCNN1A-8998 UGAGCUGGCAAAUAGAAAAGGCA 23 12847 SCNN1A-8999 AUGAGCUGGCAAAUAGAAAAGGCA 24 12848 SCNN1A-9000 GUGAGAGGGGGCAAGGCA 18 12849 SCNN1A-9001 AGUGAGAGGGGGCAAGGCA 19 12850 SCNN1A-5868 GAGUGAGAGGGGGCAAGGCA 20 9717 SCNN1A-9002 AGAGUGAGAGGGGGCAAGGCA 21 12851 SCNN1A-9003 UAGAGUGAGAGGGGGCAAGGCA 22 12852 SCNN1A-9004 CUAGAGUGAGAGGGGGCAAGGCA 23 12853 SCNN1A-9005 CCUAGAGUGAGAGGGGGCAAGGCA 24 12854 SCNN1A-9006 UCUGGGAUAUGUGGGGCA 18 12855 SCNN1A-9007 CUCUGGGAUAUGUGGGGCA 19 12856 SCNN1A-9008 UCUCUGGGAUAUGUGGGGCA 20 12857 SCNN1A-9009 GUCUCUGGGAUAUGUGGGGCA 21 12858 SCNN1A-9010 GGUCUCUGGGAUAUGUGGGGCA 22 12859 SCNN1A-9011 GGGUCUCUGGGAUAUGUGGGGCA 23 12860 SCNN1A-9012 GGGGUCUCUGGGAUAUGUGGGGCA 24 12861 SCNN1A-9013 CUUCCUGAGUCUCCUGCA 18 12862 SCNN1A-9014 GCUUCCUGAGUCUCCUGCA 19 12863 SCNN1A-9015 GGCUUCCUGAGUCUCCUGCA 20 12864 SCNN1A-9016 AGGCUUCCUGAGUCUCCUGCA 21 12865 SCNN1A-9017 AAGGCUUCCUGAGUCUCCUGCA 22 12866 SCNN1A-9018 GAAGGCUUCCUGAGUCUCCUGCA 23 12867 SCNN1A-9019 GGAAGGCUUCCUGAGUCUCCUGCA 24 12868 SCNN1A-9020 GCUGAGCACCUUAUUGCA 18 12869 SCNN1A-9021 UGCUGAGCACCUUAUUGCA 19 12870 SCNN1A-5184 GUGCUGAGCACCUUAUUGCA 20 9033 SCNN1A-9022 GGUGCUGAGCACCUUAUUGCA 21 12871 SCNN1A-9023 GGGUGCUGAGCACCUUAUUGCA 22 12872 SCNN1A-9024 AGGGUGCUGAGCACCUUAUUGCA 23 12873 SCNN1A-9025 CAGGGUGCUGAGCACCUUAUUGCA 24 12874 SCNN1A-9026 CGAAAGGUGGCCCUAUCA 18 12875 SCNN1A-9027 UCGAAAGGUGGCCCUAUCA 19 12876 SCNN1A-5540 CUCGAAAGGUGGCCCUAUCA 20 9389 SCNN1A-9028 ACUCGAAAGGUGGCCCUAUCA 21 12877 SCNN1A-9029 AACUCGAAAGGUGGCCCUAUCA 22 12878 SCNN1A-9030 AAACUCGAAAGGUGGCCCUAUCA 23 12879 SCNN1A-9031 AAAACUCGAAAGGUGGCCCUAUCA 24 12880 SCNN1A-9032 AUGUAAGGACCUGGCUCA 18 12881 SCNN1A-9033 AAUGUAAGGACCUGGCUCA 19 12882 SCNN1A-5542 CAAUGUAAGGACCUGGCUCA 20 9391 SCNN1A-9034 CCAAUGUAAGGACCUGGCUCA 21 12883 SCNN1A-9035 CCCAAUGUAAGGACCUGGCUCA 22 12884 SCNN1A-9036 GCCCAAUGUAAGGACCUGGCUCA 23 12885 SCNN1A-9037 UGCCCAAUGUAAGGACCUGGCUCA 24 12886 SCNN1A-1814 AGCCCAUACCAGGUCUCA 18 5663 SCNN1A-1815 CAGCCCAUACCAGGUCUCA 19 5664 SCNN1A-1 GCAGCCCAUACCAGGUCUCA 20 503 SCNN1A-1816 UGCAGCCCAUACCAGGUCUCA 21 5665 SCNN1A-1817 CUGCAGCCCAUACCAGGUCUCA 22 5666 SCNN1A-1818 UCUGCAGCCCAUACCAGGUCUCA 23 5667 SCNN1A-1819 CUCUGCAGCCCAUACCAGGUCUCA 24 5668 SCNN1A-9038 GCAUUGCAAUUCUUCUCA 18 12887 SCNN1A-9039 GGCAUUGCAAUUCUUCUCA 19 12888 SCNN1A-9040 AGGCAUUGCAAUUCUUCUCA 20 12889 SCNN1A-9041 CAGGCAUUGCAAUUCUUCUCA 21 12890 SCNN1A-9042 CCAGGCAUUGCAAUUCUUCUCA 22 12891 SCNN1A-9043 ACCAGGCAUUGCAAUUCUUCUCA 23 12892 SCNN1A-9044 GACCAGGCAUUGCAAUUCUUCUCA 24 12893 SCNN1A-9045 AGUGCAGAGACCUUUUCA 18 12894 SCNN1A-9046 CAGUGCAGAGACCUUUUCA 19 12895 SCNN1A-9047 ACAGUGCAGAGACCUUUUCA 20 12896 SCNN1A-9048 GACAGUGCAGAGACCUUUUCA 21 12897 SCNN1A-9049 GGACAGUGCAGAGACCUUUUCA 22 12898 SCNN1A-9050 GGGACAGUGCAGAGACCUUUUCA 23 12899 SCNN1A-9051 GGGGACAGUGCAGAGACCUUUUCA 24 12900 SCNN1A-9052 CAAGAGACUGCCGCAAGA 18 12901 SCNN1A-9053 GCAAGAGACUGCCGCAAGA 19 12902 SCNN1A-9054 CGCAAGAGACUGCCGCAAGA 20 12903 SCNN1A-9055 UCGCAAGAGACUGCCGCAAGA 21 12904 SCNN1A-9056 GUCGCAAGAGACUGCCGCAAGA 22 12905 SCNN1A-9057 AGUCGCAAGAGACUGCCGCAAGA 23 12906 SCNN1A-9058 AAGUCGCAAGAGACUGCCGCAAGA 24 12907 SCNN1A-9059 GAAGGGGGCAGAGACAGA 18 12908 SCNN1A-9060 GGAAGGGGGCAGAGACAGA 19 12909 SCNN1A-9061 AGGAAGGGGGCAGAGACAGA 20 12910 SCNN1A-9062 AAGGAAGGGGGCAGAGACAGA 21 12911 SCNN1A-9063 AAAGGAAGGGGGCAGAGACAGA 22 12912 SCNN1A-9064 CAAAGGAAGGGGGCAGAGACAGA 23 12913 SCNN1A-9065 CCAAAGGAAGGGGGCAGAGACAGA 24 12914 SCNN1A-9066 GAGAGGAGGCAGGCCAGA 18 12915 SCNN1A-9067 AGAGAGGAGGCAGGCCAGA 19 12916 SCNN1A-9068 GAGAGAGGAGGCAGGCCAGA 20 12917 SCNN1A-9069 AGAGAGAGGAGGCAGGCCAGA 21 12918 SCNN1A-9070 UAGAGAGAGGAGGCAGGCCAGA 22 12919 SCNN1A-9071 UUAGAGAGAGGAGGCAGGCCAGA 23 12920 SCNN1A-9072 AUUAGAGAGAGGAGGCAGGCCAGA 24 12921 SCNN1A-9073 AGAGAAACAGAAGGCAGA 18 12922 SCNN1A-9074 AAGAGAAACAGAAGGCAGA 19 12923 SCNN1A-9075 AAAGAGAAACAGAAGGCAGA 20 12924 SCNN1A-9076 CAAAGAGAAACAGAAGGCAGA 21 12925 SCNN1A-9077 CCAAAGAGAAACAGAAGGCAGA 22 12926 SCNN1A-9078 CCCAAAGAGAAACAGAAGGCAGA 23 12927 SCNN1A-9079 ACCCAAAGAGAAACAGAAGGCAGA 24 12928 SCNN1A-9080 AAAGGAAGGGGGCAGAGA 18 12929 SCNN1A-9081 CAAAGGAAGGGGGCAGAGA 19 12930 SCNN1A-9082 CCAAAGGAAGGGGGCAGAGA 20 12931 SCNN1A-9083 ACCAAAGGAAGGGGGCAGAGA 21 12932 SCNN1A-9084 GACCAAAGGAAGGGGGCAGAGA 22 12933 SCNN1A-9085 AGACCAAAGGAAGGGGGCAGAGA 23 12934 SCNN1A-9086 AAGACCAAAGGAAGGGGGCAGAGA 24 12935 SCNN1A-9087 GAGAGGCAGGAUUAGAGA 18 12936 SCNN1A-9088 AGAGAGGCAGGAUUAGAGA 19 12937 SCNN1A-9089 AAGAGAGGCAGGAUUAGAGA 20 12938 SCNN1A-9090 GAAGAGAGGCAGGAUUAGAGA 21 12939 SCNN1A-9091 GGAAGAGAGGCAGGAUUAGAGA 22 12940 SCNN1A-9092 AGGAAGAGAGGCAGGAUUAGAGA 23 12941 SCNN1A-9093 GAGGAAGAGAGGCAGGAUUAGAGA 24 12942 SCNN1A-9094 GACCUGGCUCAAGGGAGA 18 12943 SCNN1A-9095 GGACCUGGCUCAAGGGAGA 19 12944 SCNN1A-9096 AGGACCUGGCUCAAGGGAGA 20 12945 SCNN1A-9097 AAGGACCUGGCUCAAGGGAGA 21 12946 SCNN1A-9098 UAAGGACCUGGCUCAAGGGAGA 22 12947 SCNN1A-9099 GUAAGGACCUGGCUCAAGGGAGA 23 12948 SCNN1A-9100 UGUAAGGACCUGGCUCAAGGGAGA 24 12949 SCNN1A-9101 UGAGGGCCUAGAGUGAGA 18 12950 SCNN1A-9102 CUGAGGGCCUAGAGUGAGA 19 12951 SCNN1A-5188 GCUGAGGGCCUAGAGUGAGA 20 9037 SCNN1A-9103 AGCUGAGGGCCUAGAGUGAGA 21 12952 SCNN1A-9104 GAGCUGAGGGCCUAGAGUGAGA 22 12953 SCNN1A-9105 GGAGCUGAGGGCCUAGAGUGAGA 23 12954 SCNN1A-9106 UGGAGCUGAGGGCCUAGAGUGAGA 24 12955 SCNN1A-9107 AAACAGAAGGCAGAUAGA 18 12956 SCNN1A-9108 GAAACAGAAGGCAGAUAGA 19 12957 SCNN1A-9109 AGAAACAGAAGGCAGAUAGA 20 12958 SCNN1A-9110 GAGAAACAGAAGGCAGAUAGA 21 12959 SCNN1A-9111 AGAGAAACAGAAGGCAGAUAGA 22 12960 SCNN1A-9112 AAGAGAAACAGAAGGCAGAUAGA 23 12961 SCNN1A-9113 AAAGAGAAACAGAAGGCAGAUAGA 24 12962 SCNN1A-9114 UGGAGCUGAGGGCCUAGA 18 12963 SCNN1A-9115 CUGGAGCUGAGGGCCUAGA 19 12964 SCNN1A-9116 GCUGGAGCUGAGGGCCUAGA 20 12965 SCNN1A-9117 GGCUGGAGCUGAGGGCCUAGA 21 12966 SCNN1A-9118 AGGCUGGAGCUGAGGGCCUAGA 22 12967 SCNN1A-9119 GAGGCUGGAGCUGAGGGCCUAGA 23 12968 SCNN1A-9120 AGAGGCUGGAGCUGAGGGCCUAGA 24 12969 SCNN1A-9121 AAGAGAGGCAGGAUUAGA 18 12970 SCNN1A-9122 GAAGAGAGGCAGGAUUAGA 19 12971 SCNN1A-9123 GGAAGAGAGGCAGGAUUAGA 20 12972 SCNN1A-9124 AGGAAGAGAGGCAGGAUUAGA 21 12973 SCNN1A-9125 GAGGAAGAGAGGCAGGAUUAGA 22 12974 SCNN1A-9126 AGAGGAAGAGAGGCAGGAUUAGA 23 12975 SCNN1A-9127 GAGAGGAAGAGAGGCAGGAUUAGA 24 12976 SCNN1A-9128 AGGAAGAAGACCAAAGGA 18 12977 SCNN1A-9129 GAGGAAGAAGACCAAAGGA 19 12978 SCNN1A-5873 GGAGGAAGAAGACCAAAGGA 20 9722 SCNN1A-9130 UGGAGGAAGAAGACCAAAGGA 21 12979 SCNN1A-9131 CUGGAGGAAGAAGACCAAAGGA 22 12980 SCNN1A-9132 CCUGGAGGAAGAAGACCAAAGGA 23 12981 SCNN1A-9133 UCCUGGAGGAAGAAGACCAAAGGA 24 12982 SCNN1A-9134 GGCGAGGAAUCAGCAGGA 18 12983 SCNN1A-9135 UGGCGAGGAAUCAGCAGGA 19 12984 SCNN1A-9136 GUGGCGAGGAAUCAGCAGGA 20 12985 SCNN1A-9137 GGUGGCGAGGAAUCAGCAGGA 21 12986 SCNN1A-9138 GGGUGGCGAGGAAUCAGCAGGA 22 12987 SCNN1A-9139 GGGGUGGCGAGGAAUCAGCAGGA 23 12988 SCNN1A-9140 GGGGGUGGCGAGGAAUCAGCAGGA 24 12989 SCNN1A-9141 UGGAGGAGGGAGGGAGGA 18 12990 SCNN1A-9142 GUGGAGGAGGGAGGGAGGA 19 12991 SCNN1A-9143 GGUGGAGGAGGGAGGGAGGA 20 12992 SCNN1A-9144 AGGUGGAGGAGGGAGGGAGGA 21 12993 SCNN1A-9145 AAGGUGGAGGAGGGAGGGAGGA 22 12994 SCNN1A-9146 AAAGGUGGAGGAGGGAGGGAGGA 23 12995 SCNN1A-9147 GAAAGGUGGAGGAGGGAGGGAGGA 24 12996 SCNN1A-9148 UCCAGGAAAGGUGGAGGA 18 12997 SCNN1A-9149 CUCCAGGAAAGGUGGAGGA 19 12998 SCNN1A-5877 GCUCCAGGAAAGGUGGAGGA 20 9726 SCNN1A-9150 GGCUCCAGGAAAGGUGGAGGA 21 12999 SCNN1A-9151 UGGCUCCAGGAAAGGUGGAGGA 22 13000 SCNN1A-9152 CUGGCUCCAGGAAAGGUGGAGGA 23 13001 SCNN1A-9153 GCUGGCUCCAGGAAAGGUGGAGGA 24 13002 SCNN1A-9154 AAGGCAGAUAGAGAGGGA 18 13003 SCNN1A-9155 GAAGGCAGAUAGAGAGGGA 19 13004 SCNN1A-9156 AGAAGGCAGAUAGAGAGGGA 20 13005 SCNN1A-9157 CAGAAGGCAGAUAGAGAGGGA 21 13006 SCNN1A-9158 ACAGAAGGCAGAUAGAGAGGGA 22 13007 SCNN1A-9159 AACAGAAGGCAGAUAGAGAGGGA 23 13008 SCNN1A-9160 AAACAGAAGGCAGAUAGAGAGGGA 24 13009 SCNN1A-9161 GGAAAGGUGGAGGAGGGA 18 13010 SCNN1A-9162 AGGAAAGGUGGAGGAGGGA 19 13011 SCNN1A-6095 CAGGAAAGGUGGAGGAGGGA 20 9944 SCNN1A-9163 CCAGGAAAGGUGGAGGAGGGA 21 13012 SCNN1A-9164 UCCAGGAAAGGUGGAGGAGGGA 22 13013 SCNN1A-9165 CUCCAGGAAAGGUGGAGGAGGGA 23 13014 SCNN1A-9166 GCUCCAGGAAAGGUGGAGGAGGGA 24 13015 SCNN1A-9167 GGCAAGGCAAGGGGGGGA 18 13016 SCNN1A-9168 GGGCAAGGCAAGGGGGGGA 19 13017 SCNN1A-9169 GGGGCAAGGCAAGGGGGGGA 20 13018 SCNN1A-9170 GGGGGCAAGGCAAGGGGGGGA 21 13019 SCNN1A-9171 AGGGGGCAAGGCAAGGGGGGGA 22 13020 SCNN1A-9172 GAGGGGGCAAGGCAAGGGGGGGA 23 13021 SCNN1A-9173 AGAGGGGGCAAGGCAAGGGGGGGA 24 13022 SCNN1A-1820 GUUCCAGGGGUGAUGGGA 18 5669 SCNN1A-1821 GGUUCCAGGGGUGAUGGGA 19 5670 SCNN1A-1822 GGGUUCCAGGGGUGAUGGGA 20 5671 SCNN1A-1823 CGGGUUCCAGGGGUGAUGGGA 21 5672 SCNN1A-1824 UCGGGUUCCAGGGGUGAUGGGA 22 5673 SCNN1A-1825 CUCGGGUUCCAGGGGUGAUGGGA 23 5674 SCNN1A-1826 ACUCGGGUUCCAGGGGUGAUGGGA 24 5675 SCNN1A-9174 UCCAGCCGCAACCUGGGA 18 13023 SCNN1A-9175 GUCCAGCCGCAACCUGGGA 19 13024 SCNN1A-9176 AGUCCAGCCGCAACCUGGGA 20 13025 SCNN1A-9177 CAGUCCAGCCGCAACCUGGGA 21 13026 SCNN1A-9178 CCAGUCCAGCCGCAACCUGGGA 22 13027 SCNN1A-9179 CCCAGUCCAGCCGCAACCUGGGA 23 13028 SCNN1A-9180 UCCCAGUCCAGCCGCAACCUGGGA 24 13029 SCNN1A-9181 CACGGGCUCUGUGUGGGA 18 13030 SCNN1A-9182 CCACGGGCUCUGUGUGGGA 19 13031 SCNN1A-9183 UCCACGGGCUCUGUGUGGGA 20 13032 SCNN1A-9184 AUCCACGGGCUCUGUGUGGGA 21 13033 SCNN1A-9185 AAUCCACGGGCUCUGUGUGGGA 22 13034 SCNN1A-9186 GAAUCCACGGGCUCUGUGUGGGA 23 13035 SCNN1A-9187 CGAAUCCACGGGCUCUGUGUGGGA 24 13036 SCNN1A-1827 CAUACCAGGUCUCAUGGA 18 5676 SCNN1A-1828 CCAUACCAGGUCUCAUGGA 19 5677 SCNN1A-3 CCCAUACCAGGUCUCAUGGA 20 556 SCNN1A-1829 GCCCAUACCAGGUCUCAUGGA 21 5678 SCNN1A-1830 AGCCCAUACCAGGUCUCAUGGA 22 5679 SCNN1A-1831 CAGCCCAUACCAGGUCUCAUGGA 23 5680 SCNN1A-1832 GCAGCCCAUACCAGGUCUCAUGGA 24 5681 SCNN1A-9188 CUGCCAGAUUCAACUGGA 18 13037 SCNN1A-9189 GCUGCCAGAUUCAACUGGA 19 13038 SCNN1A-9190 GGCUGCCAGAUUCAACUGGA 20 13039 SCNN1A-9191 UGGCUGCCAGAUUCAACUGGA 21 13040 SCNN1A-9192 UUGGCUGCCAGAUUCAACUGGA 22 13041 SCNN1A-9193 UUUGGCUGCCAGAUUCAACUGGA 23 13042 SCNN1A-9194 GUUUGGCUGCCAGAUUCAACUGGA 24 13043 SCNN1A-9195 UGUCUGCUGGCUUGUGGA 18 13044 SCNN1A-9196 UUGUCUGCUGGCUUGUGGA 19 13045 SCNN1A-5552 UUUGUCUGCUGGCUUGUGGA 20 9401 SCNN1A-9197 CUUUGUCUGCUGGCUUGUGGA 21 13046 SCNN1A-9198 CCUUUGUCUGCUGGCUUGUGGA 22 13047 SCNN1A-9199 GCCUUUGUCUGCUGGCUUGUGGA 23 13048 SCNN1A-9200 GGCCUUUGUCUGCUGGCUUGUGGA 24 13049 SCNN1A-9201 UGCUGCAUUAAGUUUGGA 18 13050 SCNN1A-9202 UUGCUGCAUUAAGUUUGGA 19 13051 SCNN1A-9203 UUUGCUGCAUUAAGUUUGGA 20 13052 SCNN1A-9204 UUUUGCUGCAUUAAGUUUGGA 21 13053 SCNN1A-9205 CUUUUGCUGCAUUAAGUUUGGA 22 13054 SCNN1A-9206 CCUUUUGCUGCAUUAAGUUUGGA 23 13055 SCNN1A-9207 UCCUUUUGCUGCAUUAAGUUUGGA 24 13056 SCNN1A-1839 CCACUCCGGGGCUCAUGA 18 5688 SCNN1A-1840 UCCACUCCGGGGCUCAUGA 19 5689 SCNN1A-400 AUCCACUCCGGGGCUCAUGA 20 4249 SCNN1A-1841 AAUCCACUCCGGGGCUCAUGA 21 5690 SCNN1A-1842 CAAUCCACUCCGGGGCUCAUGA 22 5691 SCNN1A-1843 CCAAUCCACUCCGGGGCUCAUGA 23 5692 SCNN1A-1844 CCCAAUCCACUCCGGGGCUCAUGA 24 5693 SCNN1A-9208 GCUGAGGGCCUAGAGUGA 18 13057 SCNN1A-9209 AGCUGAGGGCCUAGAGUGA 19 13058 SCNN1A-9210 GAGCUGAGGGCCUAGAGUGA 20 13059 SCNN1A-9211 GGAGCUGAGGGCCUAGAGUGA 21 13060 SCNN1A-9212 UGGAGCUGAGGGCCUAGAGUGA 22 13061 SCNN1A-9213 CUGGAGCUGAGGGCCUAGAGUGA 23 13062 SCNN1A-9214 GCUGGAGCUGAGGGCCUAGAGUGA 24 13063 SCNN1A-9215 GGCUCUGUGUGGGAGUGA 18 13064 SCNN1A-9216 GGGCUCUGUGUGGGAGUGA 19 13065 SCNN1A-5555 CGGGCUCUGUGUGGGAGUGA 20 9404 SCNN1A-9217 ACGGGCUCUGUGUGGGAGUGA 21 13066 SCNN1A-9218 CACGGGCUCUGUGUGGGAGUGA 22 13067 SCNN1A-9219 CCACGGGCUCUGUGUGGGAGUGA 23 13068 SCNN1A-9220 UCCACGGGCUCUGUGUGGGAGUGA 24 13069 SCNN1A-9221 GCUGCUCCCACUUAGUGA 18 13070 SCNN1A-9222 CGCUGCUCCCACUUAGUGA 19 13071 SCNN1A-9223 GCGCUGCUCCCACUUAGUGA 20 13072 SCNN1A-9224 UGCGCUGCUCCCACUUAGUGA 21 13073 SCNN1A-9225 GUGCGCUGCUCCCACUUAGUGA 22 13074 SCNN1A-9226 AGUGCGCUGCUCCCACUUAGUGA 23 13075 SCNN1A-9227 GAGUGCGCUGCUCCCACUUAGUGA 24 13076 SCNN1A-9228 GCUGCACCUGUCAGGUGA 18 13077 SCNN1A-9229 CGCUGCACCUGUCAGGUGA 19 13078 SCNN1A-5556 CCGCUGCACCUGUCAGGUGA 20 9405 SCNN1A-9230 GCCGCUGCACCUGUCAGGUGA 21 13079 SCNN1A-9231 GGCCGCUGCACCUGUCAGGUGA 22 13080 SCNN1A-9232 AGGCCGCUGCACCUGUCAGGUGA 23 13081 SCNN1A-9233 CAGGCCGCUGCACCUGUCAGGUGA 24 13082 SCNN1A-1845 CUCGGGUUCCAGGGGUGA 18 5694 SCNN1A-1846 ACUCGGGUUCCAGGGGUGA 19 5695 SCNN1A-401 CACUCGGGUUCCAGGGGUGA 20 4250 SCNN1A-1847 UCACUCGGGUUCCAGGGGUGA 21 5696 SCNN1A-1848 CUCACUCGGGUUCCAGGGGUGA 22 5697 SCNN1A-1849 CCUCACUCGGGUUCCAGGGGUGA 23 5698 SCNN1A-1850 GCCUCACUCGGGUUCCAGGGGUGA 24 5699 SCNN1A-9234 AGAAACAGAAGGCAGAUA 18 13083 SCNN1A-9235 GAGAAACAGAAGGCAGAUA 19 13084 SCNN1A-9236 AGAGAAACAGAAGGCAGAUA 20 13085 SCNN1A-9237 AAGAGAAACAGAAGGCAGAUA 21 13086 SCNN1A-9238 AAAGAGAAACAGAAGGCAGAUA 22 13087 SCNN1A-9239 CAAAGAGAAACAGAAGGCAGAUA 23 13088 SCNN1A-9240 CCAAAGAGAAACAGAAGGCAGAUA 24 13089 SCNN1A-9241 CCUUUAAUUGAGAUGCUA 18 13090 SCNN1A-9242 ACCUUUAAUUGAGAUGCUA 19 13091 SCNN1A-9243 CACCUUUAAUUGAGAUGCUA 20 13092 SCNN1A-9244 UCACCUUUAAUUGAGAUGCUA 21 13093 SCNN1A-9245 CUCACCUUUAAUUGAGAUGCUA 22 13094 SCNN1A-9246 GCUCACCUUUAAUUGAGAUGCUA 23 13095 SCNN1A-9247 UGCUCACCUUUAAUUGAGAUGCUA 24 13096 SCNN1A-9248 AGAGGAGAGGCCGUUCUA 18 13097 SCNN1A-9249 CAGAGGAGAGGCCGUUCUA 19 13098 SCNN1A-5199 GCAGAGGAGAGGCCGUUCUA 20 9048 SCNN1A-9250 AGCAGAGGAGAGGCCGUUCUA 21 13099 SCNN1A-9251 AAGCAGAGGAGAGGCCGUUCUA 22 13100 SCNN1A-9252 GAAGCAGAGGAGAGGCCGUUCUA 23 13101 SCNN1A-9253 GGAAGCAGAGGAGAGGCCGUUCUA 24 13102 SCNN1A-9254 GGAAGAGAGGCAGGAUUA 18 13103 SCNN1A-9255 AGGAAGAGAGGCAGGAUUA 19 13104 SCNN1A-9256 GAGGAAGAGAGGCAGGAUUA 20 13105 SCNN1A-9257 AGAGGAAGAGAGGCAGGAUUA 21 13106 SCNN1A-9258 GAGAGGAAGAGAGGCAGGAUUA 22 13107 SCNN1A-9259 GGAGAGGAAGAGAGGCAGGAUUA 23 13108 SCNN1A-9260 GGGAGAGGAAGAGAGGCAGGAUUA 24 13109 SCNN1A-9261 GUGCGCUGCUCCCACUUA 18 13110 SCNN1A-9262 AGUGCGCUGCUCCCACUUA 19 13111 SCNN1A-9263 GAGUGCGCUGCUCCCACUUA 20 13112 SCNN1A-9264 UGAGUGCGCUGCUCCCACUUA 21 13113 SCNN1A-9265 CUGAGUGCGCUGCUCCCACUUA 22 13114 SCNN1A-9266 CCUGAGUGCGCUGCUCCCACUUA 23 13115 SCNN1A-9267 ACCUGAGUGCGCUGCUCCCACUUA 24 13116 SCNN1A-9268 GAGGUGCUAGGACAAAAC 18 13117 SCNN1A-9269 GGAGGUGCUAGGACAAAAC 19 13118 SCNN1A-9270 GGGAGGUGCUAGGACAAAAC 20 13119 SCNN1A-9271 AGGGAGGUGCUAGGACAAAAC 21 13120 SCNN1A-9272 AAGGGAGGUGCUAGGACAAAAC 22 13121 SCNN1A-9273 AAAGGGAGGUGCUAGGACAAAAC 23 13122 SCNN1A-9274 GAAAGGGAGGUGCUAGGACAAAAC 24 13123 SCNN1A-9275 UCCCAGUCCAGCCGCAAC 18 13124 SCNN1A-9276 GUCCCAGUCCAGCCGCAAC 19 13125 SCNN1A-9277 AGUCCCAGUCCAGCCGCAAC 20 13126 SCNN1A-9278 CAGUCCCAGUCCAGCCGCAAC 21 13127 SCNN1A-9279 CCAGUCCCAGUCCAGCCGCAAC 22 13128 SCNN1A-9280 ACCAGUCCCAGUCCAGCCGCAAC 23 13129 SCNN1A-9281 AACCAGUCCCAGUCCAGCCGCAAC 24 13130 SCNN1A-9282 UUGGCUGCCAGAUUCAAC 18 13131 SCNN1A-9283 UUUGGCUGCCAGAUUCAAC 19 13132 SCNN1A-5202 GUUUGGCUGCCAGAUUCAAC 20 9051 SCNN1A-9284 GGUUUGGCUGCCAGAUUCAAC 21 13133 SCNN1A-9285 AGGUUUGGCUGCCAGAUUCAAC 22 13134 SCNN1A-9286 GAGGUUUGGCUGCCAGAUUCAAC 23 13135 SCNN1A-9287 AGAGGUUUGGCUGCCAGAUUCAAC 24 13136 SCNN1A-9288 UAGCUCCUGGAAGCACAC 18 13137 SCNN1A-9289 CUAGCUCCUGGAAGCACAC 19 13138 SCNN1A-9290 UCUAGCUCCUGGAAGCACAC 20 13139 SCNN1A-9291 CUCUAGCUCCUGGAAGCACAC 21 13140 SCNN1A-9292 CCUCUAGCUCCUGGAAGCACAC 22 13141 SCNN1A-9293 GCCUCUAGCUCCUGGAAGCACAC 23 13142 SCNN1A-9294 AGCCUCUAGCUCCUGGAAGCACAC 24 13143 SCNN1A-9295 UUUCACAUCCAGGUGCAC 18 13144 SCNN1A-9296 CUUUCACAUCCAGGUGCAC 19 13145 SCNN1A-9297 GCUUUCACAUCCAGGUGCAC 20 13146 SCNN1A-9298 GGCUUUCACAUCCAGGUGCAC 21 13147 SCNN1A-9299 CGGCUUUCACAUCCAGGUGCAC 22 13148 SCNN1A-9300 CCGGCUUUCACAUCCAGGUGCAC 23 13149 SCNN1A-9301 CCCGGCUUUCACAUCCAGGUGCAC 24 13150 SCNN1A-9302 CCUAGCCCCCAGCUUCAC 18 13151 SCNN1A-9303 GCCUAGCCCCCAGCUUCAC 19 13152 SCNN1A-9304 CGCCUAGCCCCCAGCUUCAC 20 13153 SCNN1A-9305 CCGCCUAGCCCCCAGCUUCAC 21 13154 SCNN1A-9306 CCCGCCUAGCCCCCAGCUUCAC 22 13155 SCNN1A-9307 CCCCGCCUAGCCCCCAGCUUCAC 23 13156 SCNN1A-9308 GCCCCGCCUAGCCCCCAGCUUCAC 24 13157 SCNN1A-9309 GCAGGAAAGAGGAGGGAC 18 13158 SCNN1A-9310 AGCAGGAAAGAGGAGGGAC 19 13159 SCNN1A-9311 CAGCAGGAAAGAGGAGGGAC 20 13160 SCNN1A-9312 UCAGCAGGAAAGAGGAGGGAC 21 13161 SCNN1A-9313 AUCAGCAGGAAAGAGGAGGGAC 22 13162 SCNN1A-9314 AAUCAGCAGGAAAGAGGAGGGAC 23 13163 SCNN1A-9315 GAAUCAGCAGGAAAGAGGAGGGAC 24 13164 SCNN1A-1863 GUGGGCGCAGGGUGGGAC 18 5712 SCNN1A-1864 UGUGGGCGCAGGGUGGGAC 19 5713 SCNN1A-1865 AUGUGGGCGCAGGGUGGGAC 20 5714 SCNN1A-1866 AAUGUGGGCGCAGGGUGGGAC 21 5715 SCNN1A-1867 GAAUGUGGGCGCAGGGUGGGAC 22 5716 SCNN1A-1868 AGAAUGUGGGCGCAGGGUGGGAC 23 5717 SCNN1A-1869 GAGAAUGUGGGCGCAGGGUGGGAC 24 5718 SCNN1A-9316 CCCAGUCCAGCCGCAACC 18 13165 SCNN1A-9317 UCCCAGUCCAGCCGCAACC 19 13166 SCNN1A-5213 GUCCCAGUCCAGCCGCAACC 20 9062 SCNN1A-9318 AGUCCCAGUCCAGCCGCAACC 21 13167 SCNN1A-9319 CAGUCCCAGUCCAGCCGCAACC 22 13168 SCNN1A-9320 CCAGUCCCAGUCCAGCCGCAACC 23 13169 SCNN1A-9321 ACCAGUCCCAGUCCAGCCGCAACC 24 13170 SCNN1A-9322 AGGAGAUAACCCAGCACC 18 13171 SCNN1A-9323 AAGGAGAUAACCCAGCACC 19 13172 SCNN1A-9324 CAAGGAGAUAACCCAGCACC 20 13173 SCNN1A-9325 CCAAGGAGAUAACCCAGCACC 21 13174 SCNN1A-9326 GCCAAGGAGAUAACCCAGCACC 22 13175 SCNN1A-9327 AGCCAAGGAGAUAACCCAGCACC 23 13176 SCNN1A-9328 GAGCCAAGGAGAUAACCCAGCACC 24 13177 SCNN1A-9329 CAGGAAAGAGGAGGGACC 18 13178 SCNN1A-9330 GCAGGAAAGAGGAGGGACC 19 13179 SCNN1A-5571 AGCAGGAAAGAGGAGGGACC 20 9420 SCNN1A-9331 CAGCAGGAAAGAGGAGGGACC 21 13180 SCNN1A-9332 UCAGCAGGAAAGAGGAGGGACC 22 13181 SCNN1A-9333 AUCAGCAGGAAAGAGGAGGGACC 23 13182 SCNN1A-9334 AAUCAGCAGGAAAGAGGAGGGACC 24 13183 SCNN1A-9335 CACAGACCAGGUUGGACC 18 13184 SCNN1A-9336 CCACAGACCAGGUUGGACC 19 13185 SCNN1A-9337 GCCACAGACCAGGUUGGACC 20 13186 SCNN1A-9338 AGCCACAGACCAGGUUGGACC 21 13187 SCNN1A-9339 AAGCCACAGACCAGGUUGGACC 22 13188 SCNN1A-9340 GAAGCCACAGACCAGGUUGGACC 23 13189 SCNN1A-9341 GGAAGCCACAGACCAGGUUGGACC 24 13190 SCNN1A-9342 GCGCUAAGUAGAUAGCCC 18 13191 SCNN1A-9343 AGCGCUAAGUAGAUAGCCC 19 13192 SCNN1A-9344 AAGCGCUAAGUAGAUAGCCC 20 13193 SCNN1A-9345 AAAGCGCUAAGUAGAUAGCCC 21 13194 SCNN1A-9346 AAAAGCGCUAAGUAGAUAGCCC 22 13195 SCNN1A-9347 CAAAAGCGCUAAGUAGAUAGCCC 23 13196 SCNN1A-9348 GCAAAAGCGCUAAGUAGAUAGCCC 24 13197 SCNN1A-9349 CUGCCUCCUGUGGGGCCC 18 13198 SCNN1A-9350 GCUGCCUCCUGUGGGGCCC 19 13199 SCNN1A-9351 GGCUGCCUCCUGUGGGGCCC 20 13200 SCNN1A-9352 GGGCUGCCUCCUGUGGGGCCC 21 13201 SCNN1A-9353 UGGGCUGCCUCCUGUGGGGCCC 22 13202 SCNN1A-9354 CUGGGCUGCCUCCUGUGGGGCCC 23 13203 SCNN1A-9355 UCUGGGCUGCCUCCUGUGGGGCCC 24 13204 SCNN1A-9356 CUCCCAGUUCACCUGCCC 18 13205 SCNN1A-9357 ACUCCCAGUUCACCUGCCC 19 13206 SCNN1A-9358 UACUCCCAGUUCACCUGCCC 20 13207 SCNN1A-9359 GUACUCCCAGUUCACCUGCCC 21 13208 SCNN1A-9360 AGUACUCCCAGUUCACCUGCCC 22 13209 SCNN1A-9361 CAGUACUCCCAGUUCACCUGCCC 23 13210 SCNN1A-9362 CCAGUACUCCCAGUUCACCUGCCC 24 13211 SCNN1A-9363 GCUGACCUGUGGGUGCCC 18 13212 SCNN1A-9364 GGCUGACCUGUGGGUGCCC 19 13213 SCNN1A-9365 AGGCUGACCUGUGGGUGCCC 20 13214 SCNN1A-9366 GAGGCUGACCUGUGGGUGCCC 21 13215 SCNN1A-9367 UGAGGCUGACCUGUGGGUGCCC 22 13216 SCNN1A-9368 GUGAGGCUGACCUGUGGGUGCCC 23 13217 SCNN1A-9369 GGUGAGGCUGACCUGUGGGUGCCC 24 13218 SCNN1A-9370 AGACCUUUUCACAGAGCC 18 13219 SCNN1A-9371 GAGACCUUUUCACAGAGCC 19 13220 SCNN1A-9372 AGAGACCUUUUCACAGAGCC 20 13221 SCNN1A-9373 CAGAGACCUUUUCACAGAGCC 21 13222 SCNN1A-9374 GCAGAGACCUUUUCACAGAGCC 22 13223 SCNN1A-9375 UGCAGAGACCUUUUCACAGAGCC 23 13224 SCNN1A-9376 GUGCAGAGACCUUUUCACAGAGCC 24 13225 SCNN1A-1876 GAGAGGGCACUCAGGGCC 18 5725 SCNN1A-1877 GGAGAGGGCACUCAGGGCC 19 5726 SCNN1A-1878 GGGAGAGGGCACUCAGGGCC 20 5727 SCNN1A-1879 UGGGAGAGGGCACUCAGGGCC 21 5728 SCNN1A-1880 AUGGGAGAGGGCACUCAGGGCC 22 5729 SCNN1A-1881 GAUGGGAGAGGGCACUCAGGGCC 23 5730 SCNN1A-1882 UGAUGGGAGAGGGCACUCAGGGCC 24 5731 SCNN1A-1889 UGGGACAUGGGCAUGGCC 18 5738 SCNN1A-1890 GUGGGACAUGGGCAUGGCC 19 5739 SCNN1A-347 GGUGGGACAUGGGCAUGGCC 20 4196 SCNN1A-1891 GGGUGGGACAUGGGCAUGGCC 21 5740 SCNN1A-1892 AGGGUGGGACAUGGGCAUGGCC 22 5741 SCNN1A-1893 CAGGGUGGGACAUGGGCAUGGCC 23 5742 SCNN1A-1894 GCAGGGUGGGACAUGGGCAUGGCC 24 5743 SCNN1A-9377 CAGAGAGCAGACGAAUCC 18 13226 SCNN1A-9378 CCAGAGAGCAGACGAAUCC 19 13227 SCNN1A-9379 CCCAGAGAGCAGACGAAUCC 20 13228 SCNN1A-9380 ACCCAGAGAGCAGACGAAUCC 21 13229 SCNN1A-9381 CACCCAGAGAGCAGACGAAUCC 22 13230 SCNN1A-9382 GCACCCAGAGAGCAGACGAAUCC 23 13231 SCNN1A-9383 AGCACCCAGAGAGCAGACGAAUCC 24 13232 SCNN1A-9384 GAGCUGAGACACAGAUCC 18 13233 SCNN1A-9385 GGAGCUGAGACACAGAUCC 19 13234 SCNN1A-5588 AGGAGCUGAGACACAGAUCC 20 9437 SCNN1A-9386 CAGGAGCUGAGACACAGAUCC 21 13235 SCNN1A-9387 GCAGGAGCUGAGACACAGAUCC 22 13236 SCNN1A-9388 GGCAGGAGCUGAGACACAGAUCC 23 13237 SCNN1A-9389 AGGCAGGAGCUGAGACACAGAUCC 24 13238 SCNN1A-9390 CAGAAAACUGAUUUAUCC 18 13239 SCNN1A-9391 UCAGAAAACUGAUUUAUCC 19 13240 SCNN1A-9392 CUCAGAAAACUGAUUUAUCC 20 13241 SCNN1A-9393 CCUCAGAAAACUGAUUUAUCC 21 13242 SCNN1A-9394 ACCUCAGAAAACUGAUUUAUCC 22 13243 SCNN1A-9395 AACCUCAGAAAACUGAUUUAUCC 23 13244 SCNN1A-9396 UAACCUCAGAAAACUGAUUUAUCC 24 13245 SCNN1A-9397 GAGGCAGCCCAGACCUCC 18 13246 SCNN1A-9398 GGAGGCAGCCCAGACCUCC 19 13247 SCNN1A-5591 UGGAGGCAGCCCAGACCUCC 20 9440 SCNN1A-9399 CUGGAGGCAGCCCAGACCUCC 21 13248 SCNN1A-9400 GCUGGAGGCAGCCCAGACCUCC 22 13249 SCNN1A-9401 AGCUGGAGGCAGCCCAGACCUCC 23 13250 SCNN1A-9402 AAGCUGGAGGCAGCCCAGACCUCC 24 13251 SCNN1A-9403 ACGAAUUUCUCCUCCUCC 18 13252 SCNN1A-9404 AACGAAUUUCUCCUCCUCC 19 13253 SCNN1A-9405 CAACGAAUUUCUCCUCCUCC 20 13254 SCNN1A-9406 UCAACGAAUUUCUCCUCCUCC 21 13255 SCNN1A-9407 AUCAACGAAUUUCUCCUCCUCC 22 13256 SCNN1A-9408 CAUCAACGAAUUUCUCCUCCUCC 23 13257 SCNN1A-9409 CCAUCAACGAAUUUCUCCUCCUCC 24 13258 SCNN1A-9410 UGCUGAGCCUCUAGCUCC 18 13259 SCNN1A-9411 UUGCUGAGCCUCUAGCUCC 19 13260 SCNN1A-5594 CUUGCUGAGCCUCUAGCUCC 20 9443 SCNN1A-9412 ACUUGCUGAGCCUCUAGCUCC 21 13261 SCNN1A-9413 CACUUGCUGAGCCUCUAGCUCC 22 13262 SCNN1A-9414 CCACUUGCUGAGCCUCUAGCUCC 23 13263 SCNN1A-9415 CCCACUUGCUGAGCCUCUAGCUCC 24 13264 SCNN1A-9416 CGCAGGUCUGCUGGCUCC 18 13265 SCNN1A-9417 CCGCAGGUCUGCUGGCUCC 19 13266 SCNN1A-5595 CCCGCAGGUCUGCUGGCUCC 20 9444 SCNN1A-9418 UCCCGCAGGUCUGCUGGCUCC 21 13267 SCNN1A-9419 CUCCCGCAGGUCUGCUGGCUCC 22 13268 SCNN1A-9420 ACUCCCGCAGGUCUGCUGGCUCC 23 13269 SCNN1A-9421 AACUCCCGCAGGUCUGCUGGCUCC 24 13270 SCNN1A-9422 CCUGGAGCCCUGCAGUCC 18 13271 SCNN1A-9423 UCCUGGAGCCCUGCAGUCC 19 13272 SCNN1A-6114 CUCCUGGAGCCCUGCAGUCC 20 9963 SCNN1A-9424 CCUCCUGGAGCCCUGCAGUCC 21 13273 SCNN1A-9425 ACCUCCUGGAGCCCUGCAGUCC 22 13274 SCNN1A-9426 GACCUCCUGGAGCCCUGCAGUCC 23 13275 SCNN1A-9427 AGACCUCCUGGAGCCCUGCAGUCC 24 13276 SCNN1A-9428 AAAAAGAACAGAAUGUCC 18 13277 SCNN1A-9429 AAAAAAGAACAGAAUGUCC 19 13278 SCNN1A-9430 UAAAAAAGAACAGAAUGUCC 20 13279 SCNN1A-9431 GUAAAAAAGAACAGAAUGUCC 21 13280 SCNN1A-9432 UGUAAAAAAGAACAGAAUGUCC 22 13281 SCNN1A-9433 GUGUAAAAAAGAACAGAAUGUCC 23 13282 SCNN1A-9434 AGUGUAAAAAAGAACAGAAUGUCC 24 13283 SCNN1A-9435 AAUCCAGCUGUCCCUUCC 18 13284 SCNN1A-9436 AAAUCCAGCUGUCCCUUCC 19 13285 SCNN1A-9437 AAAAUCCAGCUGUCCCUUCC 20 13286 SCNN1A-9438 AAAAAUCCAGCUGUCCCUUCC 21 13287 SCNN1A-9439 GAAAAAUCCAGCUGUCCCUUCC 22 13288 SCNN1A-9440 AGAAAAAUCCAGCUGUCCCUUCC 23 13289 SCNN1A-9441 AAGAAAAAUCCAGCUGUCCCUUCC 24 13290 SCNN1A-9442 CCCCCUUGCUCUCCUUCC 18 13291 SCNN1A-9443 CCCCCCUUGCUCUCCUUCC 19 13292 SCNN1A-5598 UCCCCCCUUGCUCUCCUUCC 20 9447 SCNN1A-9444 CUCCCCCCUUGCUCUCCUUCC 21 13293 SCNN1A-9445 ACUCCCCCCUUGCUCUCCUUCC 22 13294 SCNN1A-9446 GACUCCCCCCUUGCUCUCCUUCC 23 13295 SCNN1A-9447 GGACUCCCCCCUUGCUCUCCUUCC 24 13296 SCNN1A-1895 UCAUGAAGGGGAACAAGC 18 5744 SCNN1A-1896 CUCAUGAAGGGGAACAAGC 19 5745 SCNN1A-176 GCUCAUGAAGGGGAACAAGC 20 811 SCNN1A-1897 GGCUCAUGAAGGGGAACAAGC 21 5746 SCNN1A-1898 GGGCUCAUGAAGGGGAACAAGC 22 5747 SCNN1A-1901 GGGGCUCAUGAAGGGGAACAAGC 23 5750 SCNN1A-1902 CGGGGCUCAUGAAGGGGAACAAGC 24 5751 SCNN1A-1903 UCAUGGAGGGGAACAAGC 18 5752 SCNN1A-1904 CUCAUGGAGGGGAACAAGC 19 5753 SCNN1A-5 UCUCAUGGAGGGGAACAAGC 20 557 SCNN1A-1905 GUCUCAUGGAGGGGAACAAGC 21 5754 SCNN1A-1906 GGUCUCAUGGAGGGGAACAAGC 22 5755 SCNN1A-1907 AGGUCUCAUGGAGGGGAACAAGC 23 5756 SCNN1A-1908 CAGGUCUCAUGGAGGGGAACAAGC 24 5757 SCNN1A-9448 AACCUGGGAGUGGGAAGC 18 13297 SCNN1A-9449 CAACCUGGGAGUGGGAAGC 19 13298 SCNN1A-5228 GCAACCUGGGAGUGGGAAGC 20 9077 SCNN1A-9450 CGCAACCUGGGAGUGGGAAGC 21 13299 SCNN1A-9451 CCGCAACCUGGGAGUGGGAAGC 22 13300 SCNN1A-9452 GCCGCAACCUGGGAGUGGGAAGC 23 13301 SCNN1A-9453 AGCCGCAACCUGGGAGUGGGAAGC 24 13302 SCNN1A-1909 AGCAGUAUCAAGGUAAGC 18 5758 SCNN1A-1910 GAGCAGUAUCAAGGUAAGC 19 5759 SCNN1A-1911 UGAGCAGUAUCAAGGUAAGC 20 5760 SCNN1A-1912 AUGAGCAGUAUCAAGGUAAGC 21 5761 SCNN1A-1913 CAUGAGCAGUAUCAAGGUAAGC 22 5762 SCNN1A-1914 UCAUGAGCAGUAUCAAGGUAAGC 23 5763 SCNN1A-1915 AUCAUGAGCAGUAUCAAGGUAAGC 24 5764 SCNN1A-9454 ACAGAAUCAGGACACAGC 18 13303 SCNN1A-9455 GACAGAAUCAGGACACAGC 19 13304 SCNN1A-9456 AGACAGAAUCAGGACACAGC 20 13305 SCNN1A-9457 GAGACAGAAUCAGGACACAGC 21 13306 SCNN1A-9458 AGAGACAGAAUCAGGACACAGC 22 13307 SCNN1A-9459 CAGAGACAGAAUCAGGACACAGC 23 13308 SCNN1A-9460 GCAGAGACAGAAUCAGGACACAGC 24 13309 SCNN1A-9461 CAACUCUGUGACCACAGC 18 13310 SCNN1A-9462 GCAACUCUGUGACCACAGC 19 13311 SCNN1A-5599 UGCAACUCUGUGACCACAGC 20 9448 SCNN1A-9463 CUGCAACUCUGUGACCACAGC 21 13312 SCNN1A-9464 CCUGCAACUCUGUGACCACAGC 22 13313 SCNN1A-9465 UCCUGCAACUCUGUGACCACAGC 23 13314 SCNN1A-9466 UUCCUGCAACUCUGUGACCACAGC 24 13315 SCNN1A-9467 GGGUGGCGAGGAAUCAGC 18 13316 SCNN1A-9468 GGGGUGGCGAGGAAUCAGC 19 13317 SCNN1A-5229 GGGGGUGGCGAGGAAUCAGC 20 9078 SCNN1A-9469 AGGGGGUGGCGAGGAAUCAGC 21 13318 SCNN1A-9470 GAGGGGGUGGCGAGGAAUCAGC 22 13319 SCNN1A-9471 GGAGGGGGUGGCGAGGAAUCAGC 23 13320 SCNN1A-9472 UGGAGGGGGUGGCGAGGAAUCAGC 24 13321 SCNN1A-9473 GGCCAGAAAGAGGAGAGC 18 13322 SCNN1A-9474 AGGCCAGAAAGAGGAGAGC 19 13323 SCNN1A-6119 CAGGCCAGAAAGAGGAGAGC 20 9968 SCNN1A-9475 GCAGGCCAGAAAGAGGAGAGC 21 13324 SCNN1A-9476 GGCAGGCCAGAAAGAGGAGAGC 22 13325 SCNN1A-9477 AGGCAGGCCAGAAAGAGGAGAGC 23 13326 SCNN1A-9478 GAGGCAGGCCAGAAAGAGGAGAGC 24 13327 SCNN1A-9479 CCAGGUUGGACCCUGAGC 18 13328 SCNN1A-9480 ACCAGGUUGGACCCUGAGC 19 13329 SCNN1A-9481 GACCAGGUUGGACCCUGAGC 20 13330 SCNN1A-9482 AGACCAGGUUGGACCCUGAGC 21 13331 SCNN1A-9483 CAGACCAGGUUGGACCCUGAGC 22 13332 SCNN1A-9484 ACAGACCAGGUUGGACCCUGAGC 23 13333 SCNN1A-9485 CACAGACCAGGUUGGACCCUGAGC 24 13334 SCNN1A-9486 UGCUCCCACUUAGUGAGC 18 13335 SCNN1A-9487 CUGCUCCCACUUAGUGAGC 19 13336 SCNN1A-5230 GCUGCUCCCACUUAGUGAGC 20 9079 SCNN1A-9488 CGCUGCUCCCACUUAGUGAGC 21 13337 SCNN1A-9489 GCGCUGCUCCCACUUAGUGAGC 22 13338 SCNN1A-9490 UGCGCUGCUCCCACUUAGUGAGC 23 13339 SCNN1A-9491 GUGCGCUGCUCCCACUUAGUGAGC 24 13340 SCNN1A-9492 GUCGCAAGAGACUGCCGC 18 13341 SCNN1A-9493 AGUCGCAAGAGACUGCCGC 19 13342 SCNN1A-9494 AAGUCGCAAGAGACUGCCGC 20 13343 SCNN1A-9495 GAAGUCGCAAGAGACUGCCGC 21 13344 SCNN1A-9496 AGAAGUCGCAAGAGACUGCCGC 22 13345 SCNN1A-9497 AAGAAGUCGCAAGAGACUGCCGC 23 13346 SCNN1A-9498 UAAGAAGUCGCAAGAGACUGCCGC 24 13347 SCNN1A-9499 UUCACUUUAAGAAGUCGC 18 13348 SCNN1A-9500 UUUCACUUUAAGAAGUCGC 19 13349 SCNN1A-9501 CUUUCACUUUAAGAAGUCGC 20 13350 SCNN1A-9502 GCUUUCACUUUAAGAAGUCGC 21 13351 SCNN1A-9503 GGCUUUCACUUUAAGAAGUCGC 22 13352 SCNN1A-9504 CGGCUUUCACUUUAAGAAGUCGC 23 13353 SCNN1A-9505 CCGGCUUUCACUUUAAGAAGUCGC 24 13354 SCNN1A-9506 CUGGCAAAUAGAAAAGGC 18 13355 SCNN1A-9507 GCUGGCAAAUAGAAAAGGC 19 13356 SCNN1A-6121 AGCUGGCAAAUAGAAAAGGC 20 9970 SCNN1A-9508 GAGCUGGCAAAUAGAAAAGGC 21 13357 SCNN1A-9509 UGAGCUGGCAAAUAGAAAAGGC 22 13358 SCNN1A-9510 AUGAGCUGGCAAAUAGAAAAGGC 23 13359 SCNN1A-9511 CAUGAGCUGGCAAAUAGAAAAGGC 24 13360 SCNN1A-9512 AGUGAGAGGGGGCAAGGC 18 13361 SCNN1A-9513 GAGUGAGAGGGGGCAAGGC 19 13362 SCNN1A-9514 AGAGUGAGAGGGGGCAAGGC 20 13363 SCNN1A-9515 UAGAGUGAGAGGGGGCAAGGC 21 13364 SCNN1A-9516 CUAGAGUGAGAGGGGGCAAGGC 22 13365 SCNN1A-9517 CCUAGAGUGAGAGGGGGCAAGGC 23 13366 SCNN1A-9518 GCCUAGAGUGAGAGGGGGCAAGGC 24 13367 SCNN1A-9519 UAGAGAGAGGAGGCAGGC 18 13368 SCNN1A-9520 UUAGAGAGAGGAGGCAGGC 19 13369 SCNN1A-9521 AUUAGAGAGAGGAGGCAGGC 20 13370 SCNN1A-9522 GAUUAGAGAGAGGAGGCAGGC 21 13371 SCNN1A-9523 GGAUUAGAGAGAGGAGGCAGGC 22 13372 SCNN1A-9524 AGGAUUAGAGAGAGGAGGCAGGC 23 13373 SCNN1A-9525 CAGGAUUAGAGAGAGGAGGCAGGC 24 13374 SCNN1A-9526 AGUGGUUGGAUUUCAGGC 18 13375 SCNN1A-9527 UAGUGGUUGGAUUUCAGGC 19 13376 SCNN1A-9528 CUAGUGGUUGGAUUUCAGGC 20 13377 SCNN1A-9529 GCUAGUGGUUGGAUUUCAGGC 21 13378 SCNN1A-9530 AGCUAGUGGUUGGAUUUCAGGC 22 13379 SCNN1A-9531 AAGCUAGUGGUUGGAUUUCAGGC 23 13380 SCNN1A-9532 UAAGCUAGUGGUUGGAUUUCAGGC 24 13381 SCNN1A-9533 GAGGUCAGGGCCAGAGGC 18 13382 SCNN1A-9534 CGAGGUCAGGGCCAGAGGC 19 13383 SCNN1A-5607 UCGAGGUCAGGGCCAGAGGC 20 9456 SCNN1A-9535 CUCGAGGUCAGGGCCAGAGGC 21 13384 SCNN1A-9536 GCUCGAGGUCAGGGCCAGAGGC 22 13385 SCNN1A-9537 AGCUCGAGGUCAGGGCCAGAGGC 23 13386 SCNN1A-9538 CAGCUCGAGGUCAGGGCCAGAGGC 24 13387 SCNN1A-9539 AGAGAGGGAGUGAGAGGC 18 13388 SCNN1A-9540 UAGAGAGGGAGUGAGAGGC 19 13389 SCNN1A-6123 AUAGAGAGGGAGUGAGAGGC 20 9972 SCNN1A-9541 GAUAGAGAGGGAGUGAGAGGC 21 13390 SCNN1A-9542 AGAUAGAGAGGGAGUGAGAGGC 22 13391 SCNN1A-9543 CAGAUAGAGAGGGAGUGAGAGGC 23 13392 SCNN1A-9544 GCAGAUAGAGAGGGAGUGAGAGGC 24 13393 SCNN1A-9545 CUCUCUUCUCUGCAGGGC 18 13394 SCNN1A-9546 UCUCUCUUCUCUGCAGGGC 19 13395 SCNN1A-9547 UUCUCUCUUCUCUGCAGGGC 20 13396 SCNN1A-9548 CUUCUCUCUUCUCUGCAGGGC 21 13397 SCNN1A-9549 UCUUCUCUCUUCUCUGCAGGGC 22 13398 SCNN1A-9550 CUCUUCUCUCUUCUCUGCAGGGC 23 13399 SCNN1A-9551 CCUCUUCUCUCUUCUCUGCAGGGC 24 13400 SCNN1A-9552 ACAGCUCGAGGUCAGGGC 18 13401 SCNN1A-9553 CACAGCUCGAGGUCAGGGC 19 13402 SCNN1A-9554 ACACAGCUCGAGGUCAGGGC 20 13403 SCNN1A-9555 GACACAGCUCGAGGUCAGGGC 21 13404 SCNN1A-9556 GGACACAGCUCGAGGUCAGGGC 22 13405 SCNN1A-9557 AGGACACAGCUCGAGGUCAGGGC 23 13406 SCNN1A-9558 CAGGACACAGCUCGAGGUCAGGGC 24 13407 SCNN1A-1928 GUGGGACAUGGGCAUGGC 18 5777 SCNN1A-1929 GGUGGGACAUGGGCAUGGC 19 5778 SCNN1A-1930 GGGUGGGACAUGGGCAUGGC 20 5779 SCNN1A-1931 AGGGUGGGACAUGGGCAUGGC 21 5780 SCNN1A-1932 CAGGGUGGGACAUGGGCAUGGC 22 5781 SCNN1A-1933 GCAGGGUGGGACAUGGGCAUGGC 23 5782 SCNN1A-1934 CGCAGGGUGGGACAUGGGCAUGGC 24 5783 SCNN1A-9559 AAGGUUGGAGGGGGUGGC 18 13408 SCNN1A-9560 CAAGGUUGGAGGGGGUGGC 19 13409 SCNN1A-9561 ACAAGGUUGGAGGGGGUGGC 20 13410 SCNN1A-9562 GACAAGGUUGGAGGGGGUGGC 21 13411 SCNN1A-9563 GGACAAGGUUGGAGGGGGUGGC 22 13412 SCNN1A-9564 UGGACAAGGUUGGAGGGGGUGGC 23 13413 SCNN1A-9565 CUGGACAAGGUUGGAGGGGGUGGC 24 13414 SCNN1A-9566 AGACAGAAAGGGAGGUGC 18 13415 SCNN1A-9567 GAGACAGAAAGGGAGGUGC 19 13416 SCNN1A-9568 AGAGACAGAAAGGGAGGUGC 20 13417 SCNN1A-9569 CAGAGACAGAAAGGGAGGUGC 21 13418 SCNN1A-9570 GCAGAGACAGAAAGGGAGGUGC 22 13419 SCNN1A-9571 GGCAGAGACAGAAAGGGAGGUGC 23 13420 SCNN1A-9572 GGGCAGAGACAGAAAGGGAGGUGC 24 13421 SCNN1A-9573 UGCUGAGCACCUUAUUGC 18 13422 SCNN1A-9574 GUGCUGAGCACCUUAUUGC 19 13423 SCNN1A-5237 GGUGCUGAGCACCUUAUUGC 20 9086 SCNN1A-9575 GGGUGCUGAGCACCUUAUUGC 21 13424 SCNN1A-9576 AGGGUGCUGAGCACCUUAUUGC 22 13425 SCNN1A-9577 CAGGGUGCUGAGCACCUUAUUGC 23 13426 SCNN1A-9578 CCAGGGUGCUGAGCACCUUAUUGC 24 13427 SCNN1A-9579 GGAGCUGAGACACAGAUC 18 13428 SCNN1A-9580 AGGAGCUGAGACACAGAUC 19 13429 SCNN1A-9581 CAGGAGCUGAGACACAGAUC 20 13430 SCNN1A-9582 GCAGGAGCUGAGACACAGAUC 21 13431 SCNN1A-9583 GGCAGGAGCUGAGACACAGAUC 22 13432 SCNN1A-9584 AGGCAGGAGCUGAGACACAGAUC 23 13433 SCNN1A-9585 GAGGCAGGAGCUGAGACACAGAUC 24 13434 SCNN1A-9586 UCGAAAGGUGGCCCUAUC 18 13435 SCNN1A-9587 CUCGAAAGGUGGCCCUAUC 19 13436 SCNN1A-5626 ACUCGAAAGGUGGCCCUAUC 20 9475 SCNN1A-9588 AACUCGAAAGGUGGCCCUAUC 21 13437 SCNN1A-9589 AAACUCGAAAGGUGGCCCUAUC 22 13438 SCNN1A-9590 AAAACUCGAAAGGUGGCCCUAUC 23 13439 SCNN1A-9591 CAAAACUCGAAAGGUGGCCCUAUC 24 13440 SCNN1A-1935 CUUCCAAGGGGAGGUAUC 18 5784 SCNN1A-1936 CCUUCCAAGGGGAGGUAUC 19 5785 SCNN1A-1937 CCCUUCCAAGGGGAGGUAUC 20 5786 SCNN1A-1938 UCCCUUCCAAGGGGAGGUAUC 21 5787 SCNN1A-1939 GUCCCUUCCAAGGGGAGGUAUC 22 5788 SCNN1A-1940 UGUCCCUUCCAAGGGGAGGUAUC 23 5789 SCNN1A-1941 CUGUCCCUUCCAAGGGGAGGUAUC 24 5790 SCNN1A-1942 GCUCUCCCCAAUCCACUC 18 5791 SCNN1A-1943 UGCUCUCCCCAAUCCACUC 19 5792 SCNN1A-410 UUGCUCUCCCCAAUCCACUC 20 4259 SCNN1A-1944 CUUGCUCUCCCCAAUCCACUC 21 5793 SCNN1A-1945 CCUUGCUCUCCCCAAUCCACUC 22 5794 SCNN1A-1946 CCCUUGCUCUCCCCAAUCCACUC 23 5795 SCNN1A-1947 ACCCUUGCUCUCCCCAAUCCACUC 24 5796 SCNN1A-1948 GCCCUCCACAGUCCACUC 18 5797 SCNN1A-1949 AGCCCUCCACAGUCCACUC 19 5798 SCNN1A-170 UAGCCCUCCACAGUCCACUC 20 808 SCNN1A-1950 CUAGCCCUCCACAGUCCACUC 21 5799 SCNN1A-1951 UCUAGCCCUCCACAGUCCACUC 22 5800 SCNN1A-1952 CUCUAGCCCUCCACAGUCCACUC 23 5801 SCNN1A-1953 ACUCUAGCCCUCCACAGUCCACUC 24 5802 SCNN1A-9592 GGAGGCAGCCCAGACCUC 18 13441 SCNN1A-9593 UGGAGGCAGCCCAGACCUC 19 13442 SCNN1A-9594 CUGGAGGCAGCCCAGACCUC 20 13443 SCNN1A-9595 GCUGGAGGCAGCCCAGACCUC 21 13444 SCNN1A-9596 AGCUGGAGGCAGCCCAGACCUC 22 13445 SCNN1A-9597 AAGCUGGAGGCAGCCCAGACCUC 23 13446 SCNN1A-9598 GAAGCUGGAGGCAGCCCAGACCUC 24 13447 SCNN1A-9599 CCCAGUUCACCUGCCCUC 18 13448 SCNN1A-9600 UCCCAGUUCACCUGCCCUC 19 13449 SCNN1A-6132 CUCCCAGUUCACCUGCCCUC 20 9981 SCNN1A-9601 ACUCCCAGUUCACCUGCCCUC 21 13450 SCNN1A-9602 UACUCCCAGUUCACCUGCCCUC 22 13451 SCNN1A-9603 GUACUCCCAGUUCACCUGCCCUC 23 13452 SCNN1A-9604 AGUACUCCCAGUUCACCUGCCCUC 24 13453 SCNN1A-9605 UUGCUGAGCCUCUAGCUC 18 13454 SCNN1A-9606 CUUGCUGAGCCUCUAGCUC 19 13455 SCNN1A-9607 ACUUGCUGAGCCUCUAGCUC 20 13456 SCNN1A-9608 CACUUGCUGAGCCUCUAGCUC 21 13457 SCNN1A-9609 CCACUUGCUGAGCCUCUAGCUC 22 13458 SCNN1A-9610 CCCACUUGCUGAGCCUCUAGCUC 23 13459 SCNN1A-9611 GCCCACUUGCUGAGCCUCUAGCUC 24 13460 SCNN1A-1960 CAAUCCACUCCGGGGCUC 18 5809 SCNN1A-1961 CCAAUCCACUCCGGGGCUC 19 5810 SCNN1A-1962 CCCAAUCCACUCCGGGGCUC 20 5811 SCNN1A-1963 CCCCAAUCCACUCCGGGGCUC 21 5812 SCNN1A-1964 UCCCCAAUCCACUCCGGGGCUC 22 5813 SCNN1A-1965 CUCCCCAAUCCACUCCGGGGCUC 23 5814 SCNN1A-1966 UCUCCCCAAUCCACUCCGGGGCUC 24 5815 SCNN1A-9612 AAUGUAAGGACCUGGCUC 18 13461 SCNN1A-9613 CAAUGUAAGGACCUGGCUC 19 13462 SCNN1A-9614 CCAAUGUAAGGACCUGGCUC 20 13463 SCNN1A-9615 CCCAAUGUAAGGACCUGGCUC 21 13464 SCNN1A-9616 GCCCAAUGUAAGGACCUGGCUC 22 13465 SCNN1A-9617 UGCCCAAUGUAAGGACCUGGCUC 23 13466 SCNN1A-9618 AUGCCCAAUGUAAGGACCUGGCUC 24 13467 SCNN1A-9619 CCGCAGGUCUGCUGGCUC 18 13468 SCNN1A-9620 CCCGCAGGUCUGCUGGCUC 19 13469 SCNN1A-9621 UCCCGCAGGUCUGCUGGCUC 20 13470 SCNN1A-9622 CUCCCGCAGGUCUGCUGGCUC 21 13471 SCNN1A-9623 ACUCCCGCAGGUCUGCUGGCUC 22 13472 SCNN1A-9624 AACUCCCGCAGGUCUGCUGGCUC 23 13473 SCNN1A-9625 CAACUCCCGCAGGUCUGCUGGCUC 24 13474 SCNN1A-1967 CAGCCCAUACCAGGUCUC 18 5816 SCNN1A-1968 GCAGCCCAUACCAGGUCUC 19 5817 SCNN1A-159 UGCAGCCCAUACCAGGUCUC 20 803 SCNN1A-1969 CUGCAGCCCAUACCAGGUCUC 21 5818 SCNN1A-1970 UCUGCAGCCCAUACCAGGUCUC 22 5819 SCNN1A-1971 CUCUGCAGCCCAUACCAGGUCUC 23 5820 SCNN1A-1972 CCUCUGCAGCCCAUACCAGGUCUC 24 5821 SCNN1A-9626 CCCCCAUGAGUCUGUCUC 18 13475 SCNN1A-9627 UCCCCCAUGAGUCUGUCUC 19 13476 SCNN1A-5636 AUCCCCCAUGAGUCUGUCUC 20 9485 SCNN1A-9628 GAUCCCCCAUGAGUCUGUCUC 21 13477 SCNN1A-9629 CGAUCCCCCAUGAGUCUGUCUC 22 13478 SCNN1A-9630 CCGAUCCCCCAUGAGUCUGUCUC 23 13479 SCNN1A-9631 CCCGAUCCCCCAUGAGUCUGUCUC 24 13480 SCNN1A-9632 CAGAGAUGACACCUUCUC 18 13481 SCNN1A-9633 GCAGAGAUGACACCUUCUC 19 13482 SCNN1A-5637 AGCAGAGAUGACACCUUCUC 20 9486 SCNN1A-9634 CAGCAGAGAUGACACCUUCUC 21 13483 SCNN1A-9635 UCAGCAGAGAUGACACCUUCUC 22 13484 SCNN1A-9636 UUCAGCAGAGAUGACACCUUCUC 23 13485 SCNN1A-9637 AUUCAGCAGAGAUGACACCUUCUC 24 13486 SCNN1A-9638 UCCUGGAGCCCUGCAGUC 18 13487 SCNN1A-9639 CUCCUGGAGCCCUGCAGUC 19 13488 SCNN1A-9640 CCUCCUGGAGCCCUGCAGUC 20 13489 SCNN1A-9641 ACCUCCUGGAGCCCUGCAGUC 21 13490 SCNN1A-9642 GACCUCCUGGAGCCCUGCAGUC 22 13491 SCNN1A-9643 AGACCUCCUGGAGCCCUGCAGUC 23 13492 SCNN1A-9644 CAGACCUCCUGGAGCCCUGCAGUC 24 13493 SCNN1A-9645 CCCCCCUUGCUCUCCUUC 18 13494 SCNN1A-9646 UCCCCCCUUGCUCUCCUUC 19 13495 SCNN1A-9647 CUCCCCCCUUGCUCUCCUUC 20 13496 SCNN1A-9648 ACUCCCCCCUUGCUCUCCUUC 21 13497 SCNN1A-9649 GACUCCCCCCUUGCUCUCCUUC 22 13498 SCNN1A-9650 GGACUCCCCCCUUGCUCUCCUUC 23 13499 SCNN1A-9651 GGGACUCCCCCCUUGCUCUCCUUC 24 13500 SCNN1A-9652 UGCUUUCCCUGCCUCUUC 18 13501 SCNN1A-9653 CUGCUUUCCCUGCCUCUUC 19 13502 SCNN1A-9654 CCUGCUUUCCCUGCCUCUUC 20 13503 SCNN1A-9655 GCCUGCUUUCCCUGCCUCUUC 21 13504 SCNN1A-9656 UGCCUGCUUUCCCUGCCUCUUC 22 13505 SCNN1A-9657 GUGCCUGCUUUCCCUGCCUCUUC 23 13506 SCNN1A-9658 AGUGCCUGCUUUCCCUGCCUCUUC 24 13507 SCNN1A-9659 GCAGAGGAGAGGCCGUUC 18 13508 SCNN1A-9660 AGCAGAGGAGAGGCCGUUC 19 13509 SCNN1A-9661 AAGCAGAGGAGAGGCCGUUC 20 13510 SCNN1A-9662 GAAGCAGAGGAGAGGCCGUUC 21 13511 SCNN1A-9663 GGAAGCAGAGGAGAGGCCGUUC 22 13512 SCNN1A-9664 GGGAAGCAGAGGAGAGGCCGUUC 23 13513 SCNN1A-9665 AGGGAAGCAGAGGAGAGGCCGUUC 24 13514 SCNN1A-1973 GCAGCCUCACUCGGGUUC 18 5822 SCNN1A-1974 GGCAGCCUCACUCGGGUUC 19 5823 SCNN1A-1975 GGGCAGCCUCACUCGGGUUC 20 5824 SCNN1A-1976 GGGGCAGCCUCACUCGGGUUC 21 5825 SCNN1A-1977 AGGGGCAGCCUCACUCGGGUUC 22 5826 SCNN1A-1978 CAGGGGCAGCCUCACUCGGGUUC 23 5827 SCNN1A-1979 CCAGGGGCAGCCUCACUCGGGUUC 24 5828 SCNN1A-9666 AAGGGAGACUGGAGUUUC 18 13515 SCNN1A-9667 CAAGGGAGACUGGAGUUUC 19 13516 SCNN1A-9668 UCAAGGGAGACUGGAGUUUC 20 13517 SCNN1A-9669 CUCAAGGGAGACUGGAGUUUC 21 13518 SCNN1A-9670 GCUCAAGGGAGACUGGAGUUUC 22 13519 SCNN1A-9671 GGCUCAAGGGAGACUGGAGUUUC 23 13520 SCNN1A-9672 UGGCUCAAGGGAGACUGGAGUUUC 24 13521 SCNN1A-9673 AGGAGGCAGGCCAGAAAG 18 13522 SCNN1A-9674 GAGGAGGCAGGCCAGAAAG 19 13523 SCNN1A-6139 AGAGGAGGCAGGCCAGAAAG 20 9988 SCNN1A-9675 GAGAGGAGGCAGGCCAGAAAG 21 13524 SCNN1A-9676 AGAGAGGAGGCAGGCCAGAAAG 22 13525 SCNN1A-9677 GAGAGAGGAGGCAGGCCAGAAAG 23 13526 SCNN1A-9678 AGAGAGAGGAGGCAGGCCAGAAAG 24 13527 SCNN1A-9679 CUGCUGGCUCCAGGAAAG 18 13528 SCNN1A-9680 UCUGCUGGCUCCAGGAAAG 19 13529 SCNN1A-9681 GUCUGCUGGCUCCAGGAAAG 20 13530 SCNN1A-9682 GGUCUGCUGGCUCCAGGAAAG 21 13531 SCNN1A-9683 AGGUCUGCUGGCUCCAGGAAAG 22 13532 SCNN1A-9684 CAGGUCUGCUGGCUCCAGGAAAG 23 13533 SCNN1A-9685 GCAGGUCUGCUGGCUCCAGGAAAG 24 13534 SCNN1A-9686 GAGGAAUCAGCAGGAAAG 18 13535 SCNN1A-9687 CGAGGAAUCAGCAGGAAAG 19 13536 SCNN1A-5244 GCGAGGAAUCAGCAGGAAAG 20 9093 SCNN1A-9688 GGCGAGGAAUCAGCAGGAAAG 21 13537 SCNN1A-9689 UGGCGAGGAAUCAGCAGGAAAG 22 13538 SCNN1A-9690 GUGGCGAGGAAUCAGCAGGAAAG 23 13539 SCNN1A-9691 GGUGGCGAGGAAUCAGCAGGAAAG 24 13540 SCNN1A-1980 CUCAUGAAGGGGAACAAG 18 5829 SCNN1A-1981 GCUCAUGAAGGGGAACAAG 19 5830 SCNN1A-1982 GGCUCAUGAAGGGGAACAAG 20 5831 SCNN1A-1983 GGGCUCAUGAAGGGGAACAAG 21 5832 SCNN1A-1984 GGGGCUCAUGAAGGGGAACAAG 22 5833 SCNN1A-1985 CGGGGCUCAUGAAGGGGAACAAG 23 5834 SCNN1A-1986 CCGGGGCUCAUGAAGGGGAACAAG 24 5835 SCNN1A-1987 CUCAUGGAGGGGAACAAG 18 5836 SCNN1A-1988 UCUCAUGGAGGGGAACAAG 19 5837 SCNN1A-165 GUCUCAUGGAGGGGAACAAG 20 805 SCNN1A-1989 GGUCUCAUGGAGGGGAACAAG 21 5838 SCNN1A-1990 AGGUCUCAUGGAGGGGAACAAG 22 5839 SCNN1A-1991 CAGGUCUCAUGGAGGGGAACAAG 23 5840 SCNN1A-1992 CCAGGUCUCAUGGAGGGGAACAAG 24 5841 SCNN1A-1993 CCAGCUGUCCCUUCCAAG 18 5842 SCNN1A-1994 UCCAGCUGUCCCUUCCAAG 19 5843 SCNN1A-412 AUCCAGCUGUCCCUUCCAAG 20 4261 SCNN1A-9692 AAUCCAGCUGUCCCUUCCAAG 21 13541 SCNN1A-9693 AAAUCCAGCUGUCCCUUCCAAG 22 13542 SCNN1A-9694 AAAAUCCAGCUGUCCCUUCCAAG 23 13543 SCNN1A-9695 AAAAAUCCAGCUGUCCCUUCCAAG 24 13544 SCNN1A-9696 GAGAGGGGGCAAGGCAAG 18 13545 SCNN1A-9697 UGAGAGGGGGCAAGGCAAG 19 13546 SCNN1A-5246 GUGAGAGGGGGCAAGGCAAG 20 9095 SCNN1A-9698 AGUGAGAGGGGGCAAGGCAAG 21 13547 SCNN1A-9699 GAGUGAGAGGGGGCAAGGCAAG 22 13548 SCNN1A-9700 AGAGUGAGAGGGGGCAAGGCAAG 23 13549 SCNN1A-9701 UAGAGUGAGAGGGGGCAAGGCAAG 24 13550 SCNN1A-9702 GUGGCCCUAUCAGGGAAG 18 13551 SCNN1A-9703 GGUGGCCCUAUCAGGGAAG 19 13552 SCNN1A-9704 AGGUGGCCCUAUCAGGGAAG 20 13553 SCNN1A-9705 AAGGUGGCCCUAUCAGGGAAG 21 13554 SCNN1A-9706 AAAGGUGGCCCUAUCAGGGAAG 22 13555 SCNN1A-9707 GAAAGGUGGCCCUAUCAGGGAAG 23 13556 SCNN1A-9708 CGAAAGGUGGCCCUAUCAGGGAAG 24 13557 SCNN1A-9709 CAACCUGGGAGUGGGAAG 18 13558 SCNN1A-9710 GCAACCUGGGAGUGGGAAG 19 13559 SCNN1A-9711 CGCAACCUGGGAGUGGGAAG 20 13560 SCNN1A-9712 CCGCAACCUGGGAGUGGGAAG 21 13561 SCNN1A-9713 GCCGCAACCUGGGAGUGGGAAG 22 13562 SCNN1A-9714 AGCCGCAACCUGGGAGUGGGAAG 23 13563 SCNN1A-9715 CAGCCGCAACCUGGGAGUGGGAAG 24 13564 SCNN1A-2001 ACUCCGGGGCUCAUGAAG 18 5850 SCNN1A-2002 CACUCCGGGGCUCAUGAAG 19 5851 SCNN1A-453 CCACUCCGGGGCUCAUGAAG 20 4302 SCNN1A-2003 UCCACUCCGGGGCUCAUGAAG 21 5852 SCNN1A-2004 AUCCACUCCGGGGCUCAUGAAG 22 5853 SCNN1A-2005 AAUCCACUCCGGGGCUCAUGAAG 23 5854 SCNN1A-2006 CAAUCCACUCCGGGGCUCAUGAAG 24 5855 SCNN1A-9716 GCAACUCUGUGACCACAG 18 13565 SCNN1A-9717 UGCAACUCUGUGACCACAG 19 13566 SCNN1A-9718 CUGCAACUCUGUGACCACAG 20 13567 SCNN1A-9719 CCUGCAACUCUGUGACCACAG 21 13568 SCNN1A-9720 UCCUGCAACUCUGUGACCACAG 22 13569 SCNN1A-9721 UUCCUGCAACUCUGUGACCACAG 23 13570 SCNN1A-9722 AUUCCUGCAACUCUGUGACCACAG 24 13571 SCNN1A-9723 GGAAAGAGGAGGGACCAG 18 13572 SCNN1A-9724 AGGAAAGAGGAGGGACCAG 19 13573 SCNN1A-9725 CAGGAAAGAGGAGGGACCAG 20 13574 SCNN1A-9726 GCAGGAAAGAGGAGGGACCAG 21 13575 SCNN1A-9727 AGCAGGAAAGAGGAGGGACCAG 22 13576 SCNN1A-9728 CAGCAGGAAAGAGGAGGGACCAG 23 13577 SCNN1A-9729 UCAGCAGGAAAGAGGAGGGACCAG 24 13578 SCNN1A-9730 CUAAGUAGAUAGCCCCAG 18 13579 SCNN1A-9731 GCUAAGUAGAUAGCCCCAG 19 13580 SCNN1A-5646 CGCUAAGUAGAUAGCCCCAG 20 9495 SCNN1A-9732 GCGCUAAGUAGAUAGCCCCAG 21 13581 SCNN1A-9733 AGCGCUAAGUAGAUAGCCCCAG 22 13582 SCNN1A-9734 AAGCGCUAAGUAGAUAGCCCCAG 23 13583 SCNN1A-9735 AAAGCGCUAAGUAGAUAGCCCCAG 24 13584 SCNN1A-9736 GCCCUAUCAGGGAAGCAG 18 13585 SCNN1A-9737 GGCCCUAUCAGGGAAGCAG 19 13586 SCNN1A-5649 UGGCCCUAUCAGGGAAGCAG 20 9498 SCNN1A-9738 GUGGCCCUAUCAGGGAAGCAG 21 13587 SCNN1A-9739 GGUGGCCCUAUCAGGGAAGCAG 22 13588 SCNN1A-9740 AGGUGGCCCUAUCAGGGAAGCAG 23 13589 SCNN1A-9741 AAGGUGGCCCUAUCAGGGAAGCAG 24 13590 SCNN1A-9742 CCAGAAAGAGGAGAGCAG 18 13591 SCNN1A-9743 GCCAGAAAGAGGAGAGCAG 19 13592 SCNN1A-9744 GGCCAGAAAGAGGAGAGCAG 20 13593 SCNN1A-9745 AGGCCAGAAAGAGGAGAGCAG 21 13594 SCNN1A-9746 CAGGCCAGAAAGAGGAGAGCAG 22 13595 SCNN1A-9747 GCAGGCCAGAAAGAGGAGAGCAG 23 13596 SCNN1A-9748 GGCAGGCCAGAAAGAGGAGAGCAG 24 13597 SCNN1A-9749 CUGGGAUAUGUGGGGCAG 18 13598 SCNN1A-9750 UCUGGGAUAUGUGGGGCAG 19 13599 SCNN1A-5651 CUCUGGGAUAUGUGGGGCAG 20 9500 SCNN1A-9751 UCUCUGGGAUAUGUGGGGCAG 21 13600 SCNN1A-9752 GUCUCUGGGAUAUGUGGGGCAG 22 13601 SCNN1A-9753 GGUCUCUGGGAUAUGUGGGGCAG 23 13602 SCNN1A-9754 GGGUCUCUGGGAUAUGUGGGGCAG 24 13603 SCNN1A-9755 GGGGUGGCGAGGAAUCAG 18 13604 SCNN1A-9756 GGGGGUGGCGAGGAAUCAG 19 13605 SCNN1A-9757 AGGGGGUGGCGAGGAAUCAG 20 13606 SCNN1A-9758 GAGGGGGUGGCGAGGAAUCAG 21 13607 SCNN1A-9759 GGAGGGGGUGGCGAGGAAUCAG 22 13608 SCNN1A-9760 UGGAGGGGGUGGCGAGGAAUCAG 23 13609 SCNN1A-9761 UUGGAGGGGGUGGCGAGGAAUCAG 24 13610 SCNN1A-9762 GGCCGCUGCACCUGUCAG 18 13611 SCNN1A-9763 AGGCCGCUGCACCUGUCAG 19 13612 SCNN1A-9764 CAGGCCGCUGCACCUGUCAG 20 13613 SCNN1A-9765 CCAGGCCGCUGCACCUGUCAG 21 13614 SCNN1A-9766 GCCAGGCCGCUGCACCUGUCAG 22 13615 SCNN1A-9767 AGCCAGGCCGCUGCACCUGUCAG 23 13616 SCNN1A-9768 CAGCCAGGCCGCUGCACCUGUCAG 24 13617 SCNN1A-9769 UUGCUUGUCAAGAUUCAG 18 13618 SCNN1A-9770 CUUGCUUGUCAAGAUUCAG 19 13619 SCNN1A-9771 CCUUGCUUGUCAAGAUUCAG 20 13620 SCNN1A-9772 UCCUUGCUUGUCAAGAUUCAG 21 13621 SCNN1A-9773 CUCCUUGCUUGUCAAGAUUCAG 22 13622 SCNN1A-9774 ACUCCUUGCUUGUCAAGAUUCAG 23 13623 SCNN1A-9775 AACUCCUUGCUUGUCAAGAUUCAG 24 13624 SCNN1A-9776 GAGGCAGGCCAGAAAGAG 18 13625 SCNN1A-9777 GGAGGCAGGCCAGAAAGAG 19 13626 SCNN1A-9778 AGGAGGCAGGCCAGAAAGAG 20 13627 SCNN1A-9779 GAGGAGGCAGGCCAGAAAGAG 21 13628 SCNN1A-9780 AGAGGAGGCAGGCCAGAAAGAG 22 13629 SCNN1A-9781 GAGAGGAGGCAGGCCAGAAAGAG 23 13630 SCNN1A-9782 AGAGAGGAGGCAGGCCAGAAAGAG 24 13631 SCNN1A-9783 GGAAUCAGCAGGAAAGAG 18 13632 SCNN1A-9784 AGGAAUCAGCAGGAAAGAG 19 13633 SCNN1A-9785 GAGGAAUCAGCAGGAAAGAG 20 13634 SCNN1A-9786 CGAGGAAUCAGCAGGAAAGAG 21 13635 SCNN1A-9787 GCGAGGAAUCAGCAGGAAAGAG 22 13636 SCNN1A-9788 GGCGAGGAAUCAGCAGGAAAGAG 23 13637 SCNN1A-9789 UGGCGAGGAAUCAGCAGGAAAGAG 24 13638 SCNN1A-9790 AAGAGACUGCCGCAAGAG 18 13639 SCNN1A-9791 CAAGAGACUGCCGCAAGAG 19 13640 SCNN1A-5249 GCAAGAGACUGCCGCAAGAG 20 9098 SCNN1A-9792 CGCAAGAGACUGCCGCAAGAG 21 13641 SCNN1A-9793 UCGCAAGAGACUGCCGCAAGAG 22 13642 SCNN1A-9794 GUCGCAAGAGACUGCCGCAAGAG 23 13643 SCNN1A-9795 AGUCGCAAGAGACUGCCGCAAGAG 24 13644 SCNN1A-9796 AAGUAGAUAGCCCCAGAG 18 13645 SCNN1A-9797 UAAGUAGAUAGCCCCAGAG 19 13646 SCNN1A-9798 CUAAGUAGAUAGCCCCAGAG 20 13647 SCNN1A-9799 GCUAAGUAGAUAGCCCCAGAG 21 13648 SCNN1A-9800 CGCUAAGUAGAUAGCCCCAGAG 22 13649 SCNN1A-9801 GCGCUAAGUAGAUAGCCCCAGAG 23 13650 SCNN1A-9802 AGCGCUAAGUAGAUAGCCCCAGAG 24 13651 SCNN1A-9803 CCUAUCAGGGAAGCAGAG 18 13652 SCNN1A-9804 CCCUAUCAGGGAAGCAGAG 19 13653 SCNN1A-9805 GCCCUAUCAGGGAAGCAGAG 20 13654 SCNN1A-9806 GGCCCUAUCAGGGAAGCAGAG 21 13655 SCNN1A-9807 UGGCCCUAUCAGGGAAGCAGAG 22 13656 SCNN1A-9808 GUGGCCCUAUCAGGGAAGCAGAG 23 13657 SCNN1A-9809 GGUGGCCCUAUCAGGGAAGCAGAG 24 13658 SCNN1A-9810 AGAGGCAGGAUUAGAGAG 18 13659 SCNN1A-9811 GAGAGGCAGGAUUAGAGAG 19 13660 SCNN1A-6147 AGAGAGGCAGGAUUAGAGAG 20 9996 SCNN1A-9812 AAGAGAGGCAGGAUUAGAGAG 21 13661 SCNN1A-9813 GAAGAGAGGCAGGAUUAGAGAG 22 13662 SCNN1A-9814 GGAAGAGAGGCAGGAUUAGAGAG 23 13663 SCNN1A-9815 AGGAAGAGAGGCAGGAUUAGAGAG 24 13664 SCNN1A-9816 AGGCCAGAAAGAGGAGAG 18 13665 SCNN1A-9817 CAGGCCAGAAAGAGGAGAG 19 13666 SCNN1A-9818 GCAGGCCAGAAAGAGGAGAG 20 13667 SCNN1A-9819 GGCAGGCCAGAAAGAGGAGAG 21 13668 SCNN1A-9820 AGGCAGGCCAGAAAGAGGAGAG 22 13669 SCNN1A-9821 GAGGCAGGCCAGAAAGAGGAGAG 23 13670 SCNN1A-9822 GGAGGCAGGCCAGAAAGAGGAGAG 24 13671 SCNN1A-9823 AACAGAAGGCAGAUAGAG 18 13672 SCNN1A-9824 AAACAGAAGGCAGAUAGAG 19 13673 SCNN1A-5250 GAAACAGAAGGCAGAUAGAG 20 9099 SCNN1A-9825 AGAAACAGAAGGCAGAUAGAG 21 13674 SCNN1A-9826 GAGAAACAGAAGGCAGAUAGAG 22 13675 SCNN1A-9827 AGAGAAACAGAAGGCAGAUAGAG 23 13676 SCNN1A-9828 AAGAGAAACAGAAGGCAGAUAGAG 24 13677 SCNN1A-9829 GGGAGUGAGAGGCAGGAG 18 13678 SCNN1A-9830 AGGGAGUGAGAGGCAGGAG 19 13679 SCNN1A-9831 GAGGGAGUGAGAGGCAGGAG 20 13680 SCNN1A-9832 AGAGGGAGUGAGAGGCAGGAG 21 13681 SCNN1A-9833 GAGAGGGAGUGAGAGGCAGGAG 22 13682 SCNN1A-9834 AGAGAGGGAGUGAGAGGCAGGAG 23 13683 SCNN1A-9835 UAGAGAGGGAGUGAGAGGCAGGAG 24 13684 SCNN1A-9836 UAGAUAGCCCCAGAGGAG 18 13685 SCNN1A-9837 GUAGAUAGCCCCAGAGGAG 19 13686 SCNN1A-9838 AGUAGAUAGCCCCAGAGGAG 20 13687 SCNN1A-9839 AAGUAGAUAGCCCCAGAGGAG 21 13688 SCNN1A-9840 UAAGUAGAUAGCCCCAGAGGAG 22 13689 SCNN1A-9841 CUAAGUAGAUAGCCCCAGAGGAG 23 13690 SCNN1A-9842 GCUAAGUAGAUAGCCCCAGAGGAG 24 13691 SCNN1A-9843 GGAGGAGGGAGGGAGGAG 18 13692 SCNN1A-9844 UGGAGGAGGGAGGGAGGAG 19 13693 SCNN1A-5897 GUGGAGGAGGGAGGGAGGAG 20 9746 SCNN1A-9845 GGUGGAGGAGGGAGGGAGGAG 21 13694 SCNN1A-9846 AGGUGGAGGAGGGAGGGAGGAG 22 13695 SCNN1A-9847 AAGGUGGAGGAGGGAGGGAGGAG 23 13696 SCNN1A-9848 AAAGGUGGAGGAGGGAGGGAGGAG 24 13697 SCNN1A-2007 GGGAACAAGCUGGAGGAG 18 5856 SCNN1A-2008 GGGGAACAAGCUGGAGGAG 19 5857 SCNN1A-169 AGGGGAACAAGCUGGAGGAG 20 807 SCNN1A-2009 AAGGGGAACAAGCUGGAGGAG 21 5858 SCNN1A-2010 GAAGGGGAACAAGCUGGAGGAG 22 5859 SCNN1A-2011 UGAAGGGGAACAAGCUGGAGGAG 23 5860 SCNN1A-2012 AUGAAGGGGAACAAGCUGGAGGAG 24 5861 SCNN1A-2013 GAGGGGAACAAGCUGGAGGAG 21 5862 SCNN1A-2014 GGAGGGGAACAAGCUGGAGGAG 22 5863 SCNN1A-2015 UGGAGGGGAACAAGCUGGAGGAG 23 5864 SCNN1A-2016 AUGGAGGGGAACAAGCUGGAGGAG 24 5865 SCNN1A-9849 CUGUCAGGUGAGGGGGAG 18 13698 SCNN1A-9850 CCUGUCAGGUGAGGGGGAG 19 13699 SCNN1A-9851 ACCUGUCAGGUGAGGGGGAG 20 13700 SCNN1A-9852 CACCUGUCAGGUGAGGGGGAG 21 13701 SCNN1A-9853 GCACCUGUCAGGUGAGGGGGAG 22 13702 SCNN1A-9854 UGCACCUGUCAGGUGAGGGGGAG 23 13703 SCNN1A-9855 CUGCACCUGUCAGGUGAGGGGGAG 24 13704 SCNN1A-9856 GCAAGGCAAGGGGGGGAG 18 13705 SCNN1A-9857 GGCAAGGCAAGGGGGGGAG 19 13706 SCNN1A-5900 GGGCAAGGCAAGGGGGGGAG 20 9749 SCNN1A-9858 GGGGCAAGGCAAGGGGGGGAG 21 13707 SCNN1A-9859 GGGGGCAAGGCAAGGGGGGGAG 22 13708 SCNN1A-9860 AGGGGGCAAGGCAAGGGGGGGAG 23 13709 SCNN1A-9861 GAGGGGGCAAGGCAAGGGGGGGAG 24 13710 SCNN1A-9862 CCAGCCGCAACCUGGGAG 18 13711 SCNN1A-9863 UCCAGCCGCAACCUGGGAG 19 13712 SCNN1A-5251 GUCCAGCCGCAACCUGGGAG 20 9100 SCNN1A-9864 AGUCCAGCCGCAACCUGGGAG 21 13713 SCNN1A-9865 CAGUCCAGCCGCAACCUGGGAG 22 13714 SCNN1A-9866 CCAGUCCAGCCGCAACCUGGGAG 23 13715 SCNN1A-9867 CCCAGUCCAGCCGCAACCUGGGAG 24 13716 SCNN1A-2029 AUACCAGGUCUCAUGGAG 18 5878 SCNN1A-2030 CAUACCAGGUCUCAUGGAG 19 5879 SCNN1A-4 CCAUACCAGGUCUCAUGGAG 20 498 SCNN1A-2031 CCCAUACCAGGUCUCAUGGAG 21 5880 SCNN1A-2032 GCCCAUACCAGGUCUCAUGGAG 22 5881 SCNN1A-2033 AGCCCAUACCAGGUCUCAUGGAG 23 5882 SCNN1A-2034 CAGCCCAUACCAGGUCUCAUGGAG 24 5883 SCNN1A-9868 CAGGGCCAGAGGCUGGAG 18 13717 SCNN1A-9869 UCAGGGCCAGAGGCUGGAG 19 13718 SCNN1A-9870 GUCAGGGCCAGAGGCUGGAG 20 13719 SCNN1A-9871 GGUCAGGGCCAGAGGCUGGAG 21 13720 SCNN1A-9872 AGGUCAGGGCCAGAGGCUGGAG 22 13721 SCNN1A-9873 GAGGUCAGGGCCAGAGGCUGGAG 23 13722 SCNN1A-9874 CGAGGUCAGGGCCAGAGGCUGGAG 24 13723 SCNN1A-9875 GCUCCAGGAAAGGUGGAG 18 13724 SCNN1A-9876 GGCUCCAGGAAAGGUGGAG 19 13725 SCNN1A-9877 UGGCUCCAGGAAAGGUGGAG 20 13726 SCNN1A-9878 CUGGCUCCAGGAAAGGUGGAG 21 13727 SCNN1A-9879 GCUGGCUCCAGGAAAGGUGGAG 22 13728 SCNN1A-9880 UGCUGGCUCCAGGAAAGGUGGAG 23 13729 SCNN1A-9881 CUGCUGGCUCCAGGAAAGGUGGAG 24 13730 SCNN1A-9882 CUGAGGGCCUAGAGUGAG 18 13731 SCNN1A-9883 GCUGAGGGCCUAGAGUGAG 19 13732 SCNN1A-5657 AGCUGAGGGCCUAGAGUGAG 20 9506 SCNN1A-9884 GAGCUGAGGGCCUAGAGUGAG 21 13733 SCNN1A-9885 GGAGCUGAGGGCCUAGAGUGAG 22 13734 SCNN1A-9886 UGGAGCUGAGGGCCUAGAGUGAG 23 13735 SCNN1A-9887 CUGGAGCUGAGGGCCUAGAGUGAG 24 13736 SCNN1A-9888 CUGCUCCCACUUAGUGAG 18 13737 SCNN1A-9889 GCUGCUCCCACUUAGUGAG 19 13738 SCNN1A-5658 CGCUGCUCCCACUUAGUGAG 20 9507 SCNN1A-9890 GCGCUGCUCCCACUUAGUGAG 21 13739 SCNN1A-9891 UGCGCUGCUCCCACUUAGUGAG 22 13740 SCNN1A-9892 GUGCGCUGCUCCCACUUAGUGAG 23 13741 SCNN1A-9893 AGUGCGCUGCUCCCACUUAGUGAG 24 13742 SCNN1A-9894 CUGCACCUGUCAGGUGAG 18 13743 SCNN1A-9895 GCUGCACCUGUCAGGUGAG 19 13744 SCNN1A-5659 CGCUGCACCUGUCAGGUGAG 20 9508 SCNN1A-9896 CCGCUGCACCUGUCAGGUGAG 21 13745 SCNN1A-9897 GCCGCUGCACCUGUCAGGUGAG 22 13746 SCNN1A-9898 GGCCGCUGCACCUGUCAGGUGAG 23 13747 SCNN1A-9899 AGGCCGCUGCACCUGUCAGGUGAG 24 13748 SCNN1A-9900 GCUCCCACUUAGUGAGCG 18 13749 SCNN1A-9901 UGCUCCCACUUAGUGAGCG 19 13750 SCNN1A-5668 CUGCUCCCACUUAGUGAGCG 20 9517 SCNN1A-9902 GCUGCUCCCACUUAGUGAGCG 21 13751 SCNN1A-9903 CGCUGCUCCCACUUAGUGAGCG 22 13752 SCNN1A-9904 GCGCUGCUCCCACUUAGUGAGCG 23 13753 SCNN1A-9905 UGCGCUGCUCCCACUUAGUGAGCG 24 13754 SCNN1A-9906 GCUGGCAAAUAGAAAAGG 18 13755 SCNN1A-9907 AGCUGGCAAAUAGAAAAGG 19 13756 SCNN1A-9908 GAGCUGGCAAAUAGAAAAGG 20 13757 SCNN1A-9909 UGAGCUGGCAAAUAGAAAAGG 21 13758 SCNN1A-9910 AUGAGCUGGCAAAUAGAAAAGG 22 13759 SCNN1A-9911 CAUGAGCUGGCAAAUAGAAAAGG 23 13760 SCNN1A-9912 GCAUGAGCUGGCAAAUAGAAAAGG 24 13761 SCNN1A-9913 GAGGAAGAAGACCAAAGG 18 13762 SCNN1A-9914 GGAGGAAGAAGACCAAAGG 19 13763 SCNN1A-9915 UGGAGGAAGAAGACCAAAGG 20 13764 SCNN1A-9916 CUGGAGGAAGAAGACCAAAGG 21 13765 SCNN1A-9917 CCUGGAGGAAGAAGACCAAAGG 22 13766 SCNN1A-9918 UCCUGGAGGAAGAAGACCAAAGG 23 13767 SCNN1A-9919 AUCCUGGAGGAAGAAGACCAAAGG 24 13768 SCNN1A-9920 UGCUGGCUCCAGGAAAGG 18 13769 SCNN1A-9921 CUGCUGGCUCCAGGAAAGG 19 13770 SCNN1A-6150 UCUGCUGGCUCCAGGAAAGG 20 9999 SCNN1A-9922 GUCUGCUGGCUCCAGGAAAGG 21 13771 SCNN1A-9923 GGUCUGCUGGCUCCAGGAAAGG 22 13772 SCNN1A-9924 AGGUCUGCUGGCUCCAGGAAAGG 23 13773 SCNN1A-9925 CAGGUCUGCUGGCUCCAGGAAAGG 24 13774 SCNN1A-9926 UCCCGGGUCUGGACAAGG 18 13775 SCNN1A-9927 CUCCCGGGUCUGGACAAGG 19 13776 SCNN1A-9928 CCUCCCGGGUCUGGACAAGG 20 13777 SCNN1A-9929 CCCUCCCGGGUCUGGACAAGG 21 13778 SCNN1A-9930 CCCCUCCCGGGUCUGGACAAGG 22 13779 SCNN1A-9931 GCCCCUCCCGGGUCUGGACAAGG 23 13780 SCNN1A-9932 GGCCCCUCCCGGGUCUGGACAAGG 24 13781 SCNN1A-9933 AGAGGGGGCAAGGCAAGG 18 13782 SCNN1A-9934 GAGAGGGGGCAAGGCAAGG 19 13783 SCNN1A-6152 UGAGAGGGGGCAAGGCAAGG 20 10001 SCNN1A-9935 GUGAGAGGGGGCAAGGCAAGG 21 13784 SCNN1A-9936 AGUGAGAGGGGGCAAGGCAAGG 22 13785 SCNN1A-9937 GAGUGAGAGGGGGCAAGGCAAGG 23 13786 SCNN1A-9938 AGAGUGAGAGGGGGCAAGGCAAGG 24 13787 SCNN1A-9939 AGGAAGCCACAGACCAGG 18 13788 SCNN1A-9940 GAGGAAGCCACAGACCAGG 19 13789 SCNN1A-9941 AGAGGAAGCCACAGACCAGG 20 13790 SCNN1A-9942 GAGAGGAAGCCACAGACCAGG 21 13791 SCNN1A-9943 AGAGAGGAAGCCACAGACCAGG 22 13792 SCNN1A-9944 AAGAGAGGAAGCCACAGACCAGG 23 13793 SCNN1A-9945 CAAGAGAGGAAGCCACAGACCAGG 24 13794 SCNN1A-9946 GAAAGAGGAGGGACCAGG 18 13795 SCNN1A-9947 GGAAAGAGGAGGGACCAGG 19 13796 SCNN1A-6153 AGGAAAGAGGAGGGACCAGG 20 10002 SCNN1A-9948 CAGGAAAGAGGAGGGACCAGG 21 13797 SCNN1A-9949 GCAGGAAAGAGGAGGGACCAGG 22 13798 SCNN1A-9950 AGCAGGAAAGAGGAGGGACCAGG 23 13799 SCNN1A-9951 CAGCAGGAAAGAGGAGGGACCAGG 24 13800 SCNN1A-2047 GGAGAAUGUGGGCGCAGG 18 5896 SCNN1A-2048 GGGAGAAUGUGGGCGCAGG 19 5897 SCNN1A-2049 UGGGAGAAUGUGGGCGCAGG 20 5898 SCNN1A-9952 GUGGGAGAAUGUGGGCGCAGG 21 13801 SCNN1A-9953 AGUGGGAGAAUGUGGGCGCAGG 22 13802 SCNN1A-9954 GAGUGGGAGAAUGUGGGCGCAGG 23 13803 SCNN1A-9955 GGAGUGGGAGAAUGUGGGCGCAGG 24 13804 SCNN1A-9956 UGAGCACCUUAUUGCAGG 18 13805 SCNN1A-9957 CUGAGCACCUUAUUGCAGG 19 13806 SCNN1A-9958 GCUGAGCACCUUAUUGCAGG 20 13807 SCNN1A-9959 UGCUGAGCACCUUAUUGCAGG 21 13808 SCNN1A-9960 GUGCUGAGCACCUUAUUGCAGG 22 13809 SCNN1A-9961 GGUGCUGAGCACCUUAUUGCAGG 23 13810 SCNN1A-9962 GGGUGCUGAGCACCUUAUUGCAGG 24 13811 SCNN1A-9963 UGUGUAUCAAUGCUCAGG 18 13812 SCNN1A-9964 GUGUGUAUCAAUGCUCAGG 19 13813 SCNN1A-9965 GGUGUGUAUCAAUGCUCAGG 20 13814 SCNN1A-9966 CGGUGUGUAUCAAUGCUCAGG 21 13815 SCNN1A-9967 CCGGUGUGUAUCAAUGCUCAGG 22 13816 SCNN1A-9968 CCCGGUGUGUAUCAAUGCUCAGG 23 13817 SCNN1A-9969 CCCCGGUGUGUAUCAAUGCUCAGG 24 13818 SCNN1A-9970 GAAUCAGCAGGAAAGAGG 18 13819 SCNN1A-9971 GGAAUCAGCAGGAAAGAGG 19 13820 SCNN1A-6155 AGGAAUCAGCAGGAAAGAGG 20 10004 SCNN1A-9972 GAGGAAUCAGCAGGAAAGAGG 21 13821 SCNN1A-9973 CGAGGAAUCAGCAGGAAAGAGG 22 13822 SCNN1A-9974 GCGAGGAAUCAGCAGGAAAGAGG 23 13823 SCNN1A-9975 GGCGAGGAAUCAGCAGGAAAGAGG 24 13824 SCNN1A-9976 AGUAGAUAGCCCCAGAGG 18 13825 SCNN1A-9977 AAGUAGAUAGCCCCAGAGG 19 13826 SCNN1A-5678 UAAGUAGAUAGCCCCAGAGG 20 9527 SCNN1A-9978 CUAAGUAGAUAGCCCCAGAGG 21 13827 SCNN1A-9979 GCUAAGUAGAUAGCCCCAGAGG 22 13828 SCNN1A-9980 CGCUAAGUAGAUAGCCCCAGAGG 23 13829 SCNN1A-9981 GCGCUAAGUAGAUAGCCCCAGAGG 24 13830 SCNN1A-9982 CGAGGUCAGGGCCAGAGG 18 13831 SCNN1A-9983 UCGAGGUCAGGGCCAGAGG 19 13832 SCNN1A-9984 CUCGAGGUCAGGGCCAGAGG 20 13833 SCNN1A-9985 GCUCGAGGUCAGGGCCAGAGG 21 13834 SCNN1A-9986 AGCUCGAGGUCAGGGCCAGAGG 22 13835 SCNN1A-9987 CAGCUCGAGGUCAGGGCCAGAGG 23 13836 SCNN1A-9988 ACAGCUCGAGGUCAGGGCCAGAGG 24 13837 SCNN1A-9989 AGGCAAGGGGGGGAGAGG 18 13838 SCNN1A-9990 AAGGCAAGGGGGGGAGAGG 19 13839 SCNN1A-9991 CAAGGCAAGGGGGGGAGAGG 20 13840 SCNN1A-9992 GCAAGGCAAGGGGGGGAGAGG 21 13841 SCNN1A-9993 GGCAAGGCAAGGGGGGGAGAGG 22 13842 SCNN1A-9994 GGGCAAGGCAAGGGGGGGAGAGG 23 13843 SCNN1A-9995 GGGGCAAGGCAAGGGGGGGAGAGG 24 13844 SCNN1A-9996 UAGAGAGGGAGUGAGAGG 18 13845 SCNN1A-9997 AUAGAGAGGGAGUGAGAGG 19 13846 SCNN1A-9998 GAUAGAGAGGGAGUGAGAGG 20 13847 SCNN1A-9999 AGAUAGAGAGGGAGUGAGAGG 21 13848 SCNN1A-10000 CAGAUAGAGAGGGAGUGAGAGG 22 13849 SCNN1A-10001 GCAGAUAGAGAGGGAGUGAGAGG 23 13850 SCNN1A-10002 GGCAGAUAGAGAGGGAGUGAGAGG 24 13851 SCNN1A-10003 AGAUAGCCCCAGAGGAGG 18 13852 SCNN1A-10004 UAGAUAGCCCCAGAGGAGG 19 13853 SCNN1A-5261 GUAGAUAGCCCCAGAGGAGG 20 9110 SCNN1A-10005 AGUAGAUAGCCCCAGAGGAGG 21 13854 SCNN1A-10006 AAGUAGAUAGCCCCAGAGGAGG 22 13855 SCNN1A-10007 UAAGUAGAUAGCCCCAGAGGAGG 23 13856 SCNN1A-10008 CUAAGUAGAUAGCCCCAGAGGAGG 24 13857 SCNN1A-10009 CAGGAAAGGUGGAGGAGG 18 13858 SCNN1A-10010 CCAGGAAAGGUGGAGGAGG 19 13859 SCNN1A-10011 UCCAGGAAAGGUGGAGGAGG 20 13860 SCNN1A-10012 CUCCAGGAAAGGUGGAGGAGG 21 13861 SCNN1A-10013 GCUCCAGGAAAGGUGGAGGAGG 22 13862 SCNN1A-10014 GGCUCCAGGAAAGGUGGAGGAGG 23 13863 SCNN1A-10015 UGGCUCCAGGAAAGGUGGAGGAGG 24 13864 SCNN1A-10016 AAAGGUGGAGGAGGGAGG 18 13865 SCNN1A-10017 GAAAGGUGGAGGAGGGAGG 19 13866 SCNN1A-10018 GGAAAGGUGGAGGAGGGAGG 20 13867 SCNN1A-10019 AGGAAAGGUGGAGGAGGGAGG 21 13868 SCNN1A-10020 CAGGAAAGGUGGAGGAGGGAGG 22 13869 SCNN1A-10021 CCAGGAAAGGUGGAGGAGGGAGG 23 13870 SCNN1A-10022 UCCAGGAAAGGUGGAGGAGGGAGG 24 13871 SCNN1A-10023 CUGGCUUGUGGAGGGAGG 18 13872 SCNN1A-10024 GCUGGCUUGUGGAGGGAGG 19 13873 SCNN1A-10025 UGCUGGCUUGUGGAGGGAGG 20 13874 SCNN1A-10026 CUGCUGGCUUGUGGAGGGAGG 21 13875 SCNN1A-10027 UCUGCUGGCUUGUGGAGGGAGG 22 13876 SCNN1A-10028 GUCUGCUGGCUUGUGGAGGGAGG 23 13877 SCNN1A-10029 UGUCUGCUGGCUUGUGGAGGGAGG 24 13878 SCNN1A-10030 AGACACAGAUCCUGGAGG 18 13879 SCNN1A-10031 GAGACACAGAUCCUGGAGG 19 13880 SCNN1A-10032 UGAGACACAGAUCCUGGAGG 20 13881 SCNN1A-10033 CUGAGACACAGAUCCUGGAGG 21 13882 SCNN1A-10034 GCUGAGACACAGAUCCUGGAGG 22 13883 SCNN1A-10035 AGCUGAGACACAGAUCCUGGAGG 23 13884 SCNN1A-10036 GAGCUGAGACACAGAUCCUGGAGG 24 13885 SCNN1A-10037 CUCCAGGAAAGGUGGAGG 18 13886 SCNN1A-10038 GCUCCAGGAAAGGUGGAGG 19 13887 SCNN1A-5906 GGCUCCAGGAAAGGUGGAGG 20 9755 SCNN1A-10039 UGGCUCCAGGAAAGGUGGAGG 21 13888 SCNN1A-10040 CUGGCUCCAGGAAAGGUGGAGG 22 13889 SCNN1A-10041 GCUGGCUCCAGGAAAGGUGGAGG 23 13890 SCNN1A-10042 UGCUGGCUCCAGGAAAGGUGGAGG 24 13891 SCNN1A-10043 UCUCUGCAGGGCCUGAGG 18 13892 SCNN1A-10044 UUCUCUGCAGGGCCUGAGG 19 13893 SCNN1A-10045 CUUCUCUGCAGGGCCUGAGG 20 13894 SCNN1A-10046 UCUUCUCUGCAGGGCCUGAGG 21 13895 SCNN1A-10047 CUCUUCUCUGCAGGGCCUGAGG 22 13896 SCNN1A-10048 UCUCUUCUCUGCAGGGCCUGAGG 23 13897 SCNN1A-10049 CUCUCUUCUCUGCAGGGCCUGAGG 24 13898 SCNN1A-10050 UGCACCUGUCAGGUGAGG 18 13899 SCNN1A-10051 CUGCACCUGUCAGGUGAGG 19 13900 SCNN1A-5908 GCUGCACCUGUCAGGUGAGG 20 9757 SCNN1A-10052 CGCUGCACCUGUCAGGUGAGG 21 13901 SCNN1A-10053 CCGCUGCACCUGUCAGGUGAGG 22 13902 SCNN1A-10054 GCCGCUGCACCUGUCAGGUGAGG 23 13903 SCNN1A-10055 GGCCGCUGCACCUGUCAGGUGAGG 24 13904 SCNN1A-10056 UCCCUGGCCGGCCAGCGG 18 13905 SCNN1A-10057 AUCCCUGGCCGGCCAGCGG 19 13906 SCNN1A-10058 CAUCCCUGGCCGGCCAGCGG 20 13907 SCNN1A-10059 CCAUCCCUGGCCGGCCAGCGG 21 13908 SCNN1A-10060 UCCAUCCCUGGCCGGCCAGCGG 22 13909 SCNN1A-10061 UUCCAUCCCUGGCCGGCCAGCGG 23 13910 SCNN1A-10062 CUUCCAUCCCUGGCCGGCCAGCGG 24 13911 SCNN1A-10063 GAGGGGGCAAGGCAAGGG 18 13912 SCNN1A-10064 AGAGGGGGCAAGGCAAGGG 19 13913 SCNN1A-5910 GAGAGGGGGCAAGGCAAGGG 20 9759 SCNN1A-10065 UGAGAGGGGGCAAGGCAAGGG 21 13914 SCNN1A-10066 GUGAGAGGGGGCAAGGCAAGGG 22 13915 SCNN1A-10067 AGUGAGAGGGGGCAAGGCAAGGG 23 13916 SCNN1A-10068 GAGUGAGAGGGGGCAAGGCAAGGG 24 13917 SCNN1A-2068 GAGAAUGUGGGCGCAGGG 18 5917 SCNN1A-2069 GGAGAAUGUGGGCGCAGGG 19 5918 SCNN1A-354 GGGAGAAUGUGGGCGCAGGG 20 4203 SCNN1A-2070 UGGGAGAAUGUGGGCGCAGGG 21 5919 SCNN1A-2071 GUGGGAGAAUGUGGGCGCAGGG 22 5920 SCNN1A-2072 AGUGGGAGAAUGUGGGCGCAGGG 23 5921 SCNN1A-2073 GAGUGGGAGAAUGUGGGCGCAGGG 24 5922 SCNN1A-10069 AGGAAAGGUGGAGGAGGG 18 13918 SCNN1A-10070 CAGGAAAGGUGGAGGAGGG 19 13919 SCNN1A-6162 CCAGGAAAGGUGGAGGAGGG 20 10011 SCNN1A-10071 UCCAGGAAAGGUGGAGGAGGG 21 13920 SCNN1A-10072 CUCCAGGAAAGGUGGAGGAGGG 22 13921 SCNN1A-10073 GCUCCAGGAAAGGUGGAGGAGGG 23 13922 SCNN1A-10074 GGCUCCAGGAAAGGUGGAGGAGGG 24 13923 SCNN1A-10075 UCCCACUUAGUGAGCGGG 18 13924 SCNN1A-10076 CUCCCACUUAGUGAGCGGG 19 13925 SCNN1A-10077 GCUCCCACUUAGUGAGCGGG 20 13926 SCNN1A-10078 UGCUCCCACUUAGUGAGCGGG 21 13927 SCNN1A-10079 CUGCUCCCACUUAGUGAGCGGG 22 13928 SCNN1A-10080 GCUGCUCCCACUUAGUGAGCGGG 23 13929 SCNN1A-10081 CGCUGCUCCCACUUAGUGAGCGGG 24 13930 SCNN1A-10082 AGGGGGCAAGGCAAGGGG 18 13931 SCNN1A-10083 GAGGGGGCAAGGCAAGGGG 19 13932 SCNN1A-6163 AGAGGGGGCAAGGCAAGGGG 20 10012 SCNN1A-10084 GAGAGGGGGCAAGGCAAGGGG 21 13933 SCNN1A-10085 UGAGAGGGGGCAAGGCAAGGGG 22 13934 SCNN1A-10086 GUGAGAGGGGGCAAGGCAAGGGG 23 13935 SCNN1A-10087 AGUGAGAGGGGGCAAGGCAAGGGG 24 13936 SCNN1A-10088 CACCUGUCAGGUGAGGGG 18 13937 SCNN1A-10089 GCACCUGUCAGGUGAGGGG 19 13938 SCNN1A-10090 UGCACCUGUCAGGUGAGGGG 20 13939 SCNN1A-10091 CUGCACCUGUCAGGUGAGGGG 21 13940 SCNN1A-10092 GCUGCACCUGUCAGGUGAGGGG 22 13941 SCNN1A-10093 CGCUGCACCUGUCAGGUGAGGGG 23 13942 SCNN1A-10094 CCGCUGCACCUGUCAGGUGAGGGG 24 13943 SCNN1A-10095 CCCACUUAGUGAGCGGGG 18 13944 SCNN1A-10096 UCCCACUUAGUGAGCGGGG 19 13945 SCNN1A-5689 CUCCCACUUAGUGAGCGGGG 20 9538 SCNN1A-10097 GCUCCCACUUAGUGAGCGGGG 21 13946 SCNN1A-10098 UGCUCCCACUUAGUGAGCGGGG 22 13947 SCNN1A-10099 CUGCUCCCACUUAGUGAGCGGGG 23 13948 SCNN1A-10100 GCUGCUCCCACUUAGUGAGCGGGG 24 13949 SCNN1A-10101 AAGACCAAAGGAAGGGGG 18 13950 SCNN1A-10102 GAAGACCAAAGGAAGGGGG 19 13951 SCNN1A-10103 AGAAGACCAAAGGAAGGGGG 20 13952 SCNN1A-10104 AAGAAGACCAAAGGAAGGGGG 21 13953 SCNN1A-10105 GAAGAAGACCAAAGGAAGGGGG 22 13954 SCNN1A-10106 GGAAGAAGACCAAAGGAAGGGGG 23 13955 SCNN1A-10107 AGGAAGAAGACCAAAGGAAGGGGG 24 13956 SCNN1A-10108 ACCUGUCAGGUGAGGGGG 18 13957 SCNN1A-10109 CACCUGUCAGGUGAGGGGG 19 13958 SCNN1A-5914 GCACCUGUCAGGUGAGGGGG 20 9763 SCNN1A-10110 UGCACCUGUCAGGUGAGGGGG 21 13959 SCNN1A-10111 CUGCACCUGUCAGGUGAGGGGG 22 13960 SCNN1A-10112 GCUGCACCUGUCAGGUGAGGGGG 23 13961 SCNN1A-10113 CGCUGCACCUGUCAGGUGAGGGGG 24 13962 SCNN1A-10114 GGGGCAAGGCAAGGGGGG 18 13963 SCNN1A-10115 GGGGGCAAGGCAAGGGGGG 19 13964 SCNN1A-10116 AGGGGGCAAGGCAAGGGGGG 20 13965 SCNN1A-10117 GAGGGGGCAAGGCAAGGGGGG 21 13966 SCNN1A-10118 AGAGGGGGCAAGGCAAGGGGGG 22 13967 SCNN1A-10119 GAGAGGGGGCAAGGCAAGGGGGG 23 13968 SCNN1A-10120 UGAGAGGGGGCAAGGCAAGGGGGG 24 13969 SCNN1A-10121 AGCCCUGCAGUCCUGGGG 18 13970 SCNN1A-10122 GAGCCCUGCAGUCCUGGGG 19 13971 SCNN1A-10123 GGAGCCCUGCAGUCCUGGGG 20 13972 SCNN1A-10124 UGGAGCCCUGCAGUCCUGGGG 21 13973 SCNN1A-10125 CUGGAGCCCUGCAGUCCUGGGG 22 13974 SCNN1A-10126 CCUGGAGCCCUGCAGUCCUGGGG 23 13975 SCNN1A-10127 UCCUGGAGCCCUGCAGUCCUGGGG 24 13976 SCNN1A-2080 CCAUACCAGGUCUCAUGG 18 5929 SCNN1A-2081 CCCAUACCAGGUCUCAUGG 19 5930 SCNN1A-2 GCCCAUACCAGGUCUCAUGG 20 497 SCNN1A-2082 AGCCCAUACCAGGUCUCAUGG 21 5931 SCNN1A-2083 CAGCCCAUACCAGGUCUCAUGG 22 5932 SCNN1A-2084 GCAGCCCAUACCAGGUCUCAUGG 23 5933 SCNN1A-2085 UGCAGCCCAUACCAGGUCUCAUGG 24 5934 SCNN1A-2086 GGGUUCCAGGGGUGAUGG 18 5935 SCNN1A-2087 CGGGUUCCAGGGGUGAUGG 19 5936 SCNN1A-2088 UCGGGUUCCAGGGGUGAUGG 20 5937 SCNN1A-2089 CUCGGGUUCCAGGGGUGAUGG 21 5938 SCNN1A-2090 ACUCGGGUUCCAGGGGUGAUGG 22 5939 SCNN1A-2091 CACUCGGGUUCCAGGGGUGAUGG 23 5940 SCNN1A-2092 UCACUCGGGUUCCAGGGGUGAUGG 24 5941 SCNN1A-10128 CUGAGACACAGAUCCUGG 18 13977 SCNN1A-10129 GCUGAGACACAGAUCCUGG 19 13978 SCNN1A-5693 AGCUGAGACACAGAUCCUGG 20 9542 SCNN1A-10130 GAGCUGAGACACAGAUCCUGG 21 13979 SCNN1A-10131 GGAGCUGAGACACAGAUCCUGG 22 13980 SCNN1A-10132 AGGAGCUGAGACACAGAUCCUGG 23 13981 SCNN1A-10133 CAGGAGCUGAGACACAGAUCCUGG 24 13982 SCNN1A-2093 UGAAGGGGAACAAGCUGG 18 5942 SCNN1A-2094 AUGAAGGGGAACAAGCUGG 19 5943 SCNN1A-455 CAUGAAGGGGAACAAGCUGG 20 4304 SCNN1A-2095 UCAUGAAGGGGAACAAGCUGG 21 5944 SCNN1A-2096 CUCAUGAAGGGGAACAAGCUGG 22 5945 SCNN1A-2097 GCUCAUGAAGGGGAACAAGCUGG 23 5946 SCNN1A-2098 GGCUCAUGAAGGGGAACAAGCUGG 24 5947 SCNN1A-2099 UGGAGGGGAACAAGCUGG 18 5948 SCNN1A-2100 AUGGAGGGGAACAAGCUGG 19 5949 SCNN1A-6 CAUGGAGGGGAACAAGCUGG 20 558 SCNN1A-2101 UCAUGGAGGGGAACAAGCUGG 21 5950 SCNN1A-2102 CUCAUGGAGGGGAACAAGCUGG 22 5951 SCNN1A-2103 UCUCAUGGAGGGGAACAAGCUGG 23 5952 SCNN1A-2104 GUCUCAUGGAGGGGAACAAGCUGG 24 5953 SCNN1A-10134 UGGCUCCAGGAAAGGUGG 18 13983 SCNN1A-10135 CUGGCUCCAGGAAAGGUGG 19 13984 SCNN1A-5266 GCUGGCUCCAGGAAAGGUGG 20 9115 SCNN1A-10136 UGCUGGCUCCAGGAAAGGUGG 21 13985 SCNN1A-10137 CUGCUGGCUCCAGGAAAGGUGG 22 13986 SCNN1A-10138 UCUGCUGGCUCCAGGAAAGGUGG 23 13987 SCNN1A-10139 GUCUGCUGGCUCCAGGAAAGGUGG 24 13988 SCNN1A-10140 UUGUCUGCUGGCUUGUGG 18 13989 SCNN1A-10141 UUUGUCUGCUGGCUUGUGG 19 13990 SCNN1A-5695 CUUUGUCUGCUGGCUUGUGG 20 9544 SCNN1A-10142 CCUUUGUCUGCUGGCUUGUGG 21 13991 SCNN1A-10143 GCCUUUGUCUGCUGGCUUGUGG 22 13992 SCNN1A-10144 GGCCUUUGUCUGCUGGCUUGUGG 23 13993 SCNN1A-10145 GGGCCUUUGUCUGCUGGCUUGUGG 24 13994 SCNN1A-10146 GGGUCUGGACAAGGUUGG 18 13995 SCNN1A-10147 CGGGUCUGGACAAGGUUGG 19 13996 SCNN1A-5697 CCGGGUCUGGACAAGGUUGG 20 9546 SCNN1A-10148 CCCGGGUCUGGACAAGGUUGG 21 13997 SCNN1A-10149 UCCCGGGUCUGGACAAGGUUGG 22 13998 SCNN1A-10150 CUCCCGGGUCUGGACAAGGUUGG 23 13999 SCNN1A-10151 CCUCCCGGGUCUGGACAAGGUUGG 24 14000 SCNN1A-10152 UUCUUCAUUAGGACAAUG 18 14001 SCNN1A-10153 UUUCUUCAUUAGGACAAUG 19 14002 SCNN1A-10154 GUUUCUUCAUUAGGACAAUG 20 14003 SCNN1A-10155 AGUUUCUUCAUUAGGACAAUG 21 14004 SCNN1A-10156 CAGUUUCUUCAUUAGGACAAUG 22 14005 SCNN1A-10157 UCAGUUUCUUCAUUAGGACAAUG 23 14006 SCNN1A-10158 GUCAGUUUCUUCAUUAGGACAAUG 24 14007 SCNN1A-2111 UCCACUCCGGGGCUCAUG 18 5960 SCNN1A-2112 AUCCACUCCGGGGCUCAUG 19 5961 SCNN1A-2113 AAUCCACUCCGGGGCUCAUG 20 5962 SCNN1A-2114 CAAUCCACUCCGGGGCUCAUG 21 5963 SCNN1A-2115 CCAAUCCACUCCGGGGCUCAUG 22 5964 SCNN1A-2116 CCCAAUCCACUCCGGGGCUCAUG 23 5965 SCNN1A-2117 CCCCAAUCCACUCCGGGGCUCAUG 24 5966 SCNN1A-2118 CCCAUACCAGGUCUCAUG 18 5967 SCNN1A-2119 GCCCAUACCAGGUCUCAUG 19 5968 SCNN1A-161 AGCCCAUACCAGGUCUCAUG 20 804 SCNN1A-2120 CAGCCCAUACCAGGUCUCAUG 21 5969 SCNN1A-2121 GCAGCCCAUACCAGGUCUCAUG 22 5970 SCNN1A-2122 UGCAGCCCAUACCAGGUCUCAUG 23 5971 SCNN1A-2123 CUGCAGCCCAUACCAGGUCUCAUG 24 5972 SCNN1A-10159 AGGGGUCUCUGGGAUAUG 18 14008 SCNN1A-10160 UAGGGGUCUCUGGGAUAUG 19 14009 SCNN1A-5700 CUAGGGGUCUCUGGGAUAUG 20 9549 SCNN1A-10161 UCUAGGGGUCUCUGGGAUAUG 21 14010 SCNN1A-10162 UUCUAGGGGUCUCUGGGAUAUG 22 14011 SCNN1A-10163 UUUCUAGGGGUCUCUGGGAUAUG 23 14012 SCNN1A-10164 GUUUCUAGGGGUCUCUGGGAUAUG 24 14013 SCNN1A-10165 GAGCGGGGAGGAGACCUG 18 14014 SCNN1A-10166 UGAGCGGGGAGGAGACCUG 19 14015 SCNN1A-10167 GUGAGCGGGGAGGAGACCUG 20 14016 SCNN1A-10168 AGUGAGCGGGGAGGAGACCUG 21 14017 SCNN1A-10169 UAGUGAGCGGGGAGGAGACCUG 22 14018 SCNN1A-10170 UUAGUGAGCGGGGAGGAGACCUG 23 14019 SCNN1A-10171 CUUAGUGAGCGGGGAGGAGACCUG 24 14020 SCNN1A-10172 GCUGAGACACAGAUCCUG 18 14021 SCNN1A-10173 AGCUGAGACACAGAUCCUG 19 14022 SCNN1A-10174 GAGCUGAGACACAGAUCCUG 20 14023 SCNN1A-10175 GGAGCUGAGACACAGAUCCUG 21 14024 SCNN1A-10176 AGGAGCUGAGACACAGAUCCUG 22 14025 SCNN1A-10177 CAGGAGCUGAGACACAGAUCCUG 23 14026 SCNN1A-10178 GCAGGAGCUGAGACACAGAUCCUG 24 14027 SCNN1A-10179 ACUCUGGGCUGCCUCCUG 18 14028 SCNN1A-10180 CACUCUGGGCUGCCUCCUG 19 14029 SCNN1A-5269 GCACUCUGGGCUGCCUCCUG 20 9118 SCNN1A-10181 UGCACUCUGGGCUGCCUCCUG 21 14030 SCNN1A-10182 CUGCACUCUGGGCUGCCUCCUG 22 14031 SCNN1A-10183 CCUGCACUCUGGGCUGCCUCCUG 23 14032 SCNN1A-10184 UCCUGCACUCUGGGCUGCCUCCUG 24 14033 SCNN1A-2124 AUGAAGGGGAACAAGCUG 18 5973 SCNN1A-2125 CAUGAAGGGGAACAAGCUG 19 5974 SCNN1A-2126 UCAUGAAGGGGAACAAGCUG 20 5975 SCNN1A-2127 CUCAUGAAGGGGAACAAGCUG 21 5976 SCNN1A-2128 GCUCAUGAAGGGGAACAAGCUG 22 5977 SCNN1A-2129 GGCUCAUGAAGGGGAACAAGCUG 23 5978 SCNN1A-2130 GGGCUCAUGAAGGGGAACAAGCUG 24 5979 SCNN1A-2131 AUGGAGGGGAACAAGCUG 18 5980 SCNN1A-2132 CAUGGAGGGGAACAAGCUG 19 5981 SCNN1A-167 UCAUGGAGGGGAACAAGCUG 20 806 SCNN1A-2133 CUCAUGGAGGGGAACAAGCUG 21 5982 SCNN1A-2134 UCUCAUGGAGGGGAACAAGCUG 22 5983 SCNN1A-2135 GUCUCAUGGAGGGGAACAAGCUG 23 5984 SCNN1A-2136 GGUCUCAUGGAGGGGAACAAGCUG 24 5985 SCNN1A-10185 CCUCUUCUCUCUUCUCUG 18 14034 SCNN1A-10186 ACCUCUUCUCUCUUCUCUG 19 14035 SCNN1A-10187 GACCUCUUCUCUCUUCUCUG 20 14036 SCNN1A-10188 AGACCUCUUCUCUCUUCUCUG 21 14037 SCNN1A-10189 GAGACCUCUUCUCUCUUCUCUG 22 14038 SCNN1A-10190 AGAGACCUCUUCUCUCUUCUCUG 23 14039 SCNN1A-10191 CAGAGACCUCUUCUCUCUUCUCUG 24 14040 SCNN1A-10192 GGGGCAGUGGGGACAGUG 18 14041 SCNN1A-10193 UGGGGCAGUGGGGACAGUG 19 14042 SCNN1A-10194 GUGGGGCAGUGGGGACAGUG 20 14043 SCNN1A-10195 UGUGGGGCAGUGGGGACAGUG 21 14044 SCNN1A-10196 AUGUGGGGCAGUGGGGACAGUG 22 14045 SCNN1A-10197 UAUGUGGGGCAGUGGGGACAGUG 23 14046 SCNN1A-10198 AUAUGUGGGGCAGUGGGGACAGUG 24 14047 SCNN1A-10199 GGGCUCUGUGUGGGAGUG 18 14048 SCNN1A-10200 CGGGCUCUGUGUGGGAGUG 19 14049 SCNN1A-5711 ACGGGCUCUGUGUGGGAGUG 20 9560 SCNN1A-10201 CACGGGCUCUGUGUGGGAGUG 21 14050 SCNN1A-10202 CCACGGGCUCUGUGUGGGAGUG 22 14051 SCNN1A-10203 UCCACGGGCUCUGUGUGGGAGUG 23 14052 SCNN1A-10204 AUCCACGGGCUCUGUGUGGGAGUG 24 14053 SCNN1A-10205 CCUCCUGUGGGGCCCGUG 18 14054 SCNN1A-10206 GCCUCCUGUGGGGCCCGUG 19 14055 SCNN1A-5712 UGCCUCCUGUGGGGCCCGUG 20 9561 SCNN1A-10207 CUGCCUCCUGUGGGGCCCGUG 21 14056 SCNN1A-10208 GCUGCCUCCUGUGGGGCCCGUG 22 14057 SCNN1A-10209 GGCUGCCUCCUGUGGGGCCCGUG 23 14058 SCNN1A-10210 GGGCUGCCUCCUGUGGGGCCCGUG 24 14059 SCNN1A-10211 AGCCUUCCCUGCCGCGUG 18 14060 SCNN1A-10212 CAGCCUUCCCUGCCGCGUG 19 14061 SCNN1A-10213 GCAGCCUUCCCUGCCGCGUG 20 14062 SCNN1A-10214 GGCAGCCUUCCCUGCCGCGUG 21 14063 SCNN1A-10215 CGGCAGCCUUCCCUGCCGCGUG 22 14064 SCNN1A-10216 GCGGCAGCCUUCCCUGCCGCGUG 23 14065 SCNN1A-10217 AGCGGCAGCCUUCCCUGCCGCGUG 24 14066 SCNN1A-10218 CUGGCUCCAGGAAAGGUG 18 14067 SCNN1A-10219 GCUGGCUCCAGGAAAGGUG 19 14068 SCNN1A-10220 UGCUGGCUCCAGGAAAGGUG 20 14069 SCNN1A-10221 CUGCUGGCUCCAGGAAAGGUG 21 14070 SCNN1A-10222 UCUGCUGGCUCCAGGAAAGGUG 22 14071 SCNN1A-10223 GUCUGCUGGCUCCAGGAAAGGUG 23 14072 SCNN1A-10224 GGUCUGCUGGCUCCAGGAAAGGUG 24 14073 SCNN1A-10225 CGCUGCACCUGUCAGGUG 18 14074 SCNN1A-10226 CCGCUGCACCUGUCAGGUG 19 14075 SCNN1A-5270 GCCGCUGCACCUGUCAGGUG 20 9119 SCNN1A-10227 GGCCGCUGCACCUGUCAGGUG 21 14076 SCNN1A-10228 AGGCCGCUGCACCUGUCAGGUG 22 14077 SCNN1A-10229 CAGGCCGCUGCACCUGUCAGGUG 23 14078 SCNN1A-10230 CCAGGCCGCUGCACCUGUCAGGUG 24 14079 SCNN1A-10231 GAUCAAACAGCCAGGGUG 18 14080 SCNN1A-10232 AGAUCAAACAGCCAGGGUG 19 14081 SCNN1A-10233 GAGAUCAAACAGCCAGGGUG 20 14082 SCNN1A-10234 UGAGAUCAAACAGCCAGGGUG 21 14083 SCNN1A-10235 UUGAGAUCAAACAGCCAGGGUG 22 14084 SCNN1A-10236 UUUGAGAUCAAACAGCCAGGGUG 23 14085 SCNN1A-10237 CUUUGAGAUCAAACAGCCAGGGUG 24 14086 SCNN1A-2143 ACUCGGGUUCCAGGGGUG 18 5992 SCNN1A-2144 CACUCGGGUUCCAGGGGUG 19 5993 SCNN1A-2145 UCACUCGGGUUCCAGGGGUG 20 5994 SCNN1A-2146 CUCACUCGGGUUCCAGGGGUG 21 5995 SCNN1A-2147 CCUCACUCGGGUUCCAGGGGUG 22 5996 SCNN1A-2148 GCCUCACUCGGGUUCCAGGGGUG 23 5997 SCNN1A-2149 AGCCUCACUCGGGUUCCAGGGGUG 24 5998 SCNN1A-10238 ACAAGGUUGGAGGGGGUG 18 14087 SCNN1A-10239 GACAAGGUUGGAGGGGGUG 19 14088 SCNN1A-10240 GGACAAGGUUGGAGGGGGUG 20 14089 SCNN1A-10241 UGGACAAGGUUGGAGGGGGUG 21 14090 SCNN1A-10242 CUGGACAAGGUUGGAGGGGGUG 22 14091 SCNN1A-10243 UCUGGACAAGGUUGGAGGGGGUG 23 14092 SCNN1A-10244 GUCUGGACAAGGUUGGAGGGGGUG 24 14093 SCNN1A-10245 GAAUCCACGGGCUCUGUG 18 14094 SCNN1A-10246 CGAAUCCACGGGCUCUGUG 19 14095 SCNN1A-5717 ACGAAUCCACGGGCUCUGUG 20 9566 SCNN1A-10247 GACGAAUCCACGGGCUCUGUG 21 14096 SCNN1A-10248 AGACGAAUCCACGGGCUCUGUG 22 14097 SCNN1A-10249 CAGACGAAUCCACGGGCUCUGUG 23 14098 SCNN1A-10250 GCAGACGAAUCCACGGGCUCUGUG 24 14099 SCNN1A-10251 UUUGUCUGCUGGCUUGUG 18 14100 SCNN1A-10252 CUUUGUCUGCUGGCUUGUG 19 14101 SCNN1A-10253 CCUUUGUCUGCUGGCUUGUG 20 14102 SCNN1A-10254 GCCUUUGUCUGCUGGCUUGUG 21 14103 SCNN1A-10255 GGCCUUUGUCUGCUGGCUUGUG 22 14104 SCNN1A-10256 GGGCCUUUGUCUGCUGGCUUGUG 23 14105 SCNN1A-10257 UGGGCCUUUGUCUGCUGGCUUGUG 24 14106 SCNN1A-10258 GUGCUGAGCACCUUAUUG 18 14107 SCNN1A-10259 GGUGCUGAGCACCUUAUUG 19 14108 SCNN1A-10260 GGGUGCUGAGCACCUUAUUG 20 14109 SCNN1A-10261 AGGGUGCUGAGCACCUUAUUG 21 14110 SCNN1A-10262 CAGGGUGCUGAGCACCUUAUUG 22 14111 SCNN1A-10263 CCAGGGUGCUGAGCACCUUAUUG 23 14112 SCNN1A-10264 GCCAGGGUGCUGAGCACCUUAUUG 24 14113 SCNN1A-10265 UGGAGGGCUGCCCACUUG 18 14114 SCNN1A-10266 UUGGAGGGCUGCCCACUUG 19 14115 SCNN1A-10267 CUUGGAGGGCUGCCCACUUG 20 14116 SCNN1A-10268 CCUUGGAGGGCUGCCCACUUG 21 14117 SCNN1A-10269 CCCUUGGAGGGCUGCCCACUUG 22 14118 SCNN1A-10270 GCCCUUGGAGGGCUGCCCACUUG 23 14119 SCNN1A-10271 UGCCCUUGGAGGGCUGCCCACUUG 24 14120 SCNN1A-10272 GACCUGUGGGUGCCCUUG 18 14121 SCNN1A-10273 UGACCUGUGGGUGCCCUUG 19 14122 SCNN1A-10274 CUGACCUGUGGGUGCCCUUG 20 14123 SCNN1A-10275 GCUGACCUGUGGGUGCCCUUG 21 14124 SCNN1A-10276 GGCUGACCUGUGGGUGCCCUUG 22 14125 SCNN1A-10277 AGGCUGACCUGUGGGUGCCCUUG 23 14126 SCNN1A-10278 GAGGCUGACCUGUGGGUGCCCUUG 24 14127 SCNN1A-10279 CCUUUGUCUGCUGGCUUG 18 14128 SCNN1A-10280 GCCUUUGUCUGCUGGCUUG 19 14129 SCNN1A-5271 GGCCUUUGUCUGCUGGCUUG 20 9120 SCNN1A-10281 GGGCCUUUGUCUGCUGGCUUG 21 14130 SCNN1A-10282 UGGGCCUUUGUCUGCUGGCUUG 22 14131 SCNN1A-10283 CUGGGCCUUUGUCUGCUGGCUUG 23 14132 SCNN1A-10284 GCUGGGCCUUUGUCUGCUGGCUUG 24 14133 SCNN1A-10285 CGGGUCUGGACAAGGUUG 18 14134 SCNN1A-10286 CCGGGUCUGGACAAGGUUG 19 14135 SCNN1A-10287 CCCGGGUCUGGACAAGGUUG 20 14136 SCNN1A-10288 UCCCGGGUCUGGACAAGGUUG 21 14137 SCNN1A-10289 CUCCCGGGUCUGGACAAGGUUG 22 14138 SCNN1A-10290 CCUCCCGGGUCUGGACAAGGUUG 23 14139 SCNN1A-10291 CCCUCCCGGGUCUGGACAAGGUUG 24 14140 SCNN1A-10292 GUUUGGAAAGAGAUUUUG 18 14141 SCNN1A-10293 AGUUUGGAAAGAGAUUUUG 19 14142 SCNN1A-10294 AAGUUUGGAAAGAGAUUUUG 20 14143 SCNN1A-10295 UAAGUUUGGAAAGAGAUUUUG 21 14144 SCNN1A-10296 UUAAGUUUGGAAAGAGAUUUUG 22 14145 SCNN1A-10297 AUUAAGUUUGGAAAGAGAUUUUG 23 14146 SCNN1A-10298 CAUUAAGUUUGGAAAGAGAUUUUG 24 14147 SCNN1A-10299 GUCUUAUCUCUGAGAAAU 18 14148 SCNN1A-10300 UGUCUUAUCUCUGAGAAAU 19 14149 SCNN1A-10301 AUGUCUUAUCUCUGAGAAAU 20 14150 SCNN1A-10302 UAUGUCUUAUCUCUGAGAAAU 21 14151 SCNN1A-10303 UUAUGUCUUAUCUCUGAGAAAU 22 14152 SCNN1A-10304 CUUAUGUCUUAUCUCUGAGAAAU 23 14153 SCNN1A-10305 UCUUAUGUCUUAUCUCUGAGAAAU 24 14154 SCNN1A-10306 CUGGGGCAGAGACAGAAU 18 14155 SCNN1A-10307 CCUGGGGCAGAGACAGAAU 19 14156 SCNN1A-10308 UCCUGGGGCAGAGACAGAAU 20 14157 SCNN1A-10309 GUCCUGGGGCAGAGACAGAAU 21 14158 SCNN1A-10310 AGUCCUGGGGCAGAGACAGAAU 22 14159 SCNN1A-10311 CAGUCCUGGGGCAGAGACAGAAU 23 14160 SCNN1A-10312 GCAGUCCUGGGGCAGAGACAGAAU 24 14161 SCNN1A-10313 AGGGAGGAGUGGGAGAAU 18 14162 SCNN1A-10314 GAGGGAGGAGUGGGAGAAU 19 14163 SCNN1A-10315 GGAGGGAGGAGUGGGAGAAU 20 14164 SCNN1A-10316 GGGAGGGAGGAGUGGGAGAAU 21 14165 SCNN1A-10317 AGGGAGGGAGGAGUGGGAGAAU 22 14166 SCNN1A-10318 GAGGGAGGGAGGAGUGGGAGAAU 23 14167 SCNN1A-10319 GGAGGGAGGGAGGAGUGGGAGAAU 24 14168 SCNN1A-10320 AAGGGUCAGUUUCUUCAU 18 14169 SCNN1A-10321 GAAGGGUCAGUUUCUUCAU 19 14170 SCNN1A-10322 GGAAGGGUCAGUUUCUUCAU 20 14171 SCNN1A-10323 GGGAAGGGUCAGUUUCUUCAU 21 14172 SCNN1A-10324 UGGGAAGGGUCAGUUUCUUCAU 22 14173 SCNN1A-10325 UUGGGAAGGGUCAGUUUCUUCAU 23 14174 SCNN1A-10326 CUUGGGAAGGGUCAGUUUCUUCAU 24 14175 SCNN1A-10327 GAGGAAGAGAGGCAGGAU 18 14176 SCNN1A-10328 AGAGGAAGAGAGGCAGGAU 19 14177 SCNN1A-10329 GAGAGGAAGAGAGGCAGGAU 20 14178 SCNN1A-10330 GGAGAGGAAGAGAGGCAGGAU 21 14179 SCNN1A-10331 GGGAGAGGAAGAGAGGCAGGAU 22 14180 SCNN1A-10332 GGGGAGAGGAAGAGAGGCAGGAU 23 14181 SCNN1A-10333 GGGGGAGAGGAAGAGAGGCAGGAU 24 14182 SCNN1A-2150 UCGGGUUCCAGGGGUGAU 18 5999 SCNN1A-2151 CUCGGGUUCCAGGGGUGAU 19 6000 SCNN1A-421 ACUCGGGUUCCAGGGGUGAU 20 4270 SCNN1A-2152 CACUCGGGUUCCAGGGGUGAU 21 6001 SCNN1A-2153 UCACUCGGGUUCCAGGGGUGAU 22 6002 SCNN1A-2154 CUCACUCGGGUUCCAGGGGUGAU 23 6003 SCNN1A-2155 CCUCACUCGGGUUCCAGGGGUGAU 24 6004 SCNN1A-10334 UCUCACAGAGCCCUUGAU 18 14183 SCNN1A-10335 UUCUCACAGAGCCCUUGAU 19 14184 SCNN1A-10336 CUUCUCACAGAGCCCUUGAU 20 14185 SCNN1A-10337 UCUUCUCACAGAGCCCUUGAU 21 14186 SCNN1A-10338 UUCUUCUCACAGAGCCCUUGAU 22 14187 SCNN1A-10339 AUUCUUCUCACAGAGCCCUUGAU 23 14188 SCNN1A-10340 AAUUCUUCUCACAGAGCCCUUGAU 24 14189 SCNN1A-10341 UAGGGGUCUCUGGGAUAU 18 14190 SCNN1A-10342 CUAGGGGUCUCUGGGAUAU 19 14191 SCNN1A-10343 UCUAGGGGUCUCUGGGAUAU 20 14192 SCNN1A-10344 UUCUAGGGGUCUCUGGGAUAU 21 14193 SCNN1A-10345 UUUCUAGGGGUCUCUGGGAUAU 22 14194 SCNN1A-10346 GUUUCUAGGGGUCUCUGGGAUAU 23 14195 SCNN1A-10347 AGUUUCUAGGGGUCUCUGGGAUAU 24 14196 SCNN1A-10348 CUCGAAAGGUGGCCCUAU 18 14197 SCNN1A-10349 ACUCGAAAGGUGGCCCUAU 19 14198 SCNN1A-10350 AACUCGAAAGGUGGCCCUAU 20 14199 SCNN1A-10351 AAACUCGAAAGGUGGCCCUAU 21 14200 SCNN1A-10352 AAAACUCGAAAGGUGGCCCUAU 22 14201 SCNN1A-10353 CAAAACUCGAAAGGUGGCCCUAU 23 14202 SCNN1A-10354 ACAAAACUCGAAAGGUGGCCCUAU 24 14203 SCNN1A-10355 AGCUCCUGGAAGCACACU 18 14204 SCNN1A-10356 UAGCUCCUGGAAGCACACU 19 14205 SCNN1A-5727 CUAGCUCCUGGAAGCACACU 20 9576 SCNN1A-10357 UCUAGCUCCUGGAAGCACACU 21 14206 SCNN1A-10358 CUCUAGCUCCUGGAAGCACACU 22 14207 SCNN1A-10359 CCUCUAGCUCCUGGAAGCACACU 23 14208 SCNN1A-10360 GCCUCUAGCUCCUGGAAGCACACU 24 14209 SCNN1A-2156 UGCUCUCCCCAAUCCACU 18 6005 SCNN1A-2157 UUGCUCUCCCCAAUCCACU 19 6006 SCNN1A-2158 CUUGCUCUCCCCAAUCCACU 20 6007 SCNN1A-2159 CCUUGCUCUCCCCAAUCCACU 21 6008 SCNN1A-2160 CCCUUGCUCUCCCCAAUCCACU 22 6009 SCNN1A-2161 ACCCUUGCUCUCCCCAAUCCACU 23 6010 SCNN1A-2162 GACCCUUGCUCUCCCCAAUCCACU 24 6011 SCNN1A-2163 GUGAUGGGAGAGGGCACU 18 6012 SCNN1A-2164 GGUGAUGGGAGAGGGCACU 19 6013 SCNN1A-2165 GGGUGAUGGGAGAGGGCACU 20 6014 SCNN1A-2166 GGGGUGAUGGGAGAGGGCACU 21 6015 SCNN1A-2167 AGGGGUGAUGGGAGAGGGCACU 22 6016 SCNN1A-2168 CAGGGGUGAUGGGAGAGGGCACU 23 6017 SCNN1A-2169 CCAGGGGUGAUGGGAGAGGGCACU 24 6018 SCNN1A-10361 UGACCACAUUCCUGCACU 18 14210 SCNN1A-10362 GUGACCACAUUCCUGCACU 19 14211 SCNN1A-10363 AGUGACCACAUUCCUGCACU 20 14212 SCNN1A-10364 CAGUGACCACAUUCCUGCACU 21 14213 SCNN1A-10365 CCAGUGACCACAUUCCUGCACU 22 14214 SCNN1A-10366 GCCAGUGACCACAUUCCUGCACU 23 14215 SCNN1A-10367 AGCCAGUGACCACAUUCCUGCACU 24 14216 SCNN1A-10368 AGGUGCUUUUCAGAACCU 18 14217 SCNN1A-10369 GAGGUGCUUUUCAGAACCU 19 14218 SCNN1A-10370 GGAGGUGCUUUUCAGAACCU 20 14219 SCNN1A-10371 GGGAGGUGCUUUUCAGAACCU 21 14220 SCNN1A-10372 AGGGAGGUGCUUUUCAGAACCU 22 14221 SCNN1A-10373 CAGGGAGGUGCUUUUCAGAACCU 23 14222 SCNN1A-10374 GCAGGGAGGUGCUUUUCAGAACCU 24 14223 SCNN1A-10375 UAUUUUGUUUUCUAACCU 18 14224 SCNN1A-10376 CUAUUUUGUUUUCUAACCU 19 14225 SCNN1A-10377 CCUAUUUUGUUUUCUAACCU 20 14226 SCNN1A-10378 UCCUAUUUUGUUUUCUAACCU 21 14227 SCNN1A-10379 CUCCUAUUUUGUUUUCUAACCU 22 14228 SCNN1A-10380 GCUCCUAUUUUGUUUUCUAACCU 23 14229 SCNN1A-10381 UGCUCCUAUUUUGUUUUCUAACCU 24 14230 SCNN1A-10382 UCCCAGUUCACCUGCCCU 18 14231 SCNN1A-10383 CUCCCAGUUCACCUGCCCU 19 14232 SCNN1A-5736 ACUCCCAGUUCACCUGCCCU 20 9585 SCNN1A-10384 UACUCCCAGUUCACCUGCCCU 21 14233 SCNN1A-10385 GUACUCCCAGUUCACCUGCCCU 22 14234 SCNN1A-10386 AGUACUCCCAGUUCACCUGCCCU 23 14235 SCNN1A-10387 CAGUACUCCCAGUUCACCUGCCCU 24 14236 SCNN1A-10388 CUGACCUGUGGGUGCCCU 18 14237 SCNN1A-10389 GCUGACCUGUGGGUGCCCU 19 14238 SCNN1A-5274 GGCUGACCUGUGGGUGCCCU 20 9123 SCNN1A-10390 AGGCUGACCUGUGGGUGCCCU 21 14239 SCNN1A-10391 GAGGCUGACCUGUGGGUGCCCU 22 14240 SCNN1A-10392 UGAGGCUGACCUGUGGGUGCCCU 23 14241 SCNN1A-10393 GUGAGGCUGACCUGUGGGUGCCCU 24 14242 SCNN1A-10394 AGAAAACUGAUUUAUCCU 18 14243 SCNN1A-10395 CAGAAAACUGAUUUAUCCU 19 14244 SCNN1A-6181 UCAGAAAACUGAUUUAUCCU 20 10030 SCNN1A-10396 CUCAGAAAACUGAUUUAUCCU 21 14245 SCNN1A-10397 CCUCAGAAAACUGAUUUAUCCU 22 14246 SCNN1A-10398 ACCUCAGAAAACUGAUUUAUCCU 23 14247 SCNN1A-10399 AACCUCAGAAAACUGAUUUAUCCU 24 14248 SCNN1A-10400 CACUCUGGGCUGCCUCCU 18 14249 SCNN1A-10401 GCACUCUGGGCUGCCUCCU 19 14250 SCNN1A-10402 UGCACUCUGGGCUGCCUCCU 20 14251 SCNN1A-10403 CUGCACUCUGGGCUGCCUCCU 21 14252 SCNN1A-10404 CCUGCACUCUGGGCUGCCUCCU 22 14253 SCNN1A-10405 UCCUGCACUCUGGGCUGCCUCCU 23 14254 SCNN1A-10406 UUCCUGCACUCUGGGCUGCCUCCU 24 14255 SCNN1A-10407 UCGGGAGCCCUCCUUCCU 18 14256 SCNN1A-10408 CUCGGGAGCCCUCCUUCCU 19 14257 SCNN1A-10409 CCUCGGGAGCCCUCCUUCCU 20 14258 SCNN1A-10410 CCCUCGGGAGCCCUCCUUCCU 21 14259 SCNN1A-10411 GCCCUCGGGAGCCCUCCUUCCU 22 14260 SCNN1A-10412 UGCCCUCGGGAGCCCUCCUUCCU 23 14261 SCNN1A-10413 CUGCCCUCGGGAGCCCUCCUUCCU 24 14262 SCNN1A-10414 GGGCCAGAGGCUGGAGCU 18 14263 SCNN1A-10415 AGGGCCAGAGGCUGGAGCU 19 14264 SCNN1A-10416 CAGGGCCAGAGGCUGGAGCU 20 14265 SCNN1A-10417 UCAGGGCCAGAGGCUGGAGCU 21 14266 SCNN1A-10418 GUCAGGGCCAGAGGCUGGAGCU 22 14267 SCNN1A-10419 GGUCAGGGCCAGAGGCUGGAGCU 23 14268 SCNN1A-10420 AGGUCAGGGCCAGAGGCUGGAGCU 24 14269 SCNN1A-10421 UGUGUUGCCCUCCUAGCU 18 14270 SCNN1A-10422 UUGUGUUGCCCUCCUAGCU 19 14271 SCNN1A-10423 CUUGUGUUGCCCUCCUAGCU 20 14272 SCNN1A-10424 CCUUGUGUUGCCCUCCUAGCU 21 14273 SCNN1A-10425 UCCUUGUGUUGCCCUCCUAGCU 22 14274 SCNN1A-10426 CUCCUUGUGUUGCCCUCCUAGCU 23 14275 SCNN1A-10427 UCUCCUUGUGUUGCCCUCCUAGCU 24 14276 SCNN1A-10428 GGCUCUUAUGUCUUAUCU 18 14277 SCNN1A-10429 UGGCUCUUAUGUCUUAUCU 19 14278 SCNN1A-10430 UUGGCUCUUAUGUCUUAUCU 20 14279 SCNN1A-10431 CUUGGCUCUUAUGUCUUAUCU 21 14280 SCNN1A-10432 CCUUGGCUCUUAUGUCUUAUCU 22 14281 SCNN1A-10433 CCCUUGGCUCUUAUGUCUUAUCU 23 14282 SCNN1A-10434 GCCCUUGGCUCUUAUGUCUUAUCU 24 14283 SCNN1A-10435 CUCUUAUGUCUUAUCUCU 18 14284 SCNN1A-10436 GCUCUUAUGUCUUAUCUCU 19 14285 SCNN1A-10437 GGCUCUUAUGUCUUAUCUCU 20 14286 SCNN1A-10438 UGGCUCUUAUGUCUUAUCUCU 21 14287 SCNN1A-10439 UUGGCUCUUAUGUCUUAUCUCU 22 14288 SCNN1A-10440 CUUGGCUCUUAUGUCUUAUCUCU 23 14289 SCNN1A-10441 CCUUGGCUCUUAUGUCUUAUCUCU 24 14290 SCNN1A-10442 AGAGAUGACACCUUCUCU 18 14291 SCNN1A-10443 CAGAGAUGACACCUUCUCU 19 14292 SCNN1A-5926 GCAGAGAUGACACCUUCUCU 20 9775 SCNN1A-10444 AGCAGAGAUGACACCUUCUCU 21 14293 SCNN1A-10445 CAGCAGAGAUGACACCUUCUCU 22 14294 SCNN1A-10446 UCAGCAGAGAUGACACCUUCUCU 23 14295 SCNN1A-10447 UUCAGCAGAGAUGACACCUUCUCU 24 14296 SCNN1A-10448 UGGAGUUUCUAGGGGUCU 18 14297 SCNN1A-10449 CUGGAGUUUCUAGGGGUCU 19 14298 SCNN1A-10450 ACUGGAGUUUCUAGGGGUCU 20 14299 SCNN1A-10451 GACUGGAGUUUCUAGGGGUCU 21 14300 SCNN1A-10452 AGACUGGAGUUUCUAGGGGUCU 22 14301 SCNN1A-10453 GAGACUGGAGUUUCUAGGGGUCU 23 14302 SCNN1A-10454 GGAGACUGGAGUUUCUAGGGGUCU 24 14303 SCNN1A-10455 UCCCCCAUGAGUCUGUCU 18 14304 SCNN1A-10456 AUCCCCCAUGAGUCUGUCU 19 14305 SCNN1A-10457 GAUCCCCCAUGAGUCUGUCU 20 14306 SCNN1A-10458 CGAUCCCCCAUGAGUCUGUCU 21 14307 SCNN1A-10459 CCGAUCCCCCAUGAGUCUGUCU 22 14308 SCNN1A-10460 CCCGAUCCCCCAUGAGUCUGUCU 23 14309 SCNN1A-10461 CCCCGAUCCCCCAUGAGUCUGUCU 24 14310 SCNN1A-10462 GCAGAGAUGACACCUUCU 18 14311 SCNN1A-10463 AGCAGAGAUGACACCUUCU 19 14312 SCNN1A-10464 CAGCAGAGAUGACACCUUCU 20 14313 SCNN1A-10465 UCAGCAGAGAUGACACCUUCU 21 14314 SCNN1A-10466 UUCAGCAGAGAUGACACCUUCU 22 14315 SCNN1A-10467 AUUCAGCAGAGAUGACACCUUCU 23 14316 SCNN1A-10468 GAUUCAGCAGAGAUGACACCUUCU 24 14317 SCNN1A-10469 CAGAGGAGAGGCCGUUCU 18 14318 SCNN1A-10470 GCAGAGGAGAGGCCGUUCU 19 14319 SCNN1A-5750 AGCAGAGGAGAGGCCGUUCU 20 9599 SCNN1A-10471 AAGCAGAGGAGAGGCCGUUCU 21 14320 SCNN1A-10472 GAAGCAGAGGAGAGGCCGUUCU 22 14321 SCNN1A-10473 GGAAGCAGAGGAGAGGCCGUUCU 23 14322 SCNN1A-10474 GGGAAGCAGAGGAGAGGCCGUUCU 24 14323 SCNN1A-10475 CCUUUUGCUGCAUUAAGU 18 14324 SCNN1A-10476 UCCUUUUGCUGCAUUAAGU 19 14325 SCNN1A-10477 AUCCUUUUGCUGCAUUAAGU 20 14326 SCNN1A-10478 UAUCCUUUUGCUGCAUUAAGU 21 14327 SCNN1A-10479 UUAUCCUUUUGCUGCAUUAAGU 22 14328 SCNN1A-10480 CUUAUCCUUUUGCUGCAUUAAGU 23 14329 SCNN1A-10481 CCUUAUCCUUUUGCUGCAUUAAGU 24 14330 SCNN1A-10482 UGGGAUAUGUGGGGCAGU 18 14331 SCNN1A-10483 CUGGGAUAUGUGGGGCAGU 19 14332 SCNN1A-5753 UCUGGGAUAUGUGGGGCAGU 20 9602 SCNN1A-10484 CUCUGGGAUAUGUGGGGCAGU 21 14333 SCNN1A-10485 UCUCUGGGAUAUGUGGGGCAGU 22 14334 SCNN1A-10486 GUCUCUGGGAUAUGUGGGGCAGU 23 14335 SCNN1A-10487 GGUCUCUGGGAUAUGUGGGGCAGU 24 14336 SCNN1A-10488 GAGCUGAGGGCCUAGAGU 18 14337 SCNN1A-10489 GGAGCUGAGGGCCUAGAGU 19 14338 SCNN1A-10490 UGGAGCUGAGGGCCUAGAGU 20 14339 SCNN1A-10491 CUGGAGCUGAGGGCCUAGAGU 21 14340 SCNN1A-10492 GCUGGAGCUGAGGGCCUAGAGU 22 14341 SCNN1A-10493 GGCUGGAGCUGAGGGCCUAGAGU 23 14342 SCNN1A-10494 AGGCUGGAGCUGAGGGCCUAGAGU 24 14343 SCNN1A-10495 GAGGAGGGAGGGAGGAGU 18 14344 SCNN1A-10496 GGAGGAGGGAGGGAGGAGU 19 14345 SCNN1A-6187 UGGAGGAGGGAGGGAGGAGU 20 10036 SCNN1A-10497 GUGGAGGAGGGAGGGAGGAGU 21 14346 SCNN1A-10498 GGUGGAGGAGGGAGGGAGGAGU 22 14347 SCNN1A-10499 AGGUGGAGGAGGGAGGGAGGAGU 23 14348 SCNN1A-10500 AAGGUGGAGGAGGGAGGGAGGAGU 24 14349 SCNN1A-10501 GGCAGAUAGAGAGGGAGU 18 14350 SCNN1A-10502 AGGCAGAUAGAGAGGGAGU 19 14351 SCNN1A-10503 AAGGCAGAUAGAGAGGGAGU 20 14352 SCNN1A-10504 GAAGGCAGAUAGAGAGGGAGU 21 14353 SCNN1A-10505 AGAAGGCAGAUAGAGAGGGAGU 22 14354 SCNN1A-10506 CAGAAGGCAGAUAGAGAGGGAGU 23 14355 SCNN1A-10507 ACAGAAGGCAGAUAGAGAGGGAGU 24 14356 SCNN1A-10508 CAGCCGCAACCUGGGAGU 18 14357 SCNN1A-10509 CCAGCCGCAACCUGGGAGU 19 14358 SCNN1A-5754 UCCAGCCGCAACCUGGGAGU 20 9603 SCNN1A-10510 GUCCAGCCGCAACCUGGGAGU 21 14359 SCNN1A-10511 AGUCCAGCCGCAACCUGGGAGU 22 14360 SCNN1A-10512 CAGUCCAGCCGCAACCUGGGAGU 23 14361 SCNN1A-10513 CCAGUCCAGCCGCAACCUGGGAGU 24 14362 SCNN1A-10514 CGGGCUCUGUGUGGGAGU 18 14363 SCNN1A-10515 ACGGGCUCUGUGUGGGAGU 19 14364 SCNN1A-10516 CACGGGCUCUGUGUGGGAGU 20 14365 SCNN1A-10517 CCACGGGCUCUGUGUGGGAGU 21 14366 SCNN1A-10518 UCCACGGGCUCUGUGUGGGAGU 22 14367 SCNN1A-10519 AUCCACGGGCUCUGUGUGGGAGU 23 14368 SCNN1A-10520 AAUCCACGGGCUCUGUGUGGGAGU 24 14369 SCNN1A-10521 GCCUCCUGUGGGGCCCGU 18 14370 SCNN1A-10522 UGCCUCCUGUGGGGCCCGU 19 14371 SCNN1A-10523 CUGCCUCCUGUGGGGCCCGU 20 14372 SCNN1A-10524 GCUGCCUCCUGUGGGGCCCGU 21 14373 SCNN1A-10525 GGCUGCCUCCUGUGGGGCCCGU 22 14374 SCNN1A-10526 GGGCUGCCUCCUGUGGGGCCCGU 23 14375 SCNN1A-10527 UGGGCUGCCUCCUGUGGGGCCCGU 24 14376 SCNN1A-10528 CCCGGGUCUGGACAAGGU 18 14377 SCNN1A-10529 UCCCGGGUCUGGACAAGGU 19 14378 SCNN1A-5755 CUCCCGGGUCUGGACAAGGU 20 9604 SCNN1A-10530 CCUCCCGGGUCUGGACAAGGU 21 14379 SCNN1A-10531 CCCUCCCGGGUCUGGACAAGGU 22 14380 SCNN1A-10532 CCCCUCCCGGGUCUGGACAAGGU 23 14381 SCNN1A-10533 GCCCCUCCCGGGUCUGGACAAGGU 24 14382 SCNN1A-10534 CCGCUGCACCUGUCAGGU 18 14383 SCNN1A-10535 GCCGCUGCACCUGUCAGGU 19 14384 SCNN1A-10536 GGCCGCUGCACCUGUCAGGU 20 14385 SCNN1A-10537 AGGCCGCUGCACCUGUCAGGU 21 14386 SCNN1A-10538 CAGGCCGCUGCACCUGUCAGGU 22 14387 SCNN1A-10539 CCAGGCCGCUGCACCUGUCAGGU 23 14388 SCNN1A-10540 GCCAGGCCGCUGCACCUGUCAGGU 24 14389 SCNN1A-10541 CAGGACACAGCUCGAGGU 18 14390 SCNN1A-10542 UCAGGACACAGCUCGAGGU 19 14391 SCNN1A-10543 AUCAGGACACAGCUCGAGGU 20 14392 SCNN1A-10544 AAUCAGGACACAGCUCGAGGU 21 14393 SCNN1A-10545 GAAUCAGGACACAGCUCGAGGU 22 14394 SCNN1A-10546 AGAAUCAGGACACAGCUCGAGGU 23 14395 SCNN1A-10547 CAGAAUCAGGACACAGCUCGAGGU 24 14396 SCNN1A-10548 CCUGGGCCCCUCCCGGGU 18 14397 SCNN1A-10549 ACCUGGGCCCCUCCCGGGU 19 14398 SCNN1A-10550 CACCUGGGCCCCUCCCGGGU 20 14399 SCNN1A-10551 UCACCUGGGCCCCUCCCGGGU 21 14400 SCNN1A-10552 UUCACCUGGGCCCCUCCCGGGU 22 14401 SCNN1A-10553 CUUCACCUGGGCCCCUCCCGGGU 23 14402 SCNN1A-10554 GCUUCACCUGGGCCCCUCCCGGGU 24 14403 SCNN1A-2176 UAAGCAAGGGAACCUGGU 18 6025 SCNN1A-2177 GUAAGCAAGGGAACCUGGU 19 6026 SCNN1A-2178 GGUAAGCAAGGGAACCUGGU 20 6027 SCNN1A-2179 AGGUAAGCAAGGGAACCUGGU 21 6028 SCNN1A-2180 AAGGUAAGCAAGGGAACCUGGU 22 6029 SCNN1A-2181 CAAGGUAAGCAAGGGAACCUGGU 23 6030 SCNN1A-2182 UCAAGGUAAGCAAGGGAACCUGGU 24 6031 SCNN1A-10555 GAGGACCAUGCCCAAUGU 18 14404 SCNN1A-10556 GGAGGACCAUGCCCAAUGU 19 14405 SCNN1A-10557 GGGAGGACCAUGCCCAAUGU 20 14406 SCNN1A-10558 AGGGAGGACCAUGCCCAAUGU 21 14407 SCNN1A-10559 CAGGGAGGACCAUGCCCAAUGU 22 14408 SCNN1A-10560 GCAGGGAGGACCAUGCCCAAUGU 23 14409 SCNN1A-10561 UGCAGGGAGGACCAUGCCCAAUGU 24 14410 SCNN1A-10562 CGAAUCCACGGGCUCUGU 18 14411 SCNN1A-10563 ACGAAUCCACGGGCUCUGU 19 14412 SCNN1A-10564 GACGAAUCCACGGGCUCUGU 20 14413 SCNN1A-10565 AGACGAAUCCACGGGCUCUGU 21 14414 SCNN1A-10566 CAGACGAAUCCACGGGCUCUGU 22 14415 SCNN1A-10567 GCAGACGAAUCCACGGGCUCUGU 23 14416 SCNN1A-10568 AGCAGACGAAUCCACGGGCUCUGU 24 14417 SCNN1A-10569 UGAGAUCUGCACUUUUGU 18 14418 SCNN1A-10570 CUGAGAUCUGCACUUUUGU 19 14419 SCNN1A-10571 UCUGAGAUCUGCACUUUUGU 20 14420 SCNN1A-10572 AUCUGAGAUCUGCACUUUUGU 21 14421 SCNN1A-10573 AAUCUGAGAUCUGCACUUUUGU 22 14422 SCNN1A-10574 AAAUCUGAGAUCUGCACUUUUGU 23 14423 SCNN1A-10575 GAAAUCUGAGAUCUGCACUUUUGU 24 14424 SCNN1A-10576 UAAGUUUGGAAAGAGAUU 18 14425 SCNN1A-10577 UUAAGUUUGGAAAGAGAUU 19 14426 SCNN1A-10578 AUUAAGUUUGGAAAGAGAUU 20 14427 SCNN1A-10579 CAUUAAGUUUGGAAAGAGAUU 21 14428 SCNN1A-10580 GCAUUAAGUUUGGAAAGAGAUU 22 14429 SCNN1A-10581 UGCAUUAAGUUUGGAAAGAGAUU 23 14430 SCNN1A-10582 CUGCAUUAAGUUUGGAAAGAGAUU 24 14431 SCNN1A-10583 GAAAACUGAUUUAUCCUU 18 14432 SCNN1A-10584 AGAAAACUGAUUUAUCCUU 19 14433 SCNN1A-6189 CAGAAAACUGAUUUAUCCUU 20 10038 SCNN1A-10585 UCAGAAAACUGAUUUAUCCUU 21 14434 SCNN1A-10586 CUCAGAAAACUGAUUUAUCCUU 22 14435 SCNN1A-10587 CCUCAGAAAACUGAUUUAUCCUU 23 14436 SCNN1A-10588 ACCUCAGAAAACUGAUUUAUCCUU 24 14437 SCNN1A-10589 CGGGAGCCCUCCUUCCUU 18 14438 SCNN1A-10590 UCGGGAGCCCUCCUUCCUU 19 14439 SCNN1A-5770 CUCGGGAGCCCUCCUUCCUU 20 9619 SCNN1A-10591 CCUCGGGAGCCCUCCUUCCUU 21 14440 SCNN1A-10592 CCCUCGGGAGCCCUCCUUCCUU 22 14441 SCNN1A-10593 GCCCUCGGGAGCCCUCCUUCCUU 23 14442 SCNN1A-10594 UGCCCUCGGGAGCCCUCCUUCCUU 24 14443 SCNN1A-10595 GCCUUUGUCUGCUGGCUU 18 14444 SCNN1A-10596 GGCCUUUGUCUGCUGGCUU 19 14445 SCNN1A-10597 GGGCCUUUGUCUGCUGGCUU 20 14446 SCNN1A-10598 UGGGCCUUUGUCUGCUGGCUU 21 14447 SCNN1A-10599 CUGGGCCUUUGUCUGCUGGCUU 22 14448 SCNN1A-10600 GCUGGGCCUUUGUCUGCUGGCUU 23 14449 SCNN1A-10601 GGCUGGGCCUUUGUCUGCUGGCUU 24 14450 SCNN1A-10602 CUUUUGCUGCAUUAAGUU 18 14451 SCNN1A-10603 CCUUUUGCUGCAUUAAGUU 19 14452 SCNN1A-5771 UCCUUUUGCUGCAUUAAGUU 20 9620 SCNN1A-10604 AUCCUUUUGCUGCAUUAAGUU 21 14453 SCNN1A-10605 UAUCCUUUUGCUGCAUUAAGUU 22 14454 SCNN1A-10606 UUAUCCUUUUGCUGCAUUAAGUU 23 14455 SCNN1A-10607 CUUAUCCUUUUGCUGCAUUAAGUU 24 14456 SCNN1A-10608 AAGUUUGGAAAGAGAUUU 18 14457 SCNN1A-10609 UAAGUUUGGAAAGAGAUUU 19 14458 SCNN1A-5773 UUAAGUUUGGAAAGAGAUUU 20 9622 SCNN1A-10610 AUUAAGUUUGGAAAGAGAUUU 21 14459 SCNN1A-10611 CAUUAAGUUUGGAAAGAGAUUU 22 14460 SCNN1A-10612 GCAUUAAGUUUGGAAAGAGAUUU 23 14461 SCNN1A-10613 UGCAUUAAGUUUGGAAAGAGAUUU 24 14462 SCNN1A-10614 GACACCGGCUUUCACUUU 18 14463 SCNN1A-10615 UGACACCGGCUUUCACUUU 19 14464 SCNN1A-10616 UUGACACCGGCUUUCACUUU 20 14465 SCNN1A-10617 GUUGACACCGGCUUUCACUUU 21 14466 SCNN1A-10618 GGUUGACACCGGCUUUCACUUU 22 14467 SCNN1A-10619 UGGUUGACACCGGCUUUCACUUU 23 14468 SCNN1A-10620 CUGGUUGACACCGGCUUUCACUUU 24 14469 SCNN1A-10621 AGGCAGGGAGGUGCUUUU 18 14470 SCNN1A-10622 AAGGCAGGGAGGUGCUUUU 19 14471 SCNN1A-10623 AAAGGCAGGGAGGUGCUUUU 20 14472 SCNN1A-10624 AAAAGGCAGGGAGGUGCUUUU 21 14473 SCNN1A-10625 GAAAAGGCAGGGAGGUGCUUUU 22 14474 SCNN1A-10626 AGAAAAGGCAGGGAGGUGCUUUU 23 14475 SCNN1A-10627 UAGAAAAGGCAGGGAGGUGCUUUU 24 14476

Table 47E provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the fifth tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS, starts with a 5′G and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through co Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene mplementary base pairing. Any of the targeting domains in the Table can be used with a S. aureus Cas9 molecule that generates a double stranded break (Cas9 nuclease) or a single-stranded break (Cas9 nickase).

TABLE 47E 5th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-10628 + GCCUGGUCUGGGCUGAGCCA 20 14477 SCNN1A-1302 + GGUUGAUGUUGAGGCUGA 18 5151 SCNN1A-42 + GAGGUUGAUGUUGAGGCUGA 20 519 SCNN1A-1303 + GUUGAGGUUGAUGUUGAGGCUGA 23 5152 SCNN1A-10629 + GUGAGCUCUACCUGGGAC 18 14478 SCNN1A-10630 + GCAGUGAGCUCUACCUGGGAC 21 14479 SCNN1A-1417 + GUUCCCCUUCAUGAGCCC 18 5266 SCNN1A-1420 + GCUUGUUCCCCUUCAUGAGCCC 22 5269 SCNN1A-1427 + GCACACCAGGCGGAUGGCGCC 21 5276 SCNN1A-1429 + GAGCACACCAGGCGGAUGGCGCC 23 5278 SCNN1A-1430 + GGAGCACACCAGGCGGAUGGCGCC 24 5279 SCNN1A-10631 + GAUCAUGCACUAUCCUCUAGGC 22 14480 SCNN1A-10632 + GGAUCAUGCACUAUCCUCUAGGC 23 14481 SCNN1A-1316 + GUGCUGGGAGCACACCAG 18 5165 SCNN1A-1317 + GUUGUGCUGGGAGCACACCAG 21 5166 SCNN1A-1318 + GGUUGUGCUGGGAGCACACCAG 22 5167 SCNN1A-1319 + GCGGUUGUGCUGGGAGCACACCAG 24 5168 SCNN1A-1320 + GUACUCUCCGAAAAGCAGG 19 5169 SCNN1A-1321 + GAAGUACUCUCCGAAAAGCAGG 22 5170 SCNN1A-10633 + GUGACCCUGCCACGUCCUG 19 14482 SCNN1A-10634 + GGUGACCCUGCCACGUCCUG 20 14483 SCNN1A-10635 + GUGGUGACCCUGCCACGUCCUG 22 14484 SCNN1A-10636 + GGUGGUGACCCUGCCACGUCCUG 23 14485 SCNN1A-10637 + GGGUGGUGACCCUGCCACGUCCUG 24 14486 SCNN1A-10638 + GCCACGUCCUGCCGGGUAU 19 14487 SCNN1A-1326 + GAGGGACUAACCGACCUGU 19 5175 SCNN1A-1327 + GCAGAGGGACUAACCGACCUGU 22 5176 SCNN1A-1328 + GGCAGAGGGACUAACCGACCUGU 23 5177 SCNN1A-1329 + GGGCAGAGGGACUAACCGACCUGU 24 5178 SCNN1A-1330 + GCGGGGAAGACGAGCUUGU 19 5179 SCNN1A-1331 + GACUAACCGACCUGUAGGGAUU 22 5180 SCNN1A-1332 + GGACUAACCGACCUGUAGGGAUU 23 5181 SCNN1A-1333 + GGGACUAACCGACCUGUAGGGAUU 24 5182 SCNN1A-1334 GCGGAGGAGGAGGCCCUGA 19 5183 SCNN1A-189 GGCGGAGGAGGAGGCCCUGA 20 819 SCNN1A-10639 GCUGCUGUACUCCAGCCUA 19 14488 SCNN1A-10640 GUUCUAGCCCGCUCCAGGUC 20 14489 SCNN1A-10641 GCCUGUUCUAGCCCGCUCCAGGUC 24 14490 SCNN1A-10642 GCGCCUGGAAGGGUGGUC 18 14491 SCNN1A-10643 GCCUGCGCCUGGAAGGGUGGUC 22 14492 SCNN1A-10644 GUGCCUGCGCCUGGAAGGGUGGUC 24 14493 SCNN1A-197 GCAAUUCGGCCUGCUUUUCG 20 826 SCNN1A-1337 GGCAAUUCGGCCUGCUUUUCG 21 5186 SCNN1A-10645 GCAGGCAGAGCCUCAGACCU 20 14494 SCNN1A-10646 GGCAGGCAGAGCCUCAGACCU 21 14495 SCNN1A-10647 GGGCAGGCAGAGCCUCAGACCU 22 14496 SCNN1A-1338 GCUCCUACCGAGAGCUCU 18 5187

Table 47F provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the six tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS and PAM is NNGRRT. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 47F 6th Tier Target DNA Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-10648 + CUGGUCUGGGCUGAGCCA 18 14497 SCNN1A-10649 + CCUGGUCUGGGCUGAGCCA 19 14498 SCNN1A-10650 + UGCCUGGUCUGGGCUGAGCCA 21 14499 SCNN1A-10651 + AUGCCUGGUCUGGGCUGAGCCA 22 14500 SCNN1A-10652 + AAUGCCUGGUCUGGGCUGAGCCA 23 14501 SCNN1A-10653 + CAAUGCCUGGUCUGGGCUGAGCCA 24 14502 SCNN1A-10654 + UCUUAUUUAUCUUAGAGA 18 14503 SCNN1A-10655 + UUCUUAUUUAUCUUAGAGA 19 14504 SCNN1A-10656 + UUUCUUAUUUAUCUUAGAGA 20 14505 SCNN1A-10657 + UUUUCUUAUUUAUCUUAGAGA 21 14506 SCNN1A-10658 + AUUUUCUUAUUUAUCUUAGAGA 22 14507 SCNN1A-10659 + UAUUUUCUUAUUUAUCUUAGAGA 23 14508 SCNN1A-10660 + UUAUUUUCUUAUUUAUCUUAGAGA 24 14509 SCNN1A-1340 + AGGUUGAUGUUGAGGCUGA 19 5189 SCNN1A-1341 + UGAGGUUGAUGUUGAGGCUGA 21 5190 SCNN1A-1342 + UUGAGGUUGAUGUUGAGGCUGA 22 5191 SCNN1A-1343 + AGUUGAGGUUGAUGUUGAGGCUGA 24 5192 SCNN1A-10661 + AGUGAGCUCUACCUGGGAC 19 14510 SCNN1A-6306 + CAGUGAGCUCUACCUGGGAC 20 10155 SCNN1A-10662 + AGCAGUGAGCUCUACCUGGGAC 22 14511 SCNN1A-10663 + CAGCAGUGAGCUCUACCUGGGAC 23 14512 SCNN1A-10664 + CCAGCAGUGAGCUCUACCUGGGAC 24 14513 SCNN1A-1418 + UGUUCCCCUUCAUGAGCCC 19 5267 SCNN1A-72 + UUGUUCCCCUUCAUGAGCCC 20 599 SCNN1A-1419 + CUUGUUCCCCUUCAUGAGCCC 21 5268 SCNN1A-1423 + CGCUUGUUCCCCUUCAUGAGCCC 23 5272 SCNN1A-1424 + ACGCUUGUUCCCCUUCAUGAGCCC 24 5273 SCNN1A-1425 + CACCAGGCGGAUGGCGCC 18 5274 SCNN1A-1426 + ACACCAGGCGGAUGGCGCC 19 5275 SCNN1A-223 + CACACCAGGCGGAUGGCGCC 20 846 SCNN1A-1428 + AGCACACCAGGCGGAUGGCGCC 22 5277 SCNN1A-10665 + AUGCACUAUCCUCUAGGC 18 14514 SCNN1A-10666 + CAUGCACUAUCCUCUAGGC 19 14515 SCNN1A-6323 + UCAUGCACUAUCCUCUAGGC 20 10172 SCNN1A-10667 + AUCAUGCACUAUCCUCUAGGC 21 14516 SCNN1A-10668 + AGGAUCAUGCACUAUCCUCUAGGC 24 14517 SCNN1A-1371 + UGUGCUGGGAGCACACCAG 19 5220 SCNN1A-224 + UUGUGCUGGGAGCACACCAG 20 847 SCNN1A-1372 + CGGUUGUGCUGGGAGCACACCAG 23 5221 SCNN1A-1373 + UACUCUCCGAAAAGCAGG 18 5222 SCNN1A-230 + AGUACUCUCCGAAAAGCAGG 20 851 SCNN1A-1374 + AAGUACUCUCCGAAAAGCAGG 21 5223 SCNN1A-1375 + UGAAGUACUCUCCGAAAAGCAGG 23 5224 SCNN1A-1376 + CUGAAGUACUCUCCGAAAAGCAGG 24 5225 SCNN1A-10669 + UGACCCUGCCACGUCCUG 18 14518 SCNN1A-10670 + UGGUGACCCUGCCACGUCCUG 21 14519 SCNN1A-10671 + CCACGUCCUGCCGGGUAU 18 14520 SCNN1A-6350 + UGCCACGUCCUGCCGGGUAU 20 10199 SCNN1A-10672 + CUGCCACGUCCUGCCGGGUAU 21 14521 SCNN1A-10673 + CCUGCCACGUCCUGCCGGGUAU 22 14522 SCNN1A-10674 + CCCUGCCACGUCCUGCCGGGUAU 23 14523 SCNN1A-10675 + ACCCUGCCACGUCCUGCCGGGUAU 24 14524 SCNN1A-1380 + AGGGACUAACCGACCUGU 18 5229 SCNN1A-424 + AGAGGGACUAACCGACCUGU 20 4273 SCNN1A-1381 + CAGAGGGACUAACCGACCUGU 21 5230 SCNN1A-1382 + CGGGGAAGACGAGCUUGU 18 5231 SCNN1A-237 + UGCGGGGAAGACGAGCUUGU 20 857 SCNN1A-1383 + CUGCGGGGAAGACGAGCUUGU 21 5232 SCNN1A-1384 + ACUGCGGGGAAGACGAGCUUGU 22 5233 SCNN1A-1385 + CACUGCGGGGAAGACGAGCUUGU 23 5234 SCNN1A-1386 + UCACUGCGGGGAAGACGAGCUUGU 24 5235 SCNN1A-1387 + AACCGACCUGUAGGGAUU 18 5236 SCNN1A-1388 + UAACCGACCUGUAGGGAUU 19 5237 SCNN1A-1389 + CUAACCGACCUGUAGGGAUU 20 5238 SCNN1A-1390 + ACUAACCGACCUGUAGGGAUU 21 5239 SCNN1A-1391 CGGAGGAGGAGGCCCUGA 18 5240 SCNN1A-1433 CGGCGGAGGAGGAGGCCCUGA 21 5282 SCNN1A-1434 ACGGCGGAGGAGGAGGCCCUGA 22 5283 SCNN1A-1435 CACGGCGGAGGAGGAGGCCCUGA 23 5284 SCNN1A-1436 CCACGGCGGAGGAGGAGGCCCUGA 24 5285 SCNN1A-10676 CUGCUGUACUCCAGCCUA 18 14525 SCNN1A-10677 UGCUGCUGUACUCCAGCCUA 20 14526 SCNN1A-10678 AUGCUGCUGUACUCCAGCCUA 21 14527 SCNN1A-10679 CAUGCUGCUGUACUCCAGCCUA 22 14528 SCNN1A-10680 UCAUGCUGCUGUACUCCAGCCUA 23 14529 SCNN1A-10681 AUCAUGCUGCUGUACUCCAGCCUA 24 14530 SCNN1A-10682 UCUAGCCCGCUCCAGGUC 18 14531 SCNN1A-10683 UUCUAGCCCGCUCCAGGUC 19 14532 SCNN1A-10684 UGUUCUAGCCCGCUCCAGGUC 21 14533 SCNN1A-10685 CUGUUCUAGCCCGCUCCAGGUC 22 14534 SCNN1A-10686 CCUGUUCUAGCCCGCUCCAGGUC 23 14535 SCNN1A-10687 UGCGCCUGGAAGGGUGGUC 19 14536 SCNN1A-10688 CUGCGCCUGGAAGGGUGGUC 20 14537 SCNN1A-10689 CCUGCGCCUGGAAGGGUGGUC 21 14538 SCNN1A-10690 UGCCUGCGCCUGGAAGGGUGGUC 23 14539 SCNN1A-1395 AAUUCGGCCUGCUUUUCG 18 5244 SCNN1A-1396 CAAUUCGGCCUGCUUUUCG 19 5245 SCNN1A-1397 UGGCAAUUCGGCCUGCUUUUCG 22 5246 SCNN1A-1398 CUGGCAAUUCGGCCUGCUUUUCG 23 5247 SCNN1A-1399 ACUGGCAAUUCGGCCUGCUUUUCG 24 5248 SCNN1A-10691 CCUGGUGCCUGCGCCUGG 18 14540 SCNN1A-10692 CCCUGGUGCCUGCGCCUGG 19 14541 SCNN1A-10693 UCCCUGGUGCCUGCGCCUGG 20 14542 SCNN1A-10694 UUCCCUGGUGCCUGCGCCUGG 21 14543 SCNN1A-10695 CUUCCCUGGUGCCUGCGCCUGG 22 14544 SCNN1A-10696 CCUUCCCUGGUGCCUGCGCCUGG 23 14545 SCNN1A-10697 CCCUUCCCUGGUGCCUGCGCCUGG 24 14546 SCNN1A-10698 AUACCCGGCAGGACGUGG 18 14547 SCNN1A-10699 CAUACCCGGCAGGACGUGG 19 14548 SCNN1A-10700 CCAUACCCGGCAGGACGUGG 20 14549 SCNN1A-10701 CCCAUACCCGGCAGGACGUGG 21 14550 SCNN1A-10702 UCCCAUACCCGGCAGGACGUGG 22 14551 SCNN1A-10703 CUCCCAUACCCGGCAGGACGUGG 23 14552 SCNN1A-10704 ACUCCCAUACCCGGCAGGACGUGG 24 14553 SCNN1A-10705 AGGCAGAGCCUCAGACCU 18 14554 SCNN1A-10706 CAGGCAGAGCCUCAGACCU 19 14555 SCNN1A-10707 UGGGCAGGCAGAGCCUCAGACCU 23 14556 SCNN1A-10708 CUGGGCAGGCAGAGCCUCAGACCU 24 14557 SCNN1A-1400 CGCUCCUACCGAGAGCUCU 19 5249 SCNN1A-192 CCGCUCCUACCGAGAGCUCU 20 822 SCNN1A-1401 ACCGCUCCUACCGAGAGCUCU 21 5250 SCNN1A-1402 CACCGCUCCUACCGAGAGCUCU 22 5251 SCNN1A-1403 CCACCGCUCCUACCGAGAGCUCU 23 5252 SCNN1A-1404 UCCACCGCUCCUACCGAGAGCUCU 24 5253

Table 47G provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the seven tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS and PAM is NNGRRV. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a S. aureus eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 47G 7th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-10709 + UUGGUGUUGUGAGGAAAA 18 14558 SCNN1A-10710 + CUUGGUGUUGUGAGGAAAA 19 14559 SCNN1A-10711 + GCUUGGUGUUGUGAGGAAAA 20 14560 SCNN1A-10712 + GGCUUGGUGUUGUGAGGAAAA 21 14561 SCNN1A-10713 + AGGCUUGGUGUUGUGAGGAAAA 22 14562 SCNN1A-10714 + CAGGCUUGGUGUUGUGAGGAAAA 23 14563 SCNN1A-10715 + ACAGGCUUGGUGUUGUGAGGAAAA 24 14564 SCNN1A-10716 + UUCCUUUCCCUCCCCAAA 18 14565 SCNN1A-10717 + CUUCCUUUCCCUCCCCAAA 19 14566 SCNN1A-6279 + CCUUCCUUUCCCUCCCCAAA 20 10128 SCNN1A-10718 + CCCUUCCUUUCCCUCCCCAAA 21 14567 SCNN1A-10719 + CCCCUUCCUUUCCCUCCCCAAA 22 14568 SCNN1A-10720 + UCCCCUUCCUUUCCCUCCCCAAA 23 14569 SCNN1A-10721 + GUCCCCUUCCUUUCCCUCCCCAAA 24 14570 SCNN1A-10722 + CUUCCUUUCCCUCCCCAA 18 14571 SCNN1A-10723 + CCUUCCUUUCCCUCCCCAA 19 14572 SCNN1A-6281 + CCCUUCCUUUCCCUCCCCAA 20 10130 SCNN1A-10724 + CCCCUUCCUUUCCCUCCCCAA 21 14573 SCNN1A-10725 + UCCCCUUCCUUUCCCUCCCCAA 22 14574 SCNN1A-10726 + GUCCCCUUCCUUUCCCUCCCCAA 23 14575 SCNN1A-10727 + AGUCCCCUUCCUUUCCCUCCCCAA 24 14576 SCNN1A-10728 + UUCCAGGCGCAGGCACCA 18 14577 SCNN1A-10729 + CUUCCAGGCGCAGGCACCA 19 14578 SCNN1A-6290 + CCUUCCAGGCGCAGGCACCA 20 10139 SCNN1A-10730 + CCCUUCCAGGCGCAGGCACCA 21 14579 SCNN1A-10731 + ACCCUUCCAGGCGCAGGCACCA 22 14580 SCNN1A-10732 + CACCCUUCCAGGCGCAGGCACCA 23 14581 SCNN1A-10733 + CCACCCUUCCAGGCGCAGGCACCA 24 14582 SCNN1A-10734 + CCUUCCUUUCCCUCCCCA 18 14583 SCNN1A-10735 + CCCUUCCUUUCCCUCCCCA 19 14584 SCNN1A-10736 + CCCCUUCCUUUCCCUCCCCA 20 14585 SCNN1A-10737 + UCCCCUUCCUUUCCCUCCCCA 21 14586 SCNN1A-10738 + GUCCCCUUCCUUUCCCUCCCCA 22 14587 SCNN1A-10739 + AGUCCCCUUCCUUUCCCUCCCCA 23 14588 SCNN1A-10740 + UAGUCCCCUUCCUUUCCCUCCCCA 24 14589 SCNN1A-10741 + UGAGGCUCUGCCUGCCCA 18 14590 SCNN1A-10742 + CUGAGGCUCUGCCUGCCCA 19 14591 SCNN1A-10743 + UCUGAGGCUCUGCCUGCCCA 20 14592 SCNN1A-10744 + GUCUGAGGCUCUGCCUGCCCA 21 14593 SCNN1A-10745 + GGUCUGAGGCUCUGCCUGCCCA 22 14594 SCNN1A-10746 + AGGUCUGAGGCUCUGCCUGCCCA 23 14595 SCNN1A-10747 + CAGGUCUGAGGCUCUGCCUGCCCA 24 14596 SCNN1A-10748 + GGCACCAGGGAAGGGGCA 18 14597 SCNN1A-10749 + AGGCACCAGGGAAGGGGCA 19 14598 SCNN1A-10750 + CAGGCACCAGGGAAGGGGCA 20 14599 SCNN1A-10751 + GCAGGCACCAGGGAAGGGGCA 21 14600 SCNN1A-10752 + CGCAGGCACCAGGGAAGGGGCA 22 14601 SCNN1A-10753 + GCGCAGGCACCAGGGAAGGGGCA 23 14602 SCNN1A-10754 + GGCGCAGGCACCAGGGAAGGGGCA 24 14603 SCNN1A-10755 + AGGCGCAGGCACCAGGGA 18 14604 SCNN1A-10756 + CAGGCGCAGGCACCAGGGA 19 14605 SCNN1A-6296 + CCAGGCGCAGGCACCAGGGA 20 10145 SCNN1A-10757 + UCCAGGCGCAGGCACCAGGGA 21 14606 SCNN1A-10758 + UUCCAGGCGCAGGCACCAGGGA 22 14607 SCNN1A-10759 + CUUCCAGGCGCAGGCACCAGGGA 23 14608 SCNN1A-10760 + CCUUCCAGGCGCAGGCACCAGGGA 24 14609 SCNN1A-1452 + CUAACCGACCUGUAGGGA 18 5301 SCNN1A-1453 + ACUAACCGACCUGUAGGGA 19 5302 SCNN1A-1454 + GACUAACCGACCUGUAGGGA 20 5303 SCNN1A-1455 + GGACUAACCGACCUGUAGGGA 21 5304 SCNN1A-1456 + GGGACUAACCGACCUGUAGGGA 22 5305 SCNN1A-1457 + AGGGACUAACCGACCUGUAGGGA 23 5306 SCNN1A-1458 + GAGGGACUAACCGACCUGUAGGGA 24 5307 SCNN1A-10761 + AGUGAGCUCUACCUGGGA 18 14610 SCNN1A-10762 + CAGUGAGCUCUACCUGGGA 19 14611 SCNN1A-10763 + GCAGUGAGCUCUACCUGGGA 20 14612 SCNN1A-10764 + AGCAGUGAGCUCUACCUGGGA 21 14613 SCNN1A-10765 + CAGCAGUGAGCUCUACCUGGGA 22 14614 SCNN1A-10766 + CCAGCAGUGAGCUCUACCUGGGA 23 14615 SCNN1A-10767 + GCCAGCAGUGAGCUCUACCUGGGA 24 14616 SCNN1A-10768 + CAGCAUUCUAGACCUGGA 18 14617 SCNN1A-10769 + GCAGCAUUCUAGACCUGGA 19 14618 SCNN1A-10770 + UGCAGCAUUCUAGACCUGGA 20 14619 SCNN1A-10771 + CUGCAGCAUUCUAGACCUGGA 21 14620 SCNN1A-10772 + GCUGCAGCAUUCUAGACCUGGA 22 14621 SCNN1A-10773 + UGCUGCAGCAUUCUAGACCUGGA 23 14622 SCNN1A-10774 + GUGCUGCAGCAUUCUAGACCUGGA 24 14623 SCNN1A-1459 + CCCUUCAUGAGCCCUGGA 18 5308 SCNN1A-1460 + CCCCUUCAUGAGCCCUGGA 19 5309 SCNN1A-205 + UCCCCUUCAUGAGCCCUGGA 20 833 SCNN1A-1461 + UUCCCCUUCAUGAGCCCUGGA 21 5310 SCNN1A-1462 + GUUCCCCUUCAUGAGCCCUGGA 22 5311 SCNN1A-1463 + UGUUCCCCUUCAUGAGCCCUGGA 23 5312 SCNN1A-1464 + UUGUUCCCCUUCAUGAGCCCUGGA 24 5313 SCNN1A-10775 + UAUAGUUCUUUUUUAUGA 18 14624 SCNN1A-10776 + AUAUAGUUCUUUUUUAUGA 19 14625 SCNN1A-10777 + UAUAUAGUUCUUUUUUAUGA 20 14626 SCNN1A-10778 + AUAUAUAGUUCUUUUUUAUGA 21 14627 SCNN1A-10779 + AAUAUAUAGUUCUUUUUUAUGA 22 14628 SCNN1A-10780 + AAAUAUAUAGUUCUUUUUUAUGA 23 14629 SCNN1A-10781 + AAAAUAUAUAGUUCUUUUUUAUGA 24 14630 SCNN1A-10782 + UACAAUUUUUCAGCAAUA 18 14631 SCNN1A-10783 + GUACAAUUUUUCAGCAAUA 19 14632 SCNN1A-10784 + AGUACAAUUUUUCAGCAAUA 20 14633 SCNN1A-10785 + CAGUACAAUUUUUCAGCAAUA 21 14634 SCNN1A-10786 + ACAGUACAAUUUUUCAGCAAUA 22 14635 SCNN1A-10787 + CACAGUACAAUUUUUCAGCAAUA 23 14636 SCNN1A-10788 + UCACAGUACAAUUUUUCAGCAAUA 24 14637 SCNN1A-10789 + CAGCAAUACAGAAGUAUA 18 14638 SCNN1A-10790 + UCAGCAAUACAGAAGUAUA 19 14639 SCNN1A-10791 + UUCAGCAAUACAGAAGUAUA 20 14640 SCNN1A-10792 + UUUCAGCAAUACAGAAGUAUA 21 14641 SCNN1A-10793 + UUUUCAGCAAUACAGAAGUAUA 22 14642 SCNN1A-10794 + UUUUUCAGCAAUACAGAAGUAUA 23 14643 SCNN1A-10795 + AUUUUUCAGCAAUACAGAAGUAUA 24 14644 SCNN1A-10796 + GCCACGUCCUGCCGGGUA 18 14645 SCNN1A-10797 + UGCCACGUCCUGCCGGGUA 19 14646 SCNN1A-6301 + CUGCCACGUCCUGCCGGGUA 20 10150 SCNN1A-10798 + CCUGCCACGUCCUGCCGGGUA 21 14647 SCNN1A-10799 + CCCUGCCACGUCCUGCCGGGUA 22 14648 SCNN1A-10800 + ACCCUGCCACGUCCUGCCGGGUA 23 14649 SCNN1A-10801 + GACCCUGCCACGUCCUGCCGGGUA 24 14650 SCNN1A-1478 + GUGUUGUUGCAGAAGAAC 18 5327 SCNN1A-1479 + GGUGUUGUUGCAGAAGAAC 19 5328 SCNN1A-220 + UGGUGUUGUUGCAGAAGAAC 20 843 SCNN1A-1480 + GUGGUGUUGUUGCAGAAGAAC 21 5329 SCNN1A-1481 + GGUGGUGUUGUUGCAGAAGAAC 22 5330 SCNN1A-1482 + UGGUGGUGUUGUUGCAGAAGAAC 23 5331 SCNN1A-1483 + AUGGUGGUGUUGUUGCAGAAGAAC 24 5332 SCNN1A-10802 + CCUUCCAGGCGCAGGCAC 18 14651 SCNN1A-10803 + CCCUUCCAGGCGCAGGCAC 19 14652 SCNN1A-10804 + ACCCUUCCAGGCGCAGGCAC 20 14653 SCNN1A-10805 + CACCCUUCCAGGCGCAGGCAC 21 14654 SCNN1A-10806 + CCACCCUUCCAGGCGCAGGCAC 22 14655 SCNN1A-10807 + ACCACCCUUCCAGGCGCAGGCAC 23 14656 SCNN1A-10808 + GACCACCCUUCCAGGCGCAGGCAC 24 14657 SCNN1A-10809 + AAAAUAGAAAUCUGAGAC 18 14658 SCNN1A-10810 + GAAAAUAGAAAUCUGAGAC 19 14659 SCNN1A-10811 + GGAAAAUAGAAAUCUGAGAC 20 14660 SCNN1A-10812 + AGGAAAAUAGAAAUCUGAGAC 21 14661 SCNN1A-10813 + GAGGAAAAUAGAAAUCUGAGAC 22 14662 SCNN1A-10814 + UGAGGAAAAUAGAAAUCUGAGAC 23 14663 SCNN1A-10815 + GUGAGGAAAAUAGAAAUCUGAGAC 24 14664 SCNN1A-10816 + UGCUGCAGCAUUCUAGAC 18 14665 SCNN1A-10817 + GUGCUGCAGCAUUCUAGAC 19 14666 SCNN1A-10818 + AGUGCUGCAGCAUUCUAGAC 20 14667 SCNN1A-10819 + UAGUGCUGCAGCAUUCUAGAC 21 14668 SCNN1A-10820 + CUAGUGCUGCAGCAUUCUAGAC 22 14669 SCNN1A-10821 + CCUAGUGCUGCAGCAUUCUAGAC 23 14670 SCNN1A-10822 + GCCUAGUGCUGCAGCAUUCUAGAC 24 14671 SCNN1A-10823 + AGUGAGCACCUCAGCACC 18 14672 SCNN1A-10824 + CAGUGAGCACCUCAGCACC 19 14673 SCNN1A-10825 + CCAGUGAGCACCUCAGCACC 20 14674 SCNN1A-10826 + CCCAGUGAGCACCUCAGCACC 21 14675 SCNN1A-10827 + GCCCAGUGAGCACCUCAGCACC 22 14676 SCNN1A-10828 + UGCCCAGUGAGCACCUCAGCACC 23 14677 SCNN1A-10829 + CUGCCCAGUGAGCACCUCAGCACC 24 14678 SCNN1A-10830 + CUUCCAGGCGCAGGCACC 18 14679 SCNN1A-10831 + CCUUCCAGGCGCAGGCACC 19 14680 SCNN1A-6307 + CCCUUCCAGGCGCAGGCACC 20 10156 SCNN1A-10832 + ACCCUUCCAGGCGCAGGCACC 21 14681 SCNN1A-10833 + CACCCUUCCAGGCGCAGGCACC 22 14682 SCNN1A-10834 + CCACCCUUCCAGGCGCAGGCACC 23 14683 SCNN1A-10835 + ACCACCCUUCCAGGCGCAGGCACC 24 14684 SCNN1A-10836 + GCUGCAGCAUUCUAGACC 18 14685 SCNN1A-10837 + UGCUGCAGCAUUCUAGACC 19 14686 SCNN1A-6310 + GUGCUGCAGCAUUCUAGACC 20 10159 SCNN1A-10838 + AGUGCUGCAGCAUUCUAGACC 21 14687 SCNN1A-10839 + UAGUGCUGCAGCAUUCUAGACC 22 14688 SCNN1A-10840 + CUAGUGCUGCAGCAUUCUAGACC 23 14689 SCNN1A-10841 + CCUAGUGCUGCAGCAUUCUAGACC 24 14690 SCNN1A-10842 + CCAGCAGUGAGCUCUACC 18 14691 SCNN1A-10843 + GCCAGCAGUGAGCUCUACC 19 14692 SCNN1A-6312 + UGCCAGCAGUGAGCUCUACC 20 10161 SCNN1A-1504 + UGUUCCCCUUCAUGAGCC 18 5353 SCNN1A-1505 + UUGUUCCCCUUCAUGAGCC 19 5354 SCNN1A-207 + CUUGUUCCCCUUCAUGAGCC 20 834 SCNN1A-1506 + GCUUGUUCCCCUUCAUGAGCC 21 5355 SCNN1A-1510 + CGCUUGUUCCCCUUCAUGAGCC 22 5359 SCNN1A-1511 + ACGCUUGUUCCCCUUCAUGAGCC 23 5360 SCNN1A-1512 + CACGCUUGUUCCCCUUCAUGAGCC 24 5361 SCNN1A-1513 + AGGGCCUCCUCCUCCGCC 18 5362 SCNN1A-1514 + CAGGGCCUCCUCCUCCGCC 19 5363 SCNN1A-213 + UCAGGGCCUCCUCCUCCGCC 20 838 SCNN1A-1515 + AUCAGGGCCUCCUCCUCCGCC 21 5364 SCNN1A-1516 + GAUCAGGGCCUCCUCCUCCGCC 22 5365 SCNN1A-1517 + CGAUCAGGGCCUCCUCCUCCGCC 23 5366 SCNN1A-1518 + UCGAUCAGGGCCUCCUCCUCCGCC 24 5367 SCNN1A-1519 + CAGAGCCACAGCACUGCC 18 5368 SCNN1A-1520 + GCAGAGCCACAGCACUGCC 19 5369 SCNN1A-228 + UGCAGAGCCACAGCACUGCC 20 849 SCNN1A-1521 + GUGCAGAGCCACAGCACUGCC 21 5370 SCNN1A-1522 + GGUGCAGAGCCACAGCACUGCC 22 5371 SCNN1A-1523 + AGGUGCAGAGCCACAGCACUGCC 23 5372 SCNN1A-1524 + AAGGUGCAGAGCCACAGCACUGCC 24 5373 SCNN1A-1431 + GAGUGGACUGUGGAGGGC 18 5280 SCNN1A-1432 + GGAGUGGACUGUGGAGGGC 19 5281 SCNN1A-201 + UGGAGUGGACUGUGGAGGGC 20 830 SCNN1A-1358 + CUGGAGUGGACUGUGGAGGGC 21 5207 SCNN1A-1359 + CCUGGAGUGGACUGUGGAGGGC 22 5208 SCNN1A-1360 + CCCUGGAGUGGACUGUGGAGGGC 23 5209 SCNN1A-1311 + GCCCUGGAGUGGACUGUGGAGGGC 24 5160 SCNN1A-10844 + UCUAGACCUGGAGCGGGC 18 14693 SCNN1A-10845 + UUCUAGACCUGGAGCGGGC 19 14694 SCNN1A-10846 + AUUCUAGACCUGGAGCGGGC 20 14695 SCNN1A-10847 + CAUUCUAGACCUGGAGCGGGC 21 14696 SCNN1A-10848 + GCAUUCUAGACCUGGAGCGGGC 22 14697 SCNN1A-10849 + AGCAUUCUAGACCUGGAGCGGGC 23 14698 SCNN1A-10850 + CAGCAUUCUAGACCUGGAGCGGGC 24 14699 SCNN1A-1531 + GGUGCAGAUGGUCACUGC 18 5380 SCNN1A-1532 + GGGUGCAGAUGGUCACUGC 19 5381 SCNN1A-38 + AGGGUGCAGAUGGUCACUGC 20 575 SCNN1A-1533 + GAGGGUGCAGAUGGUCACUGC 21 5382 SCNN1A-1534 + UGAGGGUGCAGAUGGUCACUGC 22 5383 SCNN1A-1535 + UUGAGGGUGCAGAUGGUCACUGC 23 5384 SCNN1A-1536 + AUUGAGGGUGCAGAUGGUCACUGC 24 5385 SCNN1A-1537 + UCCUCCGCCGUGGGCUGC 18 5386 SCNN1A-1538 + CUCCUCCGCCGUGGGCUGC 19 5387 SCNN1A-65 + CCUCCUCCGCCGUGGGCUGC 20 594 SCNN1A-1539 + UCCUCCUCCGCCGUGGGCUGC 21 5388 SCNN1A-1540 + CUCCUCCUCCGCCGUGGGCUGC 22 5389 SCNN1A-1541 + CCUCCUCCUCCGCCGUGGGCUGC 23 5390 SCNN1A-1542 + GCCUCCUCCUCCGCCGUGGGCUGC 24 5391 SCNN1A-1543 + GUCUUCAUGCGGUUGUGC 18 5392 SCNN1A-1544 + CGUCUUCAUGCGGUUGUGC 19 5393 SCNN1A-49 + CCGUCUUCAUGCGGUUGUGC 20 582 SCNN1A-1545 + GCCGUCUUCAUGCGGUUGUGC 21 5394 SCNN1A-1546 + GGCCGUCUUCAUGCGGUUGUGC 22 5395 SCNN1A-1547 + AGGCCGUCUUCAUGCGGUUGUGC 23 5396 SCNN1A-1548 + AAGGCCGUCUUCAUGCGGUUGUGC 24 5397 SCNN1A-1556 + UCACGCUUGUUCCCCUUC 18 5405 SCNN1A-1557 + CUCACGCUUGUUCCCCUUC 19 5406 SCNN1A-208 + CCUCACGCUUGUUCCCCUUC 20 835 SCNN1A-1558 + UCCUCACGCUUGUUCCCCUUC 21 5407 SCNN1A-1559 + CUCCUCACGCUUGUUCCCCUUC 22 5408 SCNN1A-1560 + GCUCCUCACGCUUGUUCCCCUUC 23 5409 SCNN1A-1561 + UGCUCCUCACGCUUGUUCCCCUUC 24 5410 SCNN1A-10851 + UCCUUUCCCUCCCCAAAG 18 14700 SCNN1A-10852 + UUCCUUUCCCUCCCCAAAG 19 14701 SCNN1A-6330 + CUUCCUUUCCCUCCCCAAAG 20 10179 SCNN1A-10853 + CCUUCCUUUCCCUCCCCAAAG 21 14702 SCNN1A-10854 + CCCUUCCUUUCCCUCCCCAAAG 22 14703 SCNN1A-10855 + CCCCUUCCUUUCCCUCCCCAAAG 23 14704 SCNN1A-10856 + UCCCCUUCCUUUCCCUCCCCAAAG 24 14705 SCNN1A-1562 + AUGGUCACUGCGGGGAAG 18 5411 SCNN1A-1563 + GAUGGUCACUGCGGGGAAG 19 5412 SCNN1A-238 + AGAUGGUCACUGCGGGGAAG 20 858 SCNN1A-1564 + CAGAUGGUCACUGCGGGGAAG 21 5413 SCNN1A-1565 + GCAGAUGGUCACUGCGGGGAAG 22 5414 SCNN1A-1566 + UGCAGAUGGUCACUGCGGGGAAG 23 5415 SCNN1A-1567 + GUGCAGAUGGUCACUGCGGGGAAG 24 5416 SCNN1A-10857 + GCACCAGGGAAGGGGCAG 18 14706 SCNN1A-10858 + GGCACCAGGGAAGGGGCAG 19 14707 SCNN1A-6334 + AGGCACCAGGGAAGGGGCAG 20 10183 SCNN1A-10859 + CAGGCACCAGGGAAGGGGCAG 21 14708 SCNN1A-10860 + GCAGGCACCAGGGAAGGGGCAG 22 14709 SCNN1A-10861 + CGCAGGCACCAGGGAAGGGGCAG 23 14710 SCNN1A-10862 + GCGCAGGCACCAGGGAAGGGGCAG 24 14711 SCNN1A-1568 + AUGGUGGUGUUGUUGCAG 18 5417 SCNN1A-1569 + GAUGGUGGUGUUGUUGCAG 19 5418 SCNN1A-221 + GGAUGGUGGUGUUGUUGCAG 20 844 SCNN1A-1570 + UGGAUGGUGGUGUUGUUGCAG 21 5419 SCNN1A-1571 + GUGGAUGGUGGUGUUGUUGCAG 22 5420 SCNN1A-1572 + CGUGGAUGGUGGUGUUGUUGCAG 23 5421 SCNN1A-1573 + CCGUGGAUGGUGGUGUUGUUGCAG 24 5422 SCNN1A-1574 + AAGACGAGCUUGUCCGAG 18 5423 SCNN1A-1575 + GAAGACGAGCUUGUCCGAG 19 5424 SCNN1A-236 + GGAAGACGAGCUUGUCCGAG 20 856 SCNN1A-1576 + GGGAAGACGAGCUUGUCCGAG 21 5425 SCNN1A-1577 + GGGGAAGACGAGCUUGUCCGAG 22 5426 SCNN1A-1578 + CGGGGAAGACGAGCUUGUCCGAG 23 5427 SCNN1A-1579 + GCGGGGAAGACGAGCUUGUCCGAG 24 5428 SCNN1A-1580 + UUGAGGCUGACGGGGUAG 18 5429 SCNN1A-1581 + GUUGAGGCUGACGGGGUAG 19 5430 SCNN1A-232 + UGUUGAGGCUGACGGGGUAG 20 853 SCNN1A-1582 + AUGUUGAGGCUGACGGGGUAG 21 5431 SCNN1A-1583 + GAUGUUGAGGCUGACGGGGUAG 22 5432 SCNN1A-1584 + UGAUGUUGAGGCUGACGGGGUAG 23 5433 SCNN1A-1585 + UUGAUGUUGAGGCUGACGGGGUAG 24 5434 SCNN1A-1586 + GAGCUCUCGGUAGGAGCG 18 5435 SCNN1A-1587 + AGAGCUCUCGGUAGGAGCG 19 5436 SCNN1A-216 + AAGAGCUCUCGGUAGGAGCG 20 840 SCNN1A-1588 + GAAGAGCUCUCGGUAGGAGCG 21 5437 SCNN1A-1589 + CGAAGAGCUCUCGGUAGGAGCG 22 5438 SCNN1A-1590 + UCGAAGAGCUCUCGGUAGGAGCG 23 5439 SCNN1A-1591 + CUCGAAGAGCUCUCGGUAGGAGCG 24 5440 SCNN1A-1592 + GUGCAGAUGGUCACUGCG 18 5441 SCNN1A-1593 + GGUGCAGAUGGUCACUGCG 19 5442 SCNN1A-39 + GGGUGCAGAUGGUCACUGCG 20 518 SCNN1A-1594 + AGGGUGCAGAUGGUCACUGCG 21 5443 SCNN1A-1595 + GAGGGUGCAGAUGGUCACUGCG 22 5444 SCNN1A-1596 + UGAGGGUGCAGAUGGUCACUGCG 23 5445 SCNN1A-1597 + UUGAGGGUGCAGAUGGUCACUGCG 24 5446 SCNN1A-1598 + UUGUUGCAGAAGAACUCG 18 5447 SCNN1A-1599 + GUUGUUGCAGAAGAACUCG 19 5448 SCNN1A-219 + UGUUGUUGCAGAAGAACUCG 20 842 SCNN1A-1600 + GUGUUGUUGCAGAAGAACUCG 21 5449 SCNN1A-1601 + GGUGUUGUUGCAGAAGAACUCG 22 5450 SCNN1A-1602 + UGGUGUUGUUGCAGAAGAACUCG 23 5451 SCNN1A-1603 + GUGGUGUUGUUGCAGAAGAACUCG 24 5452 SCNN1A-10863 + CAUGCACUAUCCUCUAGG 18 14712 SCNN1A-10864 + UCAUGCACUAUCCUCUAGG 19 14713 SCNN1A-10865 + AUCAUGCACUAUCCUCUAGG 20 14714 SCNN1A-10866 + GAUCAUGCACUAUCCUCUAGG 21 14715 SCNN1A-10867 + GGAUCAUGCACUAUCCUCUAGG 22 14716 SCNN1A-10868 + AGGAUCAUGCACUAUCCUCUAGG 23 14717 SCNN1A-10869 + CAGGAUCAUGCACUAUCCUCUAGG 24 14718 SCNN1A-1611 + AGCUCUCGGUAGGAGCGG 18 5460 SCNN1A-1612 + GAGCUCUCGGUAGGAGCGG 19 5461 SCNN1A-60 + AGAGCUCUCGGUAGGAGCGG 20 590 SCNN1A-1613 + AAGAGCUCUCGGUAGGAGCGG 21 5462 SCNN1A-1614 + GAAGAGCUCUCGGUAGGAGCGG 22 5463 SCNN1A-1615 + CGAAGAGCUCUCGGUAGGAGCGG 23 5464 SCNN1A-1616 + UCGAAGAGCUCUCGGUAGGAGCGG 24 5465 SCNN1A-1617 + AACUCGAAGAGCUCUCGG 18 5466 SCNN1A-1618 + GAACUCGAAGAGCUCUCGG 19 5467 SCNN1A-218 + AGAACUCGAAGAGCUCUCGG 20 841 SCNN1A-1619 + AAGAACUCGAAGAGCUCUCGG 21 5468 SCNN1A-1620 + GAAGAACUCGAAGAGCUCUCGG 22 5469 SCNN1A-1621 + AGAAGAACUCGAAGAGCUCUCGG 23 5470 SCNN1A-1622 + CAGAAGAACUCGAAGAGCUCUCGG 24 5471 SCNN1A-10870 + CAGGCGCAGGCACCAGGG 18 14719 SCNN1A-10871 + CCAGGCGCAGGCACCAGGG 19 14720 SCNN1A-10872 + UCCAGGCGCAGGCACCAGGG 20 14721 SCNN1A-10873 + UUCCAGGCGCAGGCACCAGGG 21 14722 SCNN1A-10874 + CUUCCAGGCGCAGGCACCAGGG 22 14723 SCNN1A-10875 + CCUUCCAGGCGCAGGCACCAGGG 23 14724 SCNN1A-10876 + CCCUUCCAGGCGCAGGCACCAGGG 24 14725 SCNN1A-10877 + CAGGCACCAGGGAAGGGG 18 14726 SCNN1A-10878 + GCAGGCACCAGGGAAGGGG 19 14727 SCNN1A-10879 + CGCAGGCACCAGGGAAGGGG 20 14728 SCNN1A-10880 + GCGCAGGCACCAGGGAAGGGG 21 14729 SCNN1A-10881 + GGCGCAGGCACCAGGGAAGGGG 22 14730 SCNN1A-10882 + AGGCGCAGGCACCAGGGAAGGGG 23 14731 SCNN1A-10883 + CAGGCGCAGGCACCAGGGAAGGGG 24 14732 SCNN1A-10884 + UGCAAUGCCUGGUCUGGG 18 14733 SCNN1A-10885 + UUGCAAUGCCUGGUCUGGG 19 14734 SCNN1A-10886 + AUUGCAAUGCCUGGUCUGGG 20 14735 SCNN1A-10887 + AAUUGCAAUGCCUGGUCUGGG 21 14736 SCNN1A-10888 + GAAUUGCAAUGCCUGGUCUGGG 22 14737 SCNN1A-10889 + AGAAUUGCAAUGCCUGGUCUGGG 23 14738 SCNN1A-10890 + AAGAAUUGCAAUGCCUGGUCUGGG 24 14739 SCNN1A-1637 + UCCGAGUUGAGGUUGAUG 18 5486 SCNN1A-1638 + GUCCGAGUUGAGGUUGAUG 19 5487 SCNN1A-235 + UGUCCGAGUUGAGGUUGAUG 20 855 SCNN1A-1639 + UUGUCCGAGUUGAGGUUGAUG 21 5488 SCNN1A-1640 + CUUGUCCGAGUUGAGGUUGAUG 22 5489 SCNN1A-1641 + GCUUGUCCGAGUUGAGGUUGAUG 23 5490 SCNN1A-1642 + AGCUUGUCCGAGUUGAGGUUGAUG 24 5491 SCNN1A-1643 + GGGUGCAGAUGGUCACUG 18 5492 SCNN1A-1644 + AGGGUGCAGAUGGUCACUG 19 5493 SCNN1A-37 + GAGGGUGCAGAUGGUCACUG 20 517 SCNN1A-1645 + UGAGGGUGCAGAUGGUCACUG 21 5494 SCNN1A-1646 + UUGAGGGUGCAGAUGGUCACUG 22 5495 SCNN1A-1647 + AUUGAGGGUGCAGAUGGUCACUG 23 5496 SCNN1A-1648 + GAUUGAGGGUGCAGAUGGUCACUG 24 5497 SCNN1A-1649 + GAGCCCUGGAGUGGACUG 18 5498 SCNN1A-1650 + UGAGCCCUGGAGUGGACUG 19 5499 SCNN1A-74 + AUGAGCCCUGGAGUGGACUG 20 601 SCNN1A-1651 + CAUGAGCCCUGGAGUGGACUG 21 5500 SCNN1A-1652 + UCAUGAGCCCUGGAGUGGACUG 22 5501 SCNN1A-1653 + UUCAUGAGCCCUGGAGUGGACUG 23 5502 SCNN1A-1654 + CUUCAUGAGCCCUGGAGUGGACUG 24 5503 SCNN1A-1655 + GAGGGACUAACCGACCUG 18 5504 SCNN1A-1656 + AGAGGGACUAACCGACCUG 19 5505 SCNN1A-1657 + CAGAGGGACUAACCGACCUG 20 5506 SCNN1A-1658 + GCAGAGGGACUAACCGACCUG 21 5507 SCNN1A-1659 + GGCAGAGGGACUAACCGACCUG 22 5508 SCNN1A-1660 + GGGCAGAGGGACUAACCGACCUG 23 5509 SCNN1A-1661 + GGGGCAGAGGGACUAACCGACCUG 24 5510 SCNN1A-1662 + AGGUUGAUGUUGAGGCUG 18 5511 SCNN1A-1663 + GAGGUUGAUGUUGAGGCUG 19 5512 SCNN1A-234 + UGAGGUUGAUGUUGAGGCUG 20 854 SCNN1A-1664 + UUGAGGUUGAUGUUGAGGCUG 21 5513 SCNN1A-1665 + GUUGAGGUUGAUGUUGAGGCUG 22 5514 SCNN1A-1666 + AGUUGAGGUUGAUGUUGAGGCUG 23 5515 SCNN1A-1667 + GAGUUGAGGUUGAUGUUGAGGCUG 24 5516 SCNN1A-1675 + CUCCUCCGCCGUGGGCUG 18 5524 SCNN1A-1676 + CCUCCUCCGCCGUGGGCUG 19 5525 SCNN1A-212 + UCCUCCUCCGCCGUGGGCUG 20 837 SCNN1A-1677 + CUCCUCCUCCGCCGUGGGCUG 21 5526 SCNN1A-1678 + CCUCCUCCUCCGCCGUGGGCUG 22 5527 SCNN1A-1679 + GCCUCCUCCUCCGCCGUGGGCUG 23 5528 SCNN1A-1680 + GGCCUCCUCCUCCGCCGUGGGCUG 24 5529 SCNN1A-1681 + UACAUCAUGCCAAAGGUG 18 5530 SCNN1A-1682 + GUACAUCAUGCCAAAGGUG 19 5531 SCNN1A-229 + AGUACAUCAUGCCAAAGGUG 20 850 SCNN1A-1683 + CAGUACAUCAUGCCAAAGGUG 21 5532 SCNN1A-1684 + CCAGUACAUCAUGCCAAAGGUG 22 5533 SCNN1A-1685 + GCCAGUACAUCAUGCCAAAGGUG 23 5534 SCNN1A-1686 + UGCCAGUACAUCAUGCCAAAGGUG 24 5535 SCNN1A-1687 + GCCCUGGAGUGGACUGUG 18 5536 SCNN1A-1688 + AGCCCUGGAGUGGACUGUG 19 5537 SCNN1A-202 + GAGCCCUGGAGUGGACUGUG 20 831 SCNN1A-1689 + UGAGCCCUGGAGUGGACUGUG 21 5538 SCNN1A-1690 + AUGAGCCCUGGAGUGGACUGUG 22 5539 SCNN1A-1691 + CAUGAGCCCUGGAGUGGACUGUG 23 5540 SCNN1A-1692 + UCAUGAGCCCUGGAGUGGACUGUG 24 5541 SCNN1A-1693 + CGUCUUCAUGCGGUUGUG 18 5542 SCNN1A-1694 + CCGUCUUCAUGCGGUUGUG 19 5543 SCNN1A-227 + GCCGUCUUCAUGCGGUUGUG 20 848 SCNN1A-1695 + GGCCGUCUUCAUGCGGUUGUG 21 5544 SCNN1A-1696 + AGGCCGUCUUCAUGCGGUUGUG 22 5545 SCNN1A-1697 + AAGGCCGUCUUCAUGCGGUUGUG 23 5546 SCNN1A-1698 + GAAGGCCGUCUUCAUGCGGUUGUG 24 5547 SCNN1A-10891 + AACAGGCUUGGUGUUGUG 18 14740 SCNN1A-10892 + GAACAGGCUUGGUGUUGUG 19 14741 SCNN1A-6347 + AGAACAGGCUUGGUGUUGUG 20 10196 SCNN1A-10893 + UAGAACAGGCUUGGUGUUGUG 21 14742 SCNN1A-10894 + CUAGAACAGGCUUGGUGUUGUG 22 14743 SCNN1A-10895 + GCUAGAACAGGCUUGGUGUUGUG 23 14744 SCNN1A-10896 + GGCUAGAACAGGCUUGGUGUUGUG 24 14745 SCNN1A-1705 + UGGAUGGUGGUGUUGUUG 18 5554 SCNN1A-1706 + GUGGAUGGUGGUGUUGUUG 19 5555 SCNN1A-222 + CGUGGAUGGUGGUGUUGUUG 20 845 SCNN1A-1707 + CCGUGGAUGGUGGUGUUGUUG 21 5556 SCNN1A-1708 + GCCGUGGAUGGUGGUGUUGUUG 22 5557 SCNN1A-1709 + CGCCGUGGAUGGUGGUGUUGUUG 23 5558 SCNN1A-1710 + GCGCCGUGGAUGGUGGUGUUGUUG 24 5559 SCNN1A-10897 + UGUGAGGAAAAUAGAAAU 18 14746 SCNN1A-10898 + UUGUGAGGAAAAUAGAAAU 19 14747 SCNN1A-10899 + GUUGUGAGGAAAAUAGAAAU 20 14748 SCNN1A-10900 + UGUUGUGAGGAAAAUAGAAAU 21 14749 SCNN1A-10901 + GUGUUGUGAGGAAAAUAGAAAU 22 14750 SCNN1A-10902 + GGUGUUGUGAGGAAAAUAGAAAU 23 14751 SCNN1A-10903 + UGGUGUUGUGAGGAAAAUAGAAAU 24 14752 SCNN1A-10904 + GGGUAUGGGAGUGGCAAU 18 14753 SCNN1A-10905 + CGGGUAUGGGAGUGGCAAU 19 14754 SCNN1A-10906 + CCGGGUAUGGGAGUGGCAAU 20 14755 SCNN1A-10907 + GCCGGGUAUGGGAGUGGCAAU 21 14756 SCNN1A-10908 + UGCCGGGUAUGGGAGUGGCAAU 22 14757 SCNN1A-10909 + CUGCCGGGUAUGGGAGUGGCAAU 23 14758 SCNN1A-10910 + CCUGCCGGGUAUGGGAGUGGCAAU 24 14759 SCNN1A-1711 + GGAGCGGUGGAACUCGAU 18 5560 SCNN1A-1712 + AGGAGCGGUGGAACUCGAU 19 5561 SCNN1A-214 + UAGGAGCGGUGGAACUCGAU 20 839 SCNN1A-1713 + GUAGGAGCGGUGGAACUCGAU 21 5562 SCNN1A-1714 + GGUAGGAGCGGUGGAACUCGAU 22 5563 SCNN1A-1715 + CGGUAGGAGCGGUGGAACUCGAU 23 5564 SCNN1A-1716 + UCGGUAGGAGCGGUGGAACUCGAU 24 5565 SCNN1A-1723 + AGGGUGCAGAUGGUCACU 18 5572 SCNN1A-1724 + GAGGGUGCAGAUGGUCACU 19 5573 SCNN1A-242 + UGAGGGUGCAGAUGGUCACU 20 859 SCNN1A-1725 + UUGAGGGUGCAGAUGGUCACU 21 5574 SCNN1A-1726 + AUUGAGGGUGCAGAUGGUCACU 22 5575 SCNN1A-1727 + GAUUGAGGGUGCAGAUGGUCACU 23 5576 SCNN1A-1728 + GGAUUGAGGGUGCAGAUGGUCACU 24 5577 SCNN1A-1729 + UGAGCCCUGGAGUGGACU 18 5578 SCNN1A-1730 + AUGAGCCCUGGAGUGGACU 19 5579 SCNN1A-204 + CAUGAGCCCUGGAGUGGACU 20 832 SCNN1A-1731 + UCAUGAGCCCUGGAGUGGACU 21 5580 SCNN1A-1732 + UUCAUGAGCCCUGGAGUGGACU 22 5581 SCNN1A-1733 + CUUCAUGAGCCCUGGAGUGGACU 23 5582 SCNN1A-1734 + CCUUCAUGAGCCCUGGAGUGGACU 24 5583 SCNN1A-1748 + UCUUCAUGCGGUUGUGCU 18 5597 SCNN1A-1749 + GUCUUCAUGCGGUUGUGCU 19 5598 SCNN1A-50 + CGUCUUCAUGCGGUUGUGCU 20 583 SCNN1A-1750 + CCGUCUUCAUGCGGUUGUGCU 21 5599 SCNN1A-1751 + GCCGUCUUCAUGCGGUUGUGCU 22 5600 SCNN1A-1752 + GGCCGUCUUCAUGCGGUUGUGCU 23 5601 SCNN1A-1753 + AGGCCGUCUUCAUGCGGUUGUGCU 24 5602 SCNN1A-10911 + UUAUUUUCUUAUUUAUCU 18 14760 SCNN1A-10912 + UUUAUUUUCUUAUUUAUCU 19 14761 SCNN1A-10913 + UUUUAUUUUCUUAUUUAUCU 20 14762 SCNN1A-10914 + CUUUUAUUUUCUUAUUUAUCU 21 14763 SCNN1A-10915 + GCUUUUAUUUUCUUAUUUAUCU 22 14764 SCNN1A-10916 + UGCUUUUAUUUUCUUAUUUAUCU 23 14765 SCNN1A-10917 + UUGCUUUUAUUUUCUUAUUUAUCU 24 14766 SCNN1A-1754 + GGGUAGCUGAAGUACUCU 18 5603 SCNN1A-1755 + GGGGUAGCUGAAGUACUCU 19 5604 SCNN1A-231 + CGGGGUAGCUGAAGUACUCU 20 852 SCNN1A-1756 + ACGGGGUAGCUGAAGUACUCU 21 5605 SCNN1A-1757 + GACGGGGUAGCUGAAGUACUCU 22 5606 SCNN1A-1758 + UGACGGGGUAGCUGAAGUACUCU 23 5607 SCNN1A-1759 + CUGACGGGGUAGCUGAAGUACUCU 24 5608 SCNN1A-1760 + UGCUGGGGCGCCGCAGGU 18 5609 SCNN1A-1761 + CUGCUGGGGCGCCGCAGGU 19 5610 SCNN1A-210 + GCUGCUGGGGCGCCGCAGGU 20 836 SCNN1A-1762 + GGCUGCUGGGGCGCCGCAGGU 21 5611 SCNN1A-1763 + GGGCUGCUGGGGCGCCGCAGGU 22 5612 SCNN1A-1764 + UGGGCUGCUGGGGCGCCGCAGGU 23 5613 SCNN1A-1765 + GUGGGCUGCUGGGGCGCCGCAGGU 24 5614 SCNN1A-10918 + CAGUUCCCACCCUCAGGU 18 14767 SCNN1A-10919 + UCAGUUCCCACCCUCAGGU 19 14768 SCNN1A-10920 + GUCAGUUCCCACCCUCAGGU 20 14769 SCNN1A-10921 + UGUCAGUUCCCACCCUCAGGU 21 14770 SCNN1A-10922 + GUGUCAGUUCCCACCCUCAGGU 22 14771 SCNN1A-10923 + GGUGUCAGUUCCCACCCUCAGGU 23 14772 SCNN1A-10924 + GGGUGUCAGUUCCCACCCUCAGGU 24 14773 SCNN1A-1766 + ACUCGAAGAGCUCUCGGU 18 5615 SCNN1A-1767 + AACUCGAAGAGCUCUCGGU 19 5616 SCNN1A-58 + GAACUCGAAGAGCUCUCGGU 20 524 SCNN1A-1768 + AGAACUCGAAGAGCUCUCGGU 21 5617 SCNN1A-1769 + AAGAACUCGAAGAGCUCUCGGU 22 5618 SCNN1A-1770 + GAAGAACUCGAAGAGCUCUCGGU 23 5619 SCNN1A-1771 + AGAAGAACUCGAAGAGCUCUCGGU 24 5620 SCNN1A-10925 + UGCCACGUCCUGCCGGGU 18 14774 SCNN1A-10926 + CUGCCACGUCCUGCCGGGU 19 14775 SCNN1A-10927 + CCUGCCACGUCCUGCCGGGU 20 14776 SCNN1A-10928 + CCCUGCCACGUCCUGCCGGGU 21 14777 SCNN1A-10929 + ACCCUGCCACGUCCUGCCGGGU 22 14778 SCNN1A-10930 + GACCCUGCCACGUCCUGCCGGGU 23 14779 SCNN1A-10931 + UGACCCUGCCACGUCCUGCCGGGU 24 14780 SCNN1A-10932 + AGAAUUGCAAUGCCUGGU 18 14781 SCNN1A-10933 + AAGAAUUGCAAUGCCUGGU 19 14782 SCNN1A-10934 + GAAGAAUUGCAAUGCCUGGU 20 14783 SCNN1A-10935 + AGAAGAAUUGCAAUGCCUGGU 21 14784 SCNN1A-10936 + GAGAAGAAUUGCAAUGCCUGGU 22 14785 SCNN1A-10937 + UGAGAAGAAUUGCAAUGCCUGGU 23 14786 SCNN1A-10938 + GUGAGAAGAAUUGCAAUGCCUGGU 24 14787 SCNN1A-10939 + UGAGACCUGGACUUUGGU 18 14788 SCNN1A-10940 + CUGAGACCUGGACUUUGGU 19 14789 SCNN1A-10941 + UCUGAGACCUGGACUUUGGU 20 14790 SCNN1A-10942 + AUCUGAGACCUGGACUUUGGU 21 14791 SCNN1A-10943 + AAUCUGAGACCUGGACUUUGGU 22 14792 SCNN1A-10944 + AAAUCUGAGACCUGGACUUUGGU 23 14793 SCNN1A-10945 + GAAAUCUGAGACCUGGACUUUGGU 24 14794 SCNN1A-10946 + GAACAGGCUUGGUGUUGU 18 14795 SCNN1A-10947 + AGAACAGGCUUGGUGUUGU 19 14796 SCNN1A-10948 + UAGAACAGGCUUGGUGUUGU 20 14797 SCNN1A-10949 + CUAGAACAGGCUUGGUGUUGU 21 14798 SCNN1A-10950 + GCUAGAACAGGCUUGGUGUUGU 22 14799 SCNN1A-10951 + GGCUAGAACAGGCUUGGUGUUGU 23 14800 SCNN1A-10952 + GGGCUAGAACAGGCUUGGUGUUGU 24 14801 SCNN1A-1784 + GCUGGGGCGCCGCAGGUU 18 5633 SCNN1A-1785 + UGCUGGGGCGCCGCAGGUU 19 5634 SCNN1A-69 + CUGCUGGGGCGCCGCAGGUU 20 597 SCNN1A-1786 + GCUGCUGGGGCGCCGCAGGUU 21 5635 SCNN1A-1787 + GGCUGCUGGGGCGCCGCAGGUU 22 5636 SCNN1A-1788 + GGGCUGCUGGGGCGCCGCAGGUU 23 5637 SCNN1A-1789 + UGGGCUGCUGGGGCGCCGCAGGUU 24 5638 SCNN1A-10953 + UAGAACAGGCUUGGUGUU 18 14802 SCNN1A-10954 + CUAGAACAGGCUUGGUGUU 19 14803 SCNN1A-10955 + GCUAGAACAGGCUUGGUGUU 20 14804 SCNN1A-10956 + GGCUAGAACAGGCUUGGUGUU 21 14805 SCNN1A-10957 + GGGCUAGAACAGGCUUGGUGUU 22 14806 SCNN1A-10958 + CGGGCUAGAACAGGCUUGGUGUU 23 14807 SCNN1A-10959 + GCGGGCUAGAACAGGCUUGGUGUU 24 14808 SCNN1A-10960 AGAAAAUAAAAGCAAAAA 18 14809 SCNN1A-10961 AAGAAAAUAAAAGCAAAAA 19 14810 SCNN1A-6277 UAAGAAAAUAAAAGCAAAAA 20 10126 SCNN1A-10962 AUAAGAAAAUAAAAGCAAAAA 21 14811 SCNN1A-10963 AAUAAGAAAAUAAAAGCAAAAA 22 14812 SCNN1A-10964 AAAUAAGAAAAUAAAAGCAAAAA 23 14813 SCNN1A-10965 UAAAUAAGAAAAUAAAAGCAAAAA 24 14814 SCNN1A-10966 AAGAAAAUAAAAGCAAAA 18 14815 SCNN1A-10967 UAAGAAAAUAAAAGCAAAA 19 14816 SCNN1A-10968 AUAAGAAAAUAAAAGCAAAA 20 14817 SCNN1A-10969 AAUAAGAAAAUAAAAGCAAAA 21 14818 SCNN1A-10970 AAAUAAGAAAAUAAAAGCAAAA 22 14819 SCNN1A-10971 UAAAUAAGAAAAUAAAAGCAAAA 23 14820 SCNN1A-10972 AUAAAUAAGAAAAUAAAAGCAAAA 24 14821 SCNN1A-10973 AUGGUCUCUGUCAUAAAA 18 14822 SCNN1A-10974 CAUGGUCUCUGUCAUAAAA 19 14823 SCNN1A-10975 GCAUGGUCUCUGUCAUAAAA 20 14824 SCNN1A-10976 AGCAUGGUCUCUGUCAUAAAA 21 14825 SCNN1A-10977 UAGCAUGGUCUCUGUCAUAAAA 22 14826 SCNN1A-10978 AUAGCAUGGUCUCUGUCAUAAAA 23 14827 SCNN1A-10979 UAUAGCAUGGUCUCUGUCAUAAAA 24 14828 SCNN1A-10980 UAAAAGAUCAUCUUUAAA 18 14829 SCNN1A-10981 UUAAAAGAUCAUCUUUAAA 19 14830 SCNN1A-10982 UUUAAAAGAUCAUCUUUAAA 20 14831 SCNN1A-10983 CUUUAAAAGAUCAUCUUUAAA 21 14832 SCNN1A-10984 ACUUUAAAAGAUCAUCUUUAAA 22 14833 SCNN1A-10985 CACUUUAAAAGAUCAUCUUUAAA 23 14834 SCNN1A-10986 ACACUUUAAAAGAUCAUCUUUAAA 24 14835 SCNN1A-10987 UUUGGGGAGGGAAAGGAA 18 14836 SCNN1A-10988 CUUUGGGGAGGGAAAGGAA 19 14837 SCNN1A-6283 CCUUUGGGGAGGGAAAGGAA 20 10132 SCNN1A-10989 CCCUUUGGGGAGGGAAAGGAA 21 14838 SCNN1A-10990 CCCCUUUGGGGAGGGAAAGGAA 22 14839 SCNN1A-10991 UCCCCUUUGGGGAGGGAAAGGAA 23 14840 SCNN1A-10992 CUCCCCUUUGGGGAGGGAAAGGAA 24 14841 SCNN1A-10993 UCCCCUUUGGGGAGGGAA 18 14842 SCNN1A-10994 CUCCCCUUUGGGGAGGGAA 19 14843 SCNN1A-6285 GCUCCCCUUUGGGGAGGGAA 20 10134 SCNN1A-10995 GGCUCCCCUUUGGGGAGGGAA 21 14844 SCNN1A-10996 UGGCUCCCCUUUGGGGAGGGAA 22 14845 SCNN1A-10997 GUGGCUCCCCUUUGGGGAGGGAA 23 14846 SCNN1A-10998 GGUGGCUCCCCUUUGGGGAGGGAA 24 14847 SCNN1A-1796 CACUCCAGGGCUCAUGAA 18 5645 SCNN1A-1797 CCACUCCAGGGCUCAUGAA 19 5646 SCNN1A-11 UCCACUCCAGGGCUCAUGAA 20 560 SCNN1A-1798 GUCCACUCCAGGGCUCAUGAA 21 5647 SCNN1A-1799 AGUCCACUCCAGGGCUCAUGAA 22 5648 SCNN1A-1800 CAGUCCACUCCAGGGCUCAUGAA 23 5649 SCNN1A-1801 ACAGUCCACUCCAGGGCUCAUGAA 24 5650 SCNN1A-10999 GGAAAGGAAGGGGACUAA 18 14848 SCNN1A-11000 GGGAAAGGAAGGGGACUAA 19 14849 SCNN1A-6288 AGGGAAAGGAAGGGGACUAA 20 10137 SCNN1A-11001 GAGGGAAAGGAAGGGGACUAA 21 14850 SCNN1A-11002 GGAGGGAAAGGAAGGGGACUAA 22 14851 SCNN1A-11003 GGGAGGGAAAGGAAGGGGACUAA 23 14852 SCNN1A-11004 GGGGAGGGAAAGGAAGGGGACUAA 24 14853 SCNN1A-11005 AGGGUGCUGAGGUGCUCA 18 14854 SCNN1A-11006 CAGGGUGCUGAGGUGCUCA 19 14855 SCNN1A-11007 CCAGGGUGCUGAGGUGCUCA 20 14856 SCNN1A-11008 UCCAGGGUGCUGAGGUGCUCA 21 14857 SCNN1A-11009 GUCCAGGGUGCUGAGGUGCUCA 22 14858 SCNN1A-11010 GGUCCAGGGUGCUGAGGUGCUCA 23 14859 SCNN1A-11011 UGGUCCAGGGUGCUGAGGUGCUCA 24 14860 SCNN1A-11012 CUUUGGGGAGGGAAAGGA 18 14861 SCNN1A-11013 CCUUUGGGGAGGGAAAGGA 19 14862 SCNN1A-6295 CCCUUUGGGGAGGGAAAGGA 20 10144 SCNN1A-11014 CCCCUUUGGGGAGGGAAAGGA 21 14863 SCNN1A-11015 UCCCCUUUGGGGAGGGAAAGGA 22 14864 SCNN1A-11016 CUCCCCUUUGGGGAGGGAAAGGA 23 14865 SCNN1A-11017 GCUCCCCUUUGGGGAGGGAAAGGA 24 14866 SCNN1A-11018 CUCCCCUUUGGGGAGGGA 18 14867 SCNN1A-11019 GCUCCCCUUUGGGGAGGGA 19 14868 SCNN1A-11020 GGCUCCCCUUUGGGGAGGGA 20 14869 SCNN1A-11021 UGGCUCCCCUUUGGGGAGGGA 21 14870 SCNN1A-11022 GUGGCUCCCCUUUGGGGAGGGA 22 14871 SCNN1A-11023 GGUGGCUCCCCUUUGGGGAGGGA 23 14872 SCNN1A-11024 UGGUGGCUCCCCUUUGGGGAGGGA 24 14873 SCNN1A-11025 GUGGCUCCCCUUUGGGGA 18 14874 SCNN1A-11026 GGUGGCUCCCCUUUGGGGA 19 14875 SCNN1A-6297 UGGUGGCUCCCCUUUGGGGA 20 10146 SCNN1A-11027 AUGGUGGCUCCCCUUUGGGGA 21 14876 SCNN1A-11028 UAUGGUGGCUCCCCUUUGGGGA 22 14877 SCNN1A-11029 UUAUGGUGGCUCCCCUUUGGGGA 23 14878 SCNN1A-11030 AUUAUGGUGGCUCCCCUUUGGGGA 24 14879 SCNN1A-1833 CCACUCCAGGGCUCAUGA 18 5682 SCNN1A-1834 UCCACUCCAGGGCUCAUGA 19 5683 SCNN1A-10 GUCCACUCCAGGGCUCAUGA 20 505 SCNN1A-1835 AGUCCACUCCAGGGCUCAUGA 21 5684 SCNN1A-1836 CAGUCCACUCCAGGGCUCAUGA 22 5685 SCNN1A-1837 ACAGUCCACUCCAGGGCUCAUGA 23 5686 SCNN1A-1838 CACAGUCCACUCCAGGGCUCAUGA 24 5687 SCNN1A-11031 GGGAAAGGAAGGGGACUA 18 14880 SCNN1A-11032 AGGGAAAGGAAGGGGACUA 19 14881 SCNN1A-6300 GAGGGAAAGGAAGGGGACUA 20 10149 SCNN1A-11033 GGAGGGAAAGGAAGGGGACUA 21 14882 SCNN1A-11034 GGGAGGGAAAGGAAGGGGACUA 22 14883 SCNN1A-11035 GGGGAGGGAAAGGAAGGGGACUA 23 14884 SCNN1A-11036 UGGGGAGGGAAAGGAAGGGGACUA 24 14885 SCNN1A-1851 CGAGUUCCACCGCUCCUA 18 5700 SCNN1A-1852 UCGAGUUCCACCGCUCCUA 19 5701 SCNN1A-190 AUCGAGUUCCACCGCUCCUA 20 820 SCNN1A-1853 GAUCGAGUUCCACCGCUCCUA 21 5702 SCNN1A-1854 UGAUCGAGUUCCACCGCUCCUA 22 5703 SCNN1A-1855 CUGAUCGAGUUCCACCGCUCCUA 23 5704 SCNN1A-1856 CCUGAUCGAGUUCCACCGCUCCUA 24 5705 SCNN1A-1857 CUCAACAUCAACCUCAAC 18 5706 SCNN1A-1858 CCUCAACAUCAACCUCAAC 19 5707 SCNN1A-198 GCCUCAACAUCAACCUCAAC 20 827 SCNN1A-1859 AGCCUCAACAUCAACCUCAAC 21 5708 SCNN1A-1860 CAGCCUCAACAUCAACCUCAAC 22 5709 SCNN1A-1861 UCAGCCUCAACAUCAACCUCAAC 23 5710 SCNN1A-1862 GUCAGCCUCAACAUCAACCUCAAC 24 5711 SCNN1A-11037 GCAGGCAGAGCCUCAGAC 18 14886 SCNN1A-11038 GGCAGGCAGAGCCUCAGAC 19 14887 SCNN1A-11039 GGGCAGGCAGAGCCUCAGAC 20 14888 SCNN1A-11040 UGGGCAGGCAGAGCCUCAGAC 21 14889 SCNN1A-11041 CUGGGCAGGCAGAGCCUCAGAC 22 14890 SCNN1A-11042 ACUGGGCAGGCAGAGCCUCAGAC 23 14891 SCNN1A-11043 CACUGGGCAGGCAGAGCCUCAGAC 24 14892 SCNN1A-1870 AGUUCCACCGCUCCUACC 18 5719 SCNN1A-1871 GAGUUCCACCGCUCCUACC 19 5720 SCNN1A-191 CGAGUUCCACCGCUCCUACC 20 821 SCNN1A-1872 UCGAGUUCCACCGCUCCUACC 21 5721 SCNN1A-1873 AUCGAGUUCCACCGCUCCUACC 22 5722 SCNN1A-1874 GAUCGAGUUCCACCGCUCCUACC 23 5723 SCNN1A-1875 UGAUCGAGUUCCACCGCUCCUACC 24 5724 SCNN1A-11044 UGCUGCUGUACUCCAGCC 18 14893 SCNN1A-11045 AUGCUGCUGUACUCCAGCC 19 14894 SCNN1A-11046 CAUGCUGCUGUACUCCAGCC 20 14895 SCNN1A-11047 UCAUGCUGCUGUACUCCAGCC 21 14896 SCNN1A-11048 AUCAUGCUGCUGUACUCCAGCC 22 14897 SCNN1A-11049 GAUCAUGCUGCUGUACUCCAGCC 23 14898 SCNN1A-11050 UGAUCAUGCUGCUGUACUCCAGCC 24 14899 SCNN1A-11051 UUCCCUGGUGCCUGCGCC 18 14900 SCNN1A-11052 CUUCCCUGGUGCCUGCGCC 19 14901 SCNN1A-6315 CCUUCCCUGGUGCCUGCGCC 20 10164 SCNN1A-11053 CCCUUCCCUGGUGCCUGCGCC 21 14902 SCNN1A-11054 CCCCUUCCCUGGUGCCUGCGCC 22 14903 SCNN1A-11055 GCCCCUUCCCUGGUGCCUGCGCC 23 14904 SCNN1A-11056 UGCCCCUUCCCUGGUGCCUGCGCC 24 14905 SCNN1A-1883 AGGAGCAGGGGCUGGGCC 18 5732 SCNN1A-1884 GAGGAGCAGGGGCUGGGCC 19 5733 SCNN1A-182 UGAGGAGCAGGGGCUGGGCC 20 815 SCNN1A-1885 GUGAGGAGCAGGGGCUGGGCC 21 5734 SCNN1A-1886 CGUGAGGAGCAGGGGCUGGGCC 22 5735 SCNN1A-1887 GCGUGAGGAGCAGGGGCUGGGCC 23 5736 SCNN1A-1888 AGCGUGAGGAGCAGGGGCUGGGCC 24 5737 SCNN1A-1895 UCAUGAAGGGGAACAAGC 18 5744 SCNN1A-1896 CUCAUGAAGGGGAACAAGC 19 5745 SCNN1A-176 GCUCAUGAAGGGGAACAAGC 20 811 SCNN1A-1897 GGCUCAUGAAGGGGAACAAGC 21 5746 SCNN1A-1898 GGGCUCAUGAAGGGGAACAAGC 22 5747 SCNN1A-1899 AGGGCUCAUGAAGGGGAACAAGC 23 5748 SCNN1A-1900 CAGGGCUCAUGAAGGGGAACAAGC 24 5749 SCNN1A-1916 GGAACAAGCGUGAGGAGC 18 5765 SCNN1A-1917 GGGAACAAGCGUGAGGAGC 19 5766 SCNN1A-14 GGGGAACAAGCGUGAGGAGC 20 506 SCNN1A-1918 AGGGGAACAAGCGUGAGGAGC 21 5767 SCNN1A-1919 AAGGGGAACAAGCGUGAGGAGC 22 5768 SCNN1A-1920 GAAGGGGAACAAGCGUGAGGAGC 23 5769 SCNN1A-1921 UGAAGGGGAACAAGCGUGAGGAGC 24 5770 SCNN1A-1922 UGCUCCCAGCACAACCGC 18 5771 SCNN1A-1923 GUGCUCCCAGCACAACCGC 19 5772 SCNN1A-193 UGUGCUCCCAGCACAACCGC 20 823 SCNN1A-1924 GUGUGCUCCCAGCACAACCGC 21 5773 SCNN1A-1925 GGUGUGCUCCCAGCACAACCGC 22 5774 SCNN1A-1926 UGGUGUGCUCCCAGCACAACCGC 23 5775 SCNN1A-1927 CUGGUGUGCUCCCAGCACAACCGC 24 5776 SCNN1A-11057 CUUCCCUGGUGCCUGCGC 18 14906 SCNN1A-11058 CCUUCCCUGGUGCCUGCGC 19 14907 SCNN1A-11059 CCCUUCCCUGGUGCCUGCGC 20 14908 SCNN1A-11060 CCCCUUCCCUGGUGCCUGCGC 21 14909 SCNN1A-11061 GCCCCUUCCCUGGUGCCUGCGC 22 14910 SCNN1A-11062 UGCCCCUUCCCUGGUGCCUGCGC 23 14911 SCNN1A-11063 CUGCCCCUUCCCUGGUGCCUGCGC 24 14912 SCNN1A-1948 GCCCUCCACAGUCCACUC 18 5797 SCNN1A-1949 AGCCCUCCACAGUCCACUC 19 5798 SCNN1A-170 UAGCCCUCCACAGUCCACUC 20 808 SCNN1A-1954 CAGUCCACUCCAGGGCUC 18 5803 SCNN1A-1955 ACAGUCCACUCCAGGGCUC 19 5804 SCNN1A-171 CACAGUCCACUCCAGGGCUC 20 809 SCNN1A-1956 CCACAGUCCACUCCAGGGCUC 21 5805 SCNN1A-1957 UCCACAGUCCACUCCAGGGCUC 22 5806 SCNN1A-1958 CUCCACAGUCCACUCCAGGGCUC 23 5807 SCNN1A-1959 CCUCCACAGUCCACUCCAGGGCUC 24 5808 SCNN1A-1995 ACUCCAGGGCUCAUGAAG 18 5844 SCNN1A-1996 CACUCCAGGGCUCAUGAAG 19 5845 SCNN1A-12 CCACUCCAGGGCUCAUGAAG 20 561 SCNN1A-1997 UCCACUCCAGGGCUCAUGAAG 21 5846 SCNN1A-1998 GUCCACUCCAGGGCUCAUGAAG 22 5847 SCNN1A-1999 AGUCCACUCCAGGGCUCAUGAAG 23 5848 SCNN1A-2000 CAGUCCACUCCAGGGCUCAUGAAG 24 5849 SCNN1A-2017 GGGAACAAGCGUGAGGAG 18 5866 SCNN1A-2018 GGGGAACAAGCGUGAGGAG 19 5867 SCNN1A-179 AGGGGAACAAGCGUGAGGAG 20 813 SCNN1A-2019 AAGGGGAACAAGCGUGAGGAG 21 5868 SCNN1A-2020 GAAGGGGAACAAGCGUGAGGAG 22 5869 SCNN1A-2021 UGAAGGGGAACAAGCGUGAGGAG 23 5870 SCNN1A-2022 AUGAAGGGGAACAAGCGUGAGGAG 24 5871 SCNN1A-2023 CAGCAGCCCACGGCGGAG 18 5872 SCNN1A-2024 CCAGCAGCCCACGGCGGAG 19 5873 SCNN1A-187 CCCAGCAGCCCACGGCGGAG 20 818 SCNN1A-2025 CCCCAGCAGCCCACGGCGGAG 21 5874 SCNN1A-2026 GCCCCAGCAGCCCACGGCGGAG 22 5875 SCNN1A-2027 CGCCCCAGCAGCCCACGGCGGAG 23 5876 SCNN1A-2028 GCGCCCCAGCAGCCCACGGCGGAG 24 5877 SCNN1A-2035 GCGCCCCAGCAGCCCACG 18 5884 SCNN1A-2036 GGCGCCCCAGCAGCCCACG 19 5885 SCNN1A-183 CGGCGCCCCAGCAGCCCACG 20 816 SCNN1A-2037 GCGGCGCCCCAGCAGCCCACG 21 5886 SCNN1A-2038 UGCGGCGCCCCAGCAGCCCACG 22 5887 SCNN1A-2039 CUGCGGCGCCCCAGCAGCCCACG 23 5888 SCNN1A-2040 CCUGCGGCGCCCCAGCAGCCCACG 24 5889 SCNN1A-2041 CCCCAGCAGCCCACGGCG 18 5890 SCNN1A-2042 GCCCCAGCAGCCCACGGCG 19 5891 SCNN1A-185 CGCCCCAGCAGCCCACGGCG 20 817 SCNN1A-2043 GCGCCCCAGCAGCCCACGGCG 21 5892 SCNN1A-2044 GGCGCCCCAGCAGCCCACGGCG 22 5893 SCNN1A-2045 CGGCGCCCCAGCAGCCCACGGCG 23 5894 SCNN1A-2046 GCGGCGCCCCAGCAGCCCACGGCG 24 5895 SCNN1A-11064 CCUUUGGGGAGGGAAAGG 18 14913 SCNN1A-11065 CCCUUUGGGGAGGGAAAGG 19 14914 SCNN1A-11066 CCCCUUUGGGGAGGGAAAGG 20 14915 SCNN1A-11067 UCCCCUUUGGGGAGGGAAAGG 21 14916 SCNN1A-11068 CUCCCCUUUGGGGAGGGAAAGG 22 14917 SCNN1A-11069 GCUCCCCUUUGGGGAGGGAAAGG 23 14918 SCNN1A-11070 GGCUCCCCUUUGGGGAGGGAAAGG 24 14919 SCNN1A-11071 UGACACCCCUGUCCCAGG 18 14920 SCNN1A-11072 CUGACACCCCUGUCCCAGG 19 14921 SCNN1A-11073 ACUGACACCCCUGUCCCAGG 20 14922 SCNN1A-11074 AACUGACACCCCUGUCCCAGG 21 14923 SCNN1A-11075 GAACUGACACCCCUGUCCCAGG 22 14924 SCNN1A-11076 GGAACUGACACCCCUGUCCCAGG 23 14925 SCNN1A-11077 GGGAACUGACACCCCUGUCCCAGG 24 14926 SCNN1A-11078 AGGUGCUCACUGGGCAGG 18 14927 SCNN1A-11079 GAGGUGCUCACUGGGCAGG 19 14928 SCNN1A-11080 UGAGGUGCUCACUGGGCAGG 20 14929 SCNN1A-11081 CUGAGGUGCUCACUGGGCAGG 21 14930 SCNN1A-11082 GCUGAGGUGCUCACUGGGCAGG 22 14931 SCNN1A-11083 UGCUGAGGUGCUCACUGGGCAGG 23 14932 SCNN1A-11084 GUGCUGAGGUGCUCACUGGGCAGG 24 14933 SCNN1A-2050 AGCAGCCCACGGCGGAGG 18 5899 SCNN1A-2051 CAGCAGCCCACGGCGGAGG 19 5900 SCNN1A-23 CCAGCAGCCCACGGCGGAGG 20 566 SCNN1A-2052 CCCAGCAGCCCACGGCGGAGG 21 5901 SCNN1A-2053 CCCCAGCAGCCCACGGCGGAGG 22 5902 SCNN1A-2054 GCCCCAGCAGCCCACGGCGGAGG 23 5903 SCNN1A-2055 CGCCCCAGCAGCCCACGGCGGAGG 24 5904 SCNN1A-11085 AGAGCCUCAGACCUGAGG 18 14934 SCNN1A-11086 CAGAGCCUCAGACCUGAGG 19 14935 SCNN1A-11087 GCAGAGCCUCAGACCUGAGG 20 14936 SCNN1A-11088 GGCAGAGCCUCAGACCUGAGG 21 14937 SCNN1A-11089 AGGCAGAGCCUCAGACCUGAGG 22 14938 SCNN1A-11090 CAGGCAGAGCCUCAGACCUGAGG 23 14939 SCNN1A-11091 GCAGGCAGAGCCUCAGACCUGAGG 24 14940 SCNN1A-2056 CGCCCCAGCAGCCCACGG 18 5905 SCNN1A-2057 GCGCCCCAGCAGCCCACGG 19 5906 SCNN1A-21 GGCGCCCCAGCAGCCCACGG 20 510 SCNN1A-2058 CGGCGCCCCAGCAGCCCACGG 21 5907 SCNN1A-2059 GCGGCGCCCCAGCAGCCCACGG 22 5908 SCNN1A-2060 UGCGGCGCCCCAGCAGCCCACGG 23 5909 SCNN1A-2061 CUGCGGCGCCCCAGCAGCCCACGG 24 5910 SCNN1A-11092 UGCCACUCCCAUACCCGG 18 14941 SCNN1A-11093 UUGCCACUCCCAUACCCGG 19 14942 SCNN1A-11094 AUUGCCACUCCCAUACCCGG 20 14943 SCNN1A-11095 CAUUGCCACUCCCAUACCCGG 21 14944 SCNN1A-11096 GCAUUGCCACUCCCAUACCCGG 22 14945 SCNN1A-11097 CGCAUUGCCACUCCCAUACCCGG 23 14946 SCNN1A-11098 UCGCAUUGCCACUCCCAUACCCGG 24 14947 SCNN1A-2062 CCCAGCAGCCCACGGCGG 18 5911 SCNN1A-2063 CCCCAGCAGCCCACGGCGG 19 5912 SCNN1A-22 GCCCCAGCAGCCCACGGCGG 20 511 SCNN1A-2064 CGCCCCAGCAGCCCACGGCGG 21 5913 SCNN1A-2065 GCGCCCCAGCAGCCCACGGCGG 22 5914 SCNN1A-2066 GGCGCCCCAGCAGCCCACGGCGG 23 5915 SCNN1A-2067 CGGCGCCCCAGCAGCCCACGGCGG 24 5916 SCNN1A-11099 GAGCCUCAGACCUGAGGG 18 14948 SCNN1A-11100 AGAGCCUCAGACCUGAGGG 19 14949 SCNN1A-6341 CAGAGCCUCAGACCUGAGGG 20 10190 SCNN1A-11101 GCAGAGCCUCAGACCUGAGGG 21 14950 SCNN1A-11102 GGCAGAGCCUCAGACCUGAGGG 22 14951 SCNN1A-11103 AGGCAGAGCCUCAGACCUGAGGG 23 14952 SCNN1A-11104 CAGGCAGAGCCUCAGACCUGAGGG 24 14953 SCNN1A-2074 AAGCGUGAGGAGCAGGGG 18 5923 SCNN1A-2075 CAAGCGUGAGGAGCAGGGG 19 5924 SCNN1A-181 ACAAGCGUGAGGAGCAGGGG 20 814 SCNN1A-2076 AACAAGCGUGAGGAGCAGGGG 21 5925 SCNN1A-2077 GAACAAGCGUGAGGAGCAGGGG 22 5926 SCNN1A-2078 GGAACAAGCGUGAGGAGCAGGGG 23 5927 SCNN1A-2079 GGGAACAAGCGUGAGGAGCAGGGG 24 5928 SCNN1A-11105 GGUGGCUCCCCUUUGGGG 18 14954 SCNN1A-11106 UGGUGGCUCCCCUUUGGGG 19 14955 SCNN1A-6342 AUGGUGGCUCCCCUUUGGGG 20 10191 SCNN1A-11107 UAUGGUGGCUCCCCUUUGGGG 21 14956 SCNN1A-11108 UUAUGGUGGCUCCCCUUUGGGG 22 14957 SCNN1A-11109 AUUAUGGUGGCUCCCCUUUGGGG 23 14958 SCNN1A-11110 AAUUAUGGUGGCUCCCCUUUGGGG 24 14959 SCNN1A-11111 UGGUGGCUCCCCUUUGGG 18 14960 SCNN1A-11112 AUGGUGGCUCCCCUUUGGG 19 14961 SCNN1A-11113 UAUGGUGGCUCCCCUUUGGG 20 14962 SCNN1A-11114 UUAUGGUGGCUCCCCUUUGGG 21 14963 SCNN1A-11115 AUUAUGGUGGCUCCCCUUUGGG 22 14964 SCNN1A-11116 AAUUAUGGUGGCUCCCCUUUGGG 23 14965 SCNN1A-11117 AAAUUAUGGUGGCUCCCCUUUGGG 24 14966 SCNN1A-2105 UCCACUCCAGGGCUCAUG 18 5954 SCNN1A-2106 GUCCACUCCAGGGCUCAUG 19 5955 SCNN1A-172 AGUCCACUCCAGGGCUCAUG 20 810 SCNN1A-2107 CAGUCCACUCCAGGGCUCAUG 21 5956 SCNN1A-2108 ACAGUCCACUCCAGGGCUCAUG 22 5957 SCNN1A-2109 CACAGUCCACUCCAGGGCUCAUG 23 5958 SCNN1A-2110 CCACAGUCCACUCCAGGGCUCAUG 24 5959 SCNN1A-2137 UGAAGGGGAACAAGCGUG 18 5986 SCNN1A-2138 AUGAAGGGGAACAAGCGUG 19 5987 SCNN1A-13 CAUGAAGGGGAACAAGCGUG 20 562 SCNN1A-2139 UCAUGAAGGGGAACAAGCGUG 21 5988 SCNN1A-2140 CUCAUGAAGGGGAACAAGCGUG 22 5989 SCNN1A-2141 GCUCAUGAAGGGGAACAAGCGUG 23 5990 SCNN1A-2142 GGCUCAUGAAGGGGAACAAGCGUG 24 5991 SCNN1A-11118 GAAGGGUGGUCCAGGGUG 18 14967 SCNN1A-11119 GGAAGGGUGGUCCAGGGUG 19 14968 SCNN1A-11120 UGGAAGGGUGGUCCAGGGUG 20 14969 SCNN1A-11121 CUGGAAGGGUGGUCCAGGGUG 21 14970 SCNN1A-11122 CCUGGAAGGGUGGUCCAGGGUG 22 14971 SCNN1A-11123 GCCUGGAAGGGUGGUCCAGGGUG 23 14972 SCNN1A-11124 CGCCUGGAAGGGUGGUCCAGGGUG 24 14973 SCNN1A-11125 CUAUAUACUUCUGUAUUG 18 14974 SCNN1A-11126 UCUAUAUACUUCUGUAUUG 19 14975 SCNN1A-11127 CUCUAUAUACUUCUGUAUUG 20 14976 SCNN1A-11128 GCUCUAUAUACUUCUGUAUUG 21 14977 SCNN1A-11129 AGCUCUAUAUACUUCUGUAUUG 22 14978 SCNN1A-11130 AAGCUCUAUAUACUUCUGUAUUG 23 14979 SCNN1A-11131 GAAGCUCUAUAUACUUCUGUAUUG 24 14980 SCNN1A-11132 AAGCAAAAAUGGAAGUUG 18 14981 SCNN1A-11133 AAAGCAAAAAUGGAAGUUG 19 14982 SCNN1A-11134 AAAAGCAAAAAUGGAAGUUG 20 14983 SCNN1A-11135 UAAAAGCAAAAAUGGAAGUUG 21 14984 SCNN1A-11136 AUAAAAGCAAAAAUGGAAGUUG 22 14985 SCNN1A-11137 AAUAAAAGCAAAAAUGGAAGUUG 23 14986 SCNN1A-11138 AAAUAAAAGCAAAAAUGGAAGUUG 24 14987 SCNN1A-11139 UAUGGUGGCUCCCCUUUG 18 14988 SCNN1A-11140 UUAUGGUGGCUCCCCUUUG 19 14989 SCNN1A-6348 AUUAUGGUGGCUCCCCUUUG 20 10197 SCNN1A-11141 AAUUAUGGUGGCUCCCCUUUG 21 14990 SCNN1A-11142 AAAUUAUGGUGGCUCCCCUUUG 22 14991 SCNN1A-11143 CAAAUUAUGGUGGCUCCCCUUUG 23 14992 SCNN1A-11144 ACAAAUUAUGGUGGCUCCCCUUUG 24 14993 SCNN1A-11145 CCUGUCUCUAAGAUAAAU 18 14994 SCNN1A-11146 UCCUGUCUCUAAGAUAAAU 19 14995 SCNN1A-11147 AUCCUGUCUCUAAGAUAAAU 20 14996 SCNN1A-11148 GAUCCUGUCUCUAAGAUAAAU 21 14997 SCNN1A-11149 UGAUCCUGUCUCUAAGAUAAAU 22 14998 SCNN1A-11150 AUGAUCCUGUCUCUAAGAUAAAU 23 14999 SCNN1A-11151 CAUGAUCCUGUCUCUAAGAUAAAU 24 15000 SCNN1A-11152 AGGGAAAGGAAGGGGACU 18 15001 SCNN1A-11153 GAGGGAAAGGAAGGGGACU 19 15002 SCNN1A-11154 GGAGGGAAAGGAAGGGGACU 20 15003 SCNN1A-11155 GGGAGGGAAAGGAAGGGGACU 21 15004 SCNN1A-11156 GGGGAGGGAAAGGAAGGGGACU 22 15005 SCNN1A-11157 UGGGGAGGGAAAGGAAGGGGACU 23 15006 SCNN1A-11158 UUGGGGAGGGAAAGGAAGGGGACU 24 15007 SCNN1A-11159 AAUUAUGGUGGCUCCCCU 18 15008 SCNN1A-11160 AAAUUAUGGUGGCUCCCCU 19 15009 SCNN1A-11161 CAAAUUAUGGUGGCUCCCCU 20 15010 SCNN1A-11162 ACAAAUUAUGGUGGCUCCCCU 21 15011 SCNN1A-11163 UACAAAUUAUGGUGGCUCCCCU 22 15012 SCNN1A-11164 AUACAAAUUAUGGUGGCUCCCCU 23 15013 SCNN1A-11165 UAUACAAAUUAUGGUGGCUCCCCU 24 15014 SCNN1A-2170 AUGAAGGGGAACAAGCGU 18 6019 SCNN1A-2171 CAUGAAGGGGAACAAGCGU 19 6020 SCNN1A-177 UCAUGAAGGGGAACAAGCGU 20 812 SCNN1A-2172 CUCAUGAAGGGGAACAAGCGU 21 6021 SCNN1A-2173 GCUCAUGAAGGGGAACAAGCGU 22 6022 SCNN1A-2174 GGCUCAUGAAGGGGAACAAGCGU 23 6023 SCNN1A-2175 GGGCUCAUGAAGGGGAACAAGCGU 24 6024 SCNN1A-11166 AGCCUCAGACCUGAGGGU 18 15015 SCNN1A-11167 GAGCCUCAGACCUGAGGGU 19 15016 SCNN1A-6357 AGAGCCUCAGACCUGAGGGU 20 10206 SCNN1A-11168 CAGAGCCUCAGACCUGAGGGU 21 15017 SCNN1A-11169 GCAGAGCCUCAGACCUGAGGGU 22 15018 SCNN1A-11170 GGCAGAGCCUCAGACCUGAGGGU 23 15019 SCNN1A-11171 AGGCAGAGCCUCAGACCUGAGGGU 24 15020 SCNN1A-11172 AUUAUGGUGGCUCCCCUU 18 15021 SCNN1A-11173 AAUUAUGGUGGCUCCCCUU 19 15022 SCNN1A-6360 AAAUUAUGGUGGCUCCCCUU 20 10209 SCNN1A-11174 CAAAUUAUGGUGGCUCCCCUU 21 15023 SCNN1A-11175 ACAAAUUAUGGUGGCUCCCCUU 22 15024 SCNN1A-11176 UACAAAUUAUGGUGGCUCCCCUU 23 15025 SCNN1A-11177 AUACAAAUUAUGGUGGCUCCCCUU 24 15026 SCNN1A-2183 CCGCAUGAAGACGGCCUU 18 6032 SCNN1A-2184 ACCGCAUGAAGACGGCCUU 19 6033 SCNN1A-194 AACCGCAUGAAGACGGCCUU 20 824 SCNN1A-2185 CAACCGCAUGAAGACGGCCUU 21 6034 SCNN1A-2186 ACAACCGCAUGAAGACGGCCUU 22 6035 SCNN1A-2187 CACAACCGCAUGAAGACGGCCUU 23 6036 SCNN1A-2188 GCACAACCGCAUGAAGACGGCCUU 24 6037 SCNN1A-11178 UUAUGGUGGCUCCCCUUU 18 15027 SCNN1A-11179 AUUAUGGUGGCUCCCCUUU 19 15028 SCNN1A-6361 AAUUAUGGUGGCUCCCCUUU 20 10210 SCNN1A-11180 AAAUUAUGGUGGCUCCCCUUU 21 15029 SCNN1A-11181 CAAAUUAUGGUGGCUCCCCUUU 22 15030 SCNN1A-11182 ACAAAUUAUGGUGGCUCCCCUUU 23 15031 SCNN1A-11183 UACAAAUUAUGGUGGCUCCCCUUU 24 15032 SCNN1A-2189 GGCAAUUCGGCCUGCUUU 18 6038 SCNN1A-2190 UGGCAAUUCGGCCUGCUUU 19 6039 SCNN1A-195 CUGGCAAUUCGGCCUGCUUU 20 825 SCNN1A-2191 ACUGGCAAUUCGGCCUGCUUU 21 6040 SCNN1A-2192 UACUGGCAAUUCGGCCUGCUUU 22 6041 SCNN1A-2193 GUACUGGCAAUUCGGCCUGCUUU 23 6042 SCNN1A-2194 UGUACUGGCAAUUCGGCCUGCUUU 24 6043 SCNN1A-2195 GCAAUUCGGCCUGCUUUU 18 6044 SCNN1A-2196 GGCAAUUCGGCCUGCUUUU 19 6045 SCNN1A-34 UGGCAAUUCGGCCUGCUUUU 20 573 SCNN1A-2197 CUGGCAAUUCGGCCUGCUUUU 21 6046 SCNN1A-2198 ACUGGCAAUUCGGCCUGCUUUU 22 6047 SCNN1A-2199 UACUGGCAAUUCGGCCUGCUUUU 23 6048 SCNN1A-2200 GUACUGGCAAUUCGGCCUGCUUUU 24 6049

Table 48A provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the first tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), have a high level of orthogonality and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

Table 48A 1st Tier Target  gRNA DNA Site Name Strand Targeting Domain Length Seq ID SCNN1A- + GUGAAAGCCGGUGUCAA 17 15033 11184 SCNN1A- GUUUUCUAACCUCAGAA 17 15034 11185 SCNN1A- GCUGCAUUAAGUUUGGA 17 15035 11186 SCNN1A-5020 + GGCUAGAGUCCUGCUCC 17  8869 SCNN1A-5021 + GUCUAGGGUCCUGCUCC 17  8870 SCNN1A- GAUGCUAAUGAGAUUCC 17 15036 11187 SCNN1A-5106 + GAAGGCGGACUCUGGGC 17  8955 SCNN1A-5022 + GAUUCCAAACCAGGUUC 17  8871 SCNN1A- + GGCCAAAAGUGCCGGAG 17 15037 11188 SCNN1A- GAUGACACCUUCUCUGG 17 15038 11189 SCNN1A- GCUGCCUUAAGCUAGUG 17 15039 11190 SCNN1A- GCUAAACUCCUUGCUUG 17 15040 11191 SCNN1A- GGAGUGAGGGAGGCCUU 17 15041 11192 SCNN1A- + GAGCAAGGGGGGAGUCCCAA 20 15042 11193 SCNN1A- GGUUUGGAAUCCUGGUUGAC 20 15043 11194 SCNN1A- + GCUCAGGGUCCAACCUGGUC 20 15044 11195 SCNN1A- + GGCCCUGACCUCGAGCUGUG 20 15045 11196 SCNN1A- GGGGGAGGAGAGGUUUGGCU 20 15046 11197 SCNN1A- GUGGGAGUGAGGGAGGCCUU 20 15047 11198 SCNN1A- + GGUUUCUAUUUGUACACUUU 20 15048 11199

Table 48B provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the second tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and have a high level of orthogonality. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 48B 2nd Tier Target  gRNA DNA Site Name Strand Targeting Domain Length Seq ID SCNN1A- + CAAGGGGGGAGUCCCAA 17 15049 11200 SCNN1A- + UCCCCUUGGAAGGGACA 17 15050 11201 SCNN1A- CUUUAAUUGAGAUGCUA 17 15051 11202 SCNN1A- UUGGAAUCCUGGUUGAC 17 15052 11203 SCNN1A- + AUGCCUGAAAUCCAACC 17 15053 11204 SCNN1A- + CACUCCCACACAGAGCC 17 15054 11205 SCNN1A- UAGGGCCCCGCCUAGCC 17 15055 11206 SCNN1A- + AGGAGGUCUGGGCUGCC 17 15056 11207 SCNN1A- + UGGUCCCUCCUCUUUCC 17 15057 11208 SCNN1A- + CACGCGGCAGGGAAGGC 17 15058 11209 SCNN1A- + CCCUAGAACGGCCUCUC 17 15059 11210 SCNN1A- + CAGGGUCCAACCUGGUC 17 15060 11211 SCNN1A- + AGUGCAGGAAUGUGGUC 17 15061 11212 SCNN1A-5426 CUCUGUGACCACAGCAG 17  9275 SCNN1A-5024 + CCCUUCAUGAGCCCCGG 17  8873 SCNN1A-6029 AAAUAGAAAAGGCAGGG 17  9878 SCNN1A- CCUCCAGCCCUUUUUGG 17 15062 11213 SCNN1A- + CCUGACCUCGAGCUGUG 17 15063 11214 SCNN1A- + CUAACAAAAGUGCAGAU 17 15064 11215 SCNN1A- UCUUUGCCUGCUAAACU 17 15065 11216 SCNN1A- + CUCUGGGGCUAUCUACU 17 15066 11217 SCNN1A- + UUCUAUUUGUACACUUU 17 15067 11218 SCNN1A- + AAAGUGAAAGCCGGUGUCAA 20 15068 11219 SCNN1A- UUUGUUUUCUAACCUCAGAA 20 15069 11220 SCNN1A- + ACCUCCCCUUGGAAGGGACA 20 15070 11221 SCNN1A-9203 UUUGCUGCAUUAAGUUUGGA 20 13052 SCNN1A-9243 CACCUUUAAUUGAGAUGCUA 20 13092 SCNN1A- + CUCAUGCCUGAAAUCCAACC 20 15071 11222 SCNN1A- + CCUCACUCCCACACAGAGCC 20 15072 11223 SCNN1A- UCCUAGGGCCCCGCCUAGCC 20 15073 11224 SCNN1A- + UCCAGGAGGUCUGGGCUGCC 20 15074 11225 SCNN1A- UGAGAUGCUAAUGAGAUUCC 20 15075 11226 SCNN1A- + UCCUGGUCCCUCCUCUUUCC 20 15076 11227 SCNN1A- + CUGCACGCGGCAGGGAAGGC 20 15077 11228 SCNN1A- + CUUCCCUAGAACGGCCUCUC 20 15078 11229 SCNN1A- + CAGAGUGCAGGAAUGUGGUC 20 15079 11230 SCNN1A-5650 CAACUCUGUGACCACAGCAG 20  9499 SCNN1A-8013 + UGGGGCCAAAAGUGCCGGAG 20 11862 SCNN1A-5027 + UUCCCCUUCAUGAGCCCCGG 20  8876 SCNN1A- UCUCCUCCAGCCCUUUUUGG 20 15080 11231 SCNN1A- CAUGCUGCCUUAAGCUAGUG 20 15081 11232 SCNN1A- CCUGCUAAACUCCUUGCUUG 20 15082 11233 SCNN1A- + CUUCUAACAAAAGUGCAGAU 20 15083 11234 SCNN1A- UCUUCUUUGCCUGCUAAACU 20 15084 11235 SCNN1A- + CUCCUCUGGGGCUAUCUACU 20 15085 11236 SCNN1A- CUCAGGCUGGGCCUUUGUCU 20 15086 11237 SCNN1A- AUCCUCCCUGCACCUUCAGU 20 15087 11238

Table 48C provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the third tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS) and start with a 5′G. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 48C 3rd Tier Target gRNA DNA Site Name Strand Targeting Domain Length Seq ID SCNN1A- GGGGGAGAGGAAGAGAG 17 15088 11239 SCNN1A- GGAGGAGAGGUUUGGCU 17 15089 11240 SCNN1A-5029 + GAGGGCUAGAGUCCUGCUCC 20  8878 SCNN1A-5030 + GAGGUCUAGGGUCCUGCUCC 20  8879 SCNN1A-5263 GGCAAAUAGAAAAGGCAGGG 20  9112

Table 48D provides exemplary targeting domains for knocking out the SCNN1A gene selected according to the fourth tier parameters. The targeting domains bind within 500 bp (e.g., upstream or downstream) of a transcription start site (TSS). It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

Table 48D 4th Tier Target gRNA DNA Site Name Strand Targeting Domain Length Seq ID SCNN1A- AGGCUGGGCCUUUGUCU 17 15090 11241 SCNN1A- CUCCCUGCACCUUCAGU 17 15091 11242 SCNN1A-5613 + UGAGAAGGCGGACUCUGGGC 20  9462 SCNN1A-5032 + CAGGAUUCCAAACCAGGUUC 20  8881 SCNN1A- AGGGGGGGAGAGGAAGAGAG 20 15092 11243 SCNN1A- AGAGAUGACACCUUCUCUGG 20 15093 11244

Table 48E provides exemplary targeting domains for knocking down the SCNN1A gene selected according to the fifth tier parameters. The targeting domains bind within the additional 500 bp (e.g., upstream or downstream) of a transcription start site (TSS), e.g., extending to 1 kb upstream and downstream of a TSS. It is contemplated herein that in an embodiment the targeting domain hybridizes to the target domain through complementary base pairing. Any of the targeting domains in the table can be used with a N. miningtidis eiCas9 molecule or eiCas9 fusion protein (e.g., an eiCas9 fused to a transcription repressor domain) to alter the SCNN1A gene (e.g., reduce or eliminate SCNN1A gene expression, SCNN1A protein function, or the level of SCNN1A protein). One or more gRNA may be used to target an eiCas9 to the promoter region of the SCNN1A gene.

TABLE 48E 5th Tier DNA Target Site gRNA Name Strand Targeting Domain Length Seq ID SCNN1A-11245 + ACCUGGAGCGGGCUAGA 17 15094 SCNN1A-11246 + AGCAAUACAGAAGUAUA 17 15095 SCNN1A-5028 + GGCCCAGCCCCUGCUCC 17 8877 SCNN1A-322 + UGGUCACUGCGGGGAAG 17 915 SCNN1A-5023 GAUGUACUGGCAAUUCG 17 8872 SCNN1A-5025 + AGGGACUAACCGACCUG 17 8874 SCNN1A-11247 + GUUUCUACAACUUCCAU 17 15096 SCNN1A-11248 CUGACCAAAGUCCAGGU 17 15097 SCNN1A-11249 + UAGACCUGGAGCGGGCUAGA 20 15098 SCNN1A-10791 + UUCAGCAAUACAGAAGUAUA 20 14640 SCNN1A-5031 + CGGGGCCCAGCCCCUGCUCC 20 8880 SCNN1A-238 + AGAUGGUCACUGCGGGGAAG 20 858 SCNN1A-5026 CAUGAUGUACUGGCAAUUCG 20 8875 SCNN1A-1657 + CAGAGGGACUAACCGACCUG 20 5506 SCNN1A-11250 + UAUGUUUCUACAACUUCCAU 20 15099 SCNN1A-11251 CUUCUGACCAAAGUCCAGGU 20 15100

III. Cas9 Molecules

Cas9 molecules of a variety of species can be used in the methods and compositions described herein. While the S. pyogenes, S. aureus and S. thermophilus Cas9 molecules are the subject of much of the disclosure herein, Cas9 molecules of, derived from, or based on the Cas9 proteins of other species listed herein can be used as well. In other words, while the much of the description herein uses S. pyogenes and S. thermophilus Cas9 molecules, Cas9 molecules from the other species can replace them, e.g., Staphylococcus aureus and Neisseria meningitidis Cas9 molecules. Additional Cas9 species include: Acidovorax avenae, Actinobacillus pleuropneumoniae, Actinobacillus succinogenes, Actinobacillus suis, Actinomyces sp., Cycliphilus denitrificans, Aminomonas paucivorans, Bacillus cereus, Bacillus smithi, Bacillus thuringiensis, Bacteroides sp., Blastopirellula marina, Bradyrhizobium sp., Brevibacillus laterosporus, Campylobacter coli, Campylobacter jejuni, Campylobacter lari, Candidatus puniceispirillum, Clostridium cellulolyticum, Clostridium perfringens, Corynebacterium accolens, Corynebacterium diphtheria, Corynebacterium matruchotii, Dinoroseobacter shibae, Eubacterium dolichum, Gamma proteobacterium, Gluconacetobacter diazotrophicus, Haemophilus parainfluenzae, Haemophilus sputorum, Helicobacter canadensis, Helicobacter cinaedi, Helicobacter mustelae, Ilyobacter polytropus, Kingella kingae, Lactobacillus crispatus, Listeria ivanovii, Listeria monocytogenes, Listeriaceae bacterium, Methylocystis sp., Methylosinus trichosporium, Mobiluncus mulieris, Neisseria bacilliformis, Neisseria cinerea, Neisseria flavescens, Neisseria lactamica, Neisseria meningitidis, Neisseria sp., Neisseria wadsworthii, Nitrosomonas sp., Parvibaculum lavamentivorans, Pasteurella multocida, Phascolarctobacterium succinatutens, Ralstonia syzygii, Rhodopseudomonas palustris, Rhodovulum sp., Simonsiella muelleri, Sphingomonas sp., Sporolactobacillus vineae, Staphylococcus lugdunensis, Streptococcus sp., Subdoligranulum sp., Tistrella mobilis, Treponema sp., or Verminephrobacter eiseniae.

A Cas9 molecule or Cas9 polypeptide, as that term is used herein, refers to a molecule or polypeptide that can interact with a guide RNA (gRNA) molecule and, in concert with the gRNA molecule, home or localizes to a site which comprises a target domain and PAM sequence. Cas9 molecule and Cas9 polypeptide, as those terms are used herein, refer to naturally occurring Cas9 molecules and to engineered, altered, or modified Cas9 molecules or Cas9 polypeptides that differ, e.g., by at least one amino acid residue, from a reference sequence, e.g., the most similar naturally occurring Cas9 molecule or a sequence of Table 50.

Cas9 Domains

Crystal structures have been determined for two different naturally occurring bacterial Cas9 molecules (Jinek et al., Science, 343(6176):1247997, 2014) and for S. pyogenes Cas9 with a guide RNA (e.g., a synthetic fusion of crRNA and tracrRNA) (Nishimasu et al., Cell, 156:935-949, 2014; and Anders et al., Nature, 2014, doi: 10.1038/nature13579).

A naturally occurring Cas9 molecule comprises two lobes: a recognition (REC) lobe and a nuclease (NUC) lobe; each of which further comprises domains described herein. FIGS. 9A-9B provide a schematic of the organization of important Cas9 domains in the primary structure. The domain nomenclature and the numbering of the amino acid residues encompassed by each domain used throughout this disclosure is as described in Nishimasu et al. The numbering of the amino acid residues is with reference to Cas9 from S. pyogenes.

The REC lobe comprises the arginine-rich bridge helix (BH), the REC1 domain, and the REC2 domain. The REC lobe does not share structural similarity with other known proteins, indicating that it is a Cas9-specific functional domain. The BH domain is a long α helix and arginine rich region and comprises amino acids 60-93 of the sequence of S. pyogenes Cas9. The REC1 domain is important for recognition of the repeat:anti-repeat duplex, e.g., of a gRNA or a tracrRNA, and is therefore critical for Cas9 activity by recognizing the target sequence. The REC1 domain comprises two REC1 motifs at amino acids 94 to 179 and 308 to 717 of the sequence of S. pyogenes Cas9. These two REC1 domains, though separated by the REC2 domain in the linear primary structure, assemble in the tertiary structure to form the REC1 domain. The REC2 domain, or parts thereof, may also play a role in the recognition of the repeat:anti-repeat duplex. The REC2 domain comprises amino acids 180-307 of the sequence of S. pyogenes Cas9.

The NUC lobe comprises the RuvC domain (also referred to herein as RuvC-like domain), the HNH domain (also referred to herein as HNH-like domain), and the PAM-interacting (PI) domain. The RuvC domain shares structural similarity to retroviral integrase superfamily members and cleaves a single strand, e.g., the non-complementary strand of the target nucleic acid molecule. The RuvC domain is assembled from the three split RuvC motifs (RuvC I, RuvCII, and RuvCIII, which are often commonly referred to in the art as RuvCI domain, or N-terminal RuvC domain, RuvCII domain, and RuvCIII domain) at amino acids 1-59, 718-769, and 909-1098, respectively, of the sequence of S. pyogenes Cas9. Similar to the REC1 domain, the three RuvC motifs are linearly separated by other domains in the primary structure, however in the tertiary structure, the three RuvC motifs assemble and form the RuvC domain. The HNH domain shares structural similarity with HNH endonucleases, and cleaves a single strand, e.g., the complementary strand of the target nucleic acid molecule. The HNH domain lies between the RuvC II-III motifs and comprises amino acids 775-908 of the sequence of S. pyogenes Cas9. The PI domain interacts with the PAM of the target nucleic acid molecule, and comprises amino acids 1099-1368 of the sequence of S. pyogenes Cas9.

A RuvC-Like Domain and an HNH-Like Domain

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises an HNH-like domain and a RuvC-like domain. In an embodiment, cleavage activity is dependent on a RuvC-like domain and an HNH-like domain. A Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, can comprise one or more of the following domains: a RuvC-like domain and an HNH-like domain. In an embodiment, a Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide and the eaCas9 molecule or eaCas9 polypeptide comprises a RuvC-like domain, e.g., a RuvC-like domain described below, and/or an HNH-like domain, e.g., an HNH-like domain described below.

RuvC-Like Domains

In an embodiment, a RuvC-like domain cleaves, a single strand, e.g., the non-complementary strand of the target nucleic acid molecule. The Cas9 molecule or Cas9 polypeptide can include more than one RuvC-like domain (e.g., one, two, three or more RuvC-like domains). In an embodiment, a RuvC-like domain is at least 5, 6, 7, 8 amino acids in length but not more than 20, 19, 18, 17, 16 or 15 amino acids in length. In an embodiment, the Cas9 molecule or Cas9 polypeptide comprises an N-terminal RuvC-like domain of about 10 to 20 amino acids, e.g., about 15 amino acids in length.

N-Terminal RuvC-Like Domains

Some naturally occurring Cas9 molecules comprise more than one RuvC-like domain with cleavage being dependent on the N-terminal RuvC-like domain. Accordingly, Cas9 molecules or Cas9 polypeptide can comprise an N-terminal RuvC-like domain. Exemplary N-terminal RuvC-like domains are described below.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an N-terminal RuvC-like domain comprising an amino acid sequence of formula I:

(SEQ ID NO: 8) D-X1-G-X2-X3-X4-X5-G-X6-X7-X8-X9,
    • wherein,
    • X1 is selected from I, V, M, L and T (e.g., selected from I, V, and L);
    • X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);
    • X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);
    • X4 is selected from S, Y, N and F (e.g., S);
    • X5 is selected from V, I, L, C, T and F (e.g., selected from V, I and L);
    • X6 is selected from W, F, V, Y, S and L (e.g., W);
    • X7 is selected from A, S, C, V and G (e.g., selected from A and S);
    • X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and
    • X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A, Y, M and R, or, e.g., selected from T, V, I, L and Δ).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO:8, by as many as 1 but no more than 2, 3, 4, or 5 residues.

In embodiment, the N-terminal RuvC-like domain is cleavage competent.

In embodiment, the N-terminal RuvC-like domain is cleavage incompetent.

In an embodiment, a eaCas9 molecule or eaCas9 polypeptide comprises an N-terminal RuvC-like domain comprising an amino acid sequence of formula II:

(SEQ ID NO: 9) D-X1-G-X2-X3-S-X5-G-X6-X7-X8-X9,,
    • wherein
    • X1 is selected from I, V, M, L and T (e.g., selected from I, V, and L);
    • X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);
    • X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);
    • X5 is selected from V, I, L, C, T and F (e.g., selected from V, I and L);
    • X6 is selected from W, F, V, Y, S and L (e.g., W);
    • X7 is selected from A, S, C, V and G (e.g., selected from A and S);
    • X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and
    • X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A, Y, M and R or selected from e.g., T, V, I, L and Δ).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO:9 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In an embodiment, the N-terminal RuvC-like domain comprises an amino acid sequence of formula III:

(SEQ ID NO: 10) D-I-G-X2-X3-S-V-G-W-A-X8-X9,
    • wherein
    • X2 is selected from T, I, V, S, N, Y, E and L (e.g., selected from T, V, and I);
    • X3 is selected from N, S, G, A, D, T, R, M and F (e.g., A or N);
    • X8 is selected from V, I, L, A, M and H (e.g., selected from V, I, M and L); and
    • X9 is selected from any amino acid or is absent (e.g., selected from T, V, I, L, Δ, F, S, A, Y, M and R or selected from e.g., T, V, I, L and Δ).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO:10 by as many as 1 but no more than, 2, 3, 4, or 5 residues.

In an embodiment, the N-terminal RuvC-like domain comprises an amino acid sequence of formula III:

(SEQ ID NO: 11) D-I-G-T-N-S-V-G-W-A-V-X,
    • wherein
    • X is a non-polar alkyl amino acid or a hydroxyl amino acid, e.g., X is selected from V, I, L and T (e.g., the eaCas9 molecule can comprise an N-terminal RuvC-like domain shown in FIGS. 2A-2G (is depicted as Y)).

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of SEQ ID NO:11 by as many as 1 but no more than, 2, 3, 4, or 5 residues.

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of an N-terminal RuvC like domain disclosed herein, e.g., in FIGS. 3A-3B or FIGS. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1, 2, 3 or all of the highly conserved residues identified in FIGS. 3A-3B or FIGS. 7A-7B are present.

In an embodiment, the N-terminal RuvC-like domain differs from a sequence of an N-terminal RuvC-like domain disclosed herein, e.g., in FIGS. 4A-4B or FIGS. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1, 2, or all of the highly conserved residues identified in FIGS. 4A-4B or FIGS. 7A-7B are present.

Additional RuvC-Like Domains

In addition to the N-terminal RuvC-like domain, the Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, can comprise one or more additional RuvC-like domains. In an embodiment, the Cas9 molecule or Cas9 polypeptide can comprise two additional RuvC-like domains. Preferably, the additional RuvC-like domain is at least 5 amino acids in length and, e.g., less than 15 amino acids in length, e.g., 5 to 10 amino acids in length, e.g., 8 amino acids in length.

An additional RuvC-like domain can comprise an amino acid sequence:

(SEQ ID NO: 12) I-X1-X2-E-X3-A-R-E,

wherein
    • X1 is V or H,
    • X2 is I, L or V (e.g., I or V); and
    • X3 is M or T.

In an embodiment, the additional RuvC-like domain comprises the amino acid sequence:

    • I-V-X2-E-M-A-R-E (SEQ ID NO:13), wherein
    • X2 is I, L or V (e.g., I or V) (e.g., the eaCas9 molecule or eaCas9 polypeptide can comprise an additional RuvC-like domain shown in FIG. 2A-2G or FIGS. 7A-7B (depicted as B)).

An additional RuvC-like domain can comprise an amino acid sequence:

(SEQ ID NO: 14) H-H-A-X1-D-A-X2-X3,

wherein
    • X1 is H or L;
    • X2 is R or V; and
    • X3 is E or V.

In an embodiment, the additional RuvC-like domain comprises the amino acid sequence: H-H-A-H-D-A-Y-L (SEQ ID NO:15).

In an embodiment, the additional RuvC-like domain differs from a sequence of SEQ ID NO: 12, 13, 14 or 15 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In some embodiments, the sequence flanking the N-terminal RuvC-like domain is a sequences of formula V:

(SEQ ID NO: 16) K-X1′-Y-X2′-X3′-X4′-Z-T-D-X9′-Y,.
    • wherein
    • X1′ is selected from K and P,
    • X2′ is selected from V, L, I, and F (e.g., V, I and L);
    • X3′ is selected from G, A and S (e.g., G),
    • X4′ is selected from L, I, V and F (e.g., L);
    • X9′ is selected from D, E, N and Q; and
    • Z is an N-terminal RuvC-like domain, e.g., as described above.

HNH-Like Domains

In an embodiment, an HNH-like domain cleaves a single stranded complementary domain, e.g., a complementary strand of a double stranded nucleic acid molecule. In an embodiment, an HNH-like domain is at least 15, 20, 25 amino acids in length but not more than 40, 35 or 30 amino acids in length, e.g., 20 to 35 amino acids in length, e.g., 25 to 30 amino acids in length. Exemplary HNH-like domains are described below.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain having an amino acid sequence of formula VI:

(SEQ ID NO: 17) X1-X2-X3-H-X4-X5-P-X6-X7-X9-X10-X11-X12-X13-X14- X15-N-X16-X17-X18-X19-X20-X21-X22-X23-N,

wherein
    • X1 is selected from D, E, Q and N (e.g., D and E);
    • X2 is selected from L, I, R, Q, V, M and K;
    • X3 is selected from D and E;
    • X4 is selected from I, V, T, A and L (e.g., A, I and V);
    • X5 is selected from V, Y, I, L, F and W (e.g., V, I and L);
    • X6 is selected from Q, H, R, K, Y, I, L, F and W;
    • X7 is selected from S, A, D, T and K (e.g., S and A);
    • X8 is selected from F, L, V, K, Y, M, I, R, A, E, D and Q (e.g., F);
    • X9 is selected from L, R, T, I, V, S, C, Y, K, F and G;
    • X10 is selected from K, Q, Y, T, F, L, W, M, A, E, G, and S;
    • X11 is selected from D, S, N, R, L and T (e.g., D);
    • X12 is selected from D, N and S;
    • X13 is selected from S, A, T, G and R (e.g., S);
    • X14 is selected from I, L, F, S, R, Y, Q, W, D, K and H (e.g., I, L and F);
    • X15 is selected from D, S, I, N, E, A, H, F, L, Q, M, G, Y and V;
    • X16 is selected from K, L, R, M, T and F (e.g., L, R and K);
    • X17 is selected from V, L, I, A and T;
    • X18 is selected from L, I, V and A (e.g., L and I);
    • X19 is selected from T, V, C, E, S and A (e.g., T and V);
    • X20 is selected from R, F, T, W, E, L, N, C, K, V, S, Q, I, Y, H and A;
    • X21 is selected from S, P, R, K, N, A, H, Q, G and L;
    • X22 is selected from D, G, T, N, S, K, A, I, E, L, Q, R and Y; and
    • X23 is selected from K, V, A, E, Y, I, C, L, S, T, G, K, M, D and F.

In an embodiment, a HNH-like domain differs from a sequence of SEQ ID NO: 17 by at least one but no more than, 2, 3, 4, or 5 residues.

In an embodiment, the HNH-like domain is cleavage competent.

In an embodiment, the HNH-like domain is cleavage incompetent.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain comprising an amino acid sequence of formula VII:

(SEQ ID NO: 18) X1-X2-X3-H-X4-X5-P-X6-S-X8-X9-X10-D-D-S-X14-X15- N-K-V-L-X19-X20-X21-X22-X23-N,
    • wherein
    • X1 is selected from D and E;
    • X2 is selected from L, I, R, Q, V, M and K;
    • X3 is selected from D and E;
    • X4 is selected from I, V, T, A and L (e.g., A, I and V);
    • X5 is selected from V, Y, I, L, F and W (e.g., V, I and L);
    • X6 is selected from Q, H, R, K, Y, I, L, F and W;
    • X8 is selected from F, L, V, K, Y, M, I, R, A, E, D and Q (e.g., F);
    • X9 is selected from L, R, T, I, V, S, C, Y, K, F and G;
    • X10 is selected from K, Q, Y, T, F, L, W, M, A, E, G, and S;
    • X14 is selected from I, L, F, S, R, Y, Q, W, D, K and H (e.g., I, L and F);
    • X15 is selected from D, S, I, N, E, A, H, F, L, Q, M, G, Y and V;
    • X19 is selected from T, V, C, E, S and A (e.g., T and V);
    • X20 is selected from R, F, T, W, E, L, N, C, K, V, S, Q, I, Y, H and A;
    • X21 is selected from S, P, R, K, N, A, H, Q, G and L;
    • X22 is selected from D, G, T, N, S, K, A, I, E, L, Q, R and Y; and
    • X23 is selected from K, V, A, E, Y, I, C, L, S, T, G, K, M, D and F.

In an embodiment, the HNH-like domain differs from a sequence of SEQ ID NO: 18 by 1, 2, 3, 4, or 5 residues.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain comprising an amino acid sequence of formula VII:

(SEQ ID NO: 19) X1-V-X3-H-I-V-P-X6-S-X8-X9-X10-D-D-S-X14-X15-N-K- V-L-T-X20-X21-X22-X23-N,
    • wherein
    • X1 is selected from D and E;
    • X3 is selected from D and E;
    • X6 is selected from Q, H, R, K, Y, I, L and W;
    • X8 is selected from F, L, V, K, Y, M, I, R, A, E, D and Q (e.g., F);
    • X9 is selected from L, R, T, I, V, S, C, Y, K, F and G;
    • X10 is selected from K, Q, Y, T, F, L, W, M, A, E, G, and S;
    • X14 is selected from I, L, F, S, R, Y, Q, W, D, K and H (e.g., I, L and F);
    • X15 is selected from D, S, I, N, E, A, H, F, L, Q, M, G, Y and V;
    • X20 is selected from R, F, T, W, E, L, N, C, K, V, S, Q, I, Y, H and A;
    • X21 is selected from S, P, R, K, N, A, H, Q, G and L;
    • X22 is selected from D, G, T, N, S, K, A, I, E, L, Q, R and Y; and
    • X23 is selected from K, V, A, E, Y, I, C, L, S, T, G, K, M, D and F.

In an embodiment, the HNH-like domain differs from a sequence of SEQ ID NO: 19 by 1, 2, 3, 4, or 5 residues.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an HNH-like domain having an amino acid sequence of formula VIII:

(SEQ ID NO: 20) D-X2-D-H-I-X5-P-Q-X7-F-X9-X10-D-X12-S-I-D-N-X16-V- L-X19-X20-S-X22-X23-N,
    • wherein
    • X2 is selected from I and V;
    • X5 is selected from I and V;
    • X7 is selected from A and S;
    • X9 is selected from I and L;
    • X10 is selected from K and T;
    • X12 is selected from D and N;
    • X16 is selected from R, K and L; X19 is selected from T and V;
    • X20 is selected from S and R;
    • X22 is selected from K, D and A; and
    • X23 is selected from E, K, G and N (e.g., the eaCas9 molecule or eaCas9 polypeptide can comprise an HNH-like domain as described herein).

In an embodiment, the HNH-like domain differs from a sequence of SEQ ID NO: 20 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises the amino acid sequence of formula IX:

(SEQ ID NO: 21) L-Y-Y-L-Q-N-G-X1′-D-M-Y-X2′-X3′-X4′-X5′-L-D-I-X6′- X7′-L-S-X8′-Y-Z-N-R-X9′-K-X10′-D-X11′-V-P,
    • wherein
    • X1′ is selected from K and R;
    • X2′ is selected from V and T;
    • X3′ is selected from G and D;
    • X4′ is selected from E, Q and D;
    • X5′ is selected from E and D;
    • X6′ is selected from D, N and H;
    • X7′ is selected from Y, R and N;
    • X8′ is selected from Q, D and N; X9′ is selected from G and E;
    • X10′ is selected from S and G;
    • X11′ is selected from D and N; and
    • Z is an HNH-like domain, e.g., as described above.

In an embodiment, the eaCas9 molecule or eaCas9 polypeptide comprises an amino acid sequence that differs from a sequence of SEQ ID NO:21 by as many as 1 but no more than 2, 3, 4, or 5 residues.

In an embodiment, the HNH-like domain differs from a sequence of an HNH-like domain disclosed herein, e.g., in FIGS. 5A-5C or FIGS. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1 or both of the highly conserved residues identified in FIGS. 5A-5C or FIGS. 7A-7B are present.

In an embodiment, the HNH-like domain differs from a sequence of an HNH-like domain disclosed herein, e.g., in FIGS. 6A-6B or FIGS. 7A-7B, as many as 1 but no more than 2, 3, 4, or 5 residues. In an embodiment, 1, 2, all 3 of the highly conserved residues identified in FIGS. 6A-6B or FIGS. 7A-7B are present.

Cas9 Activities

Nuclease and Helicase Activities

In an embodiment, the Cas9 molecule or Cas9 polypeptide is capable of cleaving a target nucleic acid molecule. Typically wild type Cas9 molecules cleave both strands of a target nucleic acid molecule. Cas9 molecules and Cas9 polypeptides can be engineered to alter nuclease cleavage (or other properties), e.g., to provide a Cas9 molecule or Cas9 polypeptide which is a nickase, or which lacks the ability to cleave target nucleic acid. A Cas9 molecule or Cas9 polypeptide that is capable of cleaving a target nucleic acid molecule is referred to herein as an eaCas9 (an enzymatically active Cas9) molecule or eaCas9 polypeptide. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide, comprises one or more of the following activities:

    • a nickase activity, i.e., the ability to cleave a single strand, e.g., the non-complementary strand or the complementary strand, of a nucleic acid molecule;
    • a double stranded nuclease activity, i.e., the ability to cleave both strands of a double stranded nucleic acid and create a double stranded break, which in an embodiment is the presence of two nickase activities;
    • an endonuclease activity;
    • an exonuclease activity; and
    • a helicase activity, i.e., the ability to unwind the helical structure of a double stranded nucleic acid.

In an embodiment, an enzymatically active Cas9 or an eaCas9 molecule or an eaCas9 polypeptide cleaves both DNA strands and results in a double stranded break. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide cleaves only one strand, e.g., the strand to which the gRNA hybridizes to, or the strand complementary to the strand the gRNA hybridizes with. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with an HNH-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with an N-terminal RuvC-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises cleavage activity associated with an HNH-like domain and cleavage activity associated with an N-terminal RuvC-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an active, or cleavage competent, HNH-like domain and an inactive, or cleavage incompetent, N-terminal RuvC-like domain. In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an inactive, or cleavage incompetent, HNH-like domain and an active, or cleavage competent, N-terminal RuvC-like domain.

Some Cas9 molecules or Cas9 polypeptides have the ability to interact with a gRNA molecule, and in conjunction with the gRNA molecule localize to a core target domain, but are incapable of cleaving the target nucleic acid, or incapable of cleaving at efficient rates. Cas9 molecules having no, or no substantial, cleavage activity are referred to herein as an eiCas9 molecule or eiCas9 polypeptide. For example, an eiCas9 molecule or eiCas9 polypeptide can lack cleavage activity or have substantially less, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule or eiCas9 polypeptide, as measured by an assay described herein.

Targeting and PAMs

A Cas9 molecule or Cas9 polypeptide, is a polypeptide that can interact with a guide RNA (gRNA) molecule and, in concert with the gRNA molecule, localizes to a site which comprises a target domain and PAM sequence.

In an embodiment, the ability of an eaCas9 molecule or eaCas9 polypeptide to interact with and cleave a target nucleic acid is PAM sequence dependent. A PAM sequence is a sequence in the target nucleic acid. In an embodiment, cleavage of the target nucleic acid occurs upstream from the PAM sequence. EaCas9 molecules from different bacterial species can recognize different sequence motifs (e.g., PAM sequences). In an embodiment, an eaCas9 molecule of S. pyogenes recognizes the sequence motif NGG and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. See, e.g., Mali et al., SCIENCE 2013; 339(6121): 823-826. In an embodiment, an eaCas9 molecule of S. thermophilus recognizes the sequence motif NGGNG and NNAGAAW (W=A or T) and directs cleavage of a core target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from these sequences. See, e.g., Horvath et al., SCIENCE 2010; 327(5962):167-170, and Deveau et al., J BACTERIOL 2008; 190(4): 1390-1400. In an embodiment, an eaCas9 molecule of S. mutans recognizes the sequence motif NGG and/or NAAR (R=A or G) and directs cleavage of a core target nucleic acid sequence 1 to 10, e.g., 3 to 5 base pairs, upstream from this sequence. See, e.g., Deveau et al., J BACTERIOL 2008; 190(4): 1390-1400. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRR (R=A or G) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRRN (R=A or G) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRRT (R=A or G) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. In an embodiment, an eaCas9 molecule of S. aureus recognizes the sequence motif NNGRRV (R=A or G, V=A, G or C) and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. In an embodiment, an eaCas9 molecule of Neisseria meningitidis recognizes the sequence motif NNNNGATT or NNNGCTT and directs cleavage of a target nucleic acid sequence 1 to 10, e.g., 3 to 5, base pairs upstream from that sequence. See, e.g., Hou et al., PNAS Early Edition 2013, 1-6. The ability of a Cas9 molecule to recognize a PAM sequence can be determined, e.g., using a transformation assay described in Jinek et al., SCIENCE 2012 337:816. In the aforementioned embodiments, N can be any nucleotide residue, e.g., any of A, G, C or T.

As is discussed herein, Cas9 molecules can be engineered to alter the PAM specificity of the Cas9 molecule.

Exemplary naturally occurring Cas9 molecules are described in Chylinski et al., RNA BIOLOGY 2013 10:5, 727-737. Such Cas9 molecules include Cas9 molecules of a cluster 1 bacterial family, cluster 2 bacterial family, cluster 3 bacterial family, cluster 4 bacterial family, cluster 5 bacterial family, cluster 6 bacterial family, a cluster 7 bacterial family, a cluster 8 bacterial family, a cluster 9 bacterial family, a cluster 10 bacterial family, a cluster 11 bacterial family, a cluster 12 bacterial family, a cluster 13 bacterial family, a cluster 14 bacterial family, a cluster 15 bacterial family, a cluster 16 bacterial family, a cluster 17 bacterial family, a cluster 18 bacterial family, a cluster 19 bacterial family, a cluster 20 bacterial family, a cluster 21 bacterial family, a cluster 22 bacterial family, a cluster 23 bacterial family, a cluster 24 bacterial family, a cluster 25 bacterial family, a cluster 26 bacterial family, a cluster 27 bacterial family, a cluster 28 bacterial family, a cluster 29 bacterial family, a cluster 30 bacterial family, a cluster 31 bacterial family, a cluster 32 bacterial family, a cluster 33 bacterial family, a cluster 34 bacterial family, a cluster 35 bacterial family, a cluster 36 bacterial family, a cluster 37 bacterial family, a cluster 38 bacterial family, a cluster 39 bacterial family, a cluster 40 bacterial family, a cluster 41 bacterial family, a cluster 42 bacterial family, a cluster 43 bacterial family, a cluster 44 bacterial family, a cluster 45 bacterial family, a cluster 46 bacterial family, a cluster 47 bacterial family, a cluster 48 bacterial family, a cluster 49 bacterial family, a cluster 50 bacterial family, a cluster 51 bacterial family, a cluster 52 bacterial family, a cluster 53 bacterial family, a cluster 54 bacterial family, a cluster 55 bacterial family, a cluster 56 bacterial family, a cluster 57 bacterial family, a cluster 58 bacterial family, a cluster 59 bacterial family, a cluster 60 bacterial family, a cluster 61 bacterial family, a cluster 62 bacterial family, a cluster 63 bacterial family, a cluster 64 bacterial family, a cluster 65 bacterial family, a cluster 66 bacterial family, a cluster 67 bacterial family, a cluster 68 bacterial family, a cluster 69 bacterial family, a cluster 70 bacterial family, a cluster 71 bacterial family, a cluster 72 bacterial family, a cluster 73 bacterial family, a cluster 74 bacterial family, a cluster 75 bacterial family, a cluster 76 bacterial family, a cluster 77 bacterial family, or a cluster 78 bacterial family.

Exemplary naturally occurring Cas9 molecules include a Cas9 molecule of a cluster 1 bacterial family. Examples include a Cas9 molecule of: S. pyogenes (e.g., strain SF370, MGAS10270, MGAS10750, MGAS2096, MGAS315, MGAS5005, MGAS6180, MGAS9429, NZ131 and SSI-1), S. thermophilus (e.g., strain LMD-9), S. pseudoporcinus (e.g., strain SPIN 20026), S. mutans (e.g., strain UA159, NN2025), S. macacae (e.g., strain NCTC11558), S. gallolyticus (e.g., strain UCN34, ATCC BAA-2069), S. equines (e.g., strain ATCC 9812, MGCS 124), S. dysdalactiae (e.g., strain GGS 124), S. bovis (e.g., strain ATCC 700338), S. anginosus (e.g., strain F0211), S. agalactiae (e.g., strain NEM316, A909), Listeria monocytogenes (e.g., strain F6854), Listeria innocua (L. innocua, e.g., strain Clip11262), Enterococcus italicus (e.g., strain DSM 15952), or Enterococcus faecium (e.g., strain 1,231,408). Additional exemplary Cas9 molecules are a Cas9 molecule of Neisseria meningitides (Hou et al., PNAS Early Edition 2013, 1-6 and a S. aureus cas9 molecule.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence:

    • having 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with;
    • differs at no more than, 2, 5, 10, 15, 20, 30, or 40% of the amino acid residues when compared with;
    • differs by at least 1, 2, 5, 10 or 20 amino acids, but by no more than 100, 80, 70, 60, 50, 40 or 30 amino acids from; or
    • is identical to any Cas9 molecule sequence described herein, or a naturally occurring Cas9 molecule sequence, e.g., a Cas9 molecule from a species listed herein or described in Chylinski et al., RNA BIOLOGY 2013 10:5, 727-737; Hou et al., PNAS Early Edition 2013, 1-6; SEQ ID NO:1-4. In an embodiment, the Cas9 molecule or Cas9 polypeptide comprises one or more of the following activities: a nickase activity; a double stranded cleavage activity (e.g., an endonuclease and/or exonuclease activity); a helicase activity; or the ability, together with a gRNA molecule, to localize to a target nucleic acid.

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises any of the amino acid sequence of the consensus sequence of FIGS. 2A-2G, wherein “*” indicates any amino acid found in the corresponding position in the amino acid sequence of a Cas9 molecule or Cas9 polypeptide of S. pyogenes, S. thermophilus, S. mutans and L. innocua, and “−” indicates any amino acid. In an embodiment, a Cas9 molecule differs from the sequence of the consensus sequence of FIGS. 2A-2G by at least 1, but no more than 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues. In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises the amino acid sequence of SEQ ID NO:7 of FIGS. 7A-7B, wherein “*” indicates any amino acid found in the corresponding position in the amino acid sequence of a Cas9 molecule or Cas9 polypeptide of S. pyogenes, or N. meningitides, “−” indicates any amino acid, and “−” indicates any amino acid or absent. In an embodiment, a Cas9 molecule or Cas9 polypeptide differs from the sequence of SEQ ID NO:6 or 7 disclosed in FIGS. 7A-7B by at least 1, but no more than 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid residues.

A comparison of the sequence of a number of Cas9 molecules indicate that certain regions are conserved. These are identified below as:

    • region 1 (residues 1 to 180, or in the case of region 1′ residues 120 to 180)
    • region 2 (residues 360 to 480);
    • region 3 (residues 660 to 720);
    • region 4 (residues 817 to 900); and
    • region 5 (residues 900 to 960);

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises regions 1-5, together with sufficient additional Cas9 molecule sequence to provide a biologically active molecule, e.g., a Cas9 molecule having at least one activity described herein. In an embodiment, each of regions 1-5, independently, have 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with the corresponding residues of a Cas9 molecule or Cas9 polypeptide described herein, e.g., a sequence from FIGS. 2A-2G or from FIGS. 7A-7B.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 1:

    • having 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with amino acids 1-180 (the numbering is according to the motif sequence in FIGS. 2A-2G; 52% of residues in the four Cas9 sequences in FIGS. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes;
    • differs by at least 1, 2, 5, 10 or 20 amino acids but by no more than 90, 80, 70, 60, 50, 40 or 30 amino acids from amino acids 1-180 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or Listeria innocua; or
    • is identical to 1-180 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 1′:

    • having 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with amino acids 120-180 (55% of residues in the four Cas9 sequences in FIGS. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;
    • differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 120-180 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua; or
    • is identical to 120-180 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 2:

    • having 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% homology with amino acids 360-480 (52% of residues in the four Cas9 sequences in FIGS. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;
    • differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 360-480 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua; or
    • is identical to 360-480 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 3:

    • having 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with amino acids 660-720 (56% of residues in the four Cas9 sequences in FIGS. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;
    • differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 660-720 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua; or
    • is identical to 660-720 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule, e.g., an eaCas9 molecule, comprises an amino acid sequence referred to as region 4:

    • having 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with amino acids 817-900 (55% of residues in the four Cas9 sequences in FIGS. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;
    • differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 817-900 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua; or
    • is identical to 817-900 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

In an embodiment, a Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, comprises an amino acid sequence referred to as region 5:

    • having 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% homology with amino acids 900-960 (60% of residues in the four Cas9 sequences in FIGS. 2A-2G are conserved) of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua;
    • differs by at least 1, 2, or 5 amino acids but by no more than 35, 30, 25, 20 or 10 amino acids from amino acids 900-960 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua; or
    • is identical to 900-960 of the amino acid sequence of Cas9 of S. pyogenes, S. thermophilus, S. mutans or L. innocua.

Engineered or Altered Cas9 Molecules and Cas9 Polypeptides

Cas9 molecules and Cas9 polypeptides described herein, e.g., naturally occurring Cas9 molecules can possess any of a number of properties, including: nickase activity, nuclease activity (e.g., endonuclease and/or exonuclease activity); helicase activity; the ability to associate functionally with a gRNA molecule; and the ability to target (or localize to) a site on a nucleic acid (e.g., PAM recognition and specificity). In an embodiment, a Cas9 molecule or Cas9 polypeptide can include all or a subset of these properties. In typical embodiments, a Cas9 molecule or Cas9 polypeptide have the ability to interact with a gRNA molecule and, in concert with the gRNA molecule, localize to a site in a nucleic acid. Other activities, e.g., PAM specificity, cleavage activity, or helicase activity can vary more widely in Cas9 molecules and Cas9 polypeptides.

Cas9 molecules include engineered Cas9 molecules and engineered Cas9 polypeptides (engineered, as used in this context, means merely that the Cas9 molecule or Cas9 polypeptide differs from a reference sequences, and implies no process or origin limitation). An engineered Cas9 molecule or Cas9 polypeptide can comprise altered enzymatic properties, e.g., altered nuclease activity, (as compared with a naturally occurring or other reference Cas9 molecule) or altered helicase activity. As discussed herein, an engineered Cas9 molecule or Cas9 polypeptide can have nickase activity (as opposed to double strand nuclease activity). In an embodiment an engineered Cas9 molecule or Cas9 polypeptide can have an alteration that alters its size, e.g., a deletion of amino acid sequence that reduces its size, e.g., without significant effect on one or more, or any Cas9 activity. In an embodiment, an engineered Cas9 molecule or Cas9 polypeptide can comprise an alteration that affects PAM recognition. E.g., an engineered Cas9 molecule can be altered to recognize a PAM sequence other than that recognized by the endogenous wild-type PI domain. In an embodiment, a Cas9 molecule or Cas9 polypeptide can differ in sequence from a naturally occurring Cas9 molecule but not have significant alteration in one or more Cas9 activities.

Cas9 molecules or Cas9 polypeptides with desired properties can be made in a number of ways, e.g., by alteration of a parental, e.g., naturally occurring Cas9 molecules or Cas9 polypeptides to provide an altered Cas9 molecule or Cas9 polypeptide having a desired property. For example, one or more mutations or differences relative to a parental Cas9 molecule, e.g., a naturally occurring or engineered Cas9 molecule, can be introduced. Such mutations and differences comprise: substitutions (e.g., conservative substitutions or substitutions of non-essential amino acids); insertions; or deletions. In an embodiment, a Cas9 molecule or Cas9 polypeptide can comprises one or more mutations or differences, e.g., at least 1, 2, 3, 4, 5, 10, 15, 20, 30, 40 or 50 mutations, but less than 200, 100, or 80 mutations relative to a reference, e.g., a parental, Cas9 molecule.

In an embodiment, a mutation or mutations do not have a substantial effect on a Cas9 activity, e.g. a Cas9 activity described herein. In an embodiment, a mutation or mutations have a substantial effect on a Cas9 activity, e.g. a Cas9 activity described herein.

Non-Cleaving and Modified-Cleavage Cas9 Molecules and Cas9 Polypeptides

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises a cleavage property that differs from naturally occurring Cas9 molecules, e.g., that differs from the naturally occurring Cas9 molecule having the closest homology. For example, a Cas9 molecule or Cas9 polypeptide can differ from naturally occurring Cas9 molecules, e.g., a Cas9 molecule of S. pyogenes, as follows: its ability to modulate, e.g., decreased or increased, cleavage of a double stranded nucleic acid (endonuclease and/or exonuclease activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S. pyogenes); its ability to modulate, e.g., decreased or increased, cleavage of a single strand of a nucleic acid, e.g., a non-complementary strand of a nucleic acid molecule or a complementary strand of a nucleic acid molecule (nickase activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S. pyogenes); or the ability to cleave a nucleic acid molecule, e.g., a double stranded or single stranded nucleic acid molecule, can be eliminated.

Modified Cleavage eaCas9 Molecules and eaCas9 Polypeptides

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises one or more of the following activities: cleavage activity associated with an N-terminal RuvC-like domain; cleavage activity associated with an HNH-like domain; cleavage activity associated with an HNH-like domain and cleavage activity associated with an N-terminal RuvC-like domain.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an active, or cleavage competent, HNH-like domain (e.g., an HNH-like domain described herein, e.g., SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20 or SEQ ID NO: 21) and an inactive, or cleavage incompetent, N-terminal RuvC-like domain. An exemplary inactive, or cleavage incompetent N-terminal RuvC-like domain can have a mutation of an aspartic acid in an N-terminal RuvC-like domain, e.g., an aspartic acid at position 9 of the consensus sequence disclosed in FIGS. 2A-2G or an aspartic acid at position 10 of SEQ ID NO: 7, e.g., can be substituted with an alanine. In an embodiment, the eaCas9 molecule or eaCas9 polypeptide differs from wild type in the N-terminal RuvC-like domain and does not cleave the target nucleic acid, or cleaves with significantly less efficiency, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule, e.g., as measured by an assay described herein. The reference Cas9 molecule can by a naturally occurring unmodified Cas9 molecule, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, or S. thermophilus. In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology.

In an embodiment, an eaCas9 molecule or eaCas9 polypeptide comprises an inactive, or cleavage incompetent, HNH domain and an active, or cleavage competent, N-terminal RuvC-like domain (e.g., a RuvC-like domain described herein, e.g., SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16). Exemplary inactive, or cleavage incompetent HNH-like domains can have a mutation at one or more of: a histidine in an HNH-like domain, e.g., a histidine shown at position 856 of the consensus sequence disclosed in FIGS. 2A-2G, e.g., can be substituted with an alanine; and one or more asparagines in an HNH-like domain, e.g., an asparagine shown at position 870 of the consensus sequence disclosed in FIGS. 2A-2G and/or at position 879 of the consensus sequence disclosed in FIGS. 2A-2G, e.g., can be substituted with an alanine. In an embodiment, the eaCas9 differs from wild type in the HNH-like domain and does not cleave the target nucleic acid, or cleaves with significantly less efficiency, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule, e.g., as measured by an assay described herein. The reference Cas9 molecule can by a naturally occurring unmodified Cas9 molecule, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, or S. thermophilus. In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology.

Alterations in the Ability to Cleave One or Both Strands of a Target Nucleic Acid

In an embodiment, exemplary Cas9 activities comprise one or more of PAM specificity, cleavage activity, and helicase activity. A mutation(s) can be present, e.g., in one or more RuvC-like domain, e.g., an N-terminal RuvC-like domain; an HNH-like domain; a region outside the RuvC-like domains and the HNH-like domain. In some embodiments, a mutation(s) is present in a RuvC-like domain, e.g., an N-terminal RuvC-like domain. In some embodiments, a mutation(s) is present in an HNH-like domain. In some embodiments, mutations are present in both a RuvC-like domain, e.g., an N-terminal RuvC-like domain and an HNH-like domain.

Exemplary mutations that may be made in the RuvC domain or HNH domain with reference to the S. pyogenes sequence include: D10A, E762A, H840A, N854A, N863A and/or D986A.

In an embodiment, a Cas9 molecule or Cas9 polypeptide is an eiCas9 molecule or eiCas9 polypeptide comprising one or more differences in a RuvC domain and/or in an HNH domain as compared to a reference Cas9 molecule, and the eiCas9 molecule or eiCas9 polypeptide does not cleave a nucleic acid, or cleaves with significantly less efficiency than does wildype, e.g., when compared with wild type in a cleavage assay, e.g., as described herein, cuts with less than 50, 25, 10, or 1% of a reference Cas9 molecule, as measured by an assay described herein.

Whether or not a particular sequence, e.g., a substitution, may affect one or more activity, such as targeting activity, cleavage activity, etc., can be evaluated or predicted, e.g., by evaluating whether the mutation is conservative or by the method described in Section IV. In an embodiment, a “non-essential” amino acid residue, as used in the context of a Cas9 molecule, is a residue that can be altered from the wild-type sequence of a Cas9 molecule, e.g., a naturally occurring Cas9 molecule, e.g., an eaCas9 molecule, without abolishing or more preferably, without substantially altering a Cas9 activity (e.g., cleavage activity), whereas changing an “essential” amino acid residue results in a substantial loss of activity (e.g., cleavage activity).

In an embodiment, a Cas9 molecule or Cas9 polypeptide comprises a cleavage property that differs from naturally occurring Cas9 molecules, e.g., that differs from the naturally occurring Cas9 molecule having the closest homology. For example, a Cas9 molecule or Cas9 polypeptide can differ from naturally occurring Cas9 molecules, e.g., a Cas9 molecule of S aureus, S. pyogenes, or C. jejuni as follows: its ability to modulate, e.g., decreased or increased, cleavage of a double stranded break (endonuclease and/or exonuclease activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S aureus, S. pyogenes, or C. jejuni); its ability to modulate, e.g., decreased or increased, cleavage of a single strand of a nucleic acid, e.g., a non-complimentary strand of a nucleic acid molecule or a complementary strand of a nucleic acid molecule (nickase activity), e.g., as compared to a naturally occurring Cas9 molecule (e.g., a Cas9 molecule of S aureus, S. pyogenes, or C. jejuni); or the ability to cleave a nucleic acid molecule, e.g., a double stranded or single stranded nucleic acid molecule, can be eliminated.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising one or more of the following activities: cleavage activity associated with a RuvC domain; cleavage activity associated with an HNH domain; cleavage activity associated with an HNH domain and cleavage activity associated with a RuvC domain.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eiCas9 molecule or eiCas9 polypeptide which does not cleave a nucleic acid molecule (either double stranded or single stranded nucleic acid molecules) or cleaves a nucleic acid molecule with significantly less efficiency, e.g., less than 20, 10, 5, 1 or 0.1% of the cleavage activity of a reference Cas9 molecule, e.g., as measured by an assay described herein. The reference Cas9 molecule can be a naturally occurring unmodified Cas9 molecule, e.g., a naturally occurring Cas9 molecule such as a Cas9 molecule of S. pyogenes, S. thermophilus, S. aureus, C. jejuni or N. meningitidis. In an embodiment, the reference Cas9 molecule is the naturally occurring Cas9 molecule having the closest sequence identity or homology. In an embodiment, the eiCas9 molecule or eiCas9 polypeptide lacks substantial cleavage activity associated with a RuvC domain and cleavage activity associated with an HNH domain.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of S. pyogenes shown in the consensus sequence disclosed in FIGS. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of S. pyogenes (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an “−” in the consensus sequence disclosed in FIGS. 2A-2G or SEQ ID NO:7.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

    • the sequence corresponding to the fixed sequence of the consensus sequence disclosed in FIGS. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in FIGS. 2A-2G;
    • the sequence corresponding to the residues identified by “*” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the “*” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. pyogenes Cas9 molecule; and,
    • the sequence corresponding to the residues identified by “−” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the “−” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. pyogenes Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of S. thermophilus shown in the consensus sequence disclosed in FIGS. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of S. thermophilus (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an “−” in the consensus sequence disclosed in FIGS. 2A-2G.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

    • the sequence corresponding to the fixed sequence of the consensus sequence disclosed in FIGS. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in FIGS. 2A-2G;
    • the sequence corresponding to the residues identified by “*” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the “*” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. thermophilus Cas9 molecule; and,
    • the sequence corresponding to the residues identified by “−” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the “−” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. thermophilus Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of S. mutans shown in the consensus sequence disclosed in FIGS. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of S. mutans (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an “−” in the consensus sequence disclosed in FIGS. 2A-2G.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

    • the sequence corresponding to the fixed sequence of the consensus sequence disclosed in FIGS. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in FIGS. 2A-2G;
    • the sequence corresponding to the residues identified by “*” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the “*” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. mutans Cas9 molecule; and,
    • the sequence corresponding to the residues identified by “−” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the “−” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an S. mutans Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide is an eaCas9 molecule or eaCas9 polypeptide comprising the fixed amino acid residues of L. innocula shown in the consensus sequence disclosed in FIGS. 2A-2G, and has one or more amino acids that differ from the amino acid sequence of L. innocula (e.g., has a substitution) at one or more residue (e.g., 2, 3, 5, 10, 15, 20, 30, 50, 70, 80, 90, 100, 200 amino acid residues) represented by an “−” in the consensus sequence disclosed in FIGS. 2A-2G.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide comprises a sequence in which:

    • the sequence corresponding to the fixed sequence of the consensus sequence disclosed in FIGS. 2A-2G differs at no more than 1, 2, 3, 4, 5, 10, 15, or 20% of the fixed residues in the consensus sequence disclosed in FIGS. 2A-2G;
    • the sequence corresponding to the residues identified by “*” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, or 40% of the “*” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an L. innocula Cas9 molecule; and,
    • the sequence corresponding to the residues identified by “−” in the consensus sequence disclosed in FIGS. 2A-2G differ at no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 55, or 60% of the “−” residues from the corresponding sequence of naturally occurring Cas9 molecule, e.g., an L. innocula Cas9 molecule.

In an embodiment, the altered Cas9 molecule or Cas9 polypeptide, e.g., an eaCas9 molecule or eaCas9 polypeptide, can be a fusion, e.g., of two of more different Cas9 molecules, e.g., of two or more naturally occurring Cas9 molecules of different species. For example, a fragment of a naturally occurring Cas9 molecule of one species can be fused to a fragment of a Cas9 molecule of a second species. As an example, a fragment of a Cas9 molecule of S. pyogenes comprising an N-terminal RuvC-like domain can be fused to a fragment of a Cas9 molecule of a species other than S. pyogenes (e.g., S. thermophilus) comprising an HNH-like domain.

Cas9 Molecules or Cas9 Polypeptides with Altered PAM Recognition or No PAM Recognition

Naturally occurring Cas9 molecules can recognize specific PAM sequences, for example, the PAM recognition sequences described above for S. pyogenes, S. thermophiles, S. mutans, S. aureus and N. meningitidis.

In an embodiment, a Cas9 molecule or Cas9 polypeptide has the same PAM specificities as a naturally occurring Cas9 molecule. In another embodiment, a Cas9 molecule or Cas9 polypeptide has a PAM specificity not associated with a naturally occurring Cas9 molecule, or a PAM specificity not associated with the naturally occurring Cas9 molecule to which it has the closest sequence homology. For example, a naturally occurring Cas9 molecule or Cas9 polypeptide can be altered, e.g., to alter PAM recognition, e.g., to alter the PAM sequence that the Cas9 molecule recognizes to decrease off target sites and/or improve specificity; or eliminate a PAM recognition requirement. In an embodiment, a Cas9 molecule or Cas9 polypeptide can be altered, e.g., to increase length of PAM recognition sequence and/or improve Cas9 specificity to high level of identity (e.g., 98%, 99% or 100% match between gRNA and a PAM sequence), e.g., to decrease off target sites and increase specificity. In an embodiment, the length of the PAM recognition sequence is at least 4, 5, 6, 7, 8, 9, 10 or 15 amino acids in length. In an embodiment, the Cas9 specificity requires at least 90%, 95%, 96%, 97%, 98%, 99% or more homology between the gRNA and the PAM sequence. Cas9 molecules or Cas9 polypeptides that recognize different PAM sequences and/or have reduced off-target activity can be generated using directed evolution. Exemplary methods and systems that can be used for directed evolution of Cas9 molecules are described, e.g., in Esvelt et al. NATURE 2011, 472(7344): 499-503. Candidate Cas9 molecules can be evaluated, e.g., by methods described in Section IV.

Alterations of the PI domain, which mediates PAM recognition, are discussed below.

Synthetic Cas9 Molecules and Cas9 Polypeptides with Altered PI Domains

Current genome-editing methods are limited in the diversity of target sequences that can be targeted by the PAM sequence that is recognized by the Cas9 molecule utilized. A synthetic Cas9 molecule (or Syn-Cas9 molecule), or synthetic Cas9 polypeptide (or Syn-Cas9 polypeptide), as that term is used herein, refers to a Cas9 molecule or Cas9 polypeptide that comprises a Cas9 core domain from one bacterial species and a functional altered PI domain, i.e., a PI domain other than that naturally associated with the Cas9 core domain, e.g., from a different bacterial species.

In an embodiment, the altered PI domain recognizes a PAM sequence that is different from the PAM sequence recognized by the naturally-occurring Cas9 from which the Cas9 core domain is derived. In an embodiment, the altered PI domain recognizes the same PAM sequence recognized by the naturally-occurring Cas9 from which the Cas9 core domain is derived, but with different affinity or specificity. A Syn-Cas9 molecule or Syn-Cas9 polypeptide can be, respectively, a Syn-eaCas9 molecule or Syn-eaCas9 polypeptide or a Syn-eiCas9 molecule Syn-eiCas9 polypeptide.

An exemplary Syn-Cas9 molecule or Syn-Cas9 polypeptide comprises:

    • a) a Cas9 core domain, e.g., a Cas9 core domain from Table 50 or 51, e.g., a S. aureus, S. pyogenes, or C. jejuni Cas9 core domain; and
    • b) an altered PI domain from a species X Cas9 sequence selected from Tables 53 and 54.

In an embodiment, the RKR motif (the PAM binding motif) of said altered PI domain comprises: differences at 1, 2, or 3 amino acid residues; a difference in amino acid sequence at the first, second, or third position; differences in amino acid sequence at the first and second positions, the first and third positions, or the second and third positions; as compared with the sequence of the RKR motif of the native or endogenous PI domain associated with the Cas9 core domain.

In an embodiment, the Cas9 core domain comprises the Cas9 core domain from a species X Cas9 from Table 50 and said altered PI domain comprises a PI domain from a species Y Cas9 from Table 50.

In an embodiment, the RKR motif of the species X Cas9 is other than the RKR motif of the species Y Cas9.

In an embodiment, the RKR motif of the altered PI domain is selected from XXY, XNG, and XNQ.

In an embodiment, the altered PI domain has at least 60, 70, 80, 90, 95, or 100% homology with the amino acid sequence of a naturally occurring PI domain of said species Y from Table 50.

In an embodiment, the altered PI domain differs by no more than 50, 40, 30, 25, 20, 15, 10, 5, 4, 3, 2, or 1 amino acid residue from the amino acid sequence of a naturally occurring PI domain of said second species from Table 50.

In an embodiment, the Cas9 core domain comprises a S. aureus core domain and altered PI domain comprises: an A. denitrificans PI domain; a C. jejuni PI domain; a H. mustelae PI domain; or an altered PI domain of species X PI domain, wherein species X is selected from Table 54.

In an embodiment, the Cas9 core domain comprises a S. pyogenes core domain and the altered PI domain comprises: an A. denitrificans PI domain; a C. jejuni PI domain; a H. mustelae PI domain; or an altered PI domain of species X PI domain, wherein species X is selected from Table 54.

In an embodiment, the Cas9 core domain comprises a C. jejuni core domain and the altered PI domain comprises: an A. denitrificans PI domain; a H. mustelae PI domain; or an altered PI domain of species X PI domain, wherein species X is selected from Table 54.

In an embodiment, the Cas9 molecule or Cas9 polypeptide further comprises a linker disposed between said Cas9 core domain and said altered PI domain.

In an embodiment, the linker comprises: a linker described elsewhere herein disposed between the Cas9 core domain and the heterologous PI domain. Suitable linkers are further described in Section V.

Exemplary altered PI domains for use in Syn-Cas9 molecules are described in Tables 53 and 54. The sequences for the 83 Cas9 orthologs referenced in Tables 53 and 54 are provided in Table 50. Table 52 provides the Cas9 orthologs with known PAM sequences and the corresponding RKR motif.

In an embodiment, a Syn-Cas9 molecule or Syn-Cas9 polypeptide may also be size-optimized, e.g., the Syn-Cas9 molecule or Syn-Cas9 polypeptide comprises one or more deletions, and optionally one or more linkers disposed between the amino acid residues flanking the deletions. In an embodiment, a Syn-Cas9 molecule or Syn-Cas9 polypeptide comprises a REC deletion.

Size-Optimized Cas9 Molecules and Cas9 Polypeptides

Engineered Cas9 molecules and engineered Cas9 polypeptides described herein include a Cas9 molecule or Cas9 polypeptide comprising a deletion that reduces the size of the molecule while still retaining desired Cas9 properties, e.g., essentially native conformation, Cas9 nuclease activity, and/or target nucleic acid molecule recognition. Provided herein are Cas9 molecules or Cas9 polypeptides comprising one or more deletions and optionally one or more linkers, wherein a linker is disposed between the amino acid residues that flank the deletion. Methods for identifying suitable deletions in a reference Cas9 molecule, methods for generating Cas9 molecules with a deletion and a linker, and methods for using such Cas9 molecules will be apparent to one of ordinary skill in the art upon review of this document.

A Cas9 molecule, e.g., a S. aureus, S. pyogenes, or C. jejuni, Cas9 molecule, having a deletion is smaller, e.g., has reduced number of amino acids, than the corresponding naturally-occurring Cas9 molecule. The smaller size of the Cas9 molecules allows increased flexibility for delivery methods, and thereby increases utility for genome-editing. A Cas9 molecule or Cas9 polypeptide can comprise one or more deletions that do not substantially affect or decrease the activity of the resultant Cas9 molecules or Cas9 polypeptides described herein. Activities that are retained in the Cas9 molecules or Cas9 polypeptides comprising a deletion as described herein include one or more of the following:

    • a nickase activity, i.e., the ability to cleave a single strand, e.g., the non-complementary strand or the complementary strand, of a nucleic acid molecule; a double stranded nuclease activity, i.e., the ability to cleave both strands of a double stranded nucleic acid and create a double stranded break, which in an embodiment is the presence of two nickase activities;
    • an endonuclease activity;
    • an exonuclease activity;
    • a helicase activity, i.e., the ability to unwind the helical structure of a double stranded nucleic acid;
    • and recognition activity of a nucleic acid molecule, e.g., a target nucleic acid or a gRNA.

Activity of the Cas9 molecules or Cas9 polypeptides described herein can be assessed using the activity assays described herein or in the art.

Identifying Regions Suitable for Deletion

Suitable regions of Cas9 molecules for deletion can be identified by a variety of methods. Naturally-occurring orthologous Cas9 molecules from various bacterial species, e.g., any one of those listed in Table 50, can be modeled onto the crystal structure of S. pyogenes Cas9 (Nishimasu et al., Cell, 156:935-949, 2014) to examine the level of conservation across the selected Cas9 orthologs with respect to the three-dimensional conformation of the protein. Less conserved or unconserved regions that are spatially located distant from regions involved in Cas9 activity, e.g., interface with the target nucleic acid molecule and/or gRNA, represent regions or domains are candidates for deletion without substantially affecting or decreasing Cas9 activity.

REC-Optimized Cas9 Molecules and Cas9 Polypeptides

A REC-optimized Cas9 molecule, or a REC-optimized Cas9 polypeptide, as that term is used herein, refers to a Cas9 molecule or Cas9 polypeptide that comprises a deletion in one or both of the REC2 domain and the RE1CT domain (collectively a REC deletion), wherein the deletion comprises at least 10% of the amino acid residues in the cognate domain. A REC-optimized Cas9 molecule or Cas9 polypeptide can be an eaCas9 molecule or eaCas9 polypeptide, or an eiCas9 molecule or eiCas9 polypeptide. An exemplary REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises:

    • a) a deletion selected from:
      • i) a REC2 deletion;
      • ii) a REC1CT deletion; or
      • iii) a REC1SUB deletion.

Optionally, a linker is disposed between the amino acid residues that flank the deletion.

In an embodiment, a Cas9 molecule or Cas9 polypeptide includes only one deletion, or only two deletions. A Cas9 molecule or Cas9 polypeptide can comprise a REC2 deletion and a REC1CT deletion. A Cas9 molecule or Cas9 polypeptide can comprise a REC2 deletion and a REC1SUB deletion.

Generally, the deletion will contain at least 10% of the amino acids in the cognate domain, e.g., a REC2 deletion will include at least 10% of the amino acids in the REC2 domain.

A deletion can comprise: at least 10, 20, 30, 40, 50, 60, 70, 80, or 90% of the amino acid residues of its cognate domain; all of the amino acid residues of its cognate domain; an amino acid residue outside its cognate domain; a plurality of amino acid residues outside its cognate domain; the amino acid residue immediately N terminal to its cognate domain; the amino acid residue immediately C terminal to its cognate domain; the amino acid residue immediately N terminal to its cognate and the amino acid residue immediately C terminal to its cognate domain; a plurality of, e.g., up to 5, 10, 15, or 20, amino acid residues N terminal to its cognate domain; a plurality of, e.g., up to 5, 10, 15, or 20, amino acid residues C terminal to its cognate domain; a plurality of, e.g., up to 5, 10, 15, or 20, amino acid residues N terminal to to its cognate domain and a plurality of e.g., up to 5, 10, 15, or 20, amino acid residues C terminal to its cognate domain.

In an embodiment, a deletion does not extend beyond: its cognate domain; the N terminal amino acid residue of its cognate domain; the C terminal amino acid residue of its cognate domain.

A REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide can include a linker disposed between the amino acid residues that flank the deletion. Any linkers known in the art that maintain the conformation or native fold of the Cas9 molecule (thereby retaining Cas9 activity) can be used between the amino acid resides that flank a REC deletion in a REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide. Linkers for use in generating recombinant proteins, e.g., multi-domain proteins, are known in the art (Chen et al., Adv Drug Delivery Rev, 65:1357-69, 2013).

In an embodiment, a REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises an amino acid sequence that, other than any REC deletion and associated linker, has at least 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 99, or 100% homology with the amino acid sequence of a naturally occurring Cas 9, e.g., a Cas9 molecule described in Table 50, e.g., a S. aureus Cas9 molecule, a S. pyogenes Cas9 molecule, or a C. jejuni Cas9 molecule.

In an embodiment, a a REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises an amino acid sequence that, other than any REC deletion and associated linker, differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25, amino acid residues from the amino acid sequence of a naturally occurring Cas 9, e.g., a Cas9 molecule described in Table 50, e.g., a S. aureus Cas9 molecule, a S. pyogenes Cas9 molecule, or a C. jejuni Cas9 molecule.

In an embodiment, a REC-optimized Cas9 molecule or REC-optimized Cas9 polypeptide comprises an amino acid sequence that, other than any REC deletion and associate linker, differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 25% of the, amino acid residues from the amino acid sequence of a naturally occurring Cas 9, e.g., a Cas9 molecule described in Table 50, e.g., a S. aureus Cas9 molecule, a S. pyogenes Cas9 molecule, or a C. jejuni Cas9 molecule.

For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. Methods of alignment of sequences for comparison are well known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman, (1970) Adv. Appl. Math. 2:482c, by the homology alignment algorithm of Needleman and Wunsch, (1970) J. Mol. Biol. 48:443, by the search for similarity method of Pearson and Lipman, (1988) Proc. Nat'l. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection (see, e.g., Brent et al., (2003) Current Protocols in Molecular Biology).

Two examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., (1977) Nuc. Acids Res. 25:3389-3402; and Altschul et al., (1990) J. Mol. Biol. 215:403-410, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information.

The percent identity between two amino acid sequences can also be determined using the algorithm of E. Meyers and W. Miller, (1988) Comput. Appl. Biosci. 4:11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch (1970) J. Mol. Biol. 48:444-453) algorithm which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossom 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.

Sequence information for exemplary REC deletions are provided for 83 naturally-occurring Cas9 orthologs in Table 50.

The amino acid sequences of exemplary Cas9 molecules from different bacterial species are shown below.

TABLE 50 Amino Acid Sequence of Cas9 Orthologs REC2 REC1CT Recsub start stop #AA start stop #AA start stop #AA Amino acid (AA (AA delete (AA (AA delete (AA (AA delete Species/Composite ID sequence pos) pos) d (n) pos) pos) d (n) pos) pos) d (n) Staphylococcus Aureus SEQ ID NO: 126 166 41 296 352 57 296 352 57 tr|J7RUA5|J7RUA5_STAAU 304 Streptococcus Pyogenes SEQ ID NO: 176 314 139 511 592 82 511 592 82 sp|Q99ZW2|CAS9_STRP1 305 Campylobacter jejuni NCTC 11168 SEQ ID NO: 137 181 45 316 360 45 316 360 45 gi|218563121|ref|YP_002344900.1 306 Bacteroides fragilis NCTC 9343 SEQ ID NO: 148 339 192 524 617 84 524 617 84 gi|60683389|ref|YP_213533.1| 307 Bifidobacterium bifidum S17 SEQ ID NO: 173 335 163 516 607 87 516 607 87 gi|310286728|ref|YP_003937986. 308 Veillonella atypica SEQ ID NO: 185 339 155 574 663 79 574 663 79 ACS-134-V-Col7a 309 gi|303229466|ref|ZP_07316256.1 Lactobacillus rhamnosus GG SEQ ID NO: 169 320 152 559 645 78 559 645 78 gi|258509199|ref|YP_003171950.1 310 Filifactor alocis ATCC 35896 SEQ ID NO: 166 314 149 508 592 76 508 592 76 gi|374307738|ref|YP_005054169.1 311 Oenococcus kitaharae DSM 17330 SEQ ID NO: 169 317 149 555 639 80 555 639 80 gi|366983953|gb|EHN59352.1| 312 Fructobacillus fructosus SEQ ID NO: 168 314 147 488 571 76 488 571 76 KCTC 3544 313 gi|339625081|ref|ZP_08660870.1 Catenibacterium mitsuokai SEQ ID NO: 173 318 146 511 594 78 511 594 78 DSM 15897 314 gi|224543312|ref|ZP_03683851.1 Finegoldia magna ATCC 29328 SEQ ID NO: 168 313 146 452 534 77 452 534 77 gi|169823755|ref|YP_001691366.1 315 Coriobacterium glomeransPW2 SEQ ID NO: 175 318 144 511 592 82 511 592 82 gi|328956315|ref|YP_004373648.1 316 Eubacterium yurii ATCC 43715 SEQ ID NO: 169 310 142 552 633 76 552 633 76 gi|306821691|ref|ZP_07455288.1 317 Peptoniphilus duerdenii ATCC SEQ ID NO: 171 311 141 535 615 76 535 615 76 BAA-1640 318 gi|304438954|ref|ZP_07398877.1 Acidaminococcus sp. D21 SEQ ID NO: 167 306 140 511 591 75 511 591 75 gi|227824983|ref|ZP_03989815.1 319 Lactobacillus farciminis KCTC 3681 SEQ ID NO: 171 310 140 542 621 85 542 621 85 gi|336394882|ref|ZP_08576281.1 320 Streptococcus sanguinis SK49 SEQ ID NO: 185 324 140 411 490 85 411 490 85 gi|422884106|ref|ZP_16930555.1 321 Coprococcus catus GD-7 SEQ ID NO: 172 310 139 556 634 76 556 634 76 gi|291520705|emb|CBK78998.1| 322 Streptococcus mutans UA159 SEQ ID NO: 176 314 139 392 470 84 392 470 84 gi|24379809|ref|NP_721764.1| 323 Streptococcus pyogenes M1 GAS SEQ ID NO: 176 314 139 523 600 82 523 600 82 gi|13622193|gb|AAK33936.1| 324 Streptococcus thermophilus LMD-9 SEQ ID NO: 176 314 139 481 558 81 481 558 81 gi|116628213|ref|YP_820832.1| 325 Fusobacterium nucleatum SEQ ID NO: 171 308 138 537 614 76 537 614 76 ATCC49256 326 gi|34762592|ref|ZP_00143587.1| Planococcus antarcticus DSM 14505 SEQ ID NO: 162 299 138 538 614 94 538 614 94 gi|389815359|ref|ZP_10206685.1 327 Treponema denticola ATCC 35405 SEQ ID NO: 169 305 137 524 600 81 524 600 81 gi|42525843|ref|NP_970941.1| 328 Solobacterium moorei F0204 SEQ ID NO: 179 314 136 544 619 77 544 619 77 gi|320528778|ref|ZP_08029929.1 329 Staphylococcus pseudintermedius SEQ ID NO: 164 299 136 531 606 92 531 606 92 ED99 330 gi|323463801|gb|ADX75954.1| Flavobacterium branchiophilum SEQ ID NO: 162 286 125 538 613 63 538 613 63 FL-15 331 gi|347536497|ref|YP_004843922.1 Ignavibacterium album JCM 16511 SEQ ID NO: 223 329 107 357 432 90 357 432 90 gi|385811609|ref|YP_005848005.1 332 Bergeyella zoohelcum ATCC 43767 SEQ ID NO: 165 261 97 529 604 56 529 604 56 gi|423317190|ref|ZP_17295095.1 333 Nitrobacter hamburgensis X14 SEQ ID NO: 169 253 85 536 611 48 536 611 48 gi|92109262|ref|YP_571550.1| 334 Odoribacter laneus YIT 12061 SEQ ID NO: 164 242 79 535 610 63 535 610 63 gi|374384763|ref|ZP_09642280.1 335 Legionella pneumophila str. Paris SEQ ID NO: 164 239 76 402 476 67 402 476 67 gi|54296138|ref|YP_122507.1| 336 Bacteroides sp. 20 3 SEQ ID NO: 198 269 72 530 604 83 530 604 83 gi|301311869|ref|ZP_07217791.1 337 Akkermansia muciniphila SEQ ID NO: 136 202 67 348 418 62 348 418 62 ATCC BAA-835 338 gi|187736489|ref|YP_001878601. Prevotella sp. C561 SEQ ID NO: 184 250 67 357 425 78 357 425 78 gi|345885718|ref|ZP_08837074.1 339 Wolinella succinogenes DSM 1740 SEQ ID NO: 157 218 36 401 468 60 401 468 60 gi|34557932|ref|NP_907747.1| 340 Alicyclobacillus hesperidum SEQ ID NO: 142 196 55 416 482 61 416 482 61 URH17-3-68 341 gi|403744858|ref|ZP_10953934.1 Caenispirillum salinarum AK4 SEQ ID NO: 161 214 54 330 393 68 330 393 68 gi|427429481|ref|ZP_18919511.1 342 Eubacterium rectale ATCC 33656 SEQ ID NO: 133 185 53 322 384 60 322 384 60 gi|238924075|ref|YP_002937591.1 343 Mycoplasma synoviae 53 SEQ ID NO: 187 239 53 319 381 80 319 381 80 gi|71894592|ref|YP278700.1| 344 Porphyromonas sp. oral taxon SEQ ID NO: 150 202 53 309 371 60 309 371 60 279str. F0450 345 gi|402847315|ref|ZP_10895610.1 Streptococcus thermophilus LMD-9 SEQ ID NO: 127 178 139 424 486 81 424 486 81 gi|116627542|ref|YP_820161.1| 346 Roseburia inulinivorans DSM 16841 SEQ ID NO: 154 204 51 318 380 69 318 380 69 gi|225377804|ref|ZP_03755025.1 347 Methylosinus trichosporium OB3b SEQ ID NO: 144 193 50 426 488 64 426 488 64 gi|296446027|ref|ZP_06887976.1 348 Ruminococcus albus 8 SEQ ID NO: 139 187 49 351 412 55 351 412 55 gi|325677756|ref|ZP_08157403.1 349 Bifidobacterium longum DJO10A SEQ ID NO: 183 230 48 370 431 44 370 431 44 gi|189440764|ref|YP_001955845. 350 Enterococcus faecalis TX0012 SEQ ID NO: 123 170 48 327 387 60 327 387 60 gi|315149830|gb|EFT93846.1| 351 Mycoplasma mobile 163K SEQ ID NO: 179 226 48 314 374 79 314 374 79 gi|47458868|ref|YP_015730.1| 352 Actinomyces coleocanis DSM 15436 SEQ ID NO: 147 193 47 358 418 40 358 418 40 gi|227494853|ref|ZP_03925169.1 353 Dinoroseobacter shibae DFL 12 SEQ ID NO: 138 184 47 338 398 48 338 398 48 gi|159042956|ref|YP_001531750.1 354 Actinomyces sp. oral taxon 180 SEQ ID NO: 183 228 46 349 409 40 349 409 40 str. F0310 355 gi|315605738|ref|ZP_07880770.1 Alcanivorax sp. W11-5 SEQ ID NO: 139 183 45 344 404 61 344 404 61 gi|407803669|ref|ZP_11150502.1 356 Aminomonas paucivorans DSM 12260 SEQ ID NO: 134 178 45 341 401 63 341 401 63 gi|312879015|ref|ZP_07738815.1 357 Mycoplasma canis PG 14 SEQ ID NO: 139 183 45 319 379 76 319 379 76 gi|384393286|gb|EIE39736.1| 358 Lactobacillus coryniformis SEQ ID NO: 141 184 44 328 387 61 328 387 61 KCTC 3535 359 gi|336393381|ref|ZP_08574780.1 Elusimicrobium minutum Pei191 SEQ ID NO: 177 219 43 322 381 47 322 381 47 gi|187250660|ref|YP_001875142.1 360 Neisseria meningitidis Z2491 SEQ ID NO: 147 189 43 360 419 61 360 419 61 gi|218767588|ref|YP_002342100.1 361 Pasteurella multocida str. Pm70 SEQ ID NO: 139 181 43 319 378 61 319 378 61 gi|15602992|ref|NP_246064.1| 362 Rhodovulum sp. PH10 SEQ ID NO: 141 183 43 319 378 48 319 378 48 gi|402849997|ref|ZP_10898214.1 363 Eubacterium dolichum DSM 3991 SEQ ID NO: 131 172 42 303 361 59 303 361 59 gi|160915782|ref|ZP_02077990.1 364 Nitratifractor salsuginis DSM 16511 SEQ ID NO: 143 184 42 347 404 61 347 404 61 gi|319957206|ref|YP_004168469.1 365 Rhodospirillum rubrum ATCC 11170 SEQ ID NO: 139 180 42 314 371 55 314 371 55 gi|83591793|ref|YP_425545.1| 366 Clostridium cellulolyticum H10 SEQ ID NO: 137 176 40 320 376 61 320 376 61 gi|220930482|ref|YP_002507391.1 367 Helicobacter mustelae 12198 SEQ ID NO: 148 187 40 298 354 48 298 354 48 gi|291276265|ref|YP_003516037.1 368 Ilyobacter polytropus DSM 2926 SEQ ID NO: 134 173 40 462 517 63 462 517 63 gi|310780384|ref|YP_003968716.1 369 Sphaerochaeta globus str. Buddy SEQ ID NO: 163 202 40 335 389 45 335 389 45 gi|325972003|ref|YP_004248194.1 370 Staphylococcus lugdunensis M23590 SEQ ID NO: 128 167 40 337 391 57 337 391 57 gi|315659848|ref|ZP_07912707.1 371 Treponema sp. JC4 SEQ ID NO: 144 183 40 328 382 63 328 382 63 gi|384109266|ref|ZP_10010146.1 372 uncultured delta SEQ ID NO: 154 193 40 313 365 55 313 365 55 proteobacterium HF0070 07E19 373 gi|297182908|gb|ADI19058.1| Alicycliphilus denitrificans K601 SEQ ID NO: 140 178 39 317 366 48 317 366 48 gi|330822845|ref|YP_004386148.1 374 Azospirillum sp. B510 SEQ ID NO: 205 243 39 342 389 46 342 389 46 gi|288957741|ref|YP_003448082.1 375 Bradyrhizobium sp. BTAil SEQ ID NO: 143 181 39 323 370 48 323 370 48 gi|148255343|ref|YP_001239928.1 376 Parvibaculum lavamentivorans DS-1 SEQ ID NO: 138 176 39 327 374 58 327 374 58 gi|154250555|ref|YP_001411379.1 377 Prevotella timonensis CRIS 5C-B1 SEQ ID NO: 170 208 39 328 375 61 328 375 61 gi|282880052|ref|ZP_06288774.1 378 Bacillus smithii 7 3 47FAA SEQ ID NO: 134 171 38 401 448 63 401 448 63 gi|365156657|ref|ZP_09352959.1 379 Cand. Puniceispirillum marinum SEQ ID NO: 135 172 38 344 391 53 344 391 53 IMCC1322 380 gi|294086111|ref|YP_003552871.1 Barnesiella intestinihominis SEQ ID NO: 140 176 37 371 417 60 371 417 60 YIT 11860 381 gi|404487228|ref|ZP_11022414.1 Ralstonia syzygii R24 SEQ ID NO: 140 176 37 395 440 50 395 440 50 gi|344171927|emb|CCA84553.1| 382 Wolinella succinogenes DSM 1740 SEQ ID NO: 145 180 36 348 392 60 348 392 60 gi|34557790|ref|NP_907605.1| 383 Mycoplasma gallisepticum str. F SEQ ID NO: 144 177 34 373 416 71 373 416 71 gi|284931710|gb|ADC31648.1| 384 Acidothermus cellulolyticus 11B SEQ ID NO: 150 182 33 341 380 58 341 380 58 gi|117929158|ref|YP_873709.1| 385 Mycoplasma ovipneumoniae SC01 SEQ ID NO: 156 184 29 381 420 62 381 420 62 gi|363542550|ref|ZP_09312133.1 386

TABLE 51 Amino Acid Sequence of Cas9 Core Domains Cas9 Start Cas9 Stop Strain Name (AA pos) (AA pos) Start and Stop numbers refer to the sequence in Table 50 Staphylococcus Aureus 1 772 Streptococcus Pyogenes 1 1099 Campulobacter Jejuni 1 741

TABLE 52 Identified PAM sequences and corresponding RKR motifs. PAM sequence RKR motif Strain Name (NA) (AA) Streptococcus pyogenes NGG RKR Streptococcus mutans NGG RKR Streptococcus NGGNG RYR thermophilus A Treponema denticola NAAAAN VAK Streptococcus NNAAAAW IYK thermophilus B Campylobacter jejuni NNNNACA NLK Pasteurella multocida GNNNCNNA KDG Neisseria meningitidis NNNNGATT or IGK Staphylococcus aureus NNGRRV (R = A NDK or G; V = A, G or C) NNGRRT (R = A or G)

TABLE 53 Altered PI Domains PI Start PI Stop Length of PI RKR motif Strain Name (AA pos) (AA pos) (AA) (AA) Start and Stop numbers refer to the sequences in Table 50 Alicycliphilus 837 1029 193 --Y denitrificans K601 Campylobacter 741 984 244 -NG jejuni NCTC 11168 Helicobacter 771 1024 254 -NQ mustelae 12198

TABLE 54 Other Altered PI Domains PI Start PI Stop Length of PI RKR motif Strain Name (AA pos) (AA pos) (AA) (AA) Start and Stop numbers refer to the sequences in Table 50 Akkermansia 871 1101 231 ALK muciniphila ATCC BAA-835 Ralstonia 821 1062 242 APY syzygii R24 Cand. 815 1035 221 AYK Puniceispirillum marinum IMCC1322 Fructobacillus 1074 1323 250 DGN fructosus KCTC 3544 Eubacterium yurii 1107 1391 285 DGY ATCC 43715 Eubacterium 779 1096 318 DKK dolichum DSM 3991 Dinoroseobacter 851 1079 229 DPI shibae DFL 12 Clostridium 767 1021 255 EGK cellulolyticum H10 Pasteurella multocida 815 1056 242 ENN str. Pm70 Mycoplasma canis 907 1233 327 EPK PG 14 Poiphyromonas sp. 935 1197 263 EPT oral taxon 279 str. F0450 Filifactor alocis 1094 1365 272 EVD ATCC 35896 Aminomonas 801 1052 252 EVY paucivorans DSM 12260 Wolinella 1034 1409 376 EYK succinogenes DSM 1740 Oenococcus 1119 1389 271 GAL kitaharae DSM 17330 Coriobacterium 1126 1384 259 GDR glomerans PW2 Peptoniphilus 1091 1364 274 GDS duerdenii ATCC BAA-1640 Bifidobacterium 1138 1420 283 GGL bifidum S17 Alicyclobacillus 876 1146 271 GGR hesperidum URH17-3-68 Roseburia 895 1152 258 GGT inulinivorans DSM 16841 Actinomyces 843 1105 263 GKK coleocanis DSM 15436 Odoribacter laneus 1103 1498 396 GKV YIT 12061 Coprococcus catus 1063 1338 276 GNQ GD-7 Enterococcus 829 1150 322 GRK faecalis TX0012 Bacillus smithii 809 1088 280 GSK 7 3 47FAA Legionella 1021 1372 352 GTM pneumophila str. Paris Bacteroides fragilis 1140 1436 297 IPV NCTC 9343 Mycoplasma 923 1265 343 IRI ovipneumoniae SC01 Actinomyces sp. 895 1181 287 KEK oral taxon 180 str. F0310 Treponema sp. JC4 832 1062 231 KIS Fusobacterium 1073 1374 302 KKV nucleatum ATCC49256 Lactobacillus 1101 1356 256 KKV farciminis KCTC 3681 Nitratifractor 840 1132 293 KMR salsuginis DSM 16511 Lactobacillus 850 1119 270 KNK colyniformis KCTC 3535 Mycoplasma 916 1236 321 KNY mobile 163K Flavobacterium 1182 1473 292 KQK branchiophilum FL-15 Prevotella 957 1218 262 KQQ timonensis CRIS 5C-B1 Methylosinus 830 1082 253 KRP trichosporium OB3b Prevotella sp. C561 1099 1424 326 KRY Mycoplasma 911 1269 359 KTA gallisepticum str. F Lactobacillus 1077 1363 287 KYG rhamnosus GG Wolinella 811 1059 249 LPN succinogenes DSM 1740 Streptococcus 1099 1388 290 MLA thermophilus LMD-9 Treponema 1092 1395 304 NDS denticola ATCC 35405 Bergeyella 1098 1415 318 NEK zoohelcum ATCC 43767 Veillonella atypica 1107 1398 292 NGF ACS-134-V-Col7a Neisseria 835 1082 248 NHN meningitidis Z2491 Ignavibacterium 1296 1688 393 NKK album JCM 16511 Ruminococcus 853 1156 304 NNF albus 8 Streptococcus 811 1121 311 NNK thermophilus LMD-9 Barnesiella 871 1153 283 NPV intestinihominis YIT 11860 Azospirillum sp. 911 1168 258 PFH B510 Rhodospirillum 863 1173 311 PRG rubrum ATCC 11170 Planococcus 1087 1333 247 PYY antarcticus DSM 14505 Staphylococcus 1073 1334 262 QIV pseudintermedius ED99 Alcanivorax sp. 843 1113 271 RIE W11-5 Bradyrhizobium sp. 811 1064 254 RIY BTAi1 Streptococcus 1099 1368 270 RKR pyogenes M1 GAS Streptococcus 1078 1345 268 RKR mutans UA159 Streptococcus 1099 1368 270 RKR Pyogenes Bacteroides sp. 1147 1517 371 RNI 20 3 S. aureus 772 1053 282 RNK Solobacterium 1062 1327 266 RSG moorei F0204 Finegoldia magna 1081 1348 268 RTE ATCC 29328 uncultured delta 770 1011 242 SGG proteobacterium HF0070 07E19 Acidaminococcus sp. 1064 1358 295 SIG D21 Eubacterium rectale 824 1114 291 SKK ATCC 33656 Caenispirillum 1048 1442 395 SLV salinarum AK4 Acidothermus 830 1138 309 SPS cellulolyticus 11B Catenibacterium 1068 1329 262 SPT mitsuokai DSM 15897 Parvibaculum 827 1037 211 TGN lavamentivorans DS-1 Staphylococcus 772 1054 283 TKK lugdunensis M23590 Streptococcus 1123 1421 299 TRM sanguinis SK49 Elusimicrobium 910 1195 286 TTG minutum Pei191 Nitrobacter 914 1166 253 VAY hamburgensis X14 Mycoplasma 991 1314 324 VGF synoviae 53 Sphaerochaeta 877 1179 303 VKG globus str. Buddy Ilyobacter 837 1092 256 VNG polytropus DSM 2926 Rhodovulum sp. 821 1059 239 VPY PH10 Bifidobacterium 904 1187 284 VRK longum DJO10A

Amino Acid Sequences Described in Table 50:

SEQ ID NO: 304 MKRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRI QRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDT GNELSTKEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQ LDQSFIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLY NALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGK PEFTNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQIS NLKGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSP VVKRSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQTNERIEEIIRTT GKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLVK QEENSKKGNRTPFQYLSSSDSKISYETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKD FINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHHAED ALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDFKD YKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHH DPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDD YPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQA EFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTIASKT QSIKKYSTDILGNLYEVKSKKHPQIIKKG SEQ ID NO: 305 MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRL KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD GTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR LSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLAS AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRV ILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD ATLIHQSITGLYETRIDLSQLGGD SEQ ID NO: 306 MARILAFDIGISSIGWAFSENDELKDCGVRIFTKVENPKTGESLALPRRLARSARKRLARRKAR LNHLKHLIANEFKLNYEDYQSFDESLAKAYKGSLISPYELRFRALNELLSKQDFARVILHIAKR RGYDDIKNSDDKEKGAILKAIKQNEEKLANYQSVGEYLYKEYFQKFKENSKEFTNVRNKKESYE RCIAQSFLKDELKLIFKKQREFGFSFSKKFEEEVLSVAFYKRALKDFSHLVGNCSFFTDEKRAP KNSPLAFMFVALTRIINLLNNLKNTEGILYTKDDLNALLNEVLKNGTLTYKQTKKLLGLSDDYE FKGEKGTYFIEFKKYKEFIKALGEHNLSQDDLNEIAKDITLIKDEIKLKKALAKYDLNQNQIDS LSKLEFKDHLNISFKALKLVTPLMLEGKKYDEACNELNLKVAINEDKKDFLPAFNETYYKDEVT NPVVLRAIKEYRKVLNALLKKYGKVHKINIELAREVGKNHSQRAKIEKEQNENYKAKKDAELEC EKLGLKINSKNILKLRLFKEQKEFCAYSGEKIKISDLQDEKMLEIDHIYPYSRSFDDSYMNKVL VFTKQNQEKLNQTPFEAFGNDSAKWQKIEVLAKNLPTKKQKRILDKNYKDKEQKNFKDRNLNDT RYIARLVLNYTKDYLDFLPLSDDENTKLNDTQKGSKVHVEAKSGMLTSALRHTWGFSAKDRNNH LHHAIDAVIIAYANNSIVKAFSDFKKEQESNSAELYAKKISELDYKNKRKFFEPFSGFRQKVLD KIDEIFVSKPERKKPSGALHEETFRKEEEFYQSYGGKEGVLKALELGKIRKVNGKIVKNGDMFR VDIFKHKKTNKFYAVPIYTMDFALKVLPNKAVARSKKGEIKDWILMDENYEFCFSLYKDSLILI QTKDMQEPEFVYYNAFTSSTVSLIVSKHDNKFETLSKNQKILFKNANEKEVIAKSIGIQNLKVF EKYIVSALGEVTKAEFRQREDFKK SEQ ID NO: 307 MKRILGLDLGTNSIGWALVNEAENKDERSSIVKLGVRVNPLTVDELTNFEKGKSITTNADRTLK RGMRRNLQRYKLRRETLTEVLKEHKLITEDTILSENGNRTTFETYRLRAKAVTEEISLEEFARV LLMINKKRGYKSSRKAKGVEEGTLIDGMDIARELYNNNLTPGELCLQLLDAGKKFLPDFYRSDL QNELDRIWEKQKEYYPEILTDVLKEELRGKKRDAVWAICAKYFVWKENYTEWNKEKGKTEQQER EHKLEGIYSKRKRDEAKRENLQWRVNGLKEKLSLEQLVIVFQEMNTQINNSSGYLGAISDRSKE LYFNKQTVGQYQMEMLDKNPNASLRNMVFYRQDYLDEFNMLWEKQAVYHKELTEELKKEIRDII IFYQRRLKSQKGLIGFCEFESRQIEVDIDGKKKIKTVGNRVISRSSPLFQEFKIWQILNNIEVT VVGKKRKRRKLKENYSALFEELNDAEQLELNGSRRLCQEEKELLAQELFIRDKMTKSEVLKLLF DNPQELDLNFKTIDGNKTGYALFQAYSKMIEMSGHEPVDFKKPVEKVVEYIKAVFDLLNWNTDI LGFNSNEELDNQPYYKLWHLLYSFEGDNTPTGNGRLIQKMTELYGFEKEYATILANVSFQDDYG SLSAKAIHKILPHLKEGNRYDVACVYAGYRHSESSLTREEIANKVLKDRLMLLPKNSLHNPVVE KILNQMVNVINVIIDIYGKPDEIRVELARELKKNAKEREELTKSIAQTTKAHEEYKTLLQTEFG LTNVSRTDILRYKLYKELESCGYKTLYSNTYISREKLFSKEFDIEHIIPQARLFDDSFSNKTLE ARSVNIEKGNKTAYDFVKEKFGESGADNSLEHYLNNIEDLFKSGKISKTKYNKLKMAEQDIPDG FIERDLRNTQYIAKKALSMLNEISHRVVATSGSVTDKLREDWQLIDVMKELNWEKYKALGLVEY FEDRDGRQIGRIKDWTKRNDHRHHAMDALTVAFTKDVFIQYFNNKNASLDPNANEHAIKNKYFQ NGRAIAPMPLREFRAEAKKHLENTLISIKAKNKVITGNINKTRKKGGVNKNMQQTPRGQLHLET IYGSGKQYLTKEEKVNASFDMRKIGTVSKSAYRDALLKRLYENDNDPKKAFAGKNSLDKQPIWL DKEQMRKVPEKVKIVTLEAIYTIRKEISPDLKVDKVIDVGVRKILIDRLNEYGNDAKKAFSNLD KNPIWLNKEKGISIKRVTISGISNAQSLHVKKDKDGKPILDENGRNIPVDFVNTGNNHHVAVYY RPVIDKRGQLVVDEAGNPKYELEEVVVSFFEAVTRANLGLPIIDKDYKTTEGWQFLFSMKQNEY FVFPNEKTGFNPKEIDLLDVENYGLISPNLFRVQKFSLKNYVFRHHLETTIKDTSSILRGITWI DFRSSKGLDTIVKVRVNHIGQIVSVGEY SEQ ID NO: 308 MSRKNYVDDYAISLDIGNASVGWSAFTPNYRLVRAKGHELIGVRLFDPADTAESRRMARTTRRR YSRRRWRLRLLDALFDQALSEIDPSFLARRKYSWVHPDDENNADCWYGSVLFDSNEQDKRFYEK YPTIYHLRKALMEDDSQHDIREIYLAIHHMVKYRGNFLVEGTLESSNAFKEDELLKLLGRITRY EMSEGEQNSDIEQDDENKLVAPANGQLADALCATRGSRSMRVDNALEALSAVNDLSREQRAIVK AIFAGLEGNKLDLAKIFVSKEFSSENKKILGIYFNKSDYEEKCVQIVDSGLLDDEEREFLDRMQ GQYNAIALKQLLGRSTSVSDSKCASYDAHRANWNLIKLQLRTKENEKDINENYGILVGWKIDSG QRKSVRGESAYENMRKKANVFFKKMIETSDLSETDKNRLIHDIEEDKLFPIQRDSDNGVIPHQL HQNELKQIIKKQGKYYPFLLDAFEKDGKQINKIEGLLTFRVPYFVGPLVVPEDLQKSDNSENHW MVRKKKGEITPWNFDEMVDKDASGRKFIERLVGTDSYLLGEPTLPKNSLLYQEYEVLNELNNVR LSVRTGNHWNDKRRMRLGREEKTLLCQRLFMKGQTVTKRTAENLLRKEYGRTYELSGLSDESKF TSSLSTYGKMCRIFGEKYVNEHRDLMEKIVELQTVFEDKETLLHQLRQLEGISEADCALLVNTH YTGWGRLSRKLLTTKAGECKISDDFAPRKHSIIEIMRAEDRNLMEIITDKQLGFSDWIEQENLG AENGSSLMEVVDDLRVSPKVKRGIIQSIRLIDDISKAVGKRPSRIFLELADDIQPSGRTISRKS RLQDLYRNANLGKEFKGIADELNACSDKDLQDDRLFLYYTQLGKDMYTGEELDLDRLSSAYDID HIIPQAVTQNDSIDNRVLVARAENARKTDSFTYMPQIADRMRNFWQILLDNGLISRVKFERLTR QNEFSEREKERFVQRSLVETRQIMKNVATLMRQRYGNSAAVIGLNAELTKEMHRYLGFSHKNRD INDYHHAQDALCVGIAGQFAANRGFFADGEVSDGAQNSYNQYLRDYLRGYREKLSAEDRKQGRA FGFIVGSMRSQDEQKRVNPRTGEVVWSEEDKDYLRKVMNYRKMLVTQKVGDDFGALYDETRYAA TDPKGIKGIPFDGAKQDTSLYGGFSSAKPAYAVLIESKGKTRLVNVTMQEYSLLGDRPSDDELR KVLAKKKSEYAKANILLRHVPKMQLIRYGGGLMVIKSAGELNNAQQLWLPYEEYCYFDDLSQGK GSLEKDDLKKLLDSILGSVQCLYPWHRFTEEELADLHVAFDKLPEDEKKNVITGIVSALHADAK TANLSIVGMTGSWRRMNNKSGYTFSDEDEFIFQSPSGLFEKRVTVGELKRKAKKEVNSKYRTNE KRLPTLSGASQP SEQ ID NO: 309 METQTSNQLITSHLKDYPKQDYFVGLDIGTNSVGWAVTNTSYELLKFHSHKMWGSRLFEEGESA VTRRGFRSMRRRLERRKLRLKLLEELFADAMAQVDSTFFIRLHESKYHYEDKTTGHSSKHILFI DEDYTDQDYFTEYPTIYHLRKDLMENGTDDIRKLFLAVHHILKYRGNFLYEGATFNSNAFTFED VLKQALVNITFNCFDTNSAISSISNILMESGKTKSDKAKAIERLVDTYTVFDEVNTPDKPQKEQ VKEDKKTLKAFANLVLGLSANLIDLFGSVEDIDDDLKKLQIVGDTYDEKRDELAKVWGDEIHII DDCKSVYDAIILMSIKEPGLTISQSKVKAFDKHKEDLVILKSLLKLDRNVYNEMFKSDKKGLHN YVHYIKQGRTEETSCSREDFYKYTKKIVEGLADSKDKEYILNEIELQTLLPLQRIKDNGVIPYQ LHLEELKVILDKCGPKFPFLHTVSDGFSVTEKLIKMLEFRIPYYVGPLNTHHNIDNGGFSWAVR KQAGRVTPWNFEEKIDREKSAAAFIKNLTNKCTYLFGEDVLPKSSLLYSEFMLLNELNNVRIDG KALAQGVKQHLIDSIFKQDHKKMTKNRIELFLKDNNYITKKHKPEITGLDGEIKNDLTSYRDMV RILGNNFDVSMAEDIITDITIFGESKKMLRQTLRNKFGSQLNDETIKKLSKLRYRDWGRLSKKL LKGIDGCDKAGNGAPKTIIELMRNDSYNLMEILGDKFSFMECIEEENAKLAQGQVVNPHDIIDE LALSPAVKRAVWQALRIVDEVAHIKKALPSRIFVEVARTNKSEKKKKDSRQKRLSDLYSAIKKD DVLQSGLQDKEFGALKSGLANYDDAALRSKKLYLYYTQMGRCAYTGNIIDLNQLNTDNYDIDHI YPRSLTKDDSFDNLVLCERTANAKKSDIYPIDNRIQTKQKPFWAFLKHQGLISERKYERLTRIA PLTADDLSGFIARQLVETNQSVKATTTLLRRLYPDIDVVFVKAENVSDFRHNNNFIKVRSLNHH HHAKDAYLNIVVGNVYHEKFTRNFRLFFKKNGANRTYNLAKMFNYDVICTNAQDGKAWDVKTSM NTVKKMMASNDVRVTRRLLEQSGALADATIYKASVAAKAKDGAYIGMKTKYSVFADVTKYGGMT KIKNAYSIIVQYTGKKGEEIKEIVPLPIYLINRNATDIELIDYVKSVIPKAKDISIKYRKLCIN QLVKVNGFYYYLGGKTNDKIYIDNAIELVVPHDIATYIKLLDKYDLLRKENKTLKASSITTSIY NINTSTVVSLNKVGIDVFDYFMSKLRTPLYMKMKGNKVDELSSTGRSKFIKMTLEEQSIYLLEV LNLLTNSKTTFDVKPLGITGSRSTIGVKIHNLDEFKIINESITGLYSNEVTIV SEQ ID NO: 310 MTKLNQPYGIGLDIGSNSIGFAVVDANSHLLRLKGETAIGARLFREGQSAADRRGSRTTRRRLS RTRWRLSFLRDFFAPHITKIDPDFFLRQKYSEISPKDKDRFKYEKRLFNDRTDAEFYEDYPSMY HLRLHLMTHTHKADPREIFLAIHHILKSRGHFLTPGAAKDFNTDKVDLEDIFPALTEAYAQVYP DLELTFDLAKADDFKAKLLDEQATPSDTQKALVNLLLSSDGEKEIVKKRKQVLTEFAKAITGLK TKFNLALGTEVDEADASNWQFSMGQLDDKWSNIETSMTDQGTEIFEQIQELYRARLLNGIVPAG MSLSQAKVADYGQHKEDLELFKTYLKKLNDHELAKTIRGLYDRYINGDDAKPFLREDFVKALTK EVTAHPNEVSEQLLNRMGQANFMLKQRTKANGAIPIQLQQRELDQIIANQSKYYDWLAAPNPVE AHRWKMPYQLDELLNFHIPYYVGPLITPKQQAESGENVFAWMVRKDPSGNITPYNFDEKVDREA SANTFIQRMKTTDTYLIGEDVLPKQSLLYQKYEVLNELNNVRINNECLGTDQKQRLIREVFERH SSVTIKQVADNLVAHGDFARRPEIRGLADEKRFLSSLSTYHQLKEILHEAIDDPTKLLDIENII TWSTVFEDHTIFETKLAEIEWLDPKKINELSGIRYRGWGQFSRKLLDGLKLGNGHTVIQELMLS NHNLMQILADETLKETMTELNQDKLKTDDIEDVINDAYTSPSNKKALRQVLRVVEDIKHAANGQ DPSWLFIETADGTGTAGKRTQSRQKQIQTVYANAAQELIDSAVRGELEDKIADKASFTDRLVLY FMQGGRDIYTGAPLNIDQLSHYDIDHILPQSLIKDDSLDNRVLVNATINREKNNVFASTLFAGK MKATWRKWHEAGLISGRKLRNLMLRPDEIDKFAKGFVARQLVETRQIIKLTEQIAAAQYPNTKI IAVKAGLSHQLREELDFPKNRDVNHYHHAFDAFLAARIGTYLLKRYPKLAPFFTYGEFAKVDVK KFREFNFIGALTHAKKNIIAKDTGEIVWDKERDIRELDRIYNFKRMLITHEVYFETADLFKQTI YAAKDSKERGGSKQLIPKKQGYPTQVYGGYTQESGSYNALVRVAEADTTAYQVIKISAQNASKI ASANLKSREKGKQLLNEIVVKQLAKRRKNWKPSANSFKIVIPRFGMGTLFQNAKYGLFMVNSDT YYRNYQELWLSRENQKLLKKLFSIKYEKTQMNHDALQVYKAIIDQVEKFFKLYDINQFRAKLSD AIERFEKLPINTDGNKIGKTETLRQILIGLQANGTRSNVKNLGIKTDLGLLQVGSGIKLDKDTQ IVYQSPSGLFKRRIPLADL SEQ ID NO: 311 MTKEYYLGLDVGTNSVGWAVTDSQYNLCKFKKKDMWGIRLFESANTAKDRRLQRGNRRRLERKK QRIDLLQEIFSPEICKIDPTFFIRLNESRLHLEDKSNDFKYPLFIEKDYSDIEYYKEFPTIFHL RKHLIESEEKQDIRLIYLALHNIIKTRGHFLIDGDLQSAKQLRPILDTFLLSLQEEQNLSVSLS ENQKDEYEEILKNRSIAKSEKVKKLKNLFEISDELEKEEKKAQSAVIENFCKFIVGNKGDVCKF LRVSKEELEIDSFSFSEGKYEDDIVKNLEEKVPEKVYLFEQMKAMYDWNILVDILETEEYISFA KVKQYEKHKTNLRLLRDIILKYCTKDEYNRMFNDEKEAGSYTAYVGKLKKNNKKYWIEKKRNPE EFYKSLGKLLDKIEPLKEDLEVLTMMIEECKNHTLLPIQKNKDNGVIPHQVHEVELKKILENAK KYYSFLTETDKDGYSVVQKIESIFRFRIPYYVGPLSTRHQEKGSNVWMVRKPGREDRIYPWNME EIIDFEKSNENFITRMTNKCTYLIGEDVLPKHSLLYSKYMVLNELNNVKVRGKKLPTSLKQKVF EDLFENKSKVTGKNLLEYLQIQDKDIQIDDLSGFDKDFKTSLKSYLDFKKQIFGEEIEKESIQN MIEDIIKWITIYGNDKEMLKRVIRANYSNQLTEEQMKKITGFQYSGWGNFSKMFLKGISGSDVS TGETFDIITAMWETDNNLMQILSKKFTFMDNVEDFNSGKVGKIDKITYDSTVKEMFLSPENKRA VWQTIQVAEEIKKVMGCEPKKIFIEMARGGEKVKKRTKSRKAQLLELYAACEEDCRELIKEIED RDERDFNSMKLFLYYTQFGKCMYSGDDIDINELIRGNSKWDRDHIYPQSKIKDDSIDNLVLVNK TYNAKKSNELLSEDIQKKMHSFWLSLLNKKLITKSKYDRLTRKGDFTDEELSGFIARQLVETRQ STKAIADIFKQIYSSEVVYVKSSLVSDFRKKPLNYLKSRRVNDYHHAKDAYLNIVVGNVYNKKF TSNPIQWMKKNRDTNYSLNKVFEHDVVINGEVIWEKCTYHEDTNTYDGGTLDRIRKIVERDNIL YTEYAYCEKGELFNATIQNKNGNSTVSLKKGLDVKKYGGYFSANTSYFSLIEFEDKKGDRARHI IGVPIYIANMLEHSPSAFLEYCEQKGYQNVRILVEKIKKNSLLIINGYPLRIRGENEVDTSFKR AIQLKLDQKNYELVRNIEKFLEKYVEKKGNYPIDENRDHITHEKMNQLYEVLLSKMKKFNKKGM ADPSDRIEKSKPKFIKLEDLIDKINVINKMLNLLRCDNDTKADLSLIELPKNAGSFVVKKNTIG KSKIILVNQSVTGLYENRREL SEQ ID NO: 312 MARDYSVGLDIGTSSVGWAAIDNKYHLIRAKSKNLIGVRLFDSAVTAEKRRGYRTTRRRLSRRH WRLRLLNDIFAGPLTDFGDENFLARLKYSWVHPQDQSNQAHFAAGLLFDSKEQDKDFYRKYPTI YHLRLALMNDDQKHDLREVYLAIHHLVKYRGHFLIEGDVKADSAFDVHTFADAIQRYAESNNSD ENLLGKIDEKKLSAALTDKHGSKSQRAETAETAFDILDLQSKKQIQAILKSVVGNQANLMAIFG LDSSAISKDEQKNYKFSFDDADIDEKIADSEALLSDTEFEFLCDLKAAFDGLTLKMLLGDDKTV SAAMVRRFNEHQKDWEYIKSHIRNAKNAGNGLYEKSKKFDGINAAYLALQSDNEDDRKKAKKIF QDEISSADIPDDVKADFLKKIDDDQFLPIQRTKNNGTIPHQLHRNELEQIIEKQGIYYPFLKDT YQENSHELNKITALINFRVPYYVGPLVEEEQKIADDGKNIPDPTNHWMVRKSNDTITPWNLSQV VDLDKSGRRFIERLTGTDTYLIGEPTLPKNSLLYQKFDVLQELNNIRVSGRRLDIRAKQDAFEH LFKVQKTVSATNLKDFLVQAGYISEDTQIEGLADVNGKNFNNALTTYNYLVSVLGREFVENPSN EELLEEITELQTVFEDKKVLRRQLDQLDGLSDHNREKLSRKHYTGWGRISKKLLTTKIVQNADK IDNQTFDVPRMNQSIIDTLYNTKMNLMEIINNAEDDFGVRAWIDKQNTTDGDEQDVYSLIDELA GPKEIKRGIVQSFRILDDITKAVGYAPKRVYLEFARKTQESHLTNSRKNQLSTLLKNAGLSELV TQVSQYDAAALQNDRLYLYFLQQGKDMYSGEKLNLDNLSNYDIDHIIPQAYTKDNSLDNRVLVS NITNRRKSDSSNYLPALIDKMRPFWSVLSKQGLLSKHKFANLTRTRDFDDMEKERFIARSLVET RQIIKNVASLIDSHFGGETKAVAIRSSLTADMRRYVDIPKNRDINDYHHAFDALLFSTVGQYTE NSGLMKKGQLSDSAGNQYNRYIKEWIHAARLNAQSQRVNPFGFVVGSMRNAAPGKLNPETGEIT PEENADWSIADLDYLHKVMNFRKITVTRRLKDQKGQLYDESRYPSVLHDAKSKASINFDKHKPV DLYGGFSSAKPAYAALIKFKNKFRLVNVLRQWTYSDKNSEDYILEQIRGKYPKAEMVLSHIPYG QLVKKDGALVTISSATELHNFEQLWLPLADYKLINTLLKTKEDNLVDILHNRLDLPEMTIESAF YKAFDSILSFAFNRYALHQNALVKLQAHRDDFNALNYEDKQQTLERILDALHASPASSDLKKIN LSSGFGRLFSPSHFTLADTDEFIFQSVTGLFSTQKTVAQLYQETK SEQ ID NO: 313 MVYDVGLDIGTGSVGWVALDENGKLARAKGKNLVGVRLFDTAQTAADRRGFRTTRRRLSRRKWR LRLLDELFSAEINEIDSSFFQRLKYSYVHPKDEENKAHYYGGYLFPTEEETKKFHRSYPTIYHL RQELMAQPNKRFDIREIYLAIHHLVKYRGHFLSSQEKITIGSTYNPEDLANAIEVYADEKGLSW ELNNPEQLTEIISGEAGYGLNKSMKADEALKLFEFDNNQDKVAIKTLLAGLTGNQIDFAKLFGK DISDKDEAKLWKLKLDDEALEEKSQTILSQLTDEEIELFHAVVQAYDGFVLIGLLNGADSVSAA MVQLYDQHREDRKLLKSLAQKAGLKHKRFSEIYEQLALATDEATIKNGISTARELVEESNLSKE VKEDTLRRLDENEFLPKQRTKANSVIPHQLHLAELQKILQNQGQYYPFLLDTFEKEDGQDNKIE ELLRFRIPYYVGPLVTKKDVEHAGGDADNHWVERNEGFEKSRVTPWNFDKVFNRDKAARDFIER LTGNDTYLIGEKTLPQNSLRYQLFTVLNELNNVRVNGKKFDSKTKADLINDLFKARKTVSLSAL KDYLKAQGKGDVTITGLADESKFNSSLSSYNDLKKTFDAEYLENEDNQETLEKIIEIQTVFEDS KIASRELSKLPLDDDQVKKLSQTHYTGWGRLSEKLLDSKIIDERGQKVSILDKLKSTSQNFMSI INNDKYGVQAWITEQNTGSSKLTFDEKVNELTTSPANKRGIKQSFAVLNDIKKAMKEEPRRVYL EFAREDQTSVRSVPRYNQLKEKYQSKSLSEEAKVLKKTLDGNKNKMSDDRYFLYFQQQGKDMYT GRPINFERLSQDYDIDHIIPQAFTKDDSLDNRVLVSRPENARKSDSFAYTDEVQKQDGSLWTSL LKSGFINRKKYERLTKAGKYLDGQKTGFIARQLVETRQIIKNVASLIEGEYENSKAVAIRSEIT ADMRLLVGIKKHREINSFHHAFDALLITAAGQYMQNRYPDRDSTNVYNEFDRYTNDYLKNLRQL SSRDEVRRLKSFGFVVGTMRKGNEDWSEENTSYLRKVMMFKNILTTKKTEKDRGPLNKETIFSP KSGKKLIPLNSKRSDTALYGGYSNVYSAYMTLVRANGKNLLIKIPISIANQIEVGNLKINDYIV NNPAIKKFEKILISKLPLGQLVNEDGNLIYLASNEYRHNAKQLWLSTTDADKIASISENSSDEE LLEAYDILTSENVKNRFPFFKKDIDKLSQVRDEFLDSDKRIAVIQTILRGLQIDAAYQAPVKII SKKVSDWHKLQQSGGIKLSDNSEMIYQSATGIFETRVKISDLL SEQ ID NO: 314 IVDYCIGLDLGTGSVGWAVVDMNHRLMKRNGKHLWGSRLFSNAETAANRRASRSIRRRYNKRRE RIRLLRAILQDMVLEKDPTFFIRLEHTSFLDEEDKAKYLGTDYKDNYNLFIDEDFNDYTYYHKY PTIYHLRKALCESTEKADPRLIYLALHHIVKYRGNFLYEGQKFNMDASNIEDKLSDIFTQFTSF NNIPYEDDEKKNLEILEILKKPLSKKAKVDEVMTLIAPEKDYKSAFKELVTGIAGNKMNVTKMI LCEPIKQGDSEIKLKFSDSNYDDQFSEVEKDLGEYVEFVDALHNVYSWVELQTIMGATHTDNAS ISEAMVSRYNKHHDDLKLLKDCIKNNVPNKYFDMFRNDSEKSKGYYNYINRPSKAPVDEFYKYV KKCIEKVDTPEAKQILNDIELENFLLKQNSRTNGSVPYQMQLDEMIKIIDNQAEYYPILKEKRE QLLSILTFRIPYYFGPLNETSEHAWIKRLEGKENQRILPWNYQDIVDVDATAEGFIKRMRSYCT YFPDEEVLPKNSLIVSKYEVYNELNKIRVDDKLLEVDVKNDIYNELFMKNKTVTEKKLKNWLVN NQCCSKDAEIKGFQKENQFSTSLTPWIDFTNIFGKIDQSNFDLIENIIYDLTVFEDKKIMKRRL KKKYALPDDKVKQILKLKYKDWSRLSKKLLDGIVADNRFGSSVTVLDVLEMSRLNLMEIINDKD LGYAQMIEEATSCPEDGKFTYEEVERLAGSPALKRGIWQSLQIVEEITKVMKCRPKYIYIEFER SEEAKERTESKIKKLENVYKDLDEQTKKEYKSVLEELKGFDNTKKISSDSLFLYFTQLGKCMYS GKKLDIDSLDKYQIDHIVPQSLVKDDSFDNRVLVVPSENQRKLDDLVVPFDIRDKMYRFWKLLF DHELISPKKFYSLIKTEYTERDEERFINRQLVETRQITKNVTQIIEDHYSTTKVAAIRANLSHE FRVKNHIYKNRDINDYHHAHDAYIVALIGGFMRDRYPNMHDSKAVYSEYMKMFRKNKNDQKRWK DGFVINSMNYPYEVDGKLIWNPDLINEIKKCFYYKDCYCTTKLDQKSGQLFNLTVLSNDAHADK GVTKAVVPVNKNRSDVHKYGGFSGLQYTIVAIEGQKKKGKKTELVKKISGVPLHLKAASINEKI NYIEEKEGLSDVRIIKDNIPVNQMIEMDGGEYLLTSPTEYVNARQLVLNEKQCALIADIYNAIY KQDYDNLDDILMIQLYIELTNKMKVLYPAYRGIAEKFESMNENYVVISKEEKANIIKQMLIVMH RGPQNGNIVYDDFKISDRIGRLKTKNHNLNNIVFISQSPTGIYTKKYKL SEQ ID NO: 315 MKSEKKYYIGLDVGTNSVGWAVTDEFYNILRAKGKDLWGVRLFEKADTAANTRIFRSGRRRNDR KGMRLQILREIFEDEIKKVDKDFYDRLDESKFWAEDKKVSGKYSLFNDKNFSDKQYFEKFPTIF HLRKYLMEEHGKVDIRYYFLAINQMMKRRGHFLIDGQISHVTDDKPLKEQLILLINDLLKIELE EELMDSIFEILADVNEKRTDKKNNLKELIKGQDFNKQEGNILNSIFESIVTGKAKIKNIISDED ILEKIKEDNKEDFVLTGDSYEENLQYFEEVLQENITLFNTLKSTYDFLILQSILKGKSTLSDAQ VERYDEHKKDLEILKKVIKKYDEDGKLFKQVFKEDNGNGYVSYIGYYLNKNKKITAKKKISNIE FTKYVKGILEKQCDCEDEDVKYLLGKIEQENFLLKQISSINSVIPHQIHLFELDKILENLAKNY PSFNNKKEEFTKIEKIRKTFTFRIPYYVGPLNDYHKNNGGNAWIFRNKGEKIRPWNFEKIVDLH KSEEEFIKRMLNQCTYLPEETVLPKSSILYSEYMVLNELNNLRINGKPLDTDVKLKLIEELFKK KTKVTLKSIRDYMVRNNFADKEDFDNSEKNLEIASNMKSYIDFNNILEDKFDVEMVEDLIEKIT IHTGNKKLLKKYIEETYPDLSSSQIQKIINLKYKDWGRLSRKLLDGIKGTKKETEKTDTVINFL RNSSDNLMQIIGSQNYSFNEYIDKLRKKYIPQEISYEVVENLYVSPSVKKMIWQVIRVTEEITK VMGYDPDKIFIEMAKSEEEKKTTISRKNKLLDLYKAIKKDERDSQYEKLLTGLNKLDDSDLRSR KLYLYYTQMGRDMYTGEKIDLDKLFDSTHYDKDHIIPQSMKKDDSIINNLVLVNKNANQTTKGN IYPVPSSIRNNPKIYNYWKYLMEKEFISKEKYNRLIRNTPLTNEELGGFINRQLVETRQSTKAI KELFEKFYQKSKIIPVKASLASDLRKDMNTLKSREVNDLHHAHDAFLNIVAGDVWNREFTSNPI NYVKENREGDKVKYSLSKDFTRPRKSKGKVIWTPEKGRKLIVDTLNKPSVLISNESHVKKGELF NATIAGKKDYKKGKIYLPLKKDDRLQDVSKYGGYKAINGAFFFLVEHTKSKKRIRSIELFPLHL LSKFYEDKNTVLDYAINVLQLQDPKIIIDKINYRTEIIIDNFSYLISTKSNDGSITVKPNEQMY WRVDEISNLKKIENKYKKDAILTEEDRKIMESYIDKIYQQFKAGKYKNRRTTDTIIEKYEIIDL DTLDNKQLYQLLVAFISLSYKTSNNAVDFTVIGLGTECGKPRITNLPDNTYLVYKSITGIYEKR IRIK SEQ ID NO: 316 MKLRGIEDDYSIGLDMGTSSVGWAVTDERGTLAHFKRKPTWGSRLFREAQTAAVARMPRGQRRR YVRRRWRLDLLQKLFEQQMEQADPDFFIRLRQSRLLRDDRAEEHADYRWPLFNDCKFTERDYYQ RFPTIYHVRSWLMETDEQADIRLIYLALHNIVKHRGNFLREGQSLSAKSARPDEALNHLRETLR VWSSERGFECSIADNGSILAMLTHPDLSPSDRRKKIAPLFDVKSDDAAADKKLGIALAGAVIGL KTEFKNIFGDFPCEDSSIYLSNDEAVDAVRSACPDDCAELFDRLCEVYSAYVLQGLLSYAPGQT ISANMVEKYRRYGEDLALLKKLVKIYAPDQYRMFFSGATYPGTGIYDAAQARGYTKYNLGPKKS EYKPSESMQYDDFRKAVEKLFAKTDARADERYRMMMDRFDKQQFLRRLKTSDNGSIYHQLHLEE LKAIVENQGRFYPFLKRDADKLVSLVSFRIPYYVGPLSTRNARTDQHGENRFAWSERKPGMQDE PIFPWNWESIIDRSKSAEKFILRMTGMCTYLQQEPVLPKSSLLYEEFCVLNELNGAHWSIDGDD EHRFDAADREGIIEELFRRKRTVSYGDVAGWMERERNQIGAHVCGGQGEKGFESKLGSYIFFCK DVFKVERLEQSDYPMIERIILWNTLFEDRKILSQRLKEEYGSRLSAEQIKTICKKRFTGWGRLS EKFLTGITVQVDEDSVSIMDVLREGCPVSGKRGRAMVMMEILRDEELGFQKKVDDFNRAFFAEN AQALGVNELPGSPAVRRSLNQSIRIVDEIASIAGKAPANIFIEVTRDEDPKKKGRRTKRRYNDL KDALEAFKKEDPELWRELCETAPNDMDERLSLYFMQRGKCLYSGRAIDIHQLSNAGIYEVDHII PRTYVKDDSLENKALVYREENQRKTDMLLIDPEIRRRMSGYWRMLHEAKLIGDKKFRNLLRSRI DDKALKGFIARQLVETGQMVKLVRSLLEARYPETNIISVKASISHDLRTAAELVKCREANDFHH AHDAFLACRVGLFIQKRHPCVYENPIGLSQVVRNYVRQQADIFKRCRTIPGSSGFIVNSFMTSG FDKETGEIFKDDWDAEAEVEGIRRSLNFRQCFISRMPFEDHGVFWDATIYSPRAKKTAALPLKQ GLNPSRYGSFSREQFAYFFIYKARNPRKEQTLFEFAQVPVRLSAQIRQDENALERYARELAKDQ GLEFIRIERSKILKNQLIEIDGDRLCITGKEEVRNACELAFAQDEMRVIRMLVSEKPVSRECVI SLFNRILLHGDQASRRLSKQLKLALLSEAFSEASDNVQRNVVLGLIAIFNGSTNMVNLSDIGGS KFAGNVRIKYKKELASPKVNVHLIDQSVTGMFERRTKIGL SEQ ID NO: 317 MENKQYYIGLDVGTNSVGWAVTDTSYNLLRAKGKDMWGARLFEKANTAAERRTKRTSRRRSERE KARKAMLKELFADEINRVDPSFFIRLEESKFFLDDRSENNRQRYTLFNDATFTDKDYYEKYKTI FHLRSALINSDEKFDVRLVFLAILNLFSHRGHFLNASLKGDGDIQGMDVFYNDLVESCEYFEIE LPRITNIDNFEKILSQKGKSRTKILEELSEELSISKKDKSKYNLIKLISGLEASVVELYNIEDI QDENKKIKIGFRESDYEESSLKVKEIIGDEYFDLVERAKSVHDMGLLSNIIGNSKYLCEARVEA YENHHKDLLKIKELLKKYDKKAYNDMFRKMTDKNYSAYVGSVNSNIAKERRSVDKRKIEDLYKY IEDTALKNIPDDNKDKIEILEKIKLGEFLKKQLTASNGVIPNQLQSRELRAILKKAENYLPFLK EKGEKNLTVSEMIIQLFEFQIPYYVGPLDKNPKKDNKANSWAKIKQGGRILPWNFEDKVDVKGS RKEFIEKMVRKCTYISDEHTLPKQSLLYEKFMVLNEINNIKIDGEKISVEAKQKIYNDLFVKGK KVSQKDIKKELISLNIMDKDSVLSGTDTVCNAYLSSIGKFTGVFKEEINKQSIVDMIEDIIFLK TVYGDEKRFVKEEIVEKYGDEIDKDKIKRILGFKFSNWGNLSKSFLELEGADVGTGEVRSIIQS LWETNFNLMELLSSRFTYMDELEKRVKKLEKPLSEWTIEDLDDMYLSSPVKRMIWQSMKIVDEI QTVIGYAPKRIFVEMTRSEGEKVRTKSRKDRLKELYNGIKEDSKQWVKELDSKDESYFRSKKMY LYYLQKGRCMYSGEVIELDKLMDDNLYDIDHIYPRSFVKDDSLDNLVLVKKEINNRKQNDPITP QIQASCQGFWKILHDQGFMSNEKYSRLTRKTQEFSDEEKLSFINRQIVETGQATKCMAQILQKS MGEDVDVVFSKARLVSEFRHKFELFKSRLINDFHHANDAYLNIVVGNSYFVKFTRNPANFIKDA RKNPDNPVYKYHMDRFFERDVKSKSEVAWIGQSEGNSGTIVIVKKTMAKNSPLITKKVEEGHGS ITKETIVGVKEIKFGRNKVEKADKTPKKPNLQAYRPIKTSDERLCNILRYGGRTSISISGYCLV EYVKKRKTIRSLEAIPVYLGRKDSLSEEKLLNYFRYNLNDGGKDSVSDIRLCLPFISTNSLVKI DGYLYYLGGKNDDRIQLYNAYQLKMKKEEVEYIRKIEKAVSMSKFDEIDREKNPVLTEEKNIEL YNKIQDKFENTVFSKRMSLVKYNKKDLSFGDFLKNKKSKFEEIDLEKQCKVLYNIIFNLSNLKE VDLSDIGGSKSTGKCRCKKNITNYKEFKLIQQSITGLYSCEKDLMTI SEQ ID NO: 318 MKNLKEYYIGLDIGTASVGWAVTDESYNIPKFNGKKMWGVRLFDDAKTAEERRTQRGSRRRLNR RKERINLLQDLFATEISKVDPNFFLRLDNSDLYREDKDEKLKSKYTLFNDKDFKDRDYHKKYPT IHHLIMDLIEDEGKKDIRLLYLACHYLLKNRGHFIFEGQKFDTKNSFDKSINDLKIHLRDEYNI DLEFNNEDLIEIITDTTLNKTNKKKELKNIVGDTKFLKAISAIMIGSSQKLVDLFEDGEFEETT VKSVDFSTTAFDDKYSEYEEALGDTISLLNILKSIYDSSILENLLKDADKSKDGNKYISKAFVK KFNKHGKDLKTLKRIIKKYLPSEYANIFRNKSINDNYVAYTKSNITSNKRTKASKFTKQEDFYK FIKKHLDTIKETKLNSSENEDLKLIDEMLTDIEFKTFIPKLKSSDNGVIPYQLKLMELKKILDN QSKYYDFLNESDEYGTVKDKVESIMEFRIPYYVGPLNPDSKYAWIKRENTKITPWNFKDIVDLD SSREEFIDRLIGRCTYLKEEKVLPKASLIYNEFMVLNELNNLKLNEFLITEEMKKAIFEELFKT KKKVTLKAVSNLLKKEFNLTGDILLSGTDGDFKQGLNSYIDFKNIIGDKVDRDDYRIKIEEIIK LIVLYEDDKTYLKKKIKSAYKNDFTDDEIKKIAALNYKDWGRLSKRFLTGIEGVDKTTGEKGSI IYFMREYNLNLMELMSGHYTFTEEVEKLNPVENRELCYEMVDELYLSPSVKRMLWQSLRVVDEI KRIIGKDPKKIFIEMARAKEAKNSRKESRKNKLLEFYKFGKKAFINEIGEERYNYLLNEINSEE ESKFRWDNLYLYYTQLGRCMYSLEPIDLADLKSNNIYDQDHIYPKSKIYDDSLENRVLVKKNLN HEKGNQYPIPEKVLNKNAYGFWKILFDKGLIGQKKYTRLTRRTPFEERELAEFIERQIVETRQA TKETANLLKNICQDSEIVYSKAENASRFRQEFDIIKCRTVNDLHHMHDAYLNIVVGNVYNTKFT KNPLNFIKDKDNVRSYNLENMFKYDVVRGSYTAWIADDSEGNVKAATIKKVKRELEGKNYRFTR MSYIGTGGLYDQNLMRKGKGQIPQKENTNKSNIEKYGGYNKASSAYFALIESDGKAGRERTLET IPIMVYNQEKYGNTEAVDKYLKDNLELQDPKILKDKIKINSLIKLDGFLYNIKGKTGDSLSIAG SVQLIVNKEEQKLIKKMDKFLVKKKDNKDIKVTSFDNIKEEELIKLYKTLSDKLNNGIYSNKRN NQAKNISEALDKFKEISIEEKIDVLNQIILLFQSYNNGCNLKSIGLSAKTGVVFIPKKLNYKEC KLINQSITGLFENEVDLLNL SEQ ID NO: 319 MGKMYYLGLDIGTNSVGYAVTDPSYHLLKFKGEPMWGAHVFAAGNQSAERRSFRTSRRRLDRRQ QRVKLVQEIFAPVISPIDPRFFIRLHESALWRDDVAETDKHIFFNDPTYTDKEYYSDYPTIHHL IVDLMESSEKHDPRLVYLAVAWLVAHRGHFLNEVDKDNIGDVLSFDAFYPEFLAFLSDNGVSPW VCESKALQATLLSRNSVNDKYKALKSLIFGSQKPEDNFDANISEDGLIQLLAGKKVKVNKLFPQ ESNDASFTLNDKEDAIEEILGTLTPDECEWIAHIRRLFDWAIMKHALKDGRTISESKVKLYEQH HHDLTQLKYFVKTYLAKEYDDIFRNVDSETTKNYVAYSYHVKEVKGTLPKNKATQEEFCKYVLG KVKNIECSEADKVDFDEMIQRLTDNSFMPKQVSGENRVIPYQLYYYELKTILNKAASYLPFLTQ CGKDAISNQDKLLSIMTFRIPYFVGPLRKDNSEHAWLERKAGKIYPWNFNDKVDLDKSEEAFIR RMTNTCTYYPGEDVLPLDSLIYEKFMILNEINNIRIDGYPISVDVKQQVFGLFEKKRRVTVKDI QNLLLSLGALDKHGKLTGIDTTIHSNYNTYHHFKSLMERGVLTRDDVERIVERMTYSDDTKRVR LWLNNNYGTLTADDVKHISRLRKHDFGRLSKMFLTGLKGVHKETGERASILDFMWNTNDNLMQL LSECYTFSDEITKLQEAYYAKAQLSLNDFLDSMYISNAVKRPIYRTLAVVNDIRKACGTAPKRI FIEMARDGESKKKRSVTRREQIKNLYRSIRKDFQQEVDFLEKILENKSDGQLQSDALYLYFAQL GRDMYTGDPIKLEHIKDQSFYNIDHIYPQSMVKDDSLDNKVLVQSEINGEKSSRYPLDAAIRNK MKPLWDAYYNHGLISLKKYQRLTRSTPFTDDEKWDFINRQLVETRQSTKALAILLKRKFPDTEI VYSKAGLSSDFRHEFGLVKSRNINDLHHAKDAFLAIVTGNVYHERFNRRWFMVNQPYSVKTKTL FTHSIKNGNFVAWNGEEDLGRIVKMLKQNKNTIHFTRFSFDRKEGLFDIQPLKASTGLVPRKAG LDVVKYGGYDKSTAAYYLLVRFTLEDKKTQHKLMMIPVEGLYKARIDHDKEFLTDYAQTTISEI LQKDKQKVINIMFPMGTRHIKLNSMISIDGFYLSIGGKSSKGKSVLCHAMVPLIVPHKIECYIK AMESFARKFKENNKLRIVEKFDKITVEDNLNLYELFLQKLQHNPYNKFFSTQFDVLTNGRSTFT KLSPEEQVQTLLNILSIFKTCRSSGCDLKSINGSAQAARIMISADLTGLSKKYSDIRLVEQSAS GLFVSKSQNLLEYL SEQ ID NO: 320 MTKKEQPYNIGLDIGTSSVGWAVTNDNYDLLNIKKKNLWGVRLFEEAQTAKETRLNRSTRRRYR RRKNRINWLNEIFSEELAKTDPSFLIRLQNSWVSKKDPDRKRDKYNLFIDGPYTDKEYYREFPT IFHLRKELILNKDKADIRLIYLALHNILKYRGNFTYEHQKFNISNLNNNLSKELIELNQQLIKY DISFPDDCDWNHISDILIGRGNATQKSSNILKDFTLDKETKKLLKEVINLILGNVAHLNTIFKT SLTKDEEKLNFSGKDIESKLDDLDSILDDDQFTVLDAANRIYSTITLNEILNGESYFSMAKVNQ YENHAIDLCKLRDMWHTTKNEEAVEQSRQAYDDYINKPKYGTKELYTSLKKFLKVALPTNLAKE AEEKISKGTYLVKPRNSENGVVPYQLNKIEMEKIIDNQSQYYPFLKENKEKLLSILSFRIPYYV GPLQSAEKNPFAWMERKSNGHARPWNFDEIVDREKSSNKFIRRMTVTDSYLVGEPVLPKNSLIY QRYEVLNELNNIRITENLKTNPIGSRLTVETKQRIYNELFKKYKKVTVKKLTKWLIAQGYYKNP ILIGLSQKDEFNSTLTTYLDMKKIFGSSFMEDNKNYDQIEELIEWLTIFEDKQILNEKLHSSKY SYTPDQIKKISNMRYKGWGRLSKKILMDITTETNTPQLLQLSNYSILDLMWATNNNFISIMSND KYDFKNYIENHNLNKNEDQNISDLVNDIHVSPALKRGITQSIKIVQEIVKFMGHAPKHIFIEVT RETKKSEITTSREKRIKRLQSKLLNKANDFKPQLREYLVPNKKIQEELKKHKNDLSSERIMLYF LQNGKSLYSEESLNINKLSDYQVDHILPRTYIPDDSLENKALVLAKENQRKADDLLLNSNVIDR NLERWTYMLNNNMIGLKKFKNLTRRVITDKDKLGFIHRQLVQTSQMVKGVANILDNMYKNQGTT CIQARANLSTAFRKALSGQDDTYHFKHPELVKNRNVNDFHHAQDAYLASFLGTYRLRRFPTNEM LLMNGEYNKFYGQVKELYSKKKKLPDSRKNGFIISPLVNGTTQYDRNTGEIIWNVGFRDKILKI FNYHQCNVTRKTEIKTGQFYDQTIYSPKNPKYKKLIAQKKDMDPNIYGGFSGDNKSSITIVKID NNKIKPVAIPIRLINDLKDKKTLQNWLEENVKHKKSIQIIKNNVPIGQIIYSKKVGLLSLNSDR EVANRQQLILPPEHSALLRLLQIPDEDLDQILAFYDKNILVEILQELITKMKKFYPFYKGEREF LIANIENFNQATTSEKVNSLEELITLLHANSTSAHLIFNNIEKKAFGRKTHGLTLNNTDFIYQS VTGLYETRIHIE SEQ ID NO: 321 MTKFNKNYSIGLDIGVSSVGYAVVTEDYRVPAFKFKVLGNTEKEKIKKNLIGSTTFVSAQPAKG TRVFRVNRRRIDRRNHRITYLRDIFQKEIEKVDKNFYRRLDESFRVLGDKSEDLQIKQPFFGDK ELETAYHKKYPTIYHLRKHLADADKNSPVADIREVYMAISHILKYRGHFLTLDKINPNNINMQN SWIDFIESCQEVFDLEISDESKNIADIFKSSENRQEKVKKILPYFQQELLKKDKSIFKQLLQLL FGLKTKFKDCFELEEEPDLNFSKENYDENLENFLGSLEEDFSDVFAKLKVLRDTILLSGMLTYT GATHARFSATMVERYEEHRKDLQRFKFFIKQNLSEQDYLDIFGRKTQNGFDVDKETKGYVGYIT NKMVLTNPQKQKTIQQNFYDYISGKITGIEGAEYFLNKISDGTFLRKLRTSDNGAIPNQIHAYE LEKIIERQGKDYPFLLENKDKLLSILTFKIPYYVGPLAKGSNSRFAWIKRATSSDILDDNDEDT RNGKIRPWNYQKLINMDETRDAFITNLIGNDIILLNEKVLPKRSLIYEEVMLQNELTRVKYKDK YGKAHFFDSELRQNIINGLFKNNSKRVNAKSLIKYLSDNHKDLNAIEIVSGVEKGKSFNSTLKT YNDLKTIFSEELLDSEIYQKELEEIIKVITVFDDKKSIKNYLTKFFGHLEILDEEKINQLSKLR YSGWGRYSAKLLLDIRDEDTGFNLLQFLRNDEENRNLTKLISDNTLSFEPKIKDIQSKSTIEDD IFDEIKKLAGSPAIKRGILNSIKIVDELVQIIGYPPHNIVIEMARENMTTEEGQKKAKTRKTKL ESALKNIENSLLENGKVPHSDEQLQSEKLYLYYLQNGKDMYTLDKTGSPAPLYLDQLDQYEVDH IIPYSFLPIDSIDNKVLTHRENNQQKLNNIPDKETVANMKPFWEKLYNAKLISQTKYQRLTTSE RTPDGVLTESMKAGFIERQLVETRQIIKHVARILDNRFSDTKIITLKSQLITNFRNTFHIAKIR ELNDYHHAHDAYLAVVVGQTLLKVYPKLAPELIYGHHAHFNRHEENKATLRKHLYSNIMRFFNN PDSKVSKDIWDCNRDLPIIKDVIYNSQINFVKRTMIKKGAFYNQNPVGKFNKQLAANNRYPLKT KALCLDTSIYGGYGPMNSALSIIIIAERFNEKKGKIETVKEFHDIFIIDYEKFNNNPFQFLNDT SENGFLKKNNINRVLGFYRIPKYSLMQKIDGTRMLFESKSNLHKATQFKLTKTQNELFFHMKRL LTKSNLMDLKSKSAIKESQNFILKHKEEFDNISNQLSAFSQKMLGNTTSLKNLIKGYNERKIKE IDIRDETIKYFYDNFIKMFSFVKSGAPKDINDFFDNKCTVARMRPKPDKKLLNATLIHQSITGL YETRIDLSKLGED SEQ ID NO: 322 MKQEYFLGLDMGTGSLGWAVTDSTYQVMRKHGKALWGTRLFESASTAEERRMFRTARRRLDRRN WRIQVLQEIFSEEISKVDPGFFLRMKESKYYPEDKRDAEGNCPELPYALFVDDNYTDKNYHKDY PTIYHLRKMLMETTEIPDIRLVYLVLHHMMKHRGHFLLSGDISQIKEFKSTFEQLIQNIQDEEL EWHISLDDAAIQFVEHVLKDRNLTRSTKKSRLIKQLNAKSACEKAILNLLSGGTVKLSDIFNNK ELDESERPKVSFADSGYDDYIGIVEAELAEQYYIIASAKAVYDWSVLVEILGNSVSISEAKIKV YQKHQADLKTLKKIVRQYMTKEDYKRVFVDTEEKLNNYSAYIGMTKKNGKKVDLKSKQCTQADF YDFLKKNVIKVIDHKEITQEIESEIEKENFLPKQVTKDNGVIPYQVHDYELKKILDNLGTRMPF IKENAEKIQQLFEFRIPYYVGPLNRVDDGKDGKFTWSVRKSDARIYPWNFTEVIDVEASAEKFI RRMTNKCTYLVGEDVLPKDSLVYSKFMVLNELNNLRLNGEKISVELKQRIYEELFCKYRKVTRK KLERYLVIEGIAKKGVEITGIDGDFKASLTAYHDFKERLTDVQLSQRAKEAIVLNVVLFGDDKK LLKQRLSKMYPNLTTGQLKGICSLSYQGWGRLSKTFLEEITVPAPGTGEVWNIMTALWQTNDNL MQLLSRNYGFTNEVEEFNTLKKETDLSYKTVDELYVSPAVKRQIWQTLKVVKEIQKVMGNAPKR VFVEMAREKQEGKRSDSRKKQLVELYRACKNEERDWITELNAQSDQQLRSDKLFLYYIQKGRCM YSGETIQLDELWDNTKYDIDHIYPQSKTMDDSLNNRVLVKKNYNAIKSDTYPLSLDIQKKMMSF WKMLQQQGFITKEKYVRLVRSDELSADELAGFIERQIVETRQSTKAVATILKEALPDTEIVYVK AGNVSNFRQTYELLKVREMNDLHHAKDAYLNIVVGNAYFVKFTKNAAWFIRNNPGRSYNLKRMF EFDIERSGEIAWKAGNKGSIVTVKKVMQKNNILVTRKAYEVKGGLFDQQIMKKGKGQVPIKGND ERLADIEKYGGYNKAAGTYFMLVKSLDKKGKEIRTIEFVPLYLKNQIEINHESAIQYLAQERGL NSPEILLSKIKIDTLFKVDGFKMWLSGRTGNQLIFKGANQLILSHQEAAILKGVVKYVNRKNEN KDAKLSERDGMTEEKLLQLYDTFLDKLSNTVYSIRLSAQIKTLTEKRAKFIGLSNEDQCIVLNE ILHMFQCQSGSANLKLIGGPGSAGILVMNNNITACKQISVINQSPTGIYEKEIDLIKL SEQ ID NO: 323 MKKPYSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTAEDRRL KRTARRRYTRRRNRILYLQEIFSEEMGKVDDSFFHRLEDSFLVTEDKRGERHPIFGNLEEEVKY HENFPTIYHLRQYLADNPEKVDLRLVYLALAHIIKFRGHFLIEGKFDTRNNDVQRLFQEFLAVY DNTFENSSLQEQNVQVEEILTDKISKSAKKDRVLKLFPNEKSNGRFAEFLKLIVGNQADFKKHF ELEEKAPLQFSKDTYEEELEVLLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSAS MIQRYNEHQMDLAQLKQFIRQKLSDKYNEVFSDVSKDGYAGYIDGKTNQEAFYKYLKGLLNKIE GSGYFLDKIEREDFLRKQRTFDNGSIPHQIHLQEMRAIIRRQAEFYPFLADNQDRIEKLLTFRI PYYVGPLARGKSDFAWLSRKSADKITPWNFDEIVDKESSAEAFINRMTNYDLYLPNQKVLPKHS LLYEKFTVYNELTKVKYKTEQGKTAFFDANMKQEIFDGVFKVYRKVTKDKLMDFLEKEFDEFRI VDLTGLDKENKVFNASYGTYHDLCKILDKDFLDNSKNEKILEDIVLTLTLFEDREMIRKRLENY SDLLTKEQVKKLERRHYTGWGRLSAELIHGIRNKESRKTILDYLIDDGNSNRNFMQLINDDALS FKEEIAKAQVIGETDNLNQVVSDIAGSPAIKKGILQSLKIVDELVKIMGHQPENIVVEMARENQ FTNQGRRNSQQRLKGLTDSIKEFGSQILKEHPVENSQLQNDRLFLYYLQNGRDMYTGEELDIDY LSQYDIDHIIPQAFIKDNSIDNRVLTSSKENRGKSDDVPSKDVVRKMKSYWSKLLSAKLITQRK FDNLTKAERGGLTDDDKAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIRQVKIVTLKS NLVSNFRKEFELYKVREINDYHHAHDAYLNAVIGKALLGVYPQLEPEFVYGDYPHFHGHKENKA TAKKFFYSNIMNFFKKDDVRTDKNGEIIWKKDEHISNIKKVLSYPQVNIVKKVEEQTGGFSKES ILPKGNSDKLIPRKTKKFYWDTKKYGGFDSPIVAYSILVIADIEKGKSKKLKTVKALVGVTIME KMTFERDPVAFLERKGYRNVQEENIIKLPKYSLFKLENGRKRLLASARELQKGNEIVLPNHLGT LLYHAKNIHKVDEPKHLDYVDKHKDEFKELLDVVSNFSKKYTLAEGNLEKIKELYAQNNGEDLK ELASSFINLLTFTAIGAPATFKFFDKNIDRKRYTSTTEILNATLIHQSITGLYETRIDLNKLGG D SEQ ID NO: 324 MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRL KRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAY HEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTY NQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMD GTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRI PYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFD SVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYA HLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTF KEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQ TTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINR LSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRK FDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKS KLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAK SEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLS MPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKG KSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLAS AGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRV ILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLD ATLIHQSITGLYETRIDLSQLGGD SEQ ID NO: 325 MTKPYSIGLDIGTNSVGWAVTTDNYKVPSKKMKVLGNTSKKYIKKNLLGVLLFDSGITAEGRRL KRTARRRYTRRRNRILYLQEIFSTEMATLDDAFFQRLDDSFLVPDDKRDSKYPIFGNLVEEKAY HDEFPTIYHLRKYLADSTKKADLRLVYLALAHMIKYRGHFLIEGEFNSKNNDIQKNFQDFLDTY NAIFESDLSLENSKQLEEIVKDKISKLEKKDRILKLFPGEKNSGIFSEFLKLIVGNQADFRKCF NLDEKASLHFSKESYDEDLETLLGYIGDDYSDVFLKAKKLYDAILLSGFLTVTDNETEAPLSSA MIKRYNEHKEDLALLKEYIRNISLKTYNEVFKDDTKNGYAGYIDGKTNQEDFYVYLKKLLAEFE GADYFLEKIDREDFLRKQRTFDNGSIPYQIHLQEMRAILDKQAKFYPFLAKNKERIEKILTFRI PYYVGPLARGNSDFAWSIRKRNEKITPWNFEDVIDKESSAEAFINRMTSFDLYLPEEKVLPKHS LLYETFNVYNELTKVRFIAESMRDYQFLDSKQKKDIVRLYFKDKRKVTDKDIIEYLHAIYGYDG IELKGIEKQFNSSLSTYHDLLNIINDKEFLDDSSNEAIIEEIIHTLTIFEDREMIKQRLSKFEN IFDKSVLKKLSRRHYTGWGKLSAKLINGIRDEKSGNTILDYLIDDGISNRNFMQLIHDDALSFK KKIQKAQIIGDEDKGNIKEVVKSLPGSPAIKKGILQSIKIVDELVKVMGGRKPESIVVEMAREN QYTNQGKSNSQQRLKRLEKSLKELGSKILKENIPAKLSKIDNNALQNDRLYLYYLQNGKDMYTG DDLDIDRLSNYDIDHIIPQAFLKDNSIDNKVLVSSASNRGKSDDVPSLEVVKKRKTFWYQLLKS KLISQRKFDNLTKAERGGLSPEDKAGFIQRQLVETRQITKHVARLLDEKFNNKKDENNRAVRTV KIITLKSTLVSQFRKDFELYKVREINDFHHAHDAYLNAVVASALLKKYPKLEPEFVYGDYPKYN SFRERKSATEKVYFYSNIMNIFKKSISLADGRVIERPLIEVNEETGESVWNKESDLATVRRVLS YPQVNVVKKVEEQNHGLDRGKPKGLFNANLSSKPKPNSNENLVGAKEYLDPKKYGGYAGISNSF TVLVKGTIEKGAKKKITNVLEFQGISILDRINYRKDKLNFLLEKGYKDIELIIELPKYSLFELS DGSRRMLASILSTNNKRGEIHKGNQIFLSQKFVKLLYHAKRISNTINENHRKYVENHKKEFEEL FYYILEFNENYVGAKKNGKLLNSAFQSWQNHSIDELCSSFIGPTGSERKGLFELTSRGSAADFE FLGVKIPRYRDYTPSSLLKDATLIHQSVTGLYETRIDLAKLGEG SEQ ID NO: 326 MKKQKFSDYYLGFDIGTNSVGWCVTDLDYNVLRFNKKDMWGSRLFDEAKTAAERRVQRNSRRRL KRRKWRLNLLEEIFSDEIMKIDSNFFRRLKESSLWLEDKNSKEKFTLFNDDNYKDYDFYKQYPT IFHLRDELIKNPEKKDIRLIYLALHSIFKSRGHFLFEGQNLKEIKNFETLYNNLISFLEDNGIN KSIDKDNIEKLEKIICDSGKGLKDKEKEFKGIFNSDKQLVAIFKLSVGSSVSLNDLFDTDEYKK EEVEKEKISFREQIYEDDKPIYYSILGEKIELLDIAKSFYDFMVLNNILSDSNYISEAKVKLYE EHKKDLKNLKYIIRKYNKENYDKLFKDKNENNYPAYIGLNKEKDKKEVVEKSRLKIDDLIKVTK GYLPKPERIEEKDKTIFNEILNKIELKTILPKQRISDNGTLPYQIHEVELEKILENQSKYYDFL NYEENGVSTKDKLLKTFKFRIPYYVGPLNSYHKDKGGNSWIVRKEEGKILPWNFEQKVDIEKSA EEFIKRMTNKCTYLNGEDVIPKDSFLYSEYIILNELNKVQVNDEFLNEENKRKIIDELFKENKK VSEKKFKEYLLVNQIANRTVELKGIKDSFNSNYVSYIKFKDIFGEKLNLDIYKEISEKSILWKC LYGDDKKIFEKKIKNEYGDILNKDEIKKINSFKFNTWGRLSEKLLTGIEFINLETGECYSSVME ALRRTNYNLMELLSSKFTLQESIDNENKEMNEVSYRDLIEESYVSPSLKRAILQTLKIYEEIKK ITGRVPKKVFIEMARGGDESMKNKKIPARQEQLKKLYDSCGNDIANFSIDIKEMKNSLSSYDNN SLRQKKLYLYYLQFGKCMYTGREIDLDRLLQNNDTYDIDHIYPRSKVIKDDSFDNLVLVLKNEN AEKSNEYPVKKEIQEKMKSFWRFLKEKNFISDEKYKRLTGKDDFELRGFMARQLVNVRQTTKEV GKILQQIEPEIKIVYSKAEIASSFREMFDFIKVRELNDTHHAKDAYLNIVAGNVYNTKFTEKPY RYLQEIKENYDVKKIYNYDIKNAWDKENSLEIVKKNMEKNTVNITRFIKEEKGELFNLNPIKKG ETSNEIISIKPKLYDGKDNKLNEKYGYYTSLKAAYFIYVEHEKKNKKVKTFERITRIDSTLIKN EKNLIKYLVSQKKLLNPKIIKKIYKEQTLIIDSYPYTFTGVDSNKKVELKNKKQLYLEKKYEQI LKNALKFVEDNQGETEENYKFIYLKKRNNNEKNETIDAVKERYNIEFNEMYDKFLEKLSSKDYK NYINNKLYTNFLNSKEKFKKLKLWEKSLILREFLKIFNKNTYGKYEIKDSQTKEKLFSFPEDTG RIRLGQSSLGNNKELLEESVTGLFVKKIKL SEQ ID NO: 327 MKNYTIGLDIGVASVGWVCIDENYKILNYNNRHAFGVHEFESAESAAGRRLKRGMRRRYNRRKK RLQLLQSLFDSYITDSGFFSKTDSQHFWKNNNEFENRSLTEVLSSLRISSRKYPTIYHLRSDLI ESNKKMDLRLVYLALHNLVKYRGHFLQEGNWSEAASAEGMDDQLLELVTRYAELENLSPLDLSE SQWKAAETLLLNRNLTKTDQSKELTAMFGKEYEPFCKLVAGLGVSLHQLFPSSEQALAYKETKT KVQLSNENVEEVMELLLEEESALLEAVQPFYQQVVLYELLKGETYVAKAKVSAFKQYQKDMASL KNLLDKTFGEKVYRSYFISDKNSQREYQKSHKVEVLCKLDQFNKEAKFAETFYKDLKKLLEDKS KTSIGTTEKDEMLRIIKAIDSNQFLQKQKGIQNAAIPHQNSLYEAEKILRNQQAHYPFITTEWI EKVKQILAFRIPYYIGPLVKDTTQSPFSWVERKGDAPITPWNFDEQIDKAASAEAFISRMRKTC TYLKGQEVLPKSSLTYERFEVLNELNGIQLRTTGAESDFRHRLSYEMKCWIIDNVFKQYKTVST KRLLQELKKSPYADELYDEHTGEIKEVFGTQKENAFATSLSGYISMKSILGAVVDDNPAMTEEL IYWIAVFEDREILHLKIQEKYPSITDVQRQKLALVKLPGWGRFSRLLIDGLPLDEQGQSVLDHM EQYSSVFMEVLKNKGFGLEKKIQKMNQHQVDGTKKIRYEDIEELAGSPALKRGIWRSVKIVEEL VSIFGEPANIVLEVAREDGEKKRTKSRKDQWEELTKTTLKNDPDLKSFIGEIKSQGDQRFNEQR FWLYVTQQGKCLYTGKALDIQNLSMYEVDHILPQNFVKDDSLDNLALVMPEANQRKNQVGQNKM PLEIIEANQQYAMRTLWERLHELKLISSGKLGRLKKPSFDEVDKDKFIARQLVETRQIIKHVRD LLDERFSKSDIHLVKAGIVSKFRRFSEIPKIRDYNNKHHAMDALFAAALIQSILGKYGKNFLAF DLSKKDRQKQWRSVKGSNKEFFLFKNFGNLRLQSPVTGEEVSGVEYMKHVYFELPWQTTKMTQT GDGMFYKESIFSPKVKQAKYVSPKTEKFVHDEVKNHSICLVEFTFMKKEKEVQETKFIDLKVIE HHQFLKEPESQLAKFLAEKETNSPIIHARIIRTIPKYQKIWIEHFPYYFISTRELHNARQFEIS YELMEKVKQLSERSSVEELKIVFGLLIDQMNDNYPIYTKSSIQDRVQKFVDTQLYDFKSFEIGF EELKKAVAANAQRSDTFGSRISKKPKPEEVAIGYESITGLKYRKPRSVVGTKR SEQ ID NO: 328 MKKEIKDYFLGLDVGTGSVGWAVTDTDYKLLKANRKDLWGMRCFETAETAEVRRLHRGARRRIE RRKKRIKLLQELFSQEIAKTDEGFFQRMKESPFYAEDKTILQENTLFNDKDFADKTYHKAYPTI NHLIKAWIENKVKPDPRLLYLACHNIIKKRGHFLFEGDFDSENQFDTSIQALFEYLREDMEVDI DADSQKVKEILKDSSLKNSEKQSRLNKILGLKPSDKQKKAITNLISGNKINFADLYDNPDLKDA EKNSISFSKDDFDALSDDLASILGDSFELLLKAKAVYNCSVLSKVIGDEQYLSFAKVKIYEKHK TDLTKLKNVIKKHFPKDYKKVFGYNKNEKNNNNYSGYVGVCKTKSKKLIINNSVNQEDFYKFLK TILSAKSEIKEVNDILTEIETGTFLPKQISKSNAEIPYQLRKMELEKILSNAEKHFSFLKQKDE KGLSHSEKIIMLLTFKIPYYIGPINDNHKKFFPDRCWVVKKEKSPSGKTTPWNFFDHIDKEKTA EAFITSRTNFCTYLVGESVLPKSSLLYSEYTVLNEINNLQIIIDGKNICDIKLKQKIYEDLFKK YKKITQKQISTFIKHEGICNKTDEVIILGIDKECTSSLKSYIELKNIFGKQVDEISTKNMLEEI IRWATIYDEGEGKTILKTKIKAEYGKYCSDEQIKKILNLKFSGWGRLSRKFLETVTSEMPGFSE PVNIITAMRETQNNLMELLSSEFTFTENIKKINSGFEDAEKQFSYDGLVKPLFLSPSVKKMLWQ TLKLVKEISHITQAPPKKIFIEMAKGAELEPARTKTRLKILQDLYNNCKNDADAFSSEIKDLSG KIENEDNLRLRSDKLYLYYTQLGKCMYCGKPIEIGHVFDTSNYDIDHIYPQSKIKDDSISNRVL VCSSCNKNKEDKYPLKSEIQSKQRGFWNFLQRNNFISLEKLNRLTRATPISDDETAKFIARQLV ETRQATKVAAKVLEKMFPETKIVYSKAETVSMFRNKFDIVKCREINDFHHAHDAYLNIVVGNVY NTKFTNNPWNFIKEKRDNPKIADTYNYYKVFDYDVKRNNITAWEKGKTIITVKDMLKRNTPIYT RQAACKKGELFNQTIMKKGLGQHPLKKEGPFSNISKYGGYNKVSAAYYTLIEYEEKGNKIRSLE TIPLYLVKDIQKDQDVLKSYLTDLLGKKEFKILVPKIKINSLLKINGFPCHITGKTNDSFLLRP AVQFCCSNNEVLYFKKIIRFSEIRSQREKIGKTISPYEDLSFRSYIKENLWKKTKNDEIGEKEF YDLLQKKNLEIYDMLLTKHKDTIYKKRPNSATIDILVKGKEKFKSLIIENQFEVILEILKLFSA TRNVSDLQHIGGSKYSGVAKIGNKISSLDNCILIYQSITGIFEKRIDLLKV SEQ ID NO: 329 MEGQMKNNGNNLQQGNYYLGLDVGTSSVGWAVTDTDYNVLKFRGKSMWGARLFDEASTAEERRT HRGNRRRLARRKYRLLLLEQLFEKEIRKIDDNFFVRLHESNLWADDKSKPSKFLLFNDTNFTDK DYLKKYPTIYHLRSDLIHNSTEHDIRLVFLALHHLIKYRGHFIYDNSANGDVKTLDEAVSDFEE YLNENDIEFNIENKKEFINVLSDKHLTKKEKKISLKKLYGDITDSENINISVLIEMLSGSSISL SNLFKDIEFDGKQNLSLDSDIEETLNDVVDILGDNIDLLIHAKEVYDIAVLTSSLGKHKYLCDA KVELFEKNKKDLMILKKYIKKNHPEDYKKIFSSPTEKKNYAAYSQTNSKNVCSQEEFCLFIKPY IRDMVKSENEDEVRIAKEVEDKSFLTKLKGTNNSVVPYQIHERELNQILKNIVAYLPFMNDEQE DISVVDKIKLIFKFKIPYYVGPLNTKSTRSWVYRSDEKIYPWNFSNVIDLDKTAHEFMNRLIGR CTYTNDPVLPMDSLLYSKYNVLNEINPIKVNGKAIPVEVKQAIYTDLFENSKKKVTRKSIYIYL LKNGYIEKEDIVSGIDIEIKSKLKSHHDFTQIVQENKCTPEEIERIIKGILVYSDDKSMLRRWL KNNIKGLSENDVKYLAKLNYKEWGRLSKTLLTDIYTINPEDGEACSILDIMWNTNATLMEILSN EKYQFKQNIENYKAENYDEKQNLHEELDDMYISPAARRSIWQALRIVDEIVDIKKSAPKKIFIE MAREKKSAMKKKRTESRKDTLLELYKSCKSQADGFYDEELFEKLSNESNSRLRRDQLYLYYTQM GRSMYTGKRIDFDKLINDKNTYDIDHIYPRSKIKDDSITNRVLVEKDINGEKTDIYPISEDIRQ KMQPFWKILKEKGLINEEKYKRLTRNYELTDEELSSFVARQLVETQQSTKALATLLKKEYPSAK IVYSKAGNVSEFRNRKDKELPKFREINDLHHAKDAYLNIVVGNVYDTKFTEKFFNNIRNENYSL KRVFDFSVPGAWDAKGSTFNTIKKYMAKNNPIIAFAPYEVKGELFDQQIVPKGKGQFPIKQGKD IEKYGGYNKLSSAFLFAVEYKGKKARERSLETVYIKDVELYLQDPIKYCESVLGLKEPQIIKPK ILMGSLFSINNKKLVVTGRSGKQYVCHHIYQLSINDEDSQYLKNIAKYLQEEPDGNIERQNILN ITSVNNIKLFDVLCTKFNSNTYEIILNSLKNDVNEGREKFSELDILEQCNILLQLLKAFKCNRE SSNLEKLNNKKQAGVIVIPHLFTKCSVFKVIHQSITGLFEKEMDLLK SEQ ID NO: 330 MGRKPYILSLDIGTGSVGYACMDKGFNVLKYHDKDALGVYLFDGALTAQERRQFRTSRRRKNRR IKRLGLLQELLAPLVQNPNFYQFQRQFAWKNDNMDFKNKSLSEVLSFLGYESKKYPTIYHLQEA LLLKDEKFDPELIYMALYHLVKYRGHFLFDHLKIENLTNNDNMHDFVELIETYENLNNIKLNLD YEKTKVIYEILKDNEMTKNDRAKRVKNMEKKLEQFSIMLLGLKFNEGKLFNHADNAEELKGANQ SHTFADNYEENLTPFLTVEQSEFIERANKIYLSLTLQDILKGKKSMAMSKVAAYDKFRNELKQV KDIVYKADSTRTQFKKIFVSSKKSLKQYDATPNDQTFSSLCLFDQYLIRPKKQYSLLIKELKKI IPQDSELYFEAENDTLLKVLNTTDNASIPMQINLYEAETILRNQQKYHAEITDEMIEKVLSLIQ FRIPYYVGPLVNDHTASKFGWMERKSNESIKPWNFDEVVDRSKSATQFIRRMTNKCSYLINEDV LPKNSLLYQEMEVLNELNATQIRLQTDPKNRKYRMMPQIKLFAVEHIFKKYKTVSHSKFLEIML NSNHRENFMNHGEKLSIFGTQDDKKFASKLSSYQDMTKIFGDIEGKRAQIEEIIQWITIFEDKK ILVQKLKECYPELTSKQINQLKKLNYSGWGRLSEKLLTHAYQGHSIIELLRHSDENFMEILTND VYGFQNFIKEENQVQSNKIQHQDIANLTTSPALKKGIWSTIKLVRELTSIFGEPEKIIMEFATE DQQKGKKQKSRKQLWDDNIKKNKLKSVDEYKYIIDVANKLNNEQLQQEKLWLYLSQNGKCMYSG QSIDLDALLSPNATKHYEVDHIFPRSFIKDDSIDNKVLVIKKMNQTKGDQVPLQFIQQPYERIA YWKSLNKAGLISDSKLHKLMKPEFTAMDKEGFIQRQLVETRQISVHVRDFLKEEYPNTKVIPMK AKMVSEFRKKFDIPKIRQMNDAHHAIDAYLNGVVYHGAQLAYPNVDLFDFNFKWEKVREKWKAL GEFNTKQKSRELFFFKKLEKMEVSQGERLISKIKLDMNHFKINYSRKLANIPQQFYNQTAVSPK TAELKYESNKSNEVVYKGLTPYQTYVVAIKSVNKKGKEKMEYQMIDHYVFDFYKFQNGNEKELA LYLAQRENKDEVLDAQIVYSLNKGDLLYINNHPCYFVSRKEVINAKQFELTVEQQLSLYNVMNN KETNVEKLLIEYDFIAEKVINEYHHYLNSKLKEKRVRTFFSESNQTHEDFIKALDELFKVVTAS ATRSDKIGSRKNSMTHRAFLGKGKDVKIAYTSISGLKTTKPKSLFKLAESRNEL SEQ ID NO: 331 MAKILGLDLGTNSIGWAVVERENIDFSLIDKGVRIFSEGVKSEKGIESSRAAERTGYRSARKIK YRRKLRKYETLKVLSLNRMCPLSIEEVEEWKKSGFKDYPLNPEFLKWLSTDEESNVNPYFFRDR ASKHKVSLFELGRAFYHIAQRRGFLSNRLDQSAEGILEEHCPKIEAIVEDLISIDEISTNITDY FFETGILDSNEKNGYAKDLDEGDKKLVSLYKSLLAILKKNESDFENCKSEIIERLNKKDVLGKV KGKIKDISQAMLDGNYKTLGQYFYSLYSKEKIRNQYTSREEHYLSEFITICKVQGIDQINEEEK INEKKFDGLAKDLYKAIFFQRPLKSQKGLIGKCSFEKSKSRCAISHPDFEEYRMWTYLNTIKIG TQSDKKLRFLTQDEKLKLVPKFYRKNDFNFDVLAKELIEKGSSFGFYKSSKKNDFFYWFNYKPT DTVAACQVAASLKNAIGEDWKTKSFKYQTINSNKEQVSRTVDYKDLWHLLTVATSDVYLYEFAI DKLGLDEKNAKAFSKTKLKKDFASLSLSAINKILPYLKEGLLYSHAVFVANIENIVDENIWKDE KQRDYIKTQISEIIENYTLEKSRFEIINGLLKEYKSENEDGKRVYYSKEAEQSFENDLKKKLVL FYKSNEIENKEQQETIFNELLPIFIQQLKDYEFIKIQRLDQKVLIFLKGKNETGQIFCTEEKGT AEEKEKKIKNRLKKLYHPSDIEKFKKKIIKDEFGNEKIVLGSPLTPSIKNPMAMRALHQLRKVL NALILEGQIDEKTIIHIEMARELNDANKRKGIQDYQNDNKKFREDAIKEIKKLYFEDCKKEVEP TEDDILRYQLWMEQNRSEIYEEGKNISICDIIGSNPAYDIEHTIPRSRSQDNSQMNKTLCSQRF NREVKKQSMPIELNNHLEILPRIAHWKEEADNLTREIEIISRSIKAAATKEIKDKKIRRRHYLT LKRDYLQGKYDRFIWEEPKVGFKNSQIPDTGIITKYAQAYLKSYFKKVESVKGGMVAEFRKIWG IQESFIDENGMKHYKVKDRSKHTHHTIDAITIACMTKEKYDVLAHAWTLEDQQNKKEARSIIEA SKPWKTFKEDLLKIEEEILVSHYTPDNVKKQAKKIVRVRGKKQFVAEVERDVNGKAVPKKAASG KTIYKLDGEGKKLPRLQQGDTIRGSLHQDSIYGAIKNPLNTDEIKYVIRKDLESIKGSDVESIV DEVVKEKIKEAIANKVLLLSSNAQQKNKLVGTVWMNEEKRIAINKVRIYANSVKNPLHIKEHSL LSKSKHVHKQKVYGQNDENYAMAIYELDGKRDFELINIFNLAKLIKQGQGFYPLHKKKEIKGKI VFVPIEKRNKRDVVLKRGQQVVFYDKEVENPKDISEIVDFKGRIYIIEGLSIQRIVRPSGKVDE YGVIMLRYFKEARKADDIKQDNFKPDGVFKLGENKPTRKMNHQFTAFVEGIDFKVLPSGKFEKI SEQ ID NO: 332 MEFKKVLGLDIGTNSIGCALLSLPKSIQDYGKGGRLEWLTSRVIPLDADYMKAFIDGKNGLPQV ITPAGKRRQKRGSRRLKHRYKLRRSRLIRVFKTLNWLPEDFPLDNPKRIKETISTEGKFSFRIS DYVPISDESYREFYREFGYPENEIEQVIEEINFRRKTKGKNKNPMIKLLPEDWVVYYLRKKALI KPTTKEELIRIIYLFNQRRGFKSSRKDLTETAILDYDEFAKRLAEKEKYSAENYETKFVSITKV KEVVELKTDGRKGKKRFKVILEDSRIEPYEIERKEKPDWEGKEYTFLVTQKLEKGKFKQNKPDL PKEEDWALCTTALDNRMGSKHPGEFFFDELLKAFKEKRGYKIRQYPVNRWRYKKELEFIWTKQC QLNPELNNLNINKEILRKLATVLYPSQSKFFGPKIKEFENSDVLHIISEDIIYYQRDLKSQKSL ISECRYEKRKGIDGEIYGLKCIPKSSPLYQEFRIWQDIHNIKVIRKESEVNGKKKINIDETQLY INENIKEKLFELFNSKDSLSEKDILELISLNIINSGIKISKKEEETTHRINLFANRKELKGNET KSRYRKVFKKLGFDGEYILNHPSKLNRLWHSDYSNDYADKEKTEKSILSSLGWKNRNGKWEKSK NYDVFNLPLEVAKAIANLPPLKKEYGSYSALAIRKMLVVMRDGKYWQHPDQIAKDQENTSLMLF DKNLIQLTNNQRKVLNKYLLTLAEVQKRSTLIKQKLNEIEHNPYKLELVSDQDLEKQVLKSFLE KKNESDYLKGLKTYQAGYLIYGKHSEKDVPIVNSPDELGEYIRKKLPNNSLRNPIVEQVIRETI FIVRDVWKSFGIIDEIHIELGRELKNNSEERKKTSESQEKNFQEKERARKLLKELLNSSNFEHY DENGNKIFSSFTVNPNPDSPLDIEKFRIWKNQSGLTDEELNKKLKDEKIPTEIEVKKYILWLTQ KCRSPYTGKIIPLSKLFDSNVYEIEHIIPRSKMKNDSTNNLVICELGVNKAKGDRLAANFISES NGKCKFGEVEYTLLKYGDYLQYCKDTFKYQKAKYKNLLATEPPEDFIERQINDTRYIGRKLAEL LTPVVKDSKNIIFTIGSITSELKITWGLNGVWKDILRPRFKRLESIINKKLIFQDEDDPNKYHF DLSINPQLDKEGLKRLDHRHHALDATIIAATTREHVRYLNSLNAADNDEEKREYFLSLCNHKIR DFKLPWENFTSEVKSKLLSCVVSYKESKPILSDPFNKYLKWEYKNGKWQKVFAIQIKNDRWKAV RRSMFKEPIGTVWIKKIKEVSLKEAIKIQAIWEEVKNDPVRKKKEKYIYDDYAQKVIAKIVQEL GLSSSMRKQDDEKLNKFINEAKVSAGVNKNLNTTNKTIYNLEGRFYEKIKVAEYVLYKAKRMPL NKKEYIEKLSLQKMFNDLPNFILEKSILDNYPEILKELESDNKYIIEPHKKNNPVNRLLLEHIL EYHNNPKEAFSTEGLEKLNKKAINKIGKPIKYITRLDGDINEEEIFRGAVFETDKGSNVYFVMY ENNQTKDREFLKPNPSISVLKAIEHKNKIDFFAPNRLGFSRIILSPGDLVYVPTNDQYVLIKDN SSNETIINWDDNEFISNRIYQVKKFTGNSCYFLKNDIASLILSYSASNGVGEFGSQNISEYSVD DPPIRIKDVCIKIRVDRLGNVRPL SEQ ID NO: 333 MKHILGLDLGTNSIGWALIERNIEEKYGKIIGMGSRIVPMGAELSKFEQGQAQTKNADRRTNRG ARRLNKRYKQRRNKLIYILQKLDMLPSQIKLKEDFSDPNKIDKITILPISKKQEQLTAFDLVSL RVKALTEKVGLEDLGKIIYKYNQLRGYAGGSLEPEKEDIFDEEQSKDKKNKSFIAFSKIVFLGE PQEEIFKNKKLNRRAIIVETEEGNFEGSTFLENIKVGDSLELLINISASKSGDTITIKLPNKTN WRKKMENIENQLKEKSKEMGREFYISEFLLELLKENRWAKIRNNTILRARYESEFEAIWNEQVK HYPFLENLDKKTLIEIVSFIFPGEKESQKKYRELGLEKGLKYIIKNQVVFYQRELKDQSHLISD CRYEPNEKAIAKSHPVFQEYKVWEQINKLIVNTKIEAGTNRKGEKKYKYIDRPIPTALKEWIFE ELQNKKEITFSAIFKKLKAEFDLREGIDFLNGMSPKDKLKGNETKLQLQKSLGELWDVLGLDSI NRQIELWNILYNEKGNEYDLTSDRTSKVLEFINKYGNNIVDDNAEETAIRISKIKFARAYSSLS LKAVERILPLVRAGKYFNNDFSQQLQSKILKLLNENVEDPFAKAAQTYLDNNQSVLSEGGVGNS IATILVYDKHTAKEYSHDELYKSYKEINLLKQGDLRNPLVEQIINEALVLIRDIWKNYGIKPNE IRVELARDLKNSAKERATIHKRNKDNQTINNKIKETLVKNKKELSLANIEKVKLWEAQRHLSPY TGQPIPLSDLFDKEKYDVDHIIPISRYFDDSFTNKVISEKSVNQEKANRTAMEYFEVGSLKYSI FTKEQFIAHVNEYFSGVKRKNLLATSIPEDPVQRQIKDTQYIAIRVKEELNKIVGNENVKTTTG SITDYLRNHWGLTDKFKLLLKERYEALLESEKFLEAEYDNYKKDFDSRKKEYEEKEVLFEEQEL TREEFIKEYKENYIRYKKNKLIIKGWSKRIDHRHHAIDALIVACTEPAHIKRLNDLNKVLQDWL VEHKSEFMPNFEGSNSELLEEILSLPENERTEIFTQIEKFRAIEMPWKGFPEQVEQKLKEIIIS HKPKDKLLLQYNKAGDRQIKLRGQLHEGTLYGISQGKEAYRIPLTKFGGSKFATEKNIQKIVSP FLSGFIANHLKEYNNKKEEAFSAEGIMDLNNKLAQYRNEKGELKPHTPISTVKIYYKDPSKNKK KKDEEDLSLQKLDREKAFNEKLYVKTGDNYLFAVLEGEIKTKKTSQIKRLYDIISFFDATNFLK EEFRNAPDKKTFDKDLLFRQYFEERNKAKLLFTLKQGDFVYLPNENEEVILDKESPLYNQYWGD LKERGKNIYVVQKFSKKQIYFIKHTIADIIKKDVEFGSQNCYETVEGRSIKENCFKLEIDRLGN IVKVIKR SEQ ID NO: 334 MHVEIDFPHFSRGDSHLAMNKNEILRGSSVLYRLGLDLGSNSLGWFVTHLEKRGDRHEPVALGP GGVRIFPDGRDPQSGTSNAVDRRMARGARKRRDRFVERRKELIAALIKYNLLPDDARERRALEV LDPYALRKTALTDTLPAHHVGRALFHLNQRRGFQSNRKTDSKQSEDGAIKQAASRLATDKGNET LGVFFADMHLRKSYEDRQTAIRAELVRLGKDHLTGNARKKIWAKVRKRLFGDEVLPRADAPHGV RARATITGTKASYDYYPTRDMLRDEFNAIWAGQSAHHATITDEARTEIEHIIFYQRPLKPAIVG KCTLDPATRPFKEDPEGYRAPWSHPLAQRFRILSEARNLEIRDTGKGSRRLTKEQSDLVVAALL ANREVKFDKLRTLLKLPAEARFNLESDRRAALDGDQTAARLSDKKGFNKAWRGFPPERQIAIVA RLEETEDENELIAWLEKECALDGAAAARVANTTLPDGHCRLGLRAIKKIVPIMQDGLDEDGVAG AGYHIAAKRAGYDHAKLPTGEQLGRLPYYGQWLQDAVVGSGDARDQKEKQYGQFPNPTVHIGLG QLRRVVNDLIDKYGPPTEISIEFTRALKLSEQQKAERQREQRRNQDKNKARAEELAKFGRPANP RNLLKMRLWEELAHDPLDRKCVYTGEQISIERLLSDEVDIDHILPVAMTLDDSPANKIICMRYA NRHKRKQTPSEAFGSSPTLQGHRYNWDDIAARATGLPRNKRWRFDANAREEFDKRGGFLARQLN ETGWLARLAKQYLGAVTDPNQIWVVPGRLTSMLRGKWGLNGLLPSDNYAGVQDKAEEFLASTDD MEFSGVKNRADHRHHAIDGLVTALTDRSLLWKMANAYDEEHEKFVIEPPWPTMRDDLKAALEKM VVSHKPDHGIEGKLHEDSAYGFVKPLDATGLKEEEAGNLVYRKAIESLNENEVDRIRDIQLRTI VRDHVNVEKTKGVALADALRQLQAPSDDYPQFKHGLRHVRILKKEKGDYLVPIANRASGVAYKA YSAGENFCVEVFETAGGKWDGEAVRRFDANKKNAGPKIAHAPQWRDANEGAKLVMRIHKGDLIR LDHEGRARIMVVHRLDAAAGRFKLADHNETGNLDKRHATNNDIDPFRWLMASYNTLKKLAAVPV RVDELGRVWRVMPN SEQ ID NO: 335 METTLGIDLGTNSIGLALVDQEEHQILYSGVRIFPEGINKDTIGLGEKEESRNATRRAKRQMRR QYFRKKLRKAKLLELLIAYDMCPLKPEDVRRWKNWDKQQKSTVRQFPDTPAFREWLKQNPYELR KQAVTEDVTRPELGRILYQMIQRRGFLSSRKGKEEGKIFTGKDRMVGIDETRKNLQKQTLGAYL YDIAPKNGEKYRFRTERVRARYTLRDMYIREFEIIWQRQAGHLGLAHEQATRKKNIFLEGSATN VRNSKLITHLQAKYGRGHVLIEDTRITVTFQLPLKEVLGGKIEIEEEQLKFKSNESVLFWQRPL RSQKSLLSKCVFEGRNFYDPVHQKWIIAGPTPAPLSHPEFEEFRAYQFINNIIYGKNEHLTAIQ REAVFELMCTESKDFNFEKIPKHLKLFEKFNFDDTTKVPACTTISQLRKLFPHPVWEEKREEIW HCFYFYDDNTLLFEKLQKDYALQTNDLEKIKKIRLSESYGNVSLKAIRRINPYLKKGYAYSTAV LLGGIRNSFGKRFEYFKEYEPEIEKAVCRILKEKNAEGEVIRKIKDYLVHNRFGFAKNDRAFQK LYHHSQAITTQAQKERLPETGNLRNPIVQQGLNELRRTVNKLLATCREKYGPSFKFDHIHVEMG RELRSSKTEREKQSRQIRENEKKNEAAKVKLAEYGLKAYRDNIQKYLLYKEIEEKGGTVCCPYT GKTLNISHTLGSDNSVQIEHIIPYSISLDDSLANKTLCDATFNREKGELTPYDFYQKDPSPEKW GASSWEEIEDRAFRLLPYAKAQRFIRRKPQESNEFISRQLNDTRYISKKAVEYLSAICSDVKAF PGQLTAELRHLWGLNNILQSAPDITFPLPVSATENHREYYVITNEQNEVIRLFPKQGETPRTEK GELLLTGEVERKVFRCKGMQEFQTDVSDGKYWRRIKLSSSVTWSPLFAPKPISADGQIVLKGRI EKGVFVCNQLKQKLKTGLPDGSYWISLPVISQTFKEGESVNNSKLTSQQVQLFGRVREGIFRCH NYQCPASGADGNFWCTLDTDTAQPAFTPIKNAPPGVGGGQIILTGDVDDKGIFHADDDLHYELP ASLPKGKYYGIFTVESCDPTLIPIELSAPKTSKGENLIEGNIWVDEHTGEVRFDPKKNREDQRH HAIDAIVIALSSQSLFQRLSTYNARRENKKRGLDSTEHFPSPWPGFAQDVRQSVVPLLVSYKQN PKTLCKISKTLYKDGKKIHSCGNAVRGQLHKETVYGQRTAPGATEKSYHIRKDIRELKTSKHIG KVVDITIRQMLLKHLQENYHIDITQEFNIPSNAFFKEGVYRIFLPNKHGEPVPIKKIRMKEELG NAERLKDNINQYVNPRNNHHVMIYQDADGNLKEEIVSFWSVIERQNQGQPIYQLPREGRNIVSI LQINDTFLIGLKEEEPEVYRNDLSTLSKHLYRVQKLSGMYYTFRHHLASTLNNEREEFRIQSLE AWKRANPVKVQIDEIGRITFLNGPLC SEQ ID NO: 336 MESSQILSPIGIDLGGKFTGVCLSHLEAFAELPNHANTKYSVILIDHNNFQLSQAQRRATRHRV RNKKRNQFVKRVALQLFQHILSRDLNAKEETALCHYLNNRGYTYVDTDLDEYIKDETTINLLKE LLPSESEHNFIDWFLQKMQSSEFRKILVSKVEEKKDDKELKNAVKNIKNFITGFEKNSVEGHRH RKVYFENIKSDITKDNQLDSIKKKIPSVCLSNLLGHLSNLQWKNLHRYLAKNPKQFDEQTFGNE FLRMLKNFRHLKGSQESLAVRNLIQQLEQSQDYISILEKTPPEITIPPYEARTNTGMEKDQSLL LNPEKLNNLYPNWRNLIPGIIDAHPFLEKDLEHTKLRDRKRIISPSKQDEKRDSYILQRYLDLN KKIDKFKIKKQLSFLGQGKQLPANLIETQKEMETHFNSSLVSVLIQIASAYNKEREDAAQGIWF DNAFSLCELSNINPPRKQKILPLLVGAILSEDFINNKDKWAKFKIFWNTHKIGRTSLKSKCKEI EEARKNSGNAFKIDYEEALNHPEHSNNKALIKIIQTIPDIIQAIQSHLGHNDSQALIYHNPFSL SQLYTILETKRDGFHKNCVAVTCENYWRSQKTEIDPEISYASRLPADSVRPFDGVLARMMQRLA YEIAMAKWEQIKHIPDNSSLLIPIYLEQNRFEFEESFKKIKGSSSDKTLEQAIEKQNIQWEEKF QRIINASMNICPYKGASIGGQGEIDHIYPRSLSKKHFGVIFNSEVNLIYCSSQGNREKKEEHYL LEHLSPLYLKHQFGTDNVSDIKNFISQNVANIKKYISFHLLTPEQQKAARHALFLDYDDEAFKT ITKFLMSQQKARVNGTQKFLGKQIMEFLSTLADSKQLQLEFSIKQITAEEVHDHRELLSKQEPK LVKSRQQSFPSHAIDATLTMSIGLKEFPQFSQELDNSWFINHLMPDEVHLNPVRSKEKYNKPNI SSTPLFKDSLYAERFIPVWVKGETFAIGFSEKDLFEIKPSNKEKLFTLLKTYSTKNPGESLQEL QAKSKAKWLYFPINKTLALEFLHHYFHKEIVTPDDTTVCHFINSLRYYTKKESITVKILKEPMP VLSVKFESSKKNVLGSFKHTIALPATKDWERLFNHPNFLALKANPAPNPKEFNEFIRKYFLSDN NPNSDIPNNGHNIKPQKHKAVRKVFSLPVIPGNAGTMMRIRRKDNKGQPLYQLQTIDDTPSMGI QINEDRLVKQEVLMDAYKTRNLSTIDGINNSEGQAYATFDNWLTLPVSTFKPEIIKLEMKPHSK TRRYIRITQSLADFIKTIDEALMIKPSDSIDDPLNMPNEIVCKNKLFGNELKPRDGKMKIVSTG KIVTYEFESDSTPQWIQTLYVTQLKKQP SEQ ID NO: 337 MKKIVGLDLGTNSIGWALINAYINKEHLYGIEACGSRIIPMDAAILGNFDKGNSISQTADRTSY RGIRRLRERHLLRRERLHRILDLLGFLPKHYSDSLNRYGKFLNDIECKLPWVKDETGSYKFIFQ ESFKEMLANFTEHHPILIANNKKVPYDWTIYYLRKKALTQKISKEELAWILLNFNQKRGYYQLR GEEEETPNKLVEYYSLKVEKVEDSGERKGKDTWYNVHLENGMIYRRTSNIPLDWEGKTKEFIVT TDLEADGSPKKDKEGNIKRSFRAPKDDDWTLIKKKTEADIDKIKMTVGAYIYDTLLQKPDQKIR GKLVRTIERKYYKNELYQILKTQSEFHEELRDKQLYIACLNELYPNNEPRRNSISTRDFCHLFI EDIIFYQRPLKSKKSLIDNCPYEENRYIDKESGEIKHASIKCIAKSHPLYQEFRLWQFIVNLRI YRKETDVDVTQELLPTEADYVTLFEWLNEKKEIDQKAFFKYPPFGFKKTTSNYRWNYVEDKPYP CNETHAQIIARLGKAHIPKAFLSKEKEETLWHILYSIEDKQEIEKALHSFANKNNLSEEFIEQF KNFPPFKKEYGSYSAKAIKKLLPLMRMGKYWSIENIDNGTRIRINKIIDGEYDENIRERVRQKA INLTDITHFRALPLWLACYLVYDRHSEVKDIVKWKTPKDIDLYLKSFKQHSLRNPIVEQVITET LRTVRDIWQQVGHIDEIHIELGREMKNPADKRARMSQQMIKNENTNLRIKALLTEFLNPEFGIE NVRPYSPSQQDLLRIYEEGVLNSILELPEDIGIILGKFNQTDTLKRPTRSEILRYKLWLEQKYR SPYTGEMIPLSKLFTPAYEIEHIIPQSRYFDDSLSNKVICESEINKLKDRSLGYEFIKNHHGEK VELAFDKPVEVLSVEAYEKLVHESYSHNRSKMKKLLMEDIPDQFIERQLNDSRYISKVVKSLLS NIVREENEQEAISKNVIPCTGGITDRLKKDWGINDVWNKIVLPRFIRLNELTESTRFTSINTNN TMIPSMPLELQKGFNKKRIDHRHHAMDAIIIACANRNIVNYLNNVSASKNTKITRRDLQTLLCH KDKTDNNGNYKWVIDKPWETFTQDTLTALQKITVSFKQNLRVINKTTNHYQHYENGKKIVSNQS KGDSWAIRKSMHKETVHGEVNLRMIKTVSFNEALKKPQAIVEMDLKKKILAMLELGYDTKRIKN YFEENKDTWQDINPSKIKVYYFTKETKDRYFAVRKPIDTSFDKKKIKESITDTGIQQIMLRHLE TKDNDPTLAFSPDGIDEMNRNILILNKGKKHQPIYKVRVYEKAEKFTVGQKGNKRTKFVEAAKG TNLFFAIYETEEIDKDTKKVIRKRSYSTIPLNVVIERQKQGLSSAPEDENGNLPKYILSPNDLV YVPTQEEINKGEVVMPIDRDRIYKMVDSSGITANFIPASTANLIFALPKATAEIYCNGENCIQN EYGIGSPQSKNQKAITGEMVKEICFPIKVDRLGNIIQVGSCILTN SEQ ID NO: 338 MSRSLTFSFDIGYASIGWAVIASASHDDADPSVCGCGTVLFPKDDCQAFKRREYRRLRRNIRSR RVRIERIGRLLVQAQIITPEMKETSGHPAPFYLASEALKGHRTLAPIELWHVLRWYAHNRGYDN NASWSNSLSEDGGNGEDTERVKHAQDLMDKHGTATMAETICRELKLEEGKADAPMEVSTPAYKN LNTAFPRLIVEKEVRRILELSAPLIPGLTAEIIELIAQHHPLTTEQRGVLLQHGIKLARRYRGS LLFGQLIPRFDNRIISRCPVTWAQVYEAELKKGNSEQSARERAEKLSKVPTANCPEFYEYRMAR ILCNIRADGEPLSAEIRRELMNQARQEGKLTKASLEKAISSRLGKETETNVSNYFTLHPDSEEA LYLNPAVEVLQRSGIGQILSPSVYRIAANRLRRGKSVTPNYLLNLLKSRGESGEALEKKIEKES KKKEADYADTPLKPKYATGRAPYARTVLKKVVEEILDGEDPTRPARGEAHPDGELKAHDGCLYC LLDTDSSVNQHQKERRLDTMTNNHLVRHRMLILDRLLKDLIQDFADGQKDRISRVCVEVGKELT TFSAMDSKKIQRELTLRQKSHTDAVNRLKRKLPGKALSANLIRKCRIAMDMNWTCPFTGATYGD HELENLELEHIVPHSFRQSNALSSLVLTWPGVNRMKGQRTGYDFVEQEQENPVPDKPNLHICSL NNYRELVEKLDDKKGHEDDRRRKKKRKALLMVRGLSHKHQSQNHEAMKEIGMTEGMMTQSSHLM KLACKSIKTSLPDAHIDMIPGAVTAEVRKAWDVFGVFKELCPEAADPDSGKILKENLRSLTHLH HALDACVLGLIPYIIPAHHNGLLRRVLAMRRIPEKLIPQVRPVANQRHYVLNDDGRMMLRDLSA SLKENIREQLMEQRVIQHVPADMGGALLKETMQRVLSVDGSGEDAMVSLSKKKDGKKEKNQVKA SKLVGVFPEGPSKLKALKAAIEIDGNYGVALDPKPVVIRHIKVFKRIMALKEQNGGKPVRILKK GMLIHLTSSKDPKHAGVWRIESIQDSKGGVKLDLQRAHCAVPKNKTHECNWREVDLISLLKKYQ MKRYPTSYTGTPR SEQ ID NO: 339 MTQKVLGLDLGTNSIGSAVRNLDLSDDLQWQLEFFSSDIFRSSVNKESNGREYSLAAQRSAHRR SRGLNEVRRRRLWATLNLLIKHGFCPMSSESLMRWCTYDKRKGLFREYPIDDKDFNAWILLDFN GDGRPDYSSPYQLRRELVTRQFDFEQPIERYKLGRALYHIAQHRGFKSSKGETLSQQETNSKPS STDEIPDVAGAMKASEEKLSKGLSTYMKEHNLLTVGAAFAQLEDEGVRVRNNNDYRAIRSQFQH EIETIFKFQQGLSVESELYERLISEKKNVGTIFYKRPLRSQRGNVGKCTLERSKPRCAIGHPLF EKFRAWTLINNIKVRMSVDTLDEQLPMKLRLDLYNECFLAFVRTEFKFEDIRKYLEKRLGIHFS YNDKTINYKDSTSVAGCPITARFRKMLGEEWESFRVEGQKERQAHSKNNISFHRVSYSIEDIWH FCYDAEEPEAVLAFAQETLRLERKKAEELVRIWSAMPQGYAMLSQKAIRNINKILMLGLKYSDA VILAKVPELVDVSDEELLSIAKDYYLVEAQVNYDKRINSIVNGLIAKYKSVSEEYRFADHNYEY LLDESDEKDIIRQIENSLGARRWSLMDANEQTDILQKVRDRYQDFFRSHERKFVESPKLGESFE NYLTKKFPMVEREQWKKLYHPSQITIYRPVSVGKDRSVLRLGNPDIGAIKNPTVLRVLNTLRRR VNQLLDDGVISPDETRVVVETARELNDANRKWALDTYNRIRHDENEKIKKILEEFYPKRDGIST DDIDKARYVIDQREVDYFTGSKTYNKDIKKYKFWLEQGGQCMYTGRTINLSNLFDPNAFDIEHT IPESLSFDSSDMNLTLCDAHYNRFIKKNHIPTDMPNYDKAITIDGKEYPAITSQLQRWVERVER LNRNVEYWKGQARRAQNKDRKDQCMREMHLWKMELEYWKKKLERFTVTEVTDGFKNSQLVDTRV ITRHAVLYLKSIFPHVDVQRGDVTAKFRKILGIQSVDEKKDRSLHSHHAIDATTLTIIPVSAKR DRMLELFAKIEEINKMLSFSGSEDRTGLIQELEGLKNKLQMEVKVCRIGHNVSEIGTFINDNII VNHHIKNQALTPVRRRLRKKGYIVGGVDNPRWQTGDALRGEIHKASYYGAITQFAKDDEGKVLM KEGRPQVNPTIKFVIRRELKYKKSAADSGFASWDDLGKAIVDKELFALMKGQFPAETSFKDACE QGIYMIKKGKNGMPDIKLHHIRHVRCEAPQSGLKIKEQTYKSEKEYKRYFYAAVGDLYAMCCYT NGKIREFRIYSLYDVSCHRKSDIEDIPEFITDKKGNRLMLDYKLRTGDMILLYKDNPAELYDLD NVNLSRRLYKINRFESQSNLVLMTHHLSTSKERGRSLGKTVDYQNLPESIRSSVKSLNFLIMGE NRDFVIKNGKIIFNHR SEQ ID NO: 340 MLVSPISVDLGGKNTGFFSFTDSLDNSQSGTVIYDESFVLSQVGRRSKRHSKRNNLRNKLVKRL FLLILQEHHGLSIDVLPDEIRGLFNKRGYTYAGFELDEKKKDALESDTLKEFLSEKLQSIDRDS DVEDFLNQIASNAESFKDYKKGFEAVFASATHSPNKKLELKDELKSEYGENAKELLAGLRVTKE ILDEFDKQENQGNLPRAKYFEELGEYIATNEKVKSFFDSNSLKLTDMTKLIGNISNYQLKELRR YFNDKEMEKGDIWIPNKLHKITERFVRSWHPKNDADRQRRAELMKDLKSKEIMELLTTTEPVMT IPPYDDMNNRGAVKCQTLRLNEEYLDKHLPNWRDIAKRLNHGKFNDDLADSTVKGYSEDSTLLH RLLDTSKEIDIYELRGKKPNELLVKTLGQSDANRLYGFAQNYYELIRQKVRAGIWVPVKNKDDS LNLEDNSNMLKRCNHNPPHKKNQIHNLVAGILGVKLDEAKFAEFEKELWSAKVGNKKLSAYCKN IEELRKTHGNTFKIDIEELRKKDPAELSKEEKAKLRLTDDVILNEWSQKIANFFDIDDKHRQRF NNLFSMAQLHTVIDTPRSGFSSTCKRCTAENRFRSETAFYNDETGEFHKKATATCQRLPADTQR PFSGKIERYIDKLGYELAKIKAKELEGMEAKEIKVPIILEQNAFEYEESLRKSKTGSNDRVINS KKDRDGKKLAKAKENAEDRLKDKDKRIKAFSSGICPYCGDTIGDDGEIDHILPRSHTLKIYGTV FNPEGNLIYVHQKCNQAKADSIYKLSDIKAGVSAQWIEEQVANIKGYKTFSVLSAEQQKAFRYA LFLQNDNEAYKKVVDWLRTDQSARVNGTQKYLAKKIQEKLTKMLPNKHLSFEFILADATEVSEL RRQYARQNPLLAKAEKQAPSSHAIDAVMAFVARYQKVFKDGTPPNADEVAKLAMLDSWNPASNE PLTKGLSTNQKIEKMIKSGDYGQKNMREVFGKSIFGENAIGERYKPIVVQEGGYYIGYPATVKK GYELKNCKVVTSKNDIAKLEKIIKNQDLISLKENQYIKIFSINKQTISELSNRYFNMNYKNLVE RDKEIVGLLEFIVENCRYYTKKVDVKFAPKYIHETKYPFYDDWRRFDEAWRYLQENQNKTSSKD RFVIDKSSLNEYYQPDKNEYKLDVDTQPIWDDFCRWYFLDRYKTANDKKSIRIKARKTFSLLAE SGVQGKVFRAKRKIPTGYAYQALPMDNNVIAGDYANILLEANSKTLSLVPKSGISIEKQLDKKL DVIKKTDVRGLAIDNNSFFNADFDTHGIRLIVENTSVKVGNFPISAIDKSAKRMIFRALFEKEK GKRKKKTTISFKESGPVQDYLKVFLKKIVKIQLRTDGSISNIVVRKNAADFTLSFRSEHIQKLL K SEQ ID NO: 341 MAYRLGLDIGITSVGWAVVALEKDESGLKPVRIQDLGVRIFDKAEDSKTGASLALPRREARSAR RRTRRRRHRLWRVKRLLEQHGILSMEQIEALYAQRTSSPDVYALRVAGLDRCLIAEEIARVLIH IAHRRGFQSNRKSEIKDSDAGKLLKAVQENENLMQSKGYRTVAEMLVSEATKTDAEGKLVHGKK HGYVSNVRNKAGEYRHTVSRQAIVDEVRKIFAAQRALGNDVMSEELEDSYLKILCSQRNFDDGP GGDSPYGHGSVSPDGVRQSIYERMVGSCTFETGEKRAPRSSYSFERFQLLTKVVNLRIYRQQED GGRYPCELTQTERARVIDCAYEQTKITYGKLRKLLDMKDTESFAGLTYGLNRSRNKTEDTVFVE MKFYHEVRKALQRAGVFIQDLSIETLDQIGWILSVWKSDDNRRKKLSTLGLSDNVIEELLPLNG SKFGHLSLKAIRKILPFLEDGYSYDVACELAGYQFQGKTEYVKQRLLPPLGEGEVTNPVVRRAL SQAIKVVNAVIRKHGSPESIHIELARELSKNLDERRKIEKAQKENQKNNEQIKDEIREILGSAH VTGRDIVKYKLFKQQQEFCMYSGEKLDVTRLFEPGYAEVDHIIPYGISFDDSYDNKVLVKTEQN RQKGNRTPLEYLRDKPEQKAKFIALVESIPLSQKKKNHLLMDKRAIDLEQEGFRERNLSDTRYI TRALMNHIQAWLLFDETASTRSKRVVCVNGAVTAYMRARWGLTKDRDAGDKHHAADAVVVACIG DSLIQRVTKYDKFKRNALADRNRYVQQVSKSEGITQYVDKETGEVFTWESFDERKFLPNEPLEP WPFFRDELLARLSDDPSKNIRAIGLLTYSETEQIDPIFVSRMPTRKVTGAAHKETIRSPRIVKV DDNKGTEIQVVVSKVALTELKLTKDGEIKDYFRPEDDPRLYNTLRERLVQFGGDAKAAFKEPVY KISKDGSVRTPVRKVKIQEKLTLGVPVHGGRGIAENGGMVRIDVFAKGGKYYFVPIYVADVLKR ELPNRLATAHKPYSEWRVVDDSYQFKFSLYPNDAVMIKPSREVDITYKDRKEPVGCRIMYFVSA NIASASISLRTHDNSGELEGLGIQGLEVFEKYVVGPLGDTHPVYKERRMPFRVERKMN SEQ ID NO: 342 MPVLSPLSPNAAQGRRRWSLALDIGEGSIGWAVAEVDAEGRVLQLTGTGVTLFPSAWSNENGTY VAHGAADRAVRGQQQRHDSRRRRLAGLARLCAPVLERSPEDLKDLTRTPPKADPRAIFFLRADA ARRPLDGPELFRVLHHMAAHRGIRLAELQEVDPPPESDADDAAPAATEDEDGTRRAAADERAFR RLMAEHMHRHGTQPTCGEIMAGRLRETPAGAQPVTRARDGLRVGGGVAVPTRALIEQEFDAIRA IQAPRHPDLPWDSLRRLVLDQAPIAVPPATPCLFLEELRRRGETFQGRTITREAIDRGLTVDPL IQALRIRETVGNLRLHERITEPDGRQRYVPRAMPELGLSHGELTAPERDTLVRALMHDPDGLAA KDGRIPYTRLRKLIGYDNSPVCFAQERDTSGGGITVNPTDPLMARWIDGWVDLPLKARSLYVRD VVARGADSAALARLLAEGAHGVPPVAAAAVPAATAAILESDIMQPGRYSVCPWAAEAILDAWAN APTEGFYDVTRGLFGFAPGEIVLEDLRRARGALLAHLPRTMAAARTPNRAAQQRGPLPAYESVI PSQLITSLRRAHKGRAADWSAADPEERNPFLRTWTGNAATDHILNQVRKTANEVITKYGNRRGW DPLPSRITVELAREAKHGVIRRNEIAKENRENEGRRKKESAALDTFCQDNTVSWQAGGLPKERA ALRLRLAQRQEFFCPYCAERPKLRATDLFSPAETEIDHVIERRMGGDGPDNLVLAHKDCNNAKG KKTPHEHAGDLLDSPALAALWQGWRKENADRLKGKGHKARTPREDKDFMDRVGWRFEEDARAKA EENQERRGRRMLHDTARATRLARLYLAAAVMPEDPAEIGAPPVETPPSPEDPTGYTAIYRTISR VQPVNGSVTHMLRQRLLQRDKNRDYQTHHAEDACLLLLAGPAVVQAFNTEAAQHGADAPDDRPV DLMPTSDAYHQQRRARALGRVPLATVDAALADIVMPESDRQDPETGRVHWRLTRAGRGLKRRID DLTRNCVILSRPRRPSETGTPGALHNATHYGRREITVDGRTDTVVTQRMNARDLVALLDNAKIV PAARLDAAAPGDTILKEICTEIADRHDRVVDPEGTHARRWISARLAALVPAHAEAVARDIAELA DLDALADADRTPEQEARRSALRQSPYLGRAISAKKADGRARAREQEILTRALLDPHWGPRGLRH LIMREARAPSLVRIRANKTDAFGRPVPDAAVWVKTDGNAVSQLWRLTSVVTDDGRRIPLPKPIE KRIEISNLEYARLNGLDEGAGVTGNNAPPRPLRQDIDRLTPLWRDHGTAPGGYLGTAVGELEDK ARSALRGKAMRQTLTDAGITAEAGWRLDSEGAVCDLEVAKGDTVKKDGKTYKVGVITQGIFGMP VDAAGSAPRTPEDCEKFEEQYGIKPWKAKGIPLA SEQ ID NO: 343 MNYTEKEKLFMKYILALDIGIASVGWAILDKESETVIEAGSNIFPEASAADNQLRRDMRGAKRN NRRLKTRINDFIKLWENNNLSIPQFKSTEIVGLKVRAITEEITLDELYLILYSYLKHRGISYLE DALDDTVSGSSAYANGLKLNAKELETHYPCEIQQERLNTIGKYRGQSQIINENGEVLDLSNVFT IGAYRKEIQRVFEIQKKYHPELTDEFCDGYMLIFNRKRKYYEGPGNEKSRTDYGRFTTKLDANG NYITEDNIFEKLIGKCSVYPDELRAAAASYTAQEYNVLNDLNNLTINGRKLEENEKHEIVERIK SSNTINMRKIISDCMGENIDDFAGARIDKSGKEIFHKFEVYNKMRKALLEIGIDISNYSREELD EIGYIMTINTDKEAMMEAFQKSWIDLSDDVKQCLINMRKTNGALFNKWQSFSLKIMNELIPEMY AQPKEQMTLLTEMGVTKGTQEEFAGLKYIPVDVVSEDIFNPVVRRSVRISFKILNAVLKKYKAL DTIVIEMPRDRNSEEQKKRINDSQKLNEKEMEYIEKKLAVTYGIKLSPSDFSSQKQLSLKLKLW NEQDGICLYSGKTIDPNDIINNPQLFEIDHIIPRSISFDDARSNKVLVYRSENQKKGNQTPYYY LTHSHSEWSFEQYKATVMNLSKKKEYAISRKKIQNLLYSEDITKMDVLKGFINRNINDTSYASR LVLNTIQNFFMANEADTKVKVIKGSYTHQMRCNLKLDKNRDESYSHHAVDAMLIGYSELGYEAY HKLQGEFIDFETGEILRKDMWDENMSDEVYADYLYGKKWANIRNEVVKAEKNVKYWHYVMRKSN RGLCNQTIRGTREYDGKQYKINKLDIRTKEGIKVFAKLAFSKKDSDRERLLVYLNDRRTFDDLC KIYEDYSDAANPFVQYEKETGDIIRKYSKKHNGPRIDKLKYKDGEVGACIDISHKYGFEKGSKK VILESLVPYRMDVYYKEENHSYYLVGVKQSDIKFEKGRNVIDEEAYARILVNEKMIQPGQSRAD LENLGFKFKLSFYKNDIIEYEKDGKIYTERLVSRTMPKQRNYIETKPIDKAKFEKQNLVGLGKT KFIKKYRYDILGNKYSCSEEKFTSFC SEQ ID NO: 344 MLRLYCANNLVLNNVQNLWKYLLLLIFDKKIIFLFKIKVILIRRYMENNNKEKIVIGFDLGVAS VGWSIVNAETKEVIDLGVRLFSEPEKADYRRAKRTTRRLLRRKKFKREKFHKLILKNAEIFGLQ SRNEILNVYKDQSSKYRNILKLKINALKEEIKPSELVWILRDYLQNRGYFYKNEKLTDEFVSNS FPSKKLHEHYEKYGFFRGSVKLDNKLDNKKDKAKEKDEEEESDAKKESEELIFSNKQWINEIVK VFENQSYLTESFKEEYLKLFNYVRPFNKGPGSKNSRTAYGVFSTDIDPETNKFKDYSNIWDKTI GKCSLFEEEIRAPKNLPSALIFNLQNEICTIKNEFTEFKNWWLNAEQKSEILKFVFTELFNWKD KKYSDKKFNKNLQDKIKKYLLNFALENFNLNEEILKNRDLENDTVLGLKGVKYYEKSNATADAA LEFSSLKPLYVFIKFLKEKKLDLNYLLGLENTEILYFLDSIYLAISYSSDLKERNEWFKKLLKE LYPKIKNNNLEIIENVEDIFEITDQEKFESFSKTHSLSREAFNHIIPLLLSNNEGKNYESLKHS NEELKKRTEKAELKAQQNQKYLKDNFLKEALVPLSVKTSVLQAIKIFNQIIKNFGKKYEISQVV IEMARELTKPNLEKLLNNATNSNIKILKEKLDQTEKFDDFTKKKFIDKIENSVVFRNKLFLWFE QDRKDPYTQLDIKINEIEDETEIDHVIPYSKSADDSWFNKLLVKKSTNQLKKNKTVWEYYQNES DPEAKWNKFVAWAKRIYLVQKSDKESKDNSEKNSIFKNKKPNLKFKNITKKLFDPYKDLGFLAR NLNDTRYATKVFRDQLNNYSKHHSKDDENKLFKVVCMNGSITSFLRKSMWRKNEEQVYRFNFWK KDRDQFFHHAVDASIIAIFSLLTKTLYNKLRVYESYDVQRREDGVYLINKETGEVKKADKDYWK DQHNFLKIRENAIEIKNVLNNVDFQNQVRYSRKANTKLNTQLFNETLYGVKEFENNFYKLEKVN LFSRKDLRKFILEDLNEESEKNKKNENGSRKRILTEKYIVDEILQILENEEFKDSKSDINALNK YMDSLPSKFSEFFSQDFINKCKKENSLILTFDAIKHNDPKKVIKIKNLKFFREDATLKNKQAVH KDSKNQIKSFYESYKCVGFIWLKNKNDLEESIFVPINSRVIHFGDKDKDIFDFDSYNKEKLLNE INLKRPENKKFNSINEIEFVKFVKPGALLLNFENQQIYYISTLESSSLRAKIKLLNKMDKGKAV SMKKITNPDEYKIIEHVNPLGINLNWTKKLENNN SEQ ID NO: 345 MLMSKHVLGLDLGVGSIGWCLIALDAQGDPAEILGMGSRVVPLNNATKAIEAFNAGAAFTASQE RTARRTMRRGFARYQLRRYRLRRELEKVGMLPDAALIQLPLLELWELRERAATAGRRLTLPELG RVLCHINQKRGYRHVKSDAAAIVGDEGEKKKDSNSAYLAGIRANDEKLQAEHKTVGQYFAEQLR QNQSESPTGGISYRIKDQIFSRQCYIDEYDQIMAVQRVHYPDILTDEFIRMLRDEVIFMQRPLK SCKHLVSLCEFEKQERVMRVQQDDGKGGWQLVERRVKFGPKVAPKSSPLFQLCCIYEAVNNIRL TRPNGSPCDITPEERAKIVAHLQSSASLSFAALKKLLKEKALIADQLTSKSGLKGNSTRVALAS ALQPYPQYHHLLDMELETRMMTVQLTDEETGEVTEREVAVVTDSYVRKPLYRLWHILYSIEERE AMRRALITQLGMKEEDLDGGLLDQLYRLDFVKPGYGNKSAKFICKLLPQLQQGLGYSEACAAVG YRHSNSPTSEEITERTLLEKIPLLQRNELRQPLVEKILNQMINLVNALKAEYGIDEVRVELARE LKMSREERERMARNNKDREERNKGVAAKIRECGLYPTKPRIQKYMLWKEAGRQCLYCGRSIEEE QCLREGGMEVEHIIPKSVLYDDSYGNKTCACRRCNKEKGNRTALEYIRAKGREAEYMKRINDLL KEKKISYSKHQRLRWLKEDIPSDFLERQLRLTQYISRQAMAILQQGIRRVSASEGGVTARLRSL WGYGKILHTLNLDRYDSMGETERVSREGEATEELHITNWSKRMDHRHHAIDALVVACTRQSYIQ RLNRLSSEFGREDKKKEDQEAQEQQATETGRLSNLERWLTQRPHFSVRTVSDKVAEILISYRPG QRVVTRGRNIYRKKMADGREVSCVQRGVLVPRGELMEASFYGKILSQGRVRIVKRYPLHDLKGE VVDPHLRELITTYNQELKSREKGAPIPPLCLDKDKKQEVRSVRCYAKTLSLDKAIPMCFDEKGE PTAFVKSASNHHLALYRTPKGKLVESIVTFWDAVDRARYGIPLVITHPREVMEQVLQRGDIPEQ VLSLLPPSDWVFVDSLQQDEMVVIGLSDEELQRALEAQNYRKISEHLYRVQKMSSSYYVFRYHL ETSVADDKNTSGRIPKFHRVQSLKAYEERNIRKVRVDLLGRISLL SEQ ID NO: 346 MSDLVLGLDIGIGSVGVGILNKVTGEIIHKNSRIFPAAQAENNLVRRTNRQGRRLARRKKHRRV RLNRLFEESGLITDFTKISINLNPYQLRVKGLTDELSNEELFIALKNMVKHRGISYLDDASDDG NSSVGDYAQIVKENSKQLETKTPGQIQLERYQTYGQLRGDFTVEKDGKKHRLINVFPTSAYRSE ALRILQTQQEFNPQITDEFINRYLEILTGKRKYYHGPGNEKSRTDYGRYRTSGETLDNIFGILI GKCTFYPDEFRAAKASYTAQEFNLLNDLNNLTVPTETKKLSKEQKNQIINYVKNEKAMGPAKLF KYIAKLLSCDVADIKGYRIDKSGKAEIHTFEAYRKMKTLETLDIEQMDRETLDKLAYVLTLNTE REGIQEALEHEFADGSFSQKQVDELVQFRKANSSIFGKGWHNFSVKLMMELIPELYETSEEQMT ILTRLGKQKTTSSSNKTKYIDEKLLTEEIYNPVVAKSVRQAIKIVNAAIKEYGDFDNIVIEMAR ETNEDDEKKAIQKIQKANKDEKDAAMLKAANQYNGKAELPHSVFHGHKQLATKIRLWHQQGERC LYTGKTISIHDLINNSNQFEVDHILPLSITFDDSLANKVLVYATANQEKGQRTPYQALDSMDDA WSFRELKAFVRESKTLSNKKKEYLLTEEDISKFDVRKKFIERNLVDTRYASRVVLNALQEHFRA HKIDTKVSVVRGQFTSQLRRHWGIEKTRDTYHHHAVDALIIAASSQLNLWKKQKNTLVSYSEDQ LLDIETGELISDDEYKESVFKAPYQHFVDTLKSKEFEDSILFSYQVDSKFNRKISDATIYATRQ AKVGKDKADETYVLGKIKDIYTQDGYDAFMKIYKKDKSKFLMYRHDPQTFEKVIEPILENYPNK QINEKGKEVPCNPFLKYKEEHGYIRKYSKKGNGPEIKSLKYYDSKLGNHIDITPKDSNNKVVLQ SVSPWRADVYFNKTTGKYEILGLKYADLQFEKGTGTYKISQEKYNDIKKKEGVDSDSEFKFTLY KNDLLLVKDTETKEQQLFRFLSRTMPKQKHYVELKPYDKQKFEGGEALIKVLGNVANSGQCKKG LGKSNISIYKVRTDVLGNQHIIKNEGDKPKLDF SEQ ID NO: 347 MNAEHGKEGLLIMEENFQYRIGLDIGITSVGWAVLQNNSQDEPVRITDLGVRIFDVAENPKNGD ALAAPRRDARTTRRRLRRRRHRLERIKFLLQENGLIEMDSFMERYYKGNLPDVYQLRYEGLDRK LKDEELAQVLIHIAKHRGFRSTRKAETKEKEGGAVLKATTENQKIMQEKGYRTVGEMLYLDEAF HTECLWNEKGYVLTPRNRPDDYKHTILRSMLVEEVHAIFAAQRAHGNQKATEGLEEAYVEIMTS QRSFDMGPGLQPDGKPSPYAMEGFGDRVGKCTFEKDEYRAPKATYTAELFVALQKINHTKLIDE FGTGRFFSEEERKTIIGLLLSSKELKYGTIRKKLNIDPSLKFNSLNYSAKKEGETEEERVLDTE KAKFASMFWTYEYSKCLKDRTEEMPVGEKADLFDRIGEILTAYKNDDSRSSRLKELGLSGEEID GLLDLSPAKYQRVSLKAMRKMQPYLEDGLIYDKACEAAGYDFRALNDGNKKHLLKGEEINAIVN DITNPVVKRSVSQTIKVINAIIQKYGSPQAVNIELAREMSKNFQDRTNLEKEMKKRQQENERAK QQIIELGKQNPTGQDILKYRLWNDQGGYCLYSGKKIPLEELFDGGYDIDHILPYSITFDDSYRN KVLVTAQENRQKGNRTPYEYFGADEKRWEDYEASVRLLVRDYKKQQKLLKKNFTEEERKEFKER NLNDTKYITRVVYNMIRQNLELEPFNHPEKKKQVWAVNGAVTSYLRKRWGLMQKDRSTDRHHAM DAVVIACCTDGMIHKISRYMQGRELAYSRNFKFPDEETGEILNRDNFTREQWDEKFGVKVPLPW NSFRDELDIRLLNEDPKNFLLTHADVQRELDYPGWMYGEEESPIEEGRYINYIRPLFVSRMPNH KVTGSAHDATIRSARDYETRGVVITKVPLTDLKLNKDNEIEGYYDKDSDRLLYQALVRQLLLHG NDGKKAFAEDFHKPKADGTEGPVVRKVKIEKKQTSGVMVRGGTGIAANGEMVRIDVFRENGKYY FVPVYTADVVRKVLPNRAATHTKPYSEWRVMDDANFVFSLYSRDLIHVKSKKDIKTNLVNGGLL LQKEIFAYYTGADIATASIAGFANDSNFKFRGLGIQSLEIFEKCQVDILGNISVVRHENRQEFH SEQ ID NO: 348 MRVLGLDAGIASLGWALIEIEESNRGELSQGTIIGAGTWMFDAPEEKTQAGAKLKSEQRRTFRG QRRVVRRRRQRMNEVRRILHSHGLLPSSDRDALKQPGLDPWRIRAEALDRLLGPVELAVALGHI ARHRGFKSNSKGAKTNDPADDTSKMKRAVNETREKLARFGSAAKMLVEDESFVLRQTPTKNGAS EIVRRFRNREGDYSRSLLRDDLAAEMRALFTAQARFQSAIATADLQTAFTKAAFFQRPLQDSEK LVGPCPFEVDEKRAPKRGYSFELFRFLSRLNHVTLRDGKQERTLTRDELALAAADFGAAAKVSF TALRKKLKLPETTVFVGVKADEESKLDVVARSGKAAEGTARLRSVIVDALGELAWGALLCSPEK LDKIAEVISFRSDIGRISEGLAQAGCNAPLVDALTAAASDGRFDPFTGAGHISSKAARNILSGL RQGMTYDKACCAADYDHTASRERGAFDVGGHGREALKRILQEERISRELVGSPTARKALIESIK QVKAIVERYGVPDRIHVELARDVGKSIEEREEITRGIEKRNRQKDKLRGLFEKEVGRPPQDGAR GKEELLRFELWSEQMGRCLYTDDYISPSQLVATDDAVQVDHILPWSRFADDSYANKTLCMAKAN QDKKGRTPYEWFKAEKTDTEWDAFIVRVEALADMKGFKKRNYKLRNAEEAAAKFRNRNLNDTRW ACRLLAEALKQLYPKGEKDKDGKERRRVFSRPGALTDRLRRAWGLQWMKKSTKGDRIPDDRHHA LDAIVIAATTESLLQRATREVQEIEDKGLHYDLVKNVTPPWPGFREQAVEAVEKVFVARAERRR ARGKAHDATIRHIAVREGEQRVYERRKVAELKLADLDRVKDAERNARLIEKLRNWIEAGSPKDD PPLSPKGDPIFKVRLVTKSKVNIALDTGNPKRPGTVDRGEMARVDVFRKASKKGKYEYYLVPIY PHDIATMKTPPIRAVQAYKPEDEWPEMDSSYEFCWSLVPMTYLQVISSKGEIFEGYYRGMNRSV GAIQLSAHSNSSDVVQGIGARTLTEFKKFNVDRFGRKHEVERELRTWRGETWRGKAYI SEQ ID NO: 349 MGNYYLGLDVGIGSIGWAVINIEKKRIEDFNVRIFKSGEIQEKNRNSRASQQCRRSRGLRRLYR RKSHRKLRLKNYLSIIGLTTSEKIDYYYETADNNVIQLRNKGLSEKLTPEEIAACLIHICNNRG YKDFYEVNVEDIEDPDERNEYKEEHDSIVLISNLMNEGGYCTPAEMICNCREFDEPNSVYRKFH NSAASKNHYLITRHMLVKEVDLILENQSKYYGILDDKTIAKIKDIIFAQRDFEIGPGKNERFRR FTGYLDSIGKCQFFKDQERGSRFTVIADIYAFVNVLSQYTYTNNRGESVFDTSFANDLINSALK NGSMDKRELKAIAKSYHIDISDKNSDTSLTKCFKYIKVVKPLFEKYGYDWDKLIENYTDTDNNV LNRIGIVLSQAQTPKRRREKLKALNIGLDDGLINELTKLKLSGTANVSYKYMQGSIEAFCEGDL YGKYQAKFNKEIPDIDENAKPQKLPPFKNEDDCEFFKNPVVFRSINETRKLINAIIDKYGYPAA VNIETADELNKTFEDRAIDTKRNNDNQKENDRIVKEIIECIKCDEVHARHLIEKYKLWEAQEGK CLYSGETITKEDMLRDKDKLFEVDHIVPYSLILDNTINNKALVYAEENQKKGQRTPLMYMNEAQ AADYRVRVNTMFKSKKCSKKKYQYLMLPDLNDQELLGGWRSRNLNDTRYICKYLVNYLRKNLRF DRSYESSDEDDLKIRDHYRVFPVKSRFTSMFRRWWLNEKTWGRYDKAELKKLTYLDHAADAIII ANCRPEYVVLAGEKLKLNKMYHQAGKRITPEYEQSKKACIDNLYKLFRMDRRTAEKLLSGHGRL TPIIPNLSEEVDKRLWDKNIYEQFWKDDKDKKSCEELYRENVASLYKGDPKFASSLSMPVISLK PDHKYRGTITGEEAIRVKEIDGKLIKLKRKSISEITAESINSIYTDDKILIDSLKTIFEQADYK DVGDYLKKTNQHFFTTSSGKRVNKVTVIEKVPSRWLRKEIDDNNFSLLNDSSYYCIELYKDSKG DNNLQGIAMSDIVHDRKTKKLYLKPDFNYPDDYYTHVMYIFPGDYLRIKSTSKKSGEQLKFEGY FISVKNVNENSFRFISDNKPCAKDKRVSITKKDIVIKLAVDLMGKVQGENNGKGISCGEPLSLL KEKN SEQ ID NO: 350 MLSRQLLGASHLARPVSYSYNVQDNDVHCSYGERCFMRGKRYRIGIDVGLNSVGLAAVEVSDEN SPVRLLNAQSVIHDGGVDPQKNKEAITRKNMSGVARRTRRMRRRKRERLHKLDMLLGKFGYPVI EPESLDKPFEEWHVRAELATRYIEDDELRRESISIALRHMARHRGWRNPYRQVDSLISDNPYSK QYGELKEKAKAYNDDATAAEEESTPAQLVVAMLDAGYAEAPRLRWRTGSKKPDAEGYLPVRLMQ EDNANELKQIFRVQRVPADEWKPLFRSVFYAVSPKGSAEQRVGQDPLAPEQARALKASLAFQEY RIANVITNLRIKDASAELRKLTVDEKQSIYDQLVSPSSEDITWSDLCDFLGFKRSQLKGVGSLT EDGEERISSRPPRLTSVQRIYESDNKIRKPLVAWWKSASDNEHEAMIRLLSNTVDIDKVREDVA YASAIEFIDGLDDDALTKLDSVDLPSGRAAYSVETLQKLTRQMLTTDDDLHEARKTLFNVTDSW RPPADPIGEPLGNPSVDRVLKNVNRYLMNCQQRWGNPVSVNIEHVRSSFSSVAFARKDKREYEK NNEKRSIFRSSLSEQLRADEQMEKVRESDLRRLEAIQRQNGQCLYCGRTITFRTCEMDHIVPRK GVGSTNTRTNFAAVCAECNRMKSNTPFAIWARSEDAQTRGVSLAEAKKRVTMFTFNPKSYAPRE VKAFKQAVIARLQQTEDDAAIDNRSIESVAWMADELHRRIDWYFNAKQYVNSASIDDAEAETMK TTVSVFQGRVTASARRAAGIEGKIHFIGQQSKTRLDRRHHAVDASVIAMMNTAAAQTLMERESL RESQRLIGLMPGERSWKEYPYEGTSRYESFHLWLDNMDVLLELLNDALDNDRIAVMQSQRYVLG NSIAHDATIHPLEKVPLGSAMSADLIRRASTPALWCALTRLPDYDEKEGLPEDSHREIRVHDTR YSADDEMGFFASQAAQIAVQEGSADIGSAIHHARVYRCWKTNAKGVRKYFYGMIRVFQTDLLRA CHDDLFTVPLPPQSISMRYGEPRVVQALQSGNAQYLGSLVVGDEIEMDFSSLDVDGQIGEYLQF FSQFSGGNLAWKHWVVDGFFNQTQLRIRPRYLAAEGLAKAFSDDVVPDGVQKIVTKQGWLPPVN TASKTAVRIVRRNAFGEPRLSSAHHMPCSWQWRHE SEQ ID NO: 351 MYSIGLDLGISSVGWSVIDERTGNVIDLGVRLFSAKNSEKNLERRTNRGGRRLIRRKTNRLKDA KKILAAVGFYEDKSLKNSCPYQLRVKGLTEPLSRGEIYKVTLHILKKRGISYLDEVDTEAAKES QDYKEQVRKNAQLLTKYTPGQIQLQRLKENNRVKTGINAQGNYQLNVFKVSAYANELATILKTQ QAFYPNELTDDWIALFVQPGIAEEAGLIYRKRPYYHGPGNEANNSPYGRWSDFQKTGEPATNIF DKLIGKDFQGELRASGLSLSAQQYNLLNDLTNLKIDGEVPLSSEQKEYILTELMTKEFTRFGVN DVVKLLGVKKERLSGWRLDKKGKPEIHTLKGYRNWRKIFAEAGIDLATLPTETIDCLAKVLTLN TEREGIENTLAFELPELSESVKLLVLDRYKELSQSISTQSWHRFSLKTLHLLIPELMNATSEQN TLLEQFQLKSDVRKRYSEYKKLPTKDVLAEIYNPTVNKTVSQAFKVIDALLVKYGKEQIRYITI EMPRDDNEEDEKKRIKELHAKNSQRKNDSQSYFMQKSGWSQEKFQTTIQKNRRFLAKLLYYYEQ DGICAYTGLPISPELLVSDSTEIDHIIPISISLDDSINNKVLVLSKANQVKGQQTPYDAWMDGS FKKINGKFSNWDDYQKWVESRHFSHKKENNLLETRNIFDSEQVEKFLARNLNDTRYASRLVLNT LQSFFTNQETKVRVVNGSFTHTLRKKWGADLDKTRETHHHHAVDATLCAVTSFVKVSRYHYAVK EETGEKVMREIDFETGEIVNEMSYWEFKKSKKYERKTYQVKWPNFREQLKPVNLHPRIKFSHQV DRKANRKLSDATIYSVREKTEVKTLKSGKQKITTDEYTIGKIKDIYTLDGWEAFKKKQDKLLMK DLDEKTYERLLSIAETTPDFQEVEEKNGKVKRVKRSPFAVYCEENDIPAIQKYAKKNNGPLIRS LKYYDGKLNKHINITKDSQGRPVEKTKNGRKVTLQSLKPYRYDIYQDLETKAYYTVQLYYSDLR FVEGKYGITEKEYMKKVAEQTKGQVVRFCFSLQKNDGLEIEWKDSQRYDVRFYNFQSANSINFK GLEQEMMPAENQFKQKPYNNGAINLNIAKYGKEGKKLRKFNTDILGKKHYLFYEKEPKNIIK SEQ ID NO: 352 MYFYKNKENKLNKKVVLGLDLGIASVGWCLTDISQKEDNKFPIILHGVRLFETVDDSDDKLLNE TRRKKRGQRRRNRRLFTRKRDFIKYLIDNNIIELEFDKNPKILVRNFIEKYINPFSKNLELKYK SVTNLPIGFHNLRKAAINEKYKLDKSELIVLLYFYLSLRGAFFDNPEDTKSKEMNKNEIEIFDK NESIKNAEFPIDKIIEFYKISGKIRSTINLKFGHQDYLKEIKQVFEKQNIDFMNYEKFAMEEKS FFSRIRNYSEGPGNEKSFSKYGLYANENGNPELIINEKGQKIYTKIFKTLWESKIGKCSYDKKL YRAPKNSFSAKVFDITNKLTDWKHKNEYISERLKRKILLSRFLNKDSKSAVEKILKEENIKFEN LSEIAYNKDDNKINLPIINAYHSLTTIFKKHLINFENYLISNENDLSKLMSFYKQQSEKLFVPN EKGSYEINQNNNVLHIFDAISNILNKFSTIQDRIRILEGYFEFSNLKKDVKSSEIYSEIAKLRE FSGTSSLSFGAYYKFIPNLISEGSKNYSTISYEEKALQNQKNNFSHSNLFEKTWVEDLIASPTV KRSLRQTMNLLKEIFKYSEKNNLEIEKIVVEVTRSSNNKHERKKIEGINKYRKEKYEELKKVYD LPNENTTLLKKLWLLRQQQGYDAYSLRKIEANDVINKPWNYDIDHIVPRSISFDDSFSNLVIVN KLDNAKKSNDLSAKQFIEKIYGIEKLKEAKENWGNWYLRNANGKAFNDKGKFIKLYTIDNLDEF DNSDFINRNLSDTSYITNALVNHLTFSNSKYKYSVVSVNGKQTSNLRNQIAFVGIKNNKETERE WKRPEGFKSINSNDFLIREEGKNDVKDDVLIKDRSFNGHHAEDAYFITIISQYFRSFKRIERLN VNYRKETRELDDLEKNNIKFKEKASFDNFLLINALDELNEKLNQMRFSRMVITKKNTQLFNETL YSGKYDKGKNTIKKVEKLNLLDNRTDKIKKIEEFFDEDKLKENELTKLHIFNHDKNLYETLKII WNEVKIEIKNKNLNEKNYFKYFVNKKLQEGKISFNEWVPILDNDFKIIRKIRYIKFSSEEKETD EIIFSQSNFLKIDQRQNFSFHNTLYWVQIWVYKNQKDQYCFISIDARNSKFEKDEIKINYEKLK TQKEKLQIINEEPILKINKGDLFENEEKELFYIVGRDEKPQKLEIKYILGKKIKDQKQIQKPVK KYFPNWKKVNLTYMGEIFKK SEQ ID NO: 353 MDNKNYRIGIDVGLNSIGFCAVEVDQHDTPLGFLNLSVYRHDAGIDPNGKKTNTTRLAMSGVAR RTRRLFRKRKRRLAALDRFIEAQGWTLPDHADYKDPYTPWLVRAELAQTPIRDENDLHEKLAIA VRHIARHRGWRSPWVPVRSLHVEQPPSDQYLALKERVEAKTLLQMPEGATPAEMVVALDLSVDV NLRPKNREKTDTRPENKKPGFLGGKLMQSDNANELRKIAKIQGLDDALLRELIELVFAADSPKG ASGELVGYDVLPGQHGKRRAEKAHPAFQRYRIASIVSNLRIRHLGSGADERLDVETQKRVFEYL LNAKPTADITWSDVAEEIGVERNLLMGTATQTADGERASAKPPVDVTNVAFATCKIKPLKEWWL NADYEARCVMVSALSHAEKLTEGTAAEVEVAEFLQNLSDEDNEKLDSFSLPIGRAAYSVDSLER LTKRMIENGEDLFEARVNEFGVSEDWRPPAEPIGARVGNPAVDRVLKAVNRYLMAAEAEWGAPL SVNIEHVREGFISKRQAVEIDRENQKRYQRNQAVRSQIADHINATSGVRGSDVTRYLAIQRQNG ECLYCGTAITFVNSEMDHIVPRAGLGSTNTRDNLVATCERCNKSKSNKPFAVWAAECGIPGVSV AEALKRVDFWIADGFASSKEHRELQKGVKDRLKRKVSDPEIDNRSMESVAWMARELAHRVQYYF DEKHTGTKVRVFRGSLTSAARKASGFESRVNFIGGNGKTRLDRRHHAMDAATVAMLRNSVAKTL VLRGNIRASERAIGAAETWKSFRGENVADRQIFESWSENMRVLVEKFNLALYNDEVSIFSSLRL QLGNGKAHDDTITKLQMHKVGDAWSLTEIDRASTPALWCALTRQPDFTWKDGLPANEDRTIIVN GTHYGPLDKVGIFGKAAASLLVRGGSVDIGSAIHHARIYRIAGKKPTYGMVRVFAPDLLRYRNE DLFNVELPPQSVSMRYAEPKVREAIREGKAEYLGWLVVGDELLLDLSSETSGQIAELQQDFPGT THWTVAGFFSPSRLRLRPVYLAQEGLGEDVSEGSKSIIAGQGWRPAVNKVFGSAMPEVIRRDGL GRKRRFSYSGLPVSWQG SEQ ID NO: 354 MRLGLDIGTSSIGWWLYETDGAGSDARITGVVDGGVRIFSDGRDPKSGASLAVDRRAARAMRRR RDRYLRRRATLMKVLAETGLMPADPAEAKALEALDPFALRAAGLDEPLPLPHLGRALFHLNQRR GFKSNRKTDRGDNESGKIKDATARLDMEMMANGARTYGEFLHKRRQKATDPRHVPSVRTRLSIA NRGGPDGKEEAGYDFYPDRRHLEEEFHKLWAAQGAHHPELTETLRDLLFEKIFFQRPLKEPEVG LCLFSGHHGVPPKDPRLPKAHPLTQRRVLYETVNQLRVTADGREARPLTREERDQVIHALDNKK PTKSLSSMVLKLPALAKVLKLRDGERFTLETGVRDAIACDPLRASPAHPDRFGPRWSILDADAQ WEVISRIRRVQSDAEHAALVDWLTEAHGLDRAHAEATAHAPLPDGYGRLGLTATTRILYQLTAD VVTYADAVKACGWHHSDGRTGECFDRLPYYGEVLERHVIPGSYHPDDDDITRFGRITNPTVHIG LNQLRRLVNRIIETHGKPHQIVVELARDLKKSEEQKRADIKRIRDTTEAAKKRSEKLEELEIED NGRNRMLLRLWEDLNPDDAMRRFCPYTGTRISAAMIFDGSCDVDHILPYSRTLDDSFPNRTLCL REANRQKRNQTPWQAWGDTPHWHAIAANLKNLPENKRWRFAPDAMTRFEGENGFLDRALKDTQY LARISRSYLDTLFTKGGHVWVVPGRFTEMLRRHWGLNSLLSDAGRGAVKAKNRTDHRHHAIDAA VIAATDPGLLNRISRAAGQGEAAGQSAELIARDTPPPWEGFRDDLRVRLDRIIVSHRADHGRID HAARKQGRDSTAGQLHQETAYSIVDDIHVASRTDLLSLKPAQLLDEPGRSGQVRDPQLRKALRV ATGGKTGKDFENALRYFASKPGPYQAIRRVRIIKPLQAQARVPVPAQDPIKAYQGGSNHLFEIW RLPDGEIEAQVITSFEAHTLEGEKRPHPAAKRLLRVHKGDMVALERDGRRVVGHVQKMDIANGL FIVPHNEANADTRNNDKSDPFKWIQIGARPAIASGIRRVSVDEIGRLRDGGTRPI SEQ ID NO: 355 MLHCIAVIRVPPSEEPGFFETHADSCALCHHGCMTYAANDKAIRYRVGIDVGLRSIGFCAVEVD DEDHPIRILNSVVHVHDAGTGGPGETESLRKRSGVAARARRRGRAEKQRLKKLDVLLEELGWGV SSNELLDSHAPWHIRKRLVSEYIEDETERRQCLSVAMAHIARHRGWRNSFSKVDTLLLEQAPSD RMQGLKERVEDRTGLQFSEEVTQGELVATLLEHDGDVTIRGFVRKGGKATKVHGVLEGKYMQSD LVAELRQICRTQRVSETTFEKLVLSIFHSKEPAPSAARQRERVGLDELQLALDPAAKQPRAERA HPAFQKFKVVATLANMRIREQSAGERSLTSEELNRVARYLLNHTESESPTWDDVARKLEVPRHR LRGSSRASLETGGGLTYPPVDDTTVRVMSAEVDWLADWWDCANDESRGHMIDAISNGCGSEPDD VEDEEVNELISSATAEDMLKLELLAKKLPSGRVAYSLKTLREVTAAILETGDDLSQAITRLYGV DPGWVPTPAPIEAPVGNPSVDRVLKQVARWLKFASKRWGVPQTVNIEHTREGLKSASLLEEERE RWERFEARREIRQKEMYKRLGISGPFRRSDQVRYEILDLQDCACLYCGNEINFQTFEVDHIIPR VDASSDSRRTNLAAVCHSCNSAKGGLAFGQWVKRGDCPSGVSLENAIKRVRSWSKDRLGLTEKA MGKRKSEVISRLKTEMPYEEFDGRSMESVAWMAIELKKRIEGYFNSDRPEGCAAVQVNAYSGRL TACARRAAHVDKRVRLIRLKGDDGHHKNRFDRRNHAMDALVIALMTPAIARTIAVREDRREAQQ LTRAFESWKNFLGSEERMQDRWESWIGDVEYACDRLNELIDADKIPVTENLRLRNSGKLHADQP ESLKKARRGSKRPRPQRYVLGDALPADVINRVTDPGLWTALVRAPGFDSQLGLPADLNRGLKLR GKRISADFPIDYFPTDSPALAVQGGYVGLEFHHARLYRIIGPKEKVKYALLRVCAIDLCGIDCD DLFEVELKPSSISMRTADAKLKEAMGNGSAKQIGWLVLGDEIQIDPTKFPKQSIGKFLKECGPV SSWRVSALDTPSKITLKPRLLSNEPLLKTSRVGGHESDLVVAECVEKIMKKTGWVVEINALCQS GLIRVIRRNALGEVRTSPKSGLPISLNLR SEQ ID NO: 356 MRYRVGLDLGTASVGAAVFSMDEQGNPMELIWHYERLFSEPLVPDMGQLKPKKAARRLARQQRR QIDRRASRLRRIAIVSRRLGIAPGRNDSGVHGNDVPTLRAMAVNERIELGQLRAVLLRMGKKRG YGGTFKAVRKVGEAGEVASGASRLEEEMVALASVQNKDSVTVGEYLAARVEHGLPSKLKVAANN EYYAPEYALFRQYLGLPAIKGRPDCLPNMYALRHQIEHEFERIWATQSQFHDVMKDHGVKEEIR NAIFFQRPLKSPADKVGRCSLQTNLPRAPRAQIAAQNFRIEKQMADLRWGMGRRAEMLNDHQKA VIRELLNQQKELSFRKIYKELERAGCPGPEGKGLNMDRAALGGRDDLSGNTTLAAWRKLGLEDR WQELDEVTQIQVINFLADLGSPEQLDTDDWSCRFMGKNGRPRNFSDEFVAFMNELRMTDGFDRL SKMGFEGGRSSYSIKALKALTEWMIAPHWRETPETHRVDEEAAIRECYPESLATPAQGGRQSKL EPPPLTGNEVVDVALRQVRHTINMMIDDLGSVPAQIVVEMAREMKGGVTRRNDIEKQNKRFASE RKKAAQSIEENGKTPTPARILRYQLWIEQGHQCPYCESNISLEQALSGAYTNFEHILPRTLTQI GRKRSELVLAHRECNDEKGNRTPYQAFGHDDRRWRIVEQRANALPKKSSRKTRLLLLKDFEGEA LTDESIDEFADRQLHESSWLAKVTTQWLSSLGSDVYVSRGSLTAELRRRWGLDTVIPQVRFESG MPVVDEEGAEITPEEFEKFRLQWEGHRVTREMRTDRRPDKRIDHRHHLVDAIVTALTSRSLYQQ YAKAWKVADEKQRHGRVDVKVELPMPILTIRDIALEAVRSVRISHKPDRYPDGRFFEATAYGIA QRLDERSGEKVDWLVSRKSLTDLAPEKKSIDVDKVRANISRIVGEAIRLHISNIFEKRVSKGMT PQQALREPIEFQGNILRKVRCFYSKADDCVRIEHSSRRGHHYKMLLNDGFAYMEVPCKEGILYG VPNLVRPSEAVGIKRAPESGDFIRFYKGDTVKNIKTGRVYTIKQILGDGGGKLILTPVTETKPA DLLSAKWGRLKVGGRNIHLLRLCAE SEQ ID NO: 357 MIGEHVRGGCLFDDHWTPNWGAFRLPNTVRTFTKAENPKDGSSLAEPRRQARGLRRRLRRKTQR LEDLRRLLAKEGVLSLSDLETLFRETPAKDPYQLRAEGLDRPLSFPEWVRVLYHITKHRGFQSN RRNPVEDGQERSRQEEEGKLLSGVGENERLLREGGYRTAGEMLARDPKFQDHRRNRAGDYSHTL SRSLLLEEARRLFQSQRTLGNPHASSNLEEAFLHLVAFQNPFASGEDIRNKAGHCSLEPDQIRA PRRSASAETFMLLQKTGNLRLIHRRTGEERPLTDKEREQIHLLAWKQEKVTHKTLRRHLEIPEE WLFTGLPYHRSGDKAEEKLFVHLAGIHEIRKALDKGPDPAVWDTLRSRRDLLDSIADTLTFYKN EDEILPRLESLGLSPENARALAPLSFSGTAHLSLSALGKLLPHLEEGKSYTQARADAGYAAPPP DRHPKLPPLEEADWRNPVVFRALTQTRKVVNALVRRYGPPWCIHLETARELSQPAKVRRRIETE QQANEKKKQQAEREFLDIVGTAPGPGDLLKMRLWREQGGFCPYCEEYLNPTRLAEPGYAEMDHI LPYSRSLDNGWHNRVLVHGKDNRDKGNRTPFEAFGGDTARWDRLVAWVQASHLSAPKKRNLLRE DFGEEAERELKDRNLTDTRFITKTAATLLRDRLTFHPEAPKDPVMTLNGRLTAFLRKQWGLHKN RKNGDLHHALDAAVLAVASRSFVYRLSSHNAAWGELPRGREAENGFSLPYPAFRSEVLARLCPT REEILLRLDQGGVGYDEAFRNGLRPVFVSRAPSRRLRGKAHMETLRSPKWKDHPEGPRTASRIP LKDLNLEKLERMVGKDRDRKLYEALRERLAAFGGNGKKAFVAPFRKPCRSGEGPLVRSLRIFDS GYSGVELRDGGEVYAVADHESMVRVDVYAKKNRFYLVPVYVADVARGIVKNRAIVAHKSEEEWD LVDGSFDFRFSLFPGDLVEIEKKDGAYLGYYKSCHRGDGRLLLDRHDRMPRESDCGTFYVSTRK DVLSMSKYQVDPLGEIRLVGSEKPPFVL SEQ ID NO: 358 MEKKRKVTLGFDLGIASVGWAIVDSETNQVYKLGSRLFDAPDTNLERRTQRGTRRLLRRRKYRN QKFYNLVKRTEVFGLSSREAIENRFRELSIKYPNIIELKTKALSQEVCPDEIAWILHDYLKNRG YFYDEKETKEDFDQQTVESMPSYKLNEFYKKYGYFKGALSQPTESEMKDNKDLKEAFFFDFSNK EWLKEINYFFNVQKNILSETFIEEFKKIFSFTRDISKGPGSDNMPSPYGIFGEFGDNGQGGRYE HIWDKNIGKCSIFTNEQRAPKYLPSALIFNFLNELANIRLYSTDKKNIQPLWKLSSVDKLNILL NLFNLPISEKKKKLTSTNINDIVKKESIKSIMISVEDIDMIKDEWAGKEPNVYGVGLSGLNIEE SAKENKFKFQDLKILNVLINLLDNVGIKFEFKDRNDIIKNLELLDNLYLFLIYQKESNNKDSSI DLFIAKNESLNIENLKLKLKEFLLGAGNEFENHNSKTHSLSKKAIDEILPKLLDNNEGWNLEAI KNYDEEIKSQIEDNSSLMAKQDKKYLNDNFLKDAILPPNVKVTFQQAILIFNKIIQKFSKDFEI DKVVIELAREMTQDQENDALKGIAKAQKSKKSLVEERLEANNIDKSVFNDKYEKLIYKIFLWIS QDFKDPYTGAQISVNEIVNNKVEIDHIIPYSLCFDDSSANKVLVHKQSNQEKSNSLPYEYIKQG HSGWNWDEFTKYVKRVFVNNVDSILSKKERLKKSENLLTASYDGYDKLGFLARNLNDTRYATIL FRDQLNNYAEHHLIDNKKMFKVIAMNGAVTSFIRKNMSYDNKLRLKDRSDFSHHAYDAAIIALF SNKTKTLYNLIDPSLNGIISKRSEGYWVIEDRYTGEIKELKKEDWTSIKNNVQARKIAKEIEEY LIDLDDEVFFSRKTKRKTNRQLYNETIYGIATKTDEDGITNYYKKEKFSILDDKDIYLRLLRER EKFVINQSNPEVIDQIIEIIESYGKENNIPSRDEAINIKYTKNKINYNLYLKQYMRSLTKSLDQ FSEEFINQMIANKTFVLYNPTKNTTRKIKFLRLVNDVKINDIRKNQVINKFNGKNNEPKAFYEN INSLGAIVFKNSANNFKTLSINTQIAIFGDKNWDIEDFKTYNMEKIEKYKEIYGIDKTYNFHSF IFPGTILLDKQNKEFYYISSIQTVRDIIEIKFLNKIEFKDENKNQDTSKTPKRLMFGIKSIMNN YEQVDISPFGINKKIFE SEQ ID NO: 359 MGYRIGLDVGITSTGYAVLKTDKNGLPYKILTLDSVIYPRAENPQTGASLAEPRRIKRGLRRRT RRTKFRKQRTQQLFIHSGLLSKPEIEQILATPQAKYSVYELRVAGLDRRLTNSELFRVLYFFIG HRGFKSNRKAELNPENEADKKQMGQLLNSIEEIRKAIAEKGYRTVGELYLKDPKYNDHKRNKGY IDGYLSTPNRQMLVDEIKQILDKQRELGNEKLTDEFYATYLLGDENRAGIFQAQRDFDEGPGAG PYAGDQIKKMVGKDIFEPTEDRAAKATYTFQYFNLLQKMTSLNYQNTTGDTWHTLNGLDRQAII DAVFAKAEKPTKTYKPTDFGELRKLLKLPDDARFNLVNYGSLQTQKEIETVEKKTRFVDFKAYH DLVKVLPEEMWQSRQLLDHIGTALTLYSSDKRRRRYFAEELNLPAELIEKLLPLNFSKFGHLSI KSMQNIIPYLEMGQVYSEATTNTGYDFRKKQISKDTIREEITNPVVRRAVTKTIKIVEQIIRRY GKPDGINIELARELGRNFKERGDIQKRQDKNRQTNDKIAAELTELGIPVNGQNIIRYKLHKEQN GVDPYTGDQIPFERAFSEGYEVDHIIPYSISWDDSYTNKVLTSAKCNREKGNRIPMVYLANNEQ RLNALTNIADNIIRNSRKRQKLLKQKLSDEELKDWKQRNINDTRFITRVLYNYFRQAIEFNPEL EKKQRVLPLNGEVTSKIRSRWGFLKVREDGDLHHAIDATVIAAITPKFIQQVTKYSQHQEVKNN QALWHDAEIKDAEYAAEAQRMDADLFNKIFNGFPLPWPEFLDELLARISDNPVEMMKSRSWNTY TPIEIAKLKPVFVVRLANHKISGPAHLDTIRSAKLFDEKGIVLSRVSITKLKINKKGQVATGDG IYDPENSNNGDKVVYSAIRQALEAHNGSGELAFPDGYLEYVDHGTKKLVRKVRVAKKVSLPVRL KNKAAADNGSMVRIDVFNTGKKFVFVPIYIKDTVEQVLPNKAIARGKSLWYQITESDQFCFSLY PGDMVHIESKTGIKPKYSNKENNTSVVPIKNFYGYFDGADIATASILVRAHDSSYTARSIGIAG LLKFEKYQVDYFGRYHKVHEKKRQLFVKRDE SEQ ID NO: 360 MQKNINTKQNHIYIKQAQKIKEKLGDKPYRIGLDLGVGSIGFAIVSMEENDGNVLLPKEIIMVG SRIFKASAGAADRKLSRGQRNNHRHTRERMRYLWKVLAEQKLALPVPADLDRKENSSEGETSAK RFLGDVLQKDIYELRVKSLDERLSLQELGYVLYHIAGHRGSSAIRTFENDSEEAQKENTENKKI AGNIKRLMAKKNYRTYGEYLYKEFFENKEKHKREKISNAANNHKFSPTRDLVIKEAEAILKKQA GKDGFHKELTEEYIEKLTKAIGYESEKLIPESGFCPYLKDEKRLPASHKLNEERRLWETLNNAR YSDPIVDIVTGEITGYYEKQFTKEQKQKLFDYLLTGSELTPAQTKKLLGLKNTNFEDIILQGRD KKAQKIKGYKLIKLESMPFWARLSEAQQDSFLYDWNSCPDEKLLTEKLSNEYHLTEEEIDNAFN EIVLSSSYAPLGKSAMLIILEKIKNDLSYTEAVEEALKEGKLTKEKQAIKDRLPYYGAVLQEST QKIIAKGFSPQFKDKGYKTPHTNKYELEYGRIANPVVHQTLNELRKLVNEIIDILGKKPCEIGL ETARELKKSAEDRSKLSREQNDNESNRNRIYEIYIRPQQQVIITRRENPRNYILKFELLEEQKS QCPFCGGQISPNDIINNQADIEHLFPIAESEDNGRNNLVISHSACNADKAKRSPWAAFASAAKD SKYDYNRILSNVKENIPHKAWRFNQGAFEKFIENKPMAARFKTDNSYISKVAHKYLACLFEKPN IICVKGSLTAQLRMAWGLQGLMIPFAKQLITEKESESFNKDVNSNKKIRLDNRHHALDAIVIAY ASRGYGNLLNKMAGKDYKINYSERNWLSKILLPPNNIVWENIDADLESFESSVKTALKNAFISV KHDHSDNGELVKGTMYKIFYSERGYTLTTYKKLSALKLTDPQKKKTPKDFLETALLKFKGRESE MKNEKIKSAIENNKRLFDVIQDNLEKAKKLLEEENEKSKAEGKKEKNINDASIYQKAISLSGDK YVQLSKKEPGKFFAISKPTPTTTGYGYDTGDSLCVDLYYDNKGKLCGEIIRKIDAQQKNPLKYK EQGFTLFERIYGGDILEVDFDIHSDKNSFRNNTGSAPENRVFIKVGTFTEITNNNIQIWFGNII KSTGGQDDSFTINSMQQYNPRKLILSSCGFIKYRSPILKNKEG SEQ ID NO: 361 MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERAEVPKTGDSLAMARRL ARSVRRLTRRRAHRLLRARRLLKREGVLQAADFDENGLIKSLPNTPWQLRAAALDRKLTPLEWS AVLLHLIKHRGYLSQRKNEGETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHI RNQRGDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPALSGDAVQKMLG HCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSERPLTDTERATLMDEPYRKSKLTYAQA RKLLGLEDTAFFKGLRYGKDNAEASTLMEMKAYHAISRALEKEGLKDKKSPLNLSPELQDEIGT AFSLFKTDEDITGRLKDRIQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGKRYDEACAEI YGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVINGVVRRYGSPARIHIETAREVGKS FKDRKEIEKRQEENRKDREKAAAKFREYFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLG RLNEKGYVEIDHALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKARVE TSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMRLTGKGKKRVFASNGQITN LLRGFWGLRKVRAENDRHHALDAVVVACSTVAMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQ KTHFPQPWEFFAQEVMIRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSR APNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREPKLYEALKARLEAHK DDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKTGVWVRNHNGIADNATMVRVDVFEKGDKYY LVPIYSWQVAKGILPDRAVVQGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCH RGTGNINIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKRPPVR SEQ ID NO: 362 MQTTNLSYILGLDLGIASVGWAVVEINENEDPIGLIDVGVRIFERAEVPKTGESLALSRRLARS TRRLIRRRAHRLLLAKRFLKREGILSTIDLEKGLPNQAWELRVAGLERRLSAIEWGAVLLHLIK HRGYLSKRKNESQTNNKELGALLSGVAQNHQLLQSDDYRTPAELALKKFAKEEGHIRNQRGAYT HTFNRLDLLAELNLLFAQQHQFGNPHCKEHIQQYMTELLMWQKPALSGEAILKMLGKCTHEKNE FKAAKHTYSAERFVWLTKLNNLRILEDGAERALNEEERQLLINHPYEKSKLTYAQVRKLLGLSE QAIFKHLRYSKENAESATFMELKAWHAIRKALENQGLKDTWQDLAKKPDLLDEIGTAFSLYKTD EDIQQYLTNKVPNSVINALLVSLNFDKFIELSLKSLRKILPLMEQGKRYDQACREIYGHHYGEA NQKTSQLLPAIPAQEIRNPVVLRTLSQARKVINAIIRQYGSPARVHIETGRELGKSFKERREIQ KQQEDNRTKRESAVQKFKELFSDFSSEPKSKDILKFRLYEQQHGKCLYSGKEINIHRLNEKGYV EIDHALPFSRTWDDSFNNKVLVLASENQNKGNQTPYEWLQGKINSERWKNFVALVLGSQCSAAK KQRLLTQVIDDNKFIDRNLNDTRYIARFLSNYIQENLLLVGKNKKNVFTPNGQITALLRSRWGL IKARENNNRHHALDAIVVACATPSMQQKITRFIRFKEVHPYKIENRYEMVDQESGEIISPHFPE PWAYFRQEVNIRVFDNHPDTVLKEMLPDRPQANHQFVQPLFVSRAPTRKMSGQGHMETIKSAKR LAEGISVLRIPLTQLKPNLLENMVNKEREPALYAGLKARLAEFNQDPAKAFATPFYKQGGQQVK AIRVEQVQKSGVLVRENNGVADNASIVRTDVFIKNNKFFLVPIYTWQVAKGILPNKAIVAHKNE DEWEEMDEGAKFKFSLFPNDLVELKTKKEYFFGYYIGLDRATGNISLKEHDGEISKGKDGVYRV GVKLALSFEKYQVDELGKNRQICRPQQRQPVR SEQ ID NO: 363 MGIRFAFDLGTNSIGWAVWRTGPGVFGEDTAASLDGSGVLIFKDGRNPKDGQSLATMRRVPRQS RKRRDRFVLRRRDLLAALRKAGLFPVDVEEGRRLAATDPYHLRAKALDESLTPHEMGRVIFHLN QRRGFRSNRKADRQDREKGKIAEGSKRLAETLAATNCRTLGEFLWSRHRGTPRTRSPTRIRMEG EGAKALYAFYPTREMVRAEFERLWTAQSRFAPDLLTPERHEEIAGILFRQRDLAPPKIGCCTFE PSERRLPRALPSVEARGIYERLAHLRITTGPVSDRGLTRPERDVLASALLAGKSLTFKAVRKTL KILPHALVNFEEAGEKGLDGALTAKLLSKPDHYGAAWHGLSFAEKDTFVGKLLDEADEERLIRR LVTENRLSEDAARRCASIPLADGYGRLGRTANTEILAALVEETDETGTVVTYAEAVRRAGERTG RNWHHSDERDGVILDRLPYYGEILQRHVVPGSGEPEEKNEAARWGRLANPTVHIGLNQLRKVVN RLIAAHGRPDQIVVELARELKLNREQKERLDRENRKNREENERRTAILAEHGQRDTAENKIRLR LFEEQARANAGIALCPYTGRAIGIAELFTSEVEIDHILPVSLTLDDSLANRVLCRREANREKRR QTPFQAFGATPAWNDIVARAAKLPPNKRWRFDPAALERFEREGGFLGRQLNETKYLSRLAKIYL GKICDPDRVYVTPGTLTGLLRARWGLNSILSDSNFKNRSDHRHHAVDAVVIGVLTRGMIQRIAH DAARAEDQDLDRVFRDVPVPFEDFRDHVRERVSTITVAVKPEHGKGGALHEDTSYGLVPDTDPN AALGNLVVRKPIRSLTAGEVDRVRDRALRARLGALAAPFRDESGRVRDAKGLAQALEAFGAENG IRRVRILKPDASVVTIADRRTGVPYRAVAPGENHHVDIVQMRDGSWRGFAASVFEVNRPGWRPE WEVKKLGGKLVMRLHKGDMVELSDKDGQRRVKVVQQIEISANRVRLSPHNDGGKLQDRHADADD PFRWDLATIPLLKDRGCVAVRVDPIGVVTLRRSNV SEQ ID NO: 364 MMEVFMGRLVLGLDIGITSVGFGIIDLDESEIVDYGVRLFKEGTAAENETRRTKRGGRRLKRRR VTRREDMLHLLKQAGIISTSFHPLNNPYDVRVKGLNERLNGEELATALLHLCKHRGSSVETIED DEAKAKEAGETKKVLSMNDQLLKSGKYVCEIQKERLRTNGHIRGHENNFKTRAYVDEAFQILSH QDLSNELKSAIITIISRKRMYYDGPGGPLSPTPYGRYTYFGQKEPIDLIEKMRGKCSLFPNEPR APKLAYSAELFNLLNDLNNLSIEGEKLTSEQKAMILKIVHEKGKITPKQLAKEVGVSLEQIRGF RIDTKGSPLLSELTGYKMIREVLEKSNDEHLEDHVFYDEIAEILTKTKDIEGRKKQISELSSDL NEESVHQLAGLTKFTAYHSLSFKALRLINEEMLKTELNQMQSITLFGLKQNNELSVKGMKNIQA DDTAILSPVAKRAQRETFKVVNRLREIYGEFDSIVVEMAREKNSEEQRKAIRERQKFFEMRNKQ VADIIGDDRKINAKLREKLVLYQEQDGKTAYSLEPIDLKLLIDDPNAYEVDHIIPISISLDDSI TNKVLVTHRENQEKGNLTPISAFVKGRFTKGSLAQYKAYCLKLKEKNIKTNKGYRKKVEQYLLN ENDIYKYDIQKEFINRNLVDTSYASRVVLNTLTTYFKQNEIPTKVFTVKGSLTNAFRRKINLKK DRDEDYGHHAIDALIIASMPKMRLLSTIFSRYKIEDIYDESTGEVFSSGDDSMYYDDRYFAFIA SLKAIKVRKFSHKIDTKPNRSVADETIYSTRVIDGKEKVVKKYKDIYDPKFTALAEDILNNAYQ EKYLMALHDPQTFDQIVKVVNYYFEEMSKSEKYFTKDKKGRIKISGMNPLSLYRDEHGMLKKYS KKGDGPAITQMKYFDGVLGNHIDISAHYQVRDKKVVLQQISPYRTDFYYSKENGYKFVTIRYKD VRWSEKKKKYVIDQQDYAMKKAEKKIDDTYEFQFSMHRDELIGITKAEGEALIYPDETWHNFNF FFHAGETPEILKFTATNNDKSNKIEVKPIHCYCKMRLMPTISKKIVRIDKYATDVVGNLYKVKK NTLKFEFD SEQ ID NO: 365 MKKILGVDLGITSFGYAILQETGKDLYRCLDNSVVMRNNPYDEKSGESSQSIRSTQKSMRRLIE KRKKRIRCVAQTMERYGILDYSETMKINDPKNNPIKNRWQLRAVDAWKRPLSPQELFAIFAHMA KHRGYKSIATEDLIYELELELGLNDPEKESEKKADERRQVYNALRHLEELRKKYGGETIAQTIH RAVEAGDLRSYRNHDDYEKMIRREDIEEEIEKVLLRQAELGALGLPEEQVSELIDELKACITDQ EMPTIDESLFGKCTFYKDELAAPAYSYLYDLYRLYKKLADLNIDGYEVTQEDREKVIEWVEKKI AQGKNLKKITHKDLRKILGLAPEQKIFGVEDERIVKGKKEPRTFVPFFFLADIAKFKELFASIQ KHPDALQIFRELAEILQRSKTPQEALDRLRALMAGKGIDTDDRELLELFKNKRSGTRELSHRYI LEALPLFLEGYDEKEVQRILGFDDREDYSRYPKSLRHLHLREGNLFEKEENPINNHAVKSLASW ALGLIADLSWRYGPFDEIILETTRDALPEKIRKEIDKAMREREKALDKIIGKYKKEFPSIDKRL ARKIQLWERQKGLDLYSGKVINLSQLLDGSADIEHIVPQSLGGLSTDYNTIVTLKSVNAAKGNR LPGDWLAGNPDYRERIGMLSEKGLIDWKKRKNLLAQSLDEIYTENTHSKGIRATSYLEALVAQV LKRYYPFPDPELRKNGIGVRMIPGKVTSKTRSLLGIKSKSRETNFHHAEDALILSTLTRGWQNR LHRMLRDNYGKSEAELKELWKKYMPHIEGLTLADYIDEAFRRFMSKGEESLFYRDMFDTIRSIS YWVDKKPLSASSHKETVYSSRHEVPTLRKNILEAFDSLNVIKDRHKLTTEEFMKRYDKEIRQKL WLHRIGNTNDESYRAVEERATQIAQILTRYQLMDAQNDKEIDEKFQQALKELITSPIEVTGKLL RKMRFVYDKLNAMQIDRGLVETDKNMLGIHISKGPNEKLIFRRMDVNNAHELQKERSGILCYLN EMLFIFNKKGLIHYGCLRSYLEKGQGSKYIALFNPRFPANPKAQPSKFTSDSKIKQVGIGSATG IIKAHLDLDGHVRSYEVFGTLPEGSIEWFKEESGYGRVEDDPHH SEQ ID NO: 366 MRPIEPWILGLDIGTDSLGWAVFSCEEKGPPTAKELLGGGVRLFDSGRDAKDHTSRQAERGAFR RARRQTRTWPWRRDRLIALFQAAGLTPPAAETRQIALALRREAVSRPLAPDALWAALLHLAHHR GFRSNRIDKRERAAAKALAKAKPAKATAKATAPAKEADDEAGFWEGAEAALRQRMAASGAPTVG ALLADDLDRGQPVRMRYNQSDRDGVVAPTRALIAEELAEIVARQSSAYPGLDWPAVTRLVLDQR PLRSKGAGPCAFLPGEDRALRALPTVQDFIIRQTLANLRLPSTSADEPRPLTDEEHAKALALLS TARFVEWPALRRALGLKRGVKFTAETERNGAKQAARGTAGNLTEAILAPLIPGWSGWDLDRKDR VFSDLWAARQDRSALLALIGDPRGPTRVTEDETAEAVADAIQIVLPTGRASLSAKAARAIAQAM APGIGYDEAVTLALGLHHSHRPRQERLARLPYYAAALPDVGLDGDPVGPPPAEDDGAAAEAYYG RIGNISVHIALNETRKIVNALLHRHGPILRLVMVETTRELKAGADERKRMIAEQAERERENAEI DVELRKSDRWMANARERRQRVRLARRQNNLCPYTSTPIGHADLLGDAYDIDHVIPLARGGRDSL DNMVLCQSDANKTKGDKTPWEAFHDKPGWIAQRDDFLARLDPQTAKALAWRFADDAGERVARKS AEDEDQGFLPRQLTDTGYIARVALRYLSLVTNEPNAVVATNGRLTGLLRLAWDITPGPAPRDLL PTPRDALRDDTAARRFLDGLTPPPLAKAVEGAVQARLAALGRSRVADAGLADALGLTLASLGGG GKNRADHRHHFIDAAMIAVTTRGLINQINQASGAGRILDLRKWPRTNFEPPYPTFRAEVMKQWD HIHPSIRPAHRDGGSLHAATVFGVRNRPDARVLVQRKPVEKLFLDANAKPLPADKIAEIIDGFA SPRMAKRFKALLARYQAAHPEVPPALAALAVARDPAFGPRGMTANTVIAGRSDGDGEDAGLITP FRANPKAAVRTMGNAVYEVWEIQVKGRPRWTHRVLTRFDRTQPAPPPPPENARLVMRLRRGDLV YWPLESGDRLFLVKKMAVDGRLALWPARLATGKATALYAQLSCPNINLNGDQGYCVQSAEGIRK EKIRTTSCTALGRLRLSKKAT SEQ ID NO: 367 MKYTLGLDVGIASVGWAVIDKDNNKIIDLGVRCFDKAEESKTGESLATARRIARGMRRRISRRS QRLRLVKKLFVQYEIIKDSSEFNRIFDTSRDGWKDPWELRYNALSRILKPYELVQVLTHITKRR GFKSNRKEDLSTTKEGVVITSIKNNSEMLRTKNYRTIGEMIFMETPENSNKRNKVDEYIHTIAR EDLLNEIKYIFSIQRKLGSPFVTEKLEHDFLNIWEFQRPFASGDSILSKVGKCTLLKEELRAPT SCYTSEYFGLLQSINNLVLVEDNNTLTLNNDQRAKIIEYAHFKNEIKYSEIRKLLDIEPEILFK AHNLTHKNPSGNNESKKFYEMKSYHKLKSTLPTDIWGKLHSNKESLDNLFYCLTVYKNDNEIKD YLQANNLDYLIEYIAKLPTFNKFKHLSLVAMKRIIPFMEKGYKYSDACNMAELDFTGSSKLEKC NKLTVEPIIENVTNPVVIRALTQARKVINAIIQKYGLPYMVNIELAREAGMTRQDRDNLKKEHE NNRKAREKISDLIRQNGRVASGLDILKWRLWEDQGGRCAYSGKPIPVCDLLNDSLTQIDHIYPY SRSMDDSYMNKVLVLTDENQNKRSYTPYEVWGSTEKWEDFEARIYSMHLPQSKEKRLLNRNFIT KDLDSFISRNLNDTRYISRFLKNYIESYLQFSNDSPKSCVVCVNGQCTAQLRSRWGLNKNREES DLHHALDAAVIACADRKIIKEITNYYNERENHNYKVKYPLPWHSFRQDLMETLAGVFISRAPRR KITGPAHDETIRSPKHFNKGLTSVKIPLTTVTLEKLETMVKNTKGGISDKAVYNVLKNRLIEHN NKPLKAFAEKIYKPLKNGTNGAIIRSIRVETPSYTGVFRNEGKGISDNSLMVRVDVFKKKDKYY LVPIYVAHMIKKELPSKAIVPLKPESQWELIDSTHEFLFSLYQNDYLVIKTKKGITEGYYRSCH RGTGSLSLMPHFANNKNVKIDIGVRTAISIEKYNVDILGNKSIVKGEPRRGMEKYNSFKSN SEQ ID NO: 368 MIRTLGIDIGIASIGWAVIEGEYTDKGLENKEIVASGVRVFTKAENPKNKESLALPRTLARSAR RRNARKKGRIQQVKHYLSKALGLDLECFVQGEKLATLFQTSKDFLSPWELRERALYRVLDKEEL ARVILHIAKRRGYDDITYGVEDNDSGKIKKAIAENSKRIKEEQCKTIGEMMYKLYFQKSLNVRN KKESYNRCVGRSELREELKTIFQIQQELKSPWVNEELIYKLLGNPDAQSKQEREGLIFYQRPLK GFGDKIGKCSHIKKGENSPYRACKHAPSAEEFVALTKSINFLKNLTNRHGLCFSQEDMCVYLGK ILQEAQKNEKGLTYSKLKLLLDLPSDFEFLGLDYSGKNPEKAVFLSLPSTFKLNKITQDRKTQD KIANILGANKDWEAILKELESLQLSKEQIQTIKDAKLNFSKHINLSLEALYHLLPLMREGKRYD EGVEILQERGIFSKPQPKNRQLLPPLSELAKEESYFDIPNPVLRRALSEFRKVVNALLEKYGGF HYFHIELTRDVCKAKSARMQLEKINKKNKSENDAASQLLEVLGLPNTYNNRLKCKLWKQQEEYC LYSGEKITIDHLKDQRALQIDHAFPLSRSLDDSQSNKVLCLTSSNQEKSNKTPYEWLGSDEKKW DMYVGRVYSSNFSPSKKRKLTQKNFKERNEEDFLARNLVDTGYIGRVTKEYIKHSLSFLPLPDG KKEHIRIISGSMTSTMRSFWGVQEKNRDHHLHHAQDAIIIACIEPSMIQKYTTYLKDKETHRLK SHQKAQILREGDHKLSLRWPMSNFKDKIQESIQNIIPSHHVSHKVTGELHQETVRTKEFYYQAF GGEEGVKKALKFGKIREINQGIVDNGAMVRVDIFKSKDKGKFYAVPIYTYDFAIGKLPNKAIVQ GKKNGIIKDWLEMDENYEFCFSLFKNDCIKIQTKEMQEAVLAIYKSTNSAKATIELEHLSKYAL KNEDEEKMFTDTDKEKNKTMTRESCGIQGLKVFQKVKLSVLGEVLEHKPRNRQNIALKTTPKHV SEQ ID NO: 369 MKYSIGLDIGIASVGWSVINKDKERIEDMGVRIFQKAENPKDGSSLASSRREKRGSRRRNRRKK HRLDRIKNILCESGLVKKNEIEKIYKNAYLKSPWELRAKSLEAKISNKEIAQILLHIAKRRGFK SFRKTDRNADDTGKLLSGIQENKKIMEEKGYLTIGDMVAKDPKFNTHVRNKAGSYLFSFSRKLL EDEVRKIQAKQKELGNTHFTDDVLEKYIEVFNSQRNFDEGPSKPSPYYSEIGQIAKMIGNCTFE SSEKRTAKNTWSGERFVFLQKLNNFRIVGLSGKRPLTEEERDIVEKEVYLKKEVRYEKLRKILY LKEEERFGDLNYSKDEKQDKKTEKTKFISLIGNYTIKKLNLSEKLKSEIEEDKSKLDKIIEILT FNKSDKTIESNLKKLELSREDIEILLSEEFSGTLNLSLKAIKKILPYLEKGLSYNEACEKADYD YKNNGIKFKRGELLPVVDKDLIANPVVLRAISQTRKVVNAIIRKYGTPHTIHVEVARDLAKSYD DRQTIIKENKKRELENEKTKKFISEEFGIKNVKGKLLLKYRLYQEQEGRCAYSRKELSLSEVIL DESMTDIDHIIPYSRSMDDSYSNKVLVLSGENRKKSNLLPKEYFDRQGRDWDTFVLNVKAMKIH PRKKSNLLKEKFTREDNKDWKSRALNDTRYISRFVANYLENALEYRDDSPKKRVFMIPGQLTAQ LRARWRLNKVRENGDLHHALDAAVVAVTDQKAINNISNISRYKELKNCKDVIPSIEYHADEETG EVYFEEVKDTRFPMPWSGFDLELQKRLESENPREEFYNLLSDKRYLGWFNYEEGFIEKLRPVFV SRMPNRGVKGQAHQETIRSSKKISNQIAVSKKPLNSIKLKDLEKMQGRDTDRKLYEALKNRLEE YDDKPEKAFAEPFYKPTNSGKRGPLVRGIKVEEKQNVGVYVNGGQASNGSMVRIDVFRKNGKFY TVPIYVHQTLLKELPNRAINGKPYKDWDLIDGSFEFLYSFYPNDLIEIEFGKSKSIKNDNKLTK TEIPEVNLSEVLGYYRGMDTSTGAATIDTQDGKIQMRIGIKTVKNIKKYQVDVLGNVYKVKREK RQTF SEQ ID NO: 370 MSKKVSRRYEEQAQEICQRLGSRPYSIGLDLGVGSIGVAVAAYDPIKKQPSDLVFVSSRIFIPS TGAAERRQKRGQRNSLRHRANRLKFLWKLLAERNLMLSYSEQDVPDPARLRFEDAVVRANPYEL RLKGLNEQLTLSELGYALYHIANHRGSSSVRTFLDEEKSSDDKKLEEQQAMTEQLAKEKGISTF IEVLTAFNTNGLIGYRNSESVKSKGVPVPTRDIISNEIDVLLQTQKQFYQEILSDEYCDRIVSA ILFENEKIVPEAGCCPYFPDEKKLPRCHFLNEERRLWEAINNARIKMPMQEGAAKRYQSASFSD EQRHILFHIARSGTDITPKLVQKEFPALKTSIIVLQGKEKAIQKIAGFRFRRLEEKSFWKRLSE EQKDDFFSAWTNTPDDKRLSKYLMKHLLLTENEVVDALKTVSLIGDYGPIGKTATQLLMKHLED GLTYTEALERGMETGEFQELSVWEQQSLLPYYGQILTGSTQALMGKYWHSAFKEKRDSEGFFKP NTNSDEEKYGRIANPVVHQTLNELRKLMNELITILGAKPQEITVELARELKVGAEKREDIIKQQ TKQEKEAVLAYSKYCEPNNLDKRYIERFRLLEDQAFVCPYCLEHISVADIAAGRADVDHIFPRD DTADNSYGNKVVAHRQCNDIKGKRTPYAAFSNTSAWGPIMHYLDETPGMWRKRRKFETNEEEYA KYLQSKGFVSRFESDNSYIAKAAKEYLRCLFNPNNVTAVGSLKGMETSILRKAWNLQGIDDLLG SRHWSKDADTSPTMRKNRDDNRHHGLDAIVALYCSRSLVQMINTMSEQGKRAVEIEAMIPIPGY ASEPNLSFEAQRELFRKKILEFMDLHAFVSMKTDNDANGALLKDTVYSILGADTQGEDLVFVVK KKIKDIGVKIGDYEEVASAIRGRITDKQPKWYPMEMKDKIEQLQSKNEAALQKYKESLVQAAAV LEESNRKLIESGKKPIQLSEKTISKKALELVGGYYYLISNNKRTKTFVVKEPSNEVKGFAFDTG SNLCLDFYHDAQGKLCGEIIRKIQAMNPSYKPAYMKQGYSLYVRLYQGDVCELRASDLTEAESN LAKTTHVRLPNAKPGRTFVIIITFTEMGSGYQIYFSNLAKSKKGQDTSFTLTTIKNYDVRKVQL SSAGLVRYVSPLLVDKIEKDEVALCGE SEQ ID NO: 371 MNQKFILGLDIGITSVGYGLIDYETKNIIDAGVRLFPEANVENNEGRRSKRGSRRLKRRRIHRL ERVKKLLEDYNLLDQSQIPQSTNPYAIRVKGLSEALSKDELVIALLHIAKRRGIHKIDVIDSND DVGNELSTKEQLNKNSKLLKDKFVCQIQLERMNEGQVRGEKNRFKTADIIKEIIQLLNVQKNFH QLDENFINKYIELVEMRREYFEGPGKGSPYGWEGDPKAWYETLMGHCTYFPDELRSVKYAYSAD LFNALNDLNNLVIQRDGLSKLEYHEKYHIIENVFKQKKKPTLKQIANEINVNPEDIKGYRITKS GKPQFTEFKLYHDLKSVLFDQSILENEDVLDQIAEILTIYQDKDSIKSKLTELDILLNEEDKEN IAQLTGYTGTHRLSLKCIRLVLEEQWYSSRNQMEIFTHLNIKPKKINLTAANKIPKAMIDEFIL SPVVKRTFGQAINLINKIIEKYGVPEDIIIELARENNSKDKQKFINEMQKKNENTRKRINEIIG KYGNQNAKRLVEKIRLHDEQEGKCLYSLESIPLEDLLNNPNHYEVDHIIPRSVSFDNSYHNKVL VKQSENSKKSNLTPYQYFNSGKSKLSYNQFKQHILNLSKSQDRISKKKKEYLLEERDINKFEVQ KEFINRNLVDTRYATRELTNYLKAYFSANNMNVKVKTINGSFTDYLRKVWKFKKERNHGYKHHA EDALIIANADFLFKENKKLKAVNSVLEKPEIESKQLDIQVDSEDNYSEMFIIPKQVQDIKDFRN FKYSHRVDKKPNRQLINDTLYSTRKKDNSTYIVQTIKDIYAKDNTTLKKQFDKSPEKFLMYQHD PRTFEKLEVIMKQYANEKNPLAKYHEETGEYLTKYSKKNNGPIVKSLKYIGNKLGSHLDVTHQF KSSTKKLVKLSIKPYRFDVYLTDKGYKFITISYLDVLKKDNYYYIPEQKYDKLKLGKAIDKNAK FIASFYKNDLIKLDGEIYKIIGVNSDTRNMIELDLPDIRYKEYCELNNIKGEPRIKKTIGKKVN SIEKLTTDVLGNVFTNTQYTKPQLLFKRGN SEQ ID NO: 372 MIMKLEKWRLGLDLGTNSIGWSVFSLDKDNSVQDLIDMGVRIFSDGRDPKTKEPLAVARRTARS QRKLIYRRKLRRKQVFKFLQEQGLFPKTKEECMTLKSLNPYELRIKALDEKLEPYELGRALFNL AVRRGFKSNRKDGSREEVSEKKSPDEIKTQADMQTHLEKAIKENGCRTITEFLYKNQGENGGIR FAPGRMTYYPTRKMYEEEFNLIRSKQEKYYPQVDWDDIYKAIFYQRPLKPQQRGYCIYENDKER TFKAMPCSQKLRILQDIGNLAYYEGGSKKRVELNDNQDKVLYELLNSKDKVTFDQMRKALCLAD SNSFNLEENRDFLIGNPTAVKMRSKNRFGKLWDEIPLEEQDLIIETIITADEDDAVYEVIKKYD LTQEQRDFIVKNTILQSGTSMLCKEVSEKLVKRLEEIADLKYHEAVESLGYKFADQTVEKYDLL PYYGKVLPGSTMEIDLSAPETNPEKHYGKISNPTVHVALNQTRVVVNALIKEYGKPSQIAIELS RDLKNNVEKKAEIARKQNQRAKENIAINDTISALYHTAFPGKSFYPNRNDRMKYRLWSELGLGN KCIYCGKGISGAELFTKEIEIEHILPFSRTLLDAESNLTVAHSSCNAFKAERSPFEAFGTNPSG YSWQEIIQRANQLKNTSKKNKFSPNAMDSFEKDSSFIARQLSDNQYIAKAALRYLKCLVENPSD VWTTNGSMTKLLRDKWEMDSILCRKFTEKEVALLGLKPEQIGNYKKNRFDHRHHAIDAVVIGLT DRSMVQKLATKNSHKGNRIEIPEFPILRSDLIEKVKNIVVSFKPDHGAEGKLSKETLLGKIKLH GKETFVCRENIVSLSEKNLDDIVDEIKSKVKDYVAKHKGQKIEAVLSDFSKENGIKKVRCVNRV QTPIEITSGKISRYLSPEDYFAAVIWEIPGEKKTFKAQYIRRNEVEKNSKGLNVVKPAVLENGK PHPAAKQVCLLHKDDYLEFSDKGKMYFCRIAGYAATNNKLDIRPVYAVSYCADWINSTNETMLT GYWKPTPTQNWVSVNVLFDKQKARLVTVSPIGRVFRK SEQ ID NO: 373 MSSKAIDSLEQLDLFKPQEYTLGLDLGIKSIGWAILSGERIANAGVYLFETAEELNSTGNKLIS KAAERGRKRRIRRMLDRKARRGRHIRYLLEREGLPTDELEEVVVHQSNRTLWDVRAEAVERKLT KQELAAVLFHLVRHRGYFPNTKKLPPDDESDSADEEQGKINRATSRLREELKASDCKTIGQFLA QNRDRQRNREGDYSNLMARKLVFEEALQILAFQRKQGHELSKDFEKTYLDVLMGQRSGRSPKLG NCSLIPSELRAPSSAPSTEWFKFLQNLGNLQISNAYREEWSIDAPRRAQIIDACSQRSTSSYWQ IRRDFQIPDEYRFNLVNYERRDPDVDLQEYLQQQERKTLANFRNWKQLEKIIGTGHPIQTLDEA ARLITLIKDDEKLSDQLADLLPEASDKAITQLCELDFTTAAKISLEAMYRILPHMNQGMGFFDA CQQESLPEIGVPPAGDRVPPFDEMYNPVVNRVLSQSRKLINAVIDEYGMPAKIRVELARDLGKG RELRERIKLDQLDKSKQNDQRAEDFRAEFQQAPRGDQSLRYRLWKEQNCTCPYSGRMIPVNSVL SEDTQIDHILPISQSFDNSLSNKVLCFTEENAQKSNRTPFEYLDAADFQRLEAISGNWPEAKRN KLLHKSFGKVAEEWKSRALNDTRYLTSALADHLRHHLPDSKIQTVNGRITGYLRKQWGLEKDRD KHTHHAVDAIVVACTTPAIVQQVTLYHQDIRRYKKLGEKRPTPWPETFRQDVLDVEEEIFITRQ PKKVSGGIQTKDTLRKHRSKPDRQRVALTKVKLADLERLVEKDASNRNLYEHLKQCLEESGDQP TKAFKAPFYMPSGPEAKQRPILSKVTLLREKPEPPKQLTELSGGRRYDSMAQGRLDIYRYKPGG KRKDEYRVVLQRMIDLMRGEENVHVFQKGVPYDQGPEIEQNYTFLFSLYFDDLVEFQRSADSEV IRGYYRTFNIANGQLKISTYLEGRQDFDFFGANRLAHFAKVQVNLLGKVIK SEQ ID NO: 374 MRSLRYRLALDLGSTSLGWALFRLDACNRPTAVIKAGVRIFSDGRNPKDGSSLAVTRRAARAMR RRRDRLLKRKTRMQAKLVEHGFFPADAGKRKALEQLNPYALRAKGLQEALLPGEFARALFHINQ RRGFKSNRKTDKKDNDSGVLKKAIGQLRQQMAEQGSRTVGEYLWTRLQQGQGVRARYREKPYTT EEGKKRIDKSYDLYIDRAMIEQEFDALWAAQAAFNPTLFHEAARADLKDTLLHQRPLRPVKPGR CTLLPEEERAPLALPSTQRFRIHQEVNHLRLLDENLREVALTLAQRDAVVTALETKAKLSFEQI RKLLKLSGSVQFNLEDAKRTELKGNATSAALARKELFGAAWSGFDEALQDEIVWQLVTEEGEGA LIAWLQTHTGVDEARAQAIVDVSLPEGYGNLSRKALARIVPALRAAVITYDKAVQAAGFDHHSQ LGFEYDASEVEDLVHPETGEIRSVFKQLPYYGKALQRHVAFGSGKPEDPDEKRYGKIANPTVHI GLNQVRMVVNALIRRYGRPTEVVIELARDLKQSREQKVEAQRRQADNQRRNARIRRSIAEVLGI GEERVRGSDIQKWICWEELSFDAADRRCPYSGVQISAAMLLSDEVEVEHILPFSKTLDDSLNNR TVAMRQANRIKRNRTPWDARAEFEAQGWSYEDILQRAERMPLRKRYRFAPDGYERWLGDDKDFL ARALNDTRYLSRVAAEYLRLVCPGTRVIPGQLTALLRGKFGLNDVLGLDGEKNRNDHRHHAVDA CVIGVTDQGLMQRFATASAQARGDGLTRLVDGMPMPWPTYRDHVERAVRHIWVSHRPDHGFEGA MMEETSYGIRKDGSIKQRRKADGSAGREISNLIRIHEATQPLRHGVSADGQPLAYKGYVGGSNY CIEITVNDKGKWEGEVISTFRAYGVVRAGGMGRLRNPHEGQNGRKLIMRLVIGDSVRLEVDGAE RTMRIVKISGSNGQIFMAPIHEANVDARNTDKQDAFTYTSKYAGSLQKAKTRRVTISPIGEVRD PGFKG SEQ ID NO: 375 MARPAFRAPRREHVNGWTPDPHRISKPFFILVSWHLLSRVVIDSSSGCFPGTSRDHTDKFAEWE CAVQPYRLSFDLGTNSIGWGLLNLDRQGKPREIRALGSRIFSDGRDPQDKASLAVARRLARQMR RRRDRYLTRRTRLMGALVRFGLMPADPAARKRLEVAVDPYLARERATRERLEPFEIGRALFHLN QRRGYKPVRTATKPDEEAGKVKEAVERLEAAIAAAGAPTLGAWFAWRKTRGETLRARLAGKGKE AAYPFYPARRMLEAEFDTLWAEQARHHPDLLTAEAREILRHRIFHQRPLKPPPVGRCTLYPDDG RAPRALPSAQRLRLFQELASLRVIHLDLSERPLTPAERDRIVAFVQGRPPKAGRKPGKVQKSVP FEKLRGLLELPPGTGFSLESDKRPELLGDETGARIAPAFGPGWTALPLEEQDALVELLLTEAEP ERAIAALTARWALDEATAAKLAGATLPDFHGRYGRRAVAELLPVLERETRGDPDGRVRPIRLDE AVKLLRGGKDHSDFSREGALLDALPYYGAVLERHVAFGTGNPADPEEKRVGRVANPTVHIALNQ LRHLVNAILARHGRPEEIVIELARDLKRSAEDRRREDKRQADNQKRNEERKRLILSLGERPTPR NLLKLRLWEEQGPVENRRCPYSGETISMRMLLSEQVDIDHILPFSVSLDDSAANKVVCLREANR IKRNRSPWEAFGHDSERWAGILARAEALPKNKRWRFAPDALEKLEGEGGLRARHLNDTRHLSRL AVEYLRCVCPKVRVSPGRLTALLRRRWGIDAILAEADGPPPEVPAETLDPSPAEKNRADHRHHA LDAVVIGCIDRSMVQRVQLAAASAEREAAAREDNIRRVLEGFKEEPWDGFRAELERRARTIVVS HRPEHGIGGALHKETAYGPVDPPEEGFNLVVRKPIDGLSKDEINSVRDPRLRRALIDRLAIRRR DANDPATALAKAAEDLAAQPASRGIRRVRVLKKESNPIRVEHGGNPSGPRSGGPFHKLLLAGEV HHVDVALRADGRRWVGHWVTLFEAHGGRGADGAAAPPRLGDGERFLMRLHKGDCLKLEHKGRVR VMQVVKLEPSSNSVVVVEPHQVKTDRSKHVKISCDQLRARGARRVTVDPLGRVRVHAPGARVGI GGDAGRTAMEPAEDIS SEQ ID NO: 376 MKRTSLRAYRLGVDLGANSLGWFVVWLDDHGQPEGLGPGGVRIFPDGRNPQSKQSNAAGRRLAR SARRRRDRYLQRRGKLMGLLVKHGLMPADEPARKRLECLDPYGLRAKALDEVLPLHHVGRALFH LNQRRGLFANRAIEQGDKDASAIKAAAGRLQTSMQACGARTLGEFLNRRHQLRATVRARSPVGG DVQARYEFYPTRAMVDAEFEAIWAAQAPHHPTMTAEAHDTIREAIFSQRAMKRPSIGKCSLDPA TSQDDVDGFRCAWSHPLAQRFRIWQDVRNLAVVETGPTSSRLGKEDQDKVARALLQTDQLSFDE IRGLLGLPSDARFNLESDRRDHLKGDATGAILSARRHFGPAWHDRSLDRQIDIVALLESALDEA AIIASLGTTHSLDEAAAQRALSALLPDGYCRLGLRAIKRVLPLMEAGRTYAEAASAAGYDHALL PGGKLSPTGYLPYYGQWLQNDVVGSDDERDTNERRWGRLPNPTVHIGIGQLRRVVNELIRWHGP PAEITVELTRDLKLSPRRLAELEREQAENQRKNDKRTSLLRKLGLPASTHNLLKLRLWDEQGDV ASECPYTGEAIGLERLVSDDVDIDHLIPFSISWDDSAANKVVCMRYANREKGNRTPFEAFGHRQ GRPYDWADIAERAARLPRGKRWRFGPGARAQFEELGDFQARLLNETSWLARVAKQYLAAVTHPH RIHVLPGRLTALLRATWELNDLLPGSDDRAAKSRKDHRHHAIDALVAALTDQALLRRMANAHDD TRRKIEVLLPWPTFRIDLETRLKAMLVSHKPDHGLQARLHEDTAYGTVEHPETEDGANLVYRKT FVDISEKEIDRIRDRRLRDLVRAHVAGERQQGKTLKAAVLSFAQRRDIAGHPNGIRHVRLTKSI KPDYLVPIRDKAGRIYKSYNAGENAFVDILQAESGRWIARATTVFQANQANESHDAPAAQPIMR VFKGDMLRIDHAGAEKFVKIVRLSPSNNLLYLVEHHQAGVFQTRHDDPEDSFRWLFASFDKLRE WNAELVRIDTLGQPWRRKRGLETGSEDATRIGWTRPKKWP SEQ ID NO: 377 MERIFGFDIGTTSIGFSVIDYSSTQSAGNIQRLGVRIFPEARDPDGTPLNQQRRQKRMMRRQLR RRRIRRKALNETLHEAGFLPAYGSADWPVVMADEPYELRRRGLEEGLSAYEFGRAIYHLAQHRH FKGRELEESDTPDPDVDDEKEAANERAATLKALKNEQTTLGAWLARRPPSDRKRGIHAHRNVVA EEFERLWEVQSKFHPALKSEEMRARISDTIFAQRPVFWRKNTLGECRFMPGEPLCPKGSWLSQQ RRMLEKLNNLAIAGGNARPLDAEERDAILSKLQQQASMSWPGVRSALKALYKQRGEPGAEKSLK FNLELGGESKLLGNALEAKLADMFGPDWPAHPRKQEIRHAVHERLWAADYGETPDKKRVIILSE KDRKAHREAAANSFVADFGITGEQAAQLQALKLPTGWEPYSIPALNLFLAELEKGERFGALVNG PDWEGWRRTNFPHRNQPTGEILDKLPSPASKEERERISQLRNPTVVRTQNELRKVVNNLIGLYG KPDRIRIEVGRDVGKSKREREEIQSGIRRNEKQRKKATEDLIKNGIANPSRDDVEKWILWKEGQ ERCPYTGDQIGFNALFREGRYEVEHIWPRSRSFDNSPRNKTLCRKDVNIEKGNRMPFEAFGHDE DRWSAIQIRLQGMVSAKGGTGMSPGKVKRFLAKTMPEDFAARQLNDTRYAAKQILAQLKRLWPD MGPEAPVKVEAVTGQVTAQLRKLWTLNNILADDGEKTRADHRHHAIDALTVACTHPGMTNKLSR YWQLRDDPRAEKPALTPPWDTIRADAEKAVSEIVVSHRVRKKVSGPLHKETTYGDTGTDIKTKS GTYRQFVTRKKIESLSKGELDEIRDPRIKEIVAAHVAGRGGDPKKAFPPYPCVSPGGPEIRKVR LTSKQQLNLMAQTGNGYADLGSNHHIAIYRLPDGKADFEIVSLFDASRRLAQRNPIVQRTRADG ASFVMSLAAGEAIMIPEGSKKGIWIVQGVWASGQVVLERDTDADHSTTTRPMPNPILKDDAKKV SIDPIGRVRPSND SEQ ID NO: 378 MNKRILGLDTGTNSLGWAVVDWDEHAQSYELIKYGDVIFQEGVKIEKGIESSKAAERSGYKAIR KQYFRRRLRKIQVLKVLVKYHLCPYLSDDDLRQWHLQKQYPKSDELMLWQRTSDEEGKNPYYDR HRCLHEKLDLTVEADRYTLGRALYHLTQRRGFLSNRLDTSADNKEDGVVKSGISQLSTEMEEAG CEYLGDYFYKLYDAQGNKVRIRQRYTDRNKHYQHEFDAICEKQELSSELIEDLQRAIFFQLPLK SQRHGVGRCTFERGKPRCADSHPDYEEFRMLCFVNNIQVKGPHDLELRPLTYEEREKIEPLFFR KSKPNFDFEDIAKALAGKKNYAWIHDKEERAYKFNYRMTQGVPGCPTIAQLKSIFGDDWKTGIA ETYTLIQKKNGSKSLQEMVDDVWNVLYSFSSVEKLKEFAHHKLQLDEESAEKFAKIKLSHSFAA LSLKAIRKFLPFLRKGMYYTHASFFANIPTIVGKEIWNKEQNRKYIMENVGELVFNYQPKHREV QGTIEMLIKDFLANNFELPAGATDKLYHPSMIETYPNAQRNEFGILQLGSPRTNAIRNPMAMRS LHILRRVVNQLLKESIIDENTEVHVEYARELNDANKRRAIADRQKEQDKQHKKYGDEIRKLYKE ETGKDIEPTQTDVLKFQLWEEQNHHCLYTGEQIGITDFIGSNPKFDIEHTIPQSVGGDSTQMNL TLCDNRFNREVKKAKLPTELANHEEILTRIEPWKNKYEQLVKERDKQRTFAGMDKAVKDIRIQK RHKLQMEIDYWRGKYERFTMTEVPEGFSRRQGTGIGLISRYAGLYLKSLFHQADSRNKSNVYVV KGVATAEFRKMWGLQSEYEKKCRDNHSHHCMDAITIACIGKREYDLMAEYYRMEETFKQGRGSK PKFSKPWATFTEDVLNIYKNLLVVHDTPNNMPKHTKKYVQTSIGKVLAQGDTARGSLHLDTYYG AIERDGEIRYVVRRPLSSFTKPEELENIVDETVKRTIKEAIADKNFKQAIAEPIYMNEEKGILI KKVRCFAKSVKQPINIRQHRDLSKKEYKQQYHVMNENNYLLAIYEGLVKNKVVREFEIVSYIEA AKYYKRSQDRNIFSSIVPTHSTKYGLPLKTKLLMGQLVLMFEENPDEIQVDNTKDLVKRLYKVV GIEKDGRIKFKYHQEARKEGLPIFSTPYKNNDDYAPIFRQSINNINILVDGIDFTIDILGKVTL KE SEQ ID NO: 379 MNYKMGLDIGIASVGWAVINLDLKRIEDLGVRIFDKAEHPQNGESLALPRRIARSARRRLRRRK HRLERIRRLLVSENVLTKEEMNLLFKQKKQIDVWQLRVDALERKLNNDELARVLLHLAKRRGFK SNRKSERNSKESSEFLKNIEENQSILAQYRSVGEMIVKDSKFAYHKRNKLDSYSNMIARDDLER EIKLIFEKQREFNNPVCTERLEEKYLNIWSSQRPFASKEDIEKKVGFCTFEPKEKRAPKATYTF QSFIVWEHINKLRLVSPDETRALTEIERNLLYKQAFSKNKMTYYDIRKLLNLSDDIHFKGLLYD PKSSLKQIENIRFLELDSYHKIRKCIENVYGKDGIRMFNETDIDTFGYALTIFKDDEDIVAYLQ NEYITKNGKRVSNLANKVYDKSLIDELLNLSFSKFAHLSMKAIRNILPYMEQGEIYSKACELAG YNFTGPKKKEKALLLPVIPNIANPVVMRALTQSRKVVNAIIKKYGSPVSIHIELARDLSHSFDE RKKIQKDQTENRKKNETAIKQLIEYELTKNPTGLDIVKFKLWSEQQGRCMYSLKPIELERLLEP GYVEVDHILPYSRSLDDSYANKVLVLTKENREKGNHTPVEYLGLGSERWKKFEKFVLANKQFSK KKKQNLLRLRYEETEEKEFKERNLNDTRYISKFFANFIKEHLKFADGDGGQKVYTINGKITAHL RSRWDFNKNREESDLHHAVDAVIVACATQGMIKKITEFYKAREQNKESAKKKEPIFPQPWPHFA DELKARLSKFPQESIEAFALGNYDRKKLESLRPVFVSRMPKRSVTGAAHQETLRRCVGIDEQSG KIQTAVKTKLSDIKLDKDGHFPMYQKESDPRTYEAIRQRLLEHNNDPKKAFQEPLYKPKKNGEP GPVIRTVKIIDTKNKVVHLDGSKTVAYNSNIVRTDVFEKDGKYYCVPVYTMDIMKGTLPNKAIE ANKPYSEWKEMTEEYTFQFSLFPNDLVRIVLPREKTIKTSTNEEIIIKDIFAYYKTIDSATGGL ELISHDRNFSLRGVGSKTLKRFEKYQVDVLGNIHKVKGEKRVGLAAPTNQKKGKTVDSLQSVSD SEQ ID NO: 380 MRRLGLDLGTNSIGWCLLDLGDDGEPVSIFRTGARIFSDGRDPKSLGSLKATRREARLTRRRRD RFIQRQKNLINALVKYGLMPADEIQRQALAYKDPYPIRKKALDEAIDPYEMGRAIFHINQRRGF KSNRKSADNEAGVVKQSIADLEMKLGEAGARTIGEFLADRQATNDTVRARRLSGTNALYEFYPD RYMLEQEFDTLWAKQAAFNPSLYIEAARERLKEIVFFQRKLKPQEVGRCIFLSDEDRISKALPS FQRFRIYQELSNLAWIDHDGVAHRITASLALRDHLFDELEHKKKLTFKAMRAILRKQGVVDYPV GFNLESDNRDHLIGNLTSCIMRDAKKMIGSAWDRLDEEEQDSFILMLQDDQKGDDEVRSILTQQ YGLSDDVAEDCLDVRLPDGHGSLSKKAIDRILPVLRDQGLIYYDAVKEAGLGEANLYDPYAALS DKLDYYGKALAGHVMGASGKFEDSDEKRYGTISNPTVHIALNQVRAVVNELIRLHGKPDEVVIE IGRDLPMGADGKRELERFQKEGRAKNERARDELKKLGHIDSRESRQKFQLWEQLAKEPVDRCCP FTGKMMSISDLFSDKVEIEHLLPFSLTLDDSMANKTVCFRQANRDKGNRAPFDAFGNSPAGYDW QEILGRSQNLPYAKRWRFLPDAMKRFEADGGFLERQLNDTRYISRYTTEYISTIIPKNKIWVVT GRLTSLLRGFWGLNSILRGHNTDDGTPAKKSRDDHRHHAIDAIVVGMTSRGLLQKVSKAARRSE DLDLTRLFEGRIDPWDGFRDEVKKHIDAIIVSHRPRKKSQGALHNDTAYGIVEHAENGASTVVH RVPITSLGKQSDIEKVRDPLIKSALLNETAGLSGKSFENAVQKWCADNSIKSLRIVETVSIIPI TDKEGVAYKGYKGDGNAYMDIYQDPTSSKWKGEIVSRFDANQKGFIPSWQSQFPTARLIMRLRI NDLLKLQDGEIEEIYRVQRLSGSKILMAPHTEANVDARDRDKNDTFKLTSKSPGKLQSASARKV HISPTGLIREG SEQ ID NO: 381 MKNILGLDLGLSSIGWSVIRENSEEQELVAMGSRVVSLTAAELSSFTQGNGVSINSQRTQKRTQ RKGYDRYQLRRTLLRNKLDTLGMLPDDSLSYLPKLQLWGLRAKAVTQRIELNELGRVLLHLNQK RGYKSIKSDFSGDKKITDYVKTVKTRYDELKEMRLTIGELFFRRLTENAFFRCKEQVYPRQAYV EEFDCIMNCQRKFYPDILTDETIRCIRDEIIYYQRPLKSCKYLVSRCEFEKRFYLNAAGKKTEA GPKVSPRTSPLFQVCRLWESINNIVVKDRRNEIVFISAEQRAALFDFLNTHEKLKGSDLLKLLG LSKTYGYRLGEQFKTGIQGNKTRVEIERALGNYPDKKRLLQFNLQEESSSMVNTETGEIIPMIS LSFEQEPLYRLWHVLYSIDDREQLQSVLRQKFGIDDDEVLERLSAIDLVKAGFGNKSSKAIRRI LPFLQLGMNYAEACEAAGYNHSNNYTKAENEARALLDRLPAIKKNELRQPVVEKILNQMVNVVN ALMEKYGRFDEIRVELARELKQSKEERSNTYKSINKNQRENEQIAKRIVEYGVPTRSRIQKYKM WEESKHCCIYCGQPVDVGDFLRGFDVEVEHIIPKSLYFDDSFANKVCSCRSCNKEKNNRTAYDY MKSKGEKALSDYVERVNTMYTNNQISKTKWQNLLTPVDKISIDFIDRQLRESQYIARKAKEILT SICYNVTATSGSVTSFLRHVWGWDTVLHDLNFDRYKKVGLTEVIEVNHRGSVIRREQIKDWSKR FDHRHHAIDALTIACTKQAYIQRLNNLRAEEGPDFNKMSLERYIQSQPHFSVAQVREAVDRILV SFRAGKRAVTPGKRYIRKNRKRISVQSVLIPRGALSEESVYGVIHVWEKDEQGHVIQKQRAVMK YPITSINREMLDKEKVVDKRIHRILSGRLAQYNDNPKEAFAKPVYIDKECRIPIRTVRCFAKPA INTLVPLKKDDKGNPVAWVNPGNNHHVAIYRDEDGKYKERTVTFWEAVDRCRVGIPAIVTQPDT IWDNILQRNDISENVLESLPDVKWQFVLSLQQNEMFILGMNEEDYRYAMDQQDYALLNKYLYRV QKLSKSDYSFRYHTETSVEDKYDGKPNLKLSMQMGKLKRVSIKSLLGLNPHKVHISVLGEIKEI S SEQ ID NO: 382 MAEKQHRWGLDIGTNSIGWAVIALIEGRPAGLVATGSRIFSDGRNPKDGSSLAVERRGPRQMRR RRDRYLRRRDRFMQALINVGLMPGDAAARKALVTENPYVLRQRGLDQALTLPEFGRALFHLNQR RGFQSNRKTDRATAKESGKVKNAIAAFRAGMGNARTVGEALARRLEDGRPVRARMVGQGKDEHY ELYIAREWIAQEFDALWASQQRFHAEVLADAARDRLRAILLFQRKLLPVPVGKCFLEPNQPRVA AALPSAQRFRLMQELNHLRVMTLADKRERPLSFQERNDLLAQLVARPKCGFDMLRKIVFGANKE AYRFTIESERRKELKGCDTAAKLAKVNALGTRWQALSLDEQDRLVCLLLDGENDAVLADALREH YGLTDAQIDTLLGLSFEDGHMRLGRSALLRVLDALESGRDEQGLPLSYDKAVVAAGYPAHTADL ENGERDALPYYGELLWRYTQDAPTAKNDAERKFGKIANPTVHIGLNQLRKLVNALIQRYGKPAQ IVVELARNLKAGLEEKERIKKQQTANLERNERIRQKLQDAGVPDNRENRLRMRLFEELGQGNGL GTPCIYSGRQISLQRLFSNDVQVDHILPFSKTLDDSFANKVLAQHDANRYKGNRGPFEAFGANR DGYAWDDIRARAAVLPRNKRNRFAETAMQDWLHNETDFLARQLTDTAYLSRVARQYLTAICSKD DVYVSPGRLTAMLRAKWGLNRVLDGVMEEQGRPAVKNRDDHRHHAIDAVVIGATDRAMLQQVAT LAARAREQDAERLIGDMPTPWPNFLEDVRAAVARCVVSHKPDHGPEGGLHNDTAYGIVAGPFED GRYRVRHRVSLFDLKPGDLSNVRCDAPLQAELEPIFEQDDARAREVALTALAERYRQRKVWLEE LMSVLPIRPRGEDGKTLPDSAPYKAYKGDSNYCYELFINERGRWDGELISTFRANQAAYRRFRN DPARFRRYTAGGRPLLMRLCINDYIAVGTAAERTIFRVVKMSENKITLAEHFEGGTLKQRDADK DDPFKYLTKSPGALRDLGARRIFVDLIGRVLDPGIKGD SEQ ID NO: 383 MIERILGVDLGISSLGWAIVEYDKDDEAANRIIDCGVRLFTAAETPKKKESPNKARREARGIRR VLNRRRVRMNMIKKLFLRAGLIQDVDLDGEGGMFYSKANRADVWELRHDGLYRLLKGDELARVL IHIAKHRGYKFIGDDEADEESGKVKKAGVVLRQNFEAAGCRTVGEWLWRERGANGKKRNKHGDY EISIHRDLLVEEVEAIFVAQQEMRSTIATDALKAAYREIAFFVRPMQRIEKMVGHCTYFPEERR APKSAPTAEKFIAISKFFSTVIIDNEGWEQKIIERKTLEELLDFAVSREKVEFRHLRKFLDLSD NEIFKGLHYKGKPKTAKKREATLFDPNEPTELEFDKVEAEKKAWISLRGAAKLREALGNEFYGR FVALGKHADEATKILTYYKDEGQKRRELTKLPLEAEMVERLVKIGFSDFLKLSLKAIRDILPAM ESGARYDEAVLMLGVPHKEKSAILPPLNKTDIDILNPTVIRAFAQFRKVANALVRKYGAFDRVH FELAREINTKGEIEDIKESQRKNEKERKEAADWIAETSFQVPLTRKNILKKRLYIQQDGRCAYT GDVIELERLFDEGYCEIDHILPRSRSADDSFANKVLCLARANQQKTDRTPYEWFGHDAARWNAF ETRTSAPSNRVRTGKGKIDRLLKKNFDENSEMAFKDRNLNDTRYMARAIKTYCEQYWVFKNSHT KAPVQVRSGKLTSVLRYQWGLESKDRESHTHHAVDAIIIAFSTQGMVQKLSEYYRFKETHREKE RPKLAVPLANFRDAVEEATRIENTETVKEGVEVKRLLISRPPRARVTGQAHEQTAKPYPRIKQV KNKKKWRLAPIDEEKFESFKADRVASANQKNFYETSTIPRVDVYHKKGKFHLVPIYLHEMVLNE LPNLSLGTNPEAMDENFFKFSIFKDDLISIQTQGTPKKPAKIIMGYFKNMHGANMVLSSINNSP CEGFTCTPVSMDKKHKDKCKLCPEENRIAGRCLQGFLDYWSQEGLRPPRKEFECDQGVKFALDV KKYQIDPLGYYYEVKQEKRLGTIPQMRSAKKLVKK SEQ ID NO: 384 MNNSIKSKPEVTIGLDLGVGSVGWAIVDNETNIIHHLGSRLFSQAKTAEDRRSFRGVRRLIRRR KYKLKRFVNLIWKYNSYFGFKNKEDILNNYQEQQKLHNTVLNLKSEALNAKIDPKALSWILHDY LKNRGHFYEDNRDFNVYPTKELAKYFDKYGYYKGIIDSKEDNDNKLEEELTKYKFSNKHWLEEV KKVLSNQTGLPEKFKEEYESLFSYVRNYSEGPGSINSVSPYGIYHLDEKEGKVVQKYNNIWDKT IGKCNIFPDEYRAPKNSPIAMIFNEINELSTIRSYSIYLTGWFINQEFKKAYLNKLLDLLIKTN GEKPIDARQFKKLREETIAESIGKETLKDVENEEKLEKEDHKWKLKGLKLNTNGKIQYNDLSSL AKFVHKLKQHLKLDFLLEDQYATLDKINFLQSLFVYLGKHLRYSNRVDSANLKEFSDSNKLFER ILQKQKDGLFKLFEQTDKDDEKILAQTHSLSTKAMLLAITRMTNLDNDEDNQKNNDKGWNFEAI KNFDQKFIDITKKNNNLSLKQNKRYLDDRFINDAILSPGVKRILREATKVFNAILKQFSEEYDV TKVVIELARELSEEKELENTKNYKKLIKKNGDKISEGLKALGISEDEIKDILKSPTKSYKFLLW LQQDHIDPYSLKEIAFDDIFTKTEKFEIDHIIPYSISFDDSSSNKLLVLAESNQAKSNQTPYEF ISSGNAGIKWEDYEAYCRKFKDGDSSLLDSTQRSKKFAKMMKTDTSSKYDIGFLARNLNDTRYA TIVFRDALEDYANNHLVEDKPMFKVVCINGSVTSFLRKNFDDSSYAKKDRDKNIHHAVDASIIS IFSNETKTLFNQLTQFADYKLFKNTDGSWKKIDPKTGVVTEVTDENWKQIRVRNQVSEIAKVIE KYIQDSNIERKARYSRKIENKTNISLFNDTVYSAKKVGYEDQIKRKNLKTLDIHESAKENKNSK VKRQFVYRKLVNVSLLNNDKLADLFAEKEDILMYRANPWVINLAEQIFNEYTENKKIKSQNVFE KYMLDLTKEFPEKFSEFLVKSMLRNKTAIIYDDKKNIVHRIKRLKMLSSELKENKLSNVIIRSK NQSGTKLSYQDTINSLALMIMRSIDPTAKKQYIRVPLNTLNLHLGDHDFDLHNMDAYLKKPKFV KYLKANEIGDEYKPWRVLTSGTLLIHKKDKKLMYISSFQNLNDVIEIKNLIETEYKENDDSDSK KKKKANRFLMTLSTILNDYILLDAKDNFDILGLSKNRIDEILNSKLGLDKIVK SEQ ID NO: 385 MGGSEVGTVPVTWRLGVDVGERSIGLAAVSYEEDKPKEILAAVSWIHDGGVGDERSGASRLALR GMARRARRLRRFRRARLRDLDMLLSELGWTPLPDKNVSPVDAWLARKRLAEEYVVDETERRRLL GYAVSHMARHRGWRNPWTTIKDLKNLPQPSDSWERTRESLEARYSVSLEPGTVGQWAGYLLQRA PGIRLNPTQQSAGRRAELSNATAFETRLRQEDVLWELRCIADVQGLPEDVVSNVIDAVFCQKRP SVPAERIGRDPLDPSQLRASRACLEFQEYRIVAAVANLRIRDGSGSRPLSLEERNAVIEALLAQ TERSLTWSDIALEILKLPNESDLTSVPEEDGPSSLAYSQFAPFDETSARIAEFIAKNRRKIPTF AQWWQEQDRTSRSDLVAALADNSIAGEEEQELLVHLPDAELEALEGLALPSGRVAYSRLTLSGL TRVMRDDGVDVHNARKTCFGVDDNWRPPLPALHEATGHPVVDRNLAILRKFLSSATMRWGPPQS IVVELARGASESRERQAEEEAARRAHRKANDRIRAELRASGLSDPSPADLVRARLLELYDCHCM YCGAPISWENSELDHIVPRTDGGSNRHENLAITCGACNKEKGRRPFASWAETSNRVQLRDVIDR VQKLKYSGNMYWTRDEFSRYKKSVVARLKRRTSDPEVIQSIESTGYAAVALRDRLLSYGEKNGV AQVAVFRGGVTAEARRWLDISIERLFSRVAIFAQSTSTKRLDRRHHAVDAVVLTTLTPGVAKTL ADARSRRVSAEFWRRPSDVNRHSTEEPQSPAYRQWKESCSGLGDLLISTAARDSIAVAAPLRLR PTGALHEETLRAFSEHTVGAAWKGAELRRIVEPEVYAAFLALTDPGGRFLKVSPSEDVLPADEN RHIVLSDRVLGPRDRVKLFPDDRGSIRVRGGAAYIASFHHARVFRWGSSHSPSFALLRVSLADL AVAGLLRDGVDVFTAELPPWTPAWRYASIALVKAVESGDAKQVGWLVPGDELDFGPEGVTTAAG DLSMFLKYFPERHWVVTGFEDDKRINLKPAFLSAEQAEVLRTERSDRPDTLTEAGEILAQFFPR CWRATVAKVLCHPGLTVIRRTALGQPRWRRGHLPYSWRPWSADPWSGGTP SEQ ID NO: 386 MHNKKNITIGFDLGIASIGWAIIDSTTSKILDWGTRTFEERKTANERRAFRSTRRNIRRKAYRN QRFINLILKYKDLFELKNISDIQRANKKDTENYEKIISFFTEIYKKCAAKHSNILEVKVKALDS KIEKLDLIWILHDYLENRGFFYDLEEENVADKYEGIEHPSILLYDFFKKNGFFKSNSSIPKDLG GYSFSNLQWVNEIKKLFEVQEINPEFSEKFLNLFTSVRDYAKGPGSEHSASEYGIFQKDEKGKV FKKYDNIWDKTIGKCSFFVEENRSPVNYPSYEIFNLLNQLINLSTDLKTTNKKIWQLSSNDRNE LLDELLKVKEKAKIISISLKKNEIKKIILKDFGFEKSDIDDQDTIEGRKIIKEEPTTKLEVTKH LLATIYSHSSDSNWININNILEFLPYLDAICIILDREKSRGQDEVLKKLTEKNIFEVLKIDREK QLDFVKSIFSNTKFNFKKIGNFSLKAIREFLPKMFEQNKNSEYLKWKDEEIRRKWEEQKSKLGK TDKKTKYLNPRIFQDEIISPGTKNTFEQAVLVLNQIIKKYSKENIIDAIIIESPREKNDKKTIE EIKKRNKKGKGKTLEKLFQILNLENKGYKLSDLETKPAKLLDRLRFYHQQDGIDLYTLDKINID QLINGSQKYEIEHIIPYSMSYDNSQANKILTEKAENLKKGKLIASEYIKRNGDEFYNKYYEKAK ELFINKYKKNKKLDSYVDLDEDSAKNRFRFLTLQDYDEFQVEFLARNLNDTRYSTKLFYHALVE HFENNEFFTYIDENSSKHKVKISTIKGHVTKYFRAKPVQKNNGPNENLNNNKPEKIEKNRENNE HHAVDAAIVAIIGNKNPQIANLLTLADNKTDKKFLLHDENYKENIETGELVKIPKFEVDKLAKV EDLKKIIQEKYEEAKKHTAIKFSRKTRTILNGGLSDETLYGFKYDEKEDKYFKIIKKKLVTSKN EELKKYFENPFGKKADGKSEYTVLMAQSHLSEFNKLKEIFEKYNGFSNKTGNAFVEYMNDLALK EPTLKAEIESAKSVEKLLYYNFKPSDQFTYHDNINNKSFKRFYKNIRIIEYKSIPIKFKILSKH DGGKSFKDTLFSLYSLVYKVYENGKESYKSIPVTSQMRNFGIDEFDFLDENLYNKEKLDIYKSD FAKPIPVNCKPVFVLKKGSILKKKSLDIDDFKETKETEEGNYYFISTISKRFNRDTAYGLKPLK LSVVKPVAEPSTNPIFKEYIPIHLDELGNEYPVKIKEHTDDEKLMCTIK

Nucleic Acids Encoding Cas9 Molecules

Nucleic acids encoding the Cas9 molecules or Cas9 polypeptides, e.g., an eaCas9 molecule or eaCas9 polypeptide are provided herein.

Exemplary nucleic acids encoding Cas9 molecules are described in Cong et al., SCIENCE 2013, 399(6121):819-823; Wang et al., CELL 2013, 153(4):910-918; Mali et al., SCIENCE 2013, 399(6121):823-826; Jinek et al., SCIENCE 2012, 337(6096):816-821. Another exemplary nucleic acid encoding a Cas9 molecule or Cas9 polypeptide is shown in FIG. 8.

In an embodiment, a nucleic acid encoding a Cas9 molecule or Cas9 polypeptide can be a synthetic nucleic acid sequence. For example, the synthetic nucleic acid molecule can be chemically modified, e.g., as described in Section VIII. In an embodiment, the Cas9 mRNA has one or more (e.g., all of the following properties: it is capped, polyadenylated, substituted with 5-methylcytidine and/or pseudouridine.

In addition, or alternatively, the synthetic nucleic acid sequence can be codon optimized, e.g., at least one non-common codon or less-common codon has been replaced by a common codon. For example, the synthetic nucleic acid can direct the synthesis of an optimized messenger mRNA, e.g., optimized for expression in a mammalian expression system, e.g., described herein.

In addition, or alternatively, a nucleic acid encoding a Cas9 molecule or Cas9 polypeptide may comprise a nuclear localization sequence (NLS). Nuclear localization sequences are known in the art.

Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of S. pyogenes.

(SEQ ID NO: 22) ATGGATAAAA AGTACAGCAT CGGGCTGGAC ATCGGTACAA  ACTCAGTGGG GTGGGCCGTG ATTACGGACG AGTACAAGGT  ACCCTCCAAA AAATTTAAAG TGCTGGGTAA CACGGACAGA  CACTCTATAA AGAAAAATCT TATTGGAGCC TTGCTGTTCG  ACTCAGGCGA GACAGCCGAA GCCACAAGGT TGAAGCGGAC  CGCCAGGAGG CGGTATACCA GGAGAAAGAA CCGCATATGC TACCTGCAAG AAATCTTCAG TAACGAGATG GCAAAGGTTG  ACGATAGCTT TTTCCATCGC CTGGAAGAAT CCTTTCTTGT  TGAGGAAGAC AAGAAGCACG AACGGCACCC CATCTTTGGC  AATATTGTCG ACGAAGTGGC ATATCACGAA AAGTACCCGA  CTATCTACCA CCTCAGGAAG AAGCTGGTGG ACTCTACCGA  TAAGGCGGAC CTCAGACTTA TTTATTTGGC ACTCGCCCAC  ATGATTAAAT TTAGAGGACA TTTCTTGATC GAGGGCGACC  TGAACCCGGA CAACAGTGAC GTCGATAAGC TGTTCATCCA  ACTTGTGCAG ACCTACAATC AACTGTTCGA AGAAAACCCT ATAAATGCTT CAGGAGTCGA CGCTAAAGCA ATCCTGTCCG  CGCGCCTCTC AAAATCTAGA AGACTTGAGA ATCTGATTGC  TCAGTTGCCC GGGGAAAAGA AAAATGGATT GTTTGGCAAC  CTGATCGCCC TCAGTCTCGG ACTGACCCCA AATTTCAAAA  GTAACTTCGA CCTGGCCGAA GACGCTAAGC TCCAGCTGTC CAAGGACACA TACGATGACG ACCTCGACAA TCTGCTGGCC  CAGATTGGGG ATCAGTACGC CGATCTCTTT TTGGCAGCAA  AGAACCTGTC CGACGCCATC CTGTTGAGCG ATATCTTGAG  AGTGAACACC GAAATTACTA AAGCACCCCT TAGCGCATCT  ATGATCAAGC GGTACGACGA GCATCATCAG GATCTGACCC TGCTGAAGGC TCTTGTGAGG CAACAGCTCC CCGAAAAATA  CAAGGAAATC TTCTTTGACC AGAGCAAAAA CGGCTACGCT  GGCTATATAG ATGGTGGGGC CAGTCAGGAG GAATTCTATA  AATTCATCAA GCCCATTCTC GAGAAAATGG ACGGCACAGA  GGAGTTGCTG GTCAAACTTA ACAGGGAGGA CCTGCTGCGG AAGCAGCGGA CCTTTGACAA CGGGTCTATC CCCCACCAGA  TTCATCTGGG CGAACTGCAC GCAATCCTGA GGAGGCAGGA  GGATTTTTAT CCTTTTCTTA AAGATAACCG CGAGAAAATA  GAAAAGATTC TTACATTCAG GATCCCGTAC TACGTGGGAC  CTCTCGCCCG GGGCAATTCA CGGTTTGCCT GGATGACAAG  GAAGTCAGAG GAGACTATTA CACCTTGGAA CTTCGAAGAA  GTGGTGGACA AGGGTGCATC TGCCCAGTCT TTCATCGAGC  GGATGACAAA TTTTGACAAG AACCTCCCTA ATGAGAAGGT  GCTGCCCAAA CATTCTCTGC TCTACGAGTA CTTTACCGTC  TACAATGAAC TGACTAAAGT CAAGTACGTC ACCGAGGGAA TGAGGAAGCC GGCATTCCTT AGTGGAGAAC AGAAGAAGGC  GATTGTAGAC CTGTTGTTCA AGACCAACAG GAAGGTGACT  GTGAAGCAAC TTAAAGAAGA CTACTTTAAG AAGATCGAAT  GTTTTGACAG TGTGGAAATT TCAGGGGTTG AAGACCGCTT  CAATGCGTCA TTGGGGACTT ACCATGATCT TCTCAAGATC ATAAAGGACA AAGACTTCCT GGACAACGAA GAAAATGAGG  ATATTCTCGA AGACATCGTC CTCACCCTGA CCCTGTTCGA  AGACAGGGAA ATGATAGAAG AGCGCTTGAA AACCTATGCC  CACCTCTTCG ACGATAAAGT TATGAAGCAG CTGAAGCGCA  GGAGATACAC AGGATGGGGA AGATTGTCAA GGAAGCTGAT CAATGGAATT AGGGATAAAC AGAGTGGCAA GACCATACTG  GATTTCCTCA AATCTGATGG CTTCGCCAAT AGGAACTTCA  TGCAACTGAT TCACGATGAC TCTCTTACCT TCAAGGAGGA  CATTCAAAAG GCTCAGGTGA GCGGGCAGGG AGACTCCCTT  CATGAACACA TCGCGAATTT GGCAGGTTCC CCCGCTATTA AAAAGGGCAT CCTTCAAACT GTCAAGGTGG TGGATGAATT  GGTCAAGGTA ATGGGCAGAC ATAAGCCAGA AAATATTGTG  ATCGAGATGG CCCGCGAAAA CCAGACCACA CAGAAGGGCC  AGAAAAATAG TAGAGAGCGG ATGAAGAGGA TCGAGGAGGG  CATCAAAGAG CTGGGATCTC AGATTCTCAA AGAACACCCC  GTAGAAAACA CACAGCTGCA GAACGAAAAA TTGTACTTGT  ACTATCTGCA GAACGGCAGA GACATGTACG TCGACCAAGA  ACTTGATATT AATAGACTGT CCGACTATGA CGTAGACCAT  ATCGTGCCCC AGTCCTTCCT GAAGGACGAC TCCATTGATA  ACAAAGTCTT GACAAGAAGC GACAAGAACA GGGGTAAAAG TGATAATGTG CCTAGCGAGG AGGTGGTGAA AAAAATGAAG  AACTACTGGC GACAGCTGCT TAATGCAAAG CTCATTACAC  AACGGAAGTT CGATAATCTG ACGAAAGCAG AGAGAGGTGG  CTTGTCTGAG TTGGACAAGG CAGGGTTTAT TAAGCGGCAG  CTGGTGGAAA CTAGGCAGAT CACAAAGCAC GTGGCGCAGA TTTTGGACAG CCGGATGAAC ACAAAATACG ACGAAAATGA  TAAACTGATA CGAGAGGTCA AAGTTATCAC GCTGAAAAGC  AAGCTGGTGT CCGATTTTCG GAAAGACTTC CAGTTCTACA  AAGTTCGCGA GATTAATAAC TACCATCATG CTCACGATGC  GTACCTGAAC GCTGTTGTCG GGACCGCCTT GATAAAGAAG TACCCAAAGC TGGAATCCGA GTTCGTATAC GGGGATTACA  AAGTGTACGA TGTGAGGAAA ATGATAGCCA AGTCCGAGCA  GGAGATTGGA AAGGCCACAG CTAAGTACTT CTTTTATTCT  AACATCATGA ATTTTTTTAA GACGGAAATT ACCCTGGCCA  ACGGAGAGAT CAGAAAGCGG CCCCTTATAG AGACAAATGG TGAAACAGGT GAAATCGTCT GGGATAAGGG CAGGGATTTC  GCTACTGTGA GGAAGGTGCT GAGTATGCCA CAGGTAAATA  TCGTGAAAAA AACCGAAGTA CAGACCGGAG GATTTTCCAA  GGAAAGCATT TTGCCTAAAA GAAACTCAGA CAAGCTCATC  GCCCGCAAGA AAGATTGGGA CCCTAAGAAA TACGGGGGAT TTGACTCACC CACCGTAGCC TATTCTGTGC TGGTGGTAGC  TAAGGTGGAA AAAGGAAAGT CTAAGAAGCT GAAGTCCGTG  AAGGAACTCT TGGGAATCAC TATCATGGAA AGATCATCCT  TTGAAAAGAA CCCTATCGAT TTCCTGGAGG CTAAGGGTTA  CAAGGAGGTC AAGAAAGACC TCATCATTAA ACTGCCAAAA  TACTCTCTCT TCGAGCTGGA AAATGGCAGG AAGAGAATGT  TGGCCAGCGC CGGAGAGCTG CAAAAGGGAA ACGAGCTTGC  TCTGCCCTCC AAATATGTTA ATTTTCTCTA TCTCGCTTCC  CACTATGAAA AGCTGAAAGG GTCTCCCGAA GATAACGAGC  AGAAGCAGCT GTTCGTCGAA CAGCACAAGC ACTATCTGGA TGAAATAATC GAACAAATAA GCGAGTTCAG CAAAAGGGTT  ATCCTGGCGG ATGCTAATTT GGACAAAGTA CTGTCTGCTT  ATAACAAGCA CCGGGATAAG CCTATTAGGG AACAAGCCGA  GAATATAATT CACCTCTTTA CACTCACGAA TCTCGGAGCC  CCCGCCGCCT TCAAATACTT TGATACGACT ATCGACCGGA AACGGTATAC CAGTACCAAA GAGGTCCTCG ATGCCACCCT  CATCCACCAG TCAATTACTG GCCTGTACGA AACACGGATC  GACCTCTCTC AACTGGGCGG CGACTAG

Provided below is the corresponding amino acid sequence of a S. pyogenes Cas9 molecule.

(SEQ ID NO: 23) MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIG ALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFF HRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTD KADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLF EENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALS LGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAK NLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQL PEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVK LNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIE KILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQS FIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAF LSGEQKKAIVDLLFKTNRKVIVKQLKEDYFKKIECFDSVEISGVEDRFN ASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLK TYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSD GFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKK GILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRI EEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRL SDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNY WRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHV AQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKVREINN YHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEI GKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGR DFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWD PKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEK NPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNE LALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQIS EFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAA FKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD*

Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of N. meningitidis.

(SEQ ID NO: 24) ATGGCCGCCTTCAAGCCCAACCCCATCAACTACATCCTGGGCCTGGACA TCGGCATCGCCAGCGTGGGCTGGGCCATGGTGGAGATCGACGAGGACGA GAACCCCATCTGCCTGATCGACCTGGGTGTGCGCGTGTTCGAGCGCGCT GAGGTGCCCAAGACTGGTGACAGTCTGGCTATGGCTCGCCGGCTTGCTC GCTCTGTTCGGCGCCTTACTCGCCGGCGCGCTCACCGCCTTCTGCGCGC TCGCCGCCTGCTGAAGCGCGAGGGTGTGCTGCAGGCTGCCGACTTCGAC GAGAACGGCCTGATCAAGAGCCTGCCCAACACTCCTTGGCAGCTGCGCG CTGCCGCTCTGGACCGCAAGCTGACTCCTCTGGAGTGGAGCGCCGTGCT GCTGCACCTGATCAAGCACCGCGGCTACCTGAGCCAGCGCAAGAACGAG GGCGAGACCGCCGACAAGGAGCTGGGTGCTCTGCTGAAGGGCGTGGCCG ACAACGCCCACGCCCTGCAGACTGGTGACTTCCGCACTCCTGCTGAGCT GGCCCTGAACAAGTTCGAGAAGGAGAGCGGCCACATCCGCAACCAGCGC GGCGACTACAGCCACACCTTCAGCCGCAAGGACCTGCAGGCCGAGCTGA TCCTGCTGTTCGAGAAGCAGAAGGAGTTCGGCAACCCCCACGTGAGCGG CGGCCTGAAGGAGGGCATCGAGACCCTGCTGATGACCCAGCGCCCCGCC CTGAGCGGCGACGCCGTGCAGAAGATGCTGGGCCACTGCACCTTCGAGC CAGCCGAGCCCAAGGCCGCCAAGAACACCTACACCGCCGAGCGCTTCAT CTGGCTGACCAAGCTGAACAACCTGCGCATCCTGGAGCAGGGCAGCGAG CGCCCCCTGACCGACACCGAGCGCGCCACCCTGATGGACGAGCCCTACC GCAAGAGCAAGCTGACCTACGCCCAGGCCCGCAAGCTGCTGGGTCTGGA GGACACCGCCTTCTTCAAGGGCCTGCGCTACGGCAAGGACAACGCCGAG GCCAGCACCCTGATGGAGATGAAGGCCTACCACGCCATCAGCCGCGCCC TGGAGAAGGAGGGCCTGAAGGACAAGAAGAGTCCTCTGAACCTGAGCCC CGAGCTGCAGGACGAGATCGGCACCGCCTTCAGCCTGTTCAAGACCGAC GAGGACATCACCGGCCGCCTGAAGGACCGCATCCAGCCCGAGATCCTGG AGGCCCTGCTGAAGCACATCAGCTTCGACAAGTTCGTGCAGATCAGCCT GAAGGCCCTGCGCCGCATCGTGCCCCTGATGGAGCAGGGCAAGCGCTAC GACGAGGCCTGCGCCGAGATCTACGGCGACCACTACGGCAAGAAGAACA CCGAGGAGAAGATCTACCTGCCTCCTATCCCCGCCGACGAGATCCGCAA CCCCGTGGTGCTGCGCGCCCTGAGCCAGGCCCGCAAGGTGATCAACGGC GTGGTGCGCCGCTACGGCAGCCCCGCCCGCATCCACATCGAGACCGCCC GCGAGGTGGGCAAGAGCTTCAAGGACCGCAAGGAGATCGAGAAGCGCCA GGAGGAGAACCGCAAGGACCGCGAGAAGGCCGCCGCCAAGTTCCGCGAG TACTTCCCCAACTTCGTGGGCGAGCCCAAGAGCAAGGACATCCTGAAGC TGCGCCTGTACGAGCAGCAGCACGGCAAGTGCCTGTACAGCGGCAAGGA GATCAACCTGGGCCGCCTGAACGAGAAGGGCTACGTGGAGATCGACCAC GCCCTGCCCTTCAGCCGCACCTGGGACGACAGCTTCAACAACAAGGTGC TGGTGCTGGGCAGCGAGAACCAGAACAAGGGCAACCAGACCCCCTACGA GTACTTCAACGGCAAGGACAACAGCCGCGAGTGGCAGGAGTTCAAGGCC CGCGTGGAGACCAGCCGCTTCCCCCGCAGCAAGAAGCAGCGCATCCTGC TGCAGAAGTTCGACGAGGACGGCTTCAAGGAGCGCAACCTGAACGACAC CCGCTACGTGAACCGCTTCCTGTGCCAGTTCGTGGCCGACCGCATGCGC CTGACCGGCAAGGGCAAGAAGCGCGTGTTCGCCAGCAACGGCCAGATCA CCAACCTGCTGCGCGGCTTCTGGGGCCTGCGCAAGGTGCGCGCCGAGAA CGACCGCCACCACGCCCTGGACGCCGTGGTGGTGGCCTGCAGCACCGTG GCCATGCAGCAGAAGATCACCCGCTTCGTGCGCTACAAGGAGATGAACG CCTTCGACGGTAAAACCATCGACAAGGAGACCGGCGAGGTGCTGCACCA GAAGACCCACTTCCCCCAGCCCTGGGAGTTCTTCGCCCAGGAGGTGATG ATCCGCGTGTTCGGCAAGCCCGACGGCAAGCCCGAGTTCGAGGAGGCCG ACACCCCCGAGAAGCTGCGCACCCTGCTGGCCGAGAAGCTGAGCAGCCG CCCTGAGGCCGTGCACGAGTACGTGACTCCTCTGTTCGTGAGCCGCGCC CCCAACCGCAAGATGAGCGGTCAGGGTCACATGGAGACCGTGAAGAGCG CCAAGCGCCTGGACGAGGGCGTGAGCGTGCTGCGCGTGCCCCTGACCCA GCTGAAGCTGAAGGACCTGGAGAAGATGGTGAACCGCGAGCGCGAGCCC AAGCTGTACGAGGCCCTGAAGGCCCGCCTGGAGGCCCACAAGGACGACC CCGCCAAGGCCTTCGCCGAGCCCTTCTACAAGTACGACAAGGCCGGCAA CCGCACCCAGCAGGTGAAGGCCGTGCGCGTGGAGCAGGTGCAGAAGACC GGCGTGTGGGTGCGCAACCACAACGGCATCGCCGACAACGCCACCATGG TGCGCGTGGACGTGTTCGAGAAGGGCGACAAGTACTACCTGGTGCCCAT CTACAGCTGGCAGGTGGCCAAGGGCATCCTGCCCGACCGCGCCGTGGTG CAGGGCAAGGACGAGGAGGACTGGCAGCTGATCGACGACAGCTTCAACT TCAAGTTCAGCCTGCACCCCAACGACCTGGTGGAGGTGATCACCAAGAA GGCCCGCATGTTCGGCTACTTCGCCAGCTGCCACCGCGGCACCGGCAAC ATCAACATCCGCATCCACGACCTGGACCACAAGATCGGCAAGAACGGCA TCCTGGAGGGCATCGGCGTGAAGACCGCCCTGAGCTTCCAGAAGTACCA GATCGACGAGCTGGGCAAGGAGATCCGCCCCTGCCGCCTGAAGAAGCGC CCTCCTGTGCGCTAA

Provided below is the corresponding amino acid sequence of a N. meningitidis Cas9 molecule.

(SEQ ID NO: 25) MAAFKPNPINYILGLDIGIASVGWAMVEIDEDENPICLIDLGVRVFERA EVPKTGDSLAMARRLARSVRRLTRRRAHRLLRARRLLKREGVLQAADFD ENGLIKSLPNTPWQLRAAALDRKLTPLEWSAVLLHLIKHRGYLSQRKNE GETADKELGALLKGVADNAHALQTGDFRTPAELALNKFEKESGHIRNQR GDYSHTFSRKDLQAELILLFEKQKEFGNPHVSGGLKEGIETLLMTQRPA LSGDAVQKMLGHCTFEPAEPKAAKNTYTAERFIWLTKLNNLRILEQGSE RPLTDTERATLMDEPYRKSKLTYAQARKLLGLEDTAFFKGLRYGKDNAE ASTLMEMKAYHAISRALEKEGLKDKKSPLNLSPELQDEIGTAFSLFKTD EDITGRLKDRIQPEILEALLKHISFDKFVQISLKALRRIVPLMEQGKRY DEACAEIYGDHYGKKNTEEKIYLPPIPADEIRNPVVLRALSQARKVING VVRRYGSPARIHIETAREVGKSFKDRKEIEKRQEENRKDREKAAAKFRE YFPNFVGEPKSKDILKLRLYEQQHGKCLYSGKEINLGRLNEKGYVEIDH ALPFSRTWDDSFNNKVLVLGSENQNKGNQTPYEYFNGKDNSREWQEFKA RVETSRFPRSKKQRILLQKFDEDGFKERNLNDTRYVNRFLCQFVADRMR LTGKGKKRVFASNGQITNLLRGFWGLRKVRAENDRHHALDAVVVACSTV AMQQKITRFVRYKEMNAFDGKTIDKETGEVLHQKTHFPQPWEFFAQEVM IRVFGKPDGKPEFEEADTPEKLRTLLAEKLSSRPEAVHEYVTPLFVSRA PNRKMSGQGHMETVKSAKRLDEGVSVLRVPLTQLKLKDLEKMVNREREP KLYEALKARLEAHKDDPAKAFAEPFYKYDKAGNRTQQVKAVRVEQVQKT GVWVRNHNGIADNATMVRVDVFEKGDKYYLVPIYSWQVAKGILPDRAVV QGKDEEDWQLIDDSFNFKFSLHPNDLVEVITKKARMFGYFASCHRGIGN INIRIHDLDHKIGKNGILEGIGVKTALSFQKYQIDELGKEIRPCRLKKR PPVR*

Provided below is an amino acid sequence of a S. aureus Cas9 molecule.

(SEQ ID NO: 26) MKRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRS KRGARRLKRRRRHRIQRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQ KLSEEEFSAALLHLAKRRGVHNVNEVEEDTGNELSTKEQISRNSKALEE KYVAELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQLDQS FIDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFFEELR SVKYAYNADLYNALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKP TLKQIAKEILVNEEDIKGYRVTSTGKPEFTNLKVYHDIKDITARKEIIE NAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQISNLKGYTGT HNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLV DDFILSPVVKRSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKM INEMQKRNRQTNERIEEIIRTTGKENAKYLIEKIKLHDMQEGKCLYSLE AIPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLVKQEENSKKGNRTP FQYLSSSDSKISYETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSV QKDFINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRR KWKFKKERNKGYKHHAEDALIIANADFIFKEWKKLDKAKKVMENQMFEE KQAESMPEIETEQEYKEIFITPHQIKHIKDFKDYKYSHRVDKKPNRELI NDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKLLMYHHD PQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKY YGNKLNAHLDITDDYPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNL DVIKKENYYEVNSKCYEEAKKLKKISNQAEFIASFYNNDLIKINGELYR VIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTIASKTQSIKK YSTDILGNLYEVKSKKHPQIIKKG*

Provided below is an exemplary codon optimized nucleic acid sequence encoding a Cas9 molecule of S. aureus Cas9.

(SEQ ID NO: 39) ATGAAAAGGAACTACATTCTGGGGCTGGACATCGGGATTACAAGCGTGG GGTATGGGATTATTGACTATGAAACAAGGGACGTGATCGACGCAGGCGT CAGACTGTTCAAGGAGGCCAACGTGGAAAACAATGAGGGACGGAGAAGC AAGAGGGGAGCCAGGCGCCTGAAACGACGGAGAAGGCACAGAATCCAGA GGGTGAAGAAACTGCTGTTCGATTACAACCTGCTGACCGACCATTCTGA GCTGAGTGGAATTAATCCTTATGAAGCCAGGGTGAAAGGCCTGAGTCAG AAGCTGTCAGAGGAAGAGTTTTCCGCAGCTCTGCTGCACCTGGCTAAGC GCCGAGGAGTGCATAACGTCAATGAGGTGGAAGAGGACACCGGCAACGA GCTGTCTACAAAGGAACAGATCTCACGCAATAGCAAAGCTCTGGAAGAG AAGTATGTCGCAGAGCTGCAGCTGGAACGGCTGAAGAAAGATGGCGAGG TGAGAGGGTCAATTAATAGGTTCAAGACAAGCGACTACGTCAAAGAAGC CAAGCAGCTGCTGAAAGTGCAGAAGGCTTACCACCAGCTGGATCAGAGC TTCATCGATACTTATATCGACCTGCTGGAGACTCGGAGAACCTACTATG AGGGACCAGGAGAAGGGAGCCCCTTCGGATGGAAAGACATCAAGGAATG GTACGAGATGCTGATGGGACATTGCACCTATTTTCCAGAAGAGCTGAGA AGCGTCAAGTACGCTTATAACGCAGATCTGTACAACGCCCTGAATGACC TGAACAACCTGGTCATCACCAGGGATGAAAACGAGAAACTGGAATACTA TGAGAAGTTCCAGATCATCGAAAACGTGTTTAAGCAGAAGAAAAAGCCT ACACTGAAACAGATTGCTAAGGAGATCCTGGTCAACGAAGAGGACATCA AGGGCTACCGGGTGACAAGCACTGGAAAACCAGAGTTCACCAATCTGAA AGTGTATCACGATATTAAGGACATCACAGCACGGAAAGAAATCATTGAG AACGCCGAACTGCTGGATCAGATTGCTAAGATCCTGACTATCTACCAGA GCTCCGAGGACATCCAGGAAGAGCTGACTAACCTGAACAGCGAGCTGAC CCAGGAAGAGATCGAACAGATTAGTAATCTGAAGGGGTACACCGGAACA CACAACCTGTCCCTGAAAGCTATCAATCTGATTCTGGATGAGCTGTGGC ATACAAACGACAATCAGATTGCAATCTTTAACCGGCTGAAGCTGGTCCC AAAAAAGGTGGACCTGAGTCAGCAGAAAGAGATCCCAACCACACTGGTG GACGATTTCATTCTGTCACCCGTGGTCAAGCGGAGCTTCATCCAGAGCA TCAAAGTGATCAACGCCATCATCAAGAAGTACGGCCTGCCCAATGATAT CATTATCGAGCTGGCTAGGGAGAAGAACAGCAAGGACGCACAGAAGATG ATCAATGAGATGCAGAAACGAAACCGGCAGACCAATGAACGCATTGAAG AGATTATCCGAACTACCGGGAAAGAGAACGCAAAGTACCTGATTGAAAA AATCAAGCTGCACGATATGCAGGAGGGAAAGTGTCTGTATTCTCTGGAG GCCATCCCCCTGGAGGACCTGCTGAACAATCCATTCAACTACGAGGTCG ATCATATTATCCCCAGAAGCGTGTCCTTCGACAATTCCTTTAACAACAA GGTGCTGGTCAAGCAGGAAGAGAACTCTAAAAAGGGCAATAGGACTCCT TTCCAGTACCTGTCTAGTTCAGATTCCAAGATCTCTTACGAAACCTTTA AAAAGCACATTCTGAATCTGGCCAAAGGAAAGGGCCGCATCAGCAAGAC CAAAAAGGAGTACCTGCTGGAAGAGCGGGACATCAACAGATTCTCCGTC CAGAAGGATTTTATTAACCGGAATCTGGTGGACACAAGATACGCTACTC GCGGCCTGATGAATCTGCTGCGATCCTATTTCCGGGTGAACAATCTGGA TGTGAAAGTCAAGTCCATCAACGGCGGGTTCACATCTTTTCTGAGGCGC AAATGGAAGTTTAAAAAGGAGCGCAACAAAGGGTACAAGCACCATGCCG AAGATGCTCTGATTATCGCAAATGCCGACTTCATCTTTAAGGAGTGGAA AAAGCTGGACAAAGCCAAGAAAGTGATGGAGAACCAGATGTTCGAAGAG AAGCAGGCCGAATCTATGCCCGAAATCGAGACAGAACAGGAGTACAAGG AGATTTTCATCACTCCTCACCAGATCAAGCATATCAAGGATTTCAAGGA CTACAAGTACTCTCACCGGGTGGATAAAAAGCCCAACAGAGAGCTGATC AATGACACCCTGTATAGTACAAGAAAAGACGATAAGGGGAATACCCTGA TTGTGAACAATCTGAACGGACTGTACGACAAAGATAATGACAAGCTGAA AAAGCTGATCAACAAAAGTCCCGAGAAGCTGCTGATGTACCACCATGAT CCTCAGACATATCAGAAACTGAAGCTGATTATGGAGCAGTACGGCGACG AGAAGAACCCACTGTATAAGTACTATGAAGAGACTGGGAACTACCTGAC CAAGTATAGCAAAAAGGATAATGGCCCCGTGATCAAGAAGATCAAGTAC TATGGGAACAAGCTGAATGCCCATCTGGACATCACAGACGATTACCCTA ACAGTCGCAACAAGGTGGTCAAGCTGTCACTGAAGCCATACAGATTCGA TGTCTATCTGGACAACGGCGTGTATAAATTTGTGACTGTCAAGAATCTG GATGTCATCAAAAAGGAGAACTACTATGAAGTGAATAGCAAGTGCTACG AAGAGGCTAAAAAGCTGAAAAAGATTAGCAACCAGGCAGAGTTCATCGC CTCCTTTTACAACAACGACCTGATTAAGATCAATGGCGAACTGTATAGG GTCATCGGGGTGAACAATGATCTGCTGAACCGCATTGAAGTGAATATGA TTGACATCACTTACCGAGAGTATCTGGAAAACATGAATGATAAGCGCCC CCCTCGAATTATCAAAACAATTGCCTCTAAGACTCAGAGTATCAAAAAG TACTCAACCGACATTCTGGGAAACCTGTATGAGGTGAAGAGCAAAAAGC ACCCTCAGATTATCAAAAAGGGC

If any of the above Cas9 sequences are fused with a peptide or polypeptide at the C-terminus, it is understood that the stop codon will be removed.

Other Cas Molecules and Cas9 Polypeptides

Various types of Cas molecules or Cas9 polypeptides can be used to practice the inventions disclosed herein. In some embodiments, Cas molecules of Type II Cas systems are used. In other embodiments, Cas molecules of other Cas systems are used. For example, Type I or Type III Cas molecules may be used. Exemplary Cas molecules (and Cas systems) are described, e.g., in Haft et al., PLOS COMPUTATIONAL BIOLOGY 2005, 1(6): e60 and Makarova et al., NATURE REVIEW MICROBIOLOGY 2011, 9:467-477, the contents of both references are incorporated herein by reference in their entirety. Exemplary Cas molecules (and Cas systems) are also shown in Table 55.

TABLE 55 Cas Systems Structure Families of (and encoded super- System Name protein family) type from (PDB of Gene or Haft acces- encoded Represent- name subtype et al.§ sions) protein#** atives cas1 Type I cas1 3GOD, COG1518 SERP2463, Type II 3LFX SPy1047 Type III and and ygbT 2YZS cas2 Type I cas2 2IVY, COG1343 SERP2462, Type II 218E and SPy1048, Type III and COG3512 SPy1723 3EXC (N-terminal domain) and ygbF cas3′ Type I‡‡ cas3 NA COG1203 APE1232 and ygcB cas3″ Subtype NA NA COG2254 APE1231 I-A and Subtype BH0336 I-B cas4 Subtype cas4 NA COG1468 APE1239 I-A and and Subtype csa1 BH0340 I-B Subtype I-C Subtype I-D Subtype II-B cas5 Subtype cas5a, 3KG4 COG1688 APE1234, I-A cas5d, (RAMP) BH0337, Subtype cas5e, devS I-B cas5h, and Subtype cas5p, ygcI I-C cas5t Subtype and I-E cmx5 cas6 Subtype cas6 3I4H COG1583 PF1131 I-A and and and Subtype cmx6 COG5551 slr7014 I-B (RAMP) Subtype I-D Subtype III-A Subtype III-B cas6e Subtype cse3 1WJ9 (RAMP) ygcH I-E cas6f Subtype csy4 2XLJ (RAMP) y1727 I-F cas7 Subtype csa2, NA COG1857 devR I-A csd2, and and ygcJ Subtype cse4, COG3649 I-B csh2, (RAMP) Subtype csp1 I-C and Subtype cst2 I-E cas8a1 Subtype cmx1, NA BH0338-like LA3191§§ I-A‡‡ cst1, and csx8, PG2018§§ csx13 and CXXC- CXX cas8a2 Subtype csa4 NA PH0918 AF0070, I-A‡‡ and AF1873, csx9 MJ0385, PF0637, PH0918 and SSO1401 cas8b Subtype csh1 NA BH0338-like MTH1090 I-B‡‡ and and TM1802 TM1802 cas8c Subtype csd1 NA BH0338-like BH0338 I-C‡‡ and csp2 cas9 Type csn1 NA COG3513 FTN_0757 II‡‡ and and csx12 SPy1046 cas10 Type cmr2, NA COG1353 MTH326, III‡‡ csm1 Rv2823c§§ and and csx11 TM1794§§ cas10d Subtype csc3 NA COG1353 slr7011 I-D‡‡ csy1 Subtype csy1 NA y1724-like y1724 I-F‡‡ csy2 Subtype csy2 NA (RAMP) y1725 I-F csy3 Subtype csy3 NA (RAMP) y1726 I-F cse1 Subtype cse1 NA YgcL-like ygcL I-E‡‡ cse2 Subtype cse2 2ZCA YgcK-like ygcK I-E csc1 Subtype csc1 NA alr1563-like alr1563 I-D (RAMP) csc2 Subtype csc1 NA COG1337 slr7012 I-D and (RAMP) csc2 csa5 Subtype csa5 NA AF1870 AF1870, I-A MJ0380, PF0643 and SS01398 csn2 Subtype csn2 NA SPy1049-like SPy1049 II-A csm2 Subtype csm2 NA COG1421 MTH1081 III-A‡‡ and SERP2460 csm3 Subtype csc2 NA COG1337 MTH1080 III-A and (RAMP) and csm3 SERP2459 csm4 Subtype csm4 NA COG1567 MTH1079 III-A (RAMP) and SERP2458 csm5 Subtype csm5 NA COG1332 MTH1078 III-A (RAMP) and SERP2457 csm6 Subtype APE2256 2WTE COG1517 APE2256 III-A and and csm6 SSO1445 cmr1 Subtype cmr1 NA COG1367 PF1130 III-B (RAMP) cmr3 Subtype cmr3 NA COG1769 PF1128 III-B (RAMP) cmr4 Subtype cmr4 NA COG1336 PF1126 III-B (RAMP) cmr5 Subtype cmr5 2ZOP COG3337 MTH324 III-B‡‡ and and 2OEB PF1125 cmr6 Subtype cmr6 NA COG1604 PF1124 III-B (RAMP) csb1 Subtype GSU0053 NA (RAMP) Balac_1306 I-U and GSU0053 csb2 Subtype NA NA (RAMP) Balac_1305 I-U§§ and GSU0054 csb3 Subtype NA NA (RAMP) Balac_1303§§ I-U csx17 Subtype NA NA NA Btus_2683 I-U csx14 Subtype NA NA NA GSU0052 I-U csx10 Subtype csx10 NA (RAMP) Caur_2274 I-U csx16 Subtype VVA1548 NA NA VVA1548 III-U csaX Subtype csaX NA NA SSO1438 III-U csx3 Subtype csx3 NA NA AF1864 III-U csx1 Subtype csa3, 1XMX COG1517 MJ1666, III-U csx1, and and NE0113, csx2, 2I71 COG4006 PF1127 DXTHG, and NE0113 TM1812 and TIGR02710 csx15 Un- NA NA TTE2665 TTE2665 known csf1 Type U csf1 NA NA AFE_1038 csf2 Type U csf2 NA (RAMP) AFE_1039 csf3 Type U csf3 NA (RAMP) AFE_1040 csf4 Type U csf4 NA NA AFE_1037

IV. Functional Analysis of Candidate Molecules

Candidate Cas9 molecules, candidate gRNA molecules, candidate Cas9 molecule/gRNA molecule complexes, can be evaluated by art-known methods or as described herein. For example, exemplary methods for evaluating the endonuclease activity of Cas9 molecule are described, e.g., in Jinek et al., SCIENCE 2012, 337(6096):816-821.

Binding and Cleavage Assay: Testing the Endonuclease Activity of Cas9 Molecule

The ability of a Cas9 molecule/gRNA molecule complex to bind to and cleave a target nucleic acid can be evaluated in a plasmid cleavage assay. In this assay, synthetic or in vitro-transcribed gRNA molecule is pre-annealed prior to the reaction by heating to 95° C. and slowly cooling down to room temperature. Native or restriction digest-linearized plasmid DNA (300 ng (˜8 nM)) is incubated for 60 min at 37° C. with purified Cas9 protein molecule (50-500 nM) and gRNA (50-500 nM, 1:1) in a Cas9 plasmid cleavage buffer (20 mM HEPES pH 7.5, 150 mM KCl, 0.5 mM DTT, 0.1 mM EDTA) with or without 10 mM MgCl2. The reactions are stopped with 5×DNA loading buffer (30% glycerol, 1.2% SDS, 250 mM EDTA), resolved by a 0.8 or 1% agarose gel electrophoresis and visualized by ethidium bromide staining. The resulting cleavage products indicate whether the Cas9 molecule cleaves both DNA strands, or only one of the two strands. For example, linear DNA products indicate the cleavage of both DNA strands. Nicked open circular products indicate that only one of the two strands is cleaved.

Alternatively, the ability of a Cas9 molecule/gRNA molecule complex to bind to and cleave a target nucleic acid can be evaluated in an oligonucleotide DNA cleavage assay. In this assay, DNA oligonucleotides (10 pmol) are radiolabeled by incubating with 5 units T4 polynucleotide kinase and ˜3-6 pmol (˜20-40 mCi) [γ-32P]-ATP in 1×T4 polynucleotide kinase reaction buffer at 37° C. for 30 min, in a 50 μL reaction. After heat inactivation (65° C. for 20 min), reactions are purified through a column to remove unincorporated label. Duplex substrates (100 nM) are generated by annealing labeled oligonucleotides with equimolar amounts of unlabeled complementary oligonucleotide at 95° C. for 3 min, followed by slow cooling to room temperature. For cleavage assays, gRNA molecules are annealed by heating to 95° C. for 30 s, followed by slow cooling to room temperature. Cas9 (500 nM final concentration) is pre-incubated with the annealed gRNA molecules (500 nM) in cleavage assay buffer (20 mM HEPES pH 7.5, 100 mM KCl, 5 mM MgCl2, 1 mM DTT, 5% glycerol) in a total volume of 9 μl. Reactions are initiated by the addition of 1 μl target DNA (10 nM) and incubated for 1 h at 37° C. Reactions are quenched by the addition of 20 μl of loading dye (5 mM EDTA, 0.025% SDS, 5% glycerol in formamide) and heated to 95° C. for 5 min. Cleavage products are resolved on 12% denaturing polyacrylamide gels containing 7 M urea and visualized by phosphorimaging. The resulting cleavage products indicate that whether the complementary strand, the non-complementary strand, or both, are cleaved.

One or both of these assays can be used to evaluate the suitability of a candidate gRNA molecule or candidate Cas9 molecule.

Binding Assay: Testing the Binding of Cas9 Molecule to Target DNA

Exemplary methods for evaluating the binding of Cas9 molecule to target DNA are described, e.g., in Jinek et al., SCIENCE 2012; 337(6096):816-821.

For example, in an electrophoretic mobility shift assay, target DNA duplexes are formed by mixing of each strand (10 nmol) in deionized water, heating to 95° C. for 3 min and slow cooling to room temperature. All DNAs are purified on 8% native gels containing 1×TBE. DNA bands are visualized by UV shadowing, excised, and eluted by soaking gel pieces in DEPC-treated H2O. Eluted DNA is ethanol precipitated and dissolved in DEPC-treated H2O. DNA samples are 5′ end labeled with [γ-32P]-ATP using T4 polynucleotide kinase for 30 min at 37° C. Polynucleotide kinase is heat denatured at 65° C. for 20 min, and unincorporated radiolabel is removed using a column. Binding assays are performed in buffer containing 20 mM HEPES pH 7.5, 100 mM KCl, 5 mM MgCl2, 1 mM DTT and 10% glycerol in a total volume of 10 μl. Cas9 protein molecule is programmed with equimolar amounts of pre-annealed gRNA molecule and titrated from 100 pM to 1 μM. Radiolabeled DNA is added to a final concentration of 20 pM. Samples are incubated for 1 h at 37° C. and resolved at 4° C. on an 8% native polyacrylamide gel containing 1×TBE and 5 mM MgCl2. Gels are dried and DNA visualized by phosphorimaging.

Differential Scanning Flourimetry (DSF)

The thermostability of Cas9-gRNA ribonucleoprotein (RNP) complexes can be measured via DSF. This technique measures the thermostability of a protein, which can increase under favorable conditions such as the addition of a binding RNA molecule, e.g., a gRNA.

The assay is performed using two different protocols, one to test the best stoichiometric ratio of gRNA:Cas9 protein and another to determine the best solution conditions for RNP formation.

To determine the best solution to form RNP complexes, a 2 uM solution of Cas9 in water+10×SYPRO Orange® (Life Techonologies cat #S-6650) and dispensed into a 384 well plate. An equimolar amount of gRNA diluted in solutions with varied pH and salt is then added. After incubating at room temperature for 10′ and brief centrifugation to remove any bubbles, a Bio-Rad CFX384™ Real-Time System C1000 Touch™ Thermal Cycler with the Bio-Rad CFX Manager software is used to run a gradient from 20° C. to 90° C. with a 1° increase in temperature every 10 seconds.

The second assay consists of mixing various concentrations of gRNA with 2 uM Cas9 in optimal buffer from assay 1 above and incubating at RT for 10′ in a 384 well plate. An equal volume of optimal buffer+10×SYPRO Orange® (Life Techonologies cat #S-6650) is added and the plate sealed with Microseal® B adhesive (MSB-1001). Following brief centrifugation to remove any bubbles, a Bio-Rad CFX384™ Real-Time System C1000 Touch™ Thermal Cycler with the Bio-Rad CFX Manager software is used to run a gradient from 20° C. to 90° C. with a 1° increase in temperature every 10 seconds.

V. Genome Editing Approaches

Mutations in the CFTR gene may be corrected using one of the approaches or pathways described herein, e.g., using HDR and/or NHEJ. In an embodiment, a mutation in the CFTR gene is corrected by homology directed repair (HDR) using a template nucleic acid (see Section V.1).

Also described herein are methods for targeted knockout of one or both alleles of the SCNN1A gene using NHEJ (see Section V.2).

V.1 HDR Repair, HDR Mediated Knockin and Template Nucleic Acids

As described herein, nuclease-induced homology directed repair (HDR) can be used to alter a target sequence and correct (e.g., repair or edit) a mutation in the genome. While not wishing to be bound by theory, it is believed that alteration of the target sequence occurs by homology-directed repair (HDR) with a donor template or template nucleic acid. For example, the donor template or the template nucleic acid provides for alteration of the target sequence. It is contemplated that a plasmid donor can be used as a template for homologous recombination. It is further contemplated that a single stranded donor template can be used as a template for alteration of the target sequence by alternate methods of homology directed repair (e.g., single strand annealing) between the target sequence and the donor template. Donor template-effected alteration of a target sequence depends on cleavage by a Cas9 molecule. Cleavage by Cas9 can comprise a double strand break or one, two or more single strand breaks.

Mutations that can be corrected by HDR using a template nucleic acid include point mutations. In an embodiment, a point mutation can be corrected by either a single double-strand break or two single strand breaks. In an embodiment, a point mutation can be corrected by (1) a single double-strand break, (2) two single strand breaks, (3) two double stranded breaks with a break occurring on each side of the target sequence, or (4) four single stranded breaks with a pair of single stranded breaks occurring on each side of the target sequence.

Mutations in the CFTR gene that can be corrected (e.g., altered) by HDR with a template nucleic acid include deletion mutation at F508 (F508del) or point mutation at G551, e.g., G551D.

Double Strand Break Mediated Correction or Knockin

In an embodiment, double strand cleavage is effected by a Cas9 molecule having cleavage activity associated with an HNH-like domain and cleavage activity associated with an RuvC-like domain, e.g., an N-terminal RuvC-like domain, e.g., a wild type Cas9. Such embodiments require only a single gRNA.

Single Strand Break Mediated Correction or Knockin

In other embodiments, two single strand breaks, or nicks, are effected by a Cas9 molecule having nickase activity, e.g., cleavage activity associated with an HNH-like domain or cleavage activity associated with an N-terminal RuvC-like domain. Such embodiments require two gRNAs, one for placement of each single strand break. In an embodiment, the Cas9 molecule having nickase activity cleaves the strand to which the gRNA hybridizes, but not the strand that is complementary to the strand to which the gRNA hybridizes. In an embodiment, the Cas9 molecule having nickase activity does not cleave the strand to which the gRNA hybridizes, but rather cleaves the strand that is complementary to the strand to which the gRNA hybridizes.

In an embodiment, the nickase has HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D10, e.g., the D10A mutation. D10A inactivates RuvC; therefore, the Cas9 nickase has (only) HNH activity and will cut on the strand to which the gRNA hybridizes (e.g., the complementary strand, which does not have the NGG PAM on it). In other embodiments, a Cas9 molecule having an H840, e.g., an H840A, mutation can be used as a nickase. H840A inactivates HNH; therefore, the Cas9 nickase has (only) RuvC activity and cuts on the non-complementary strand (e.g., the strand that has the NGG PAM and whose sequence is identical to the gRNA). In other embodiments, a Cas9 molecule having an N863, e.g., an N863A mutation can be used as a nickase. N863A inactivates HNH therefore the Cas9 nickase has (only) RuvC activity and cuts on the non-complementary strand (the strand that has the PAM and whose sequence is identical to the gRNA).

In an embodiment, in which a nickase and two gRNAs are used to position two single strand nicks, one nick is on the +strand and one nick is on the −strand of the target nucleic acid. The PAMs are outwardly facing. The gRNAs can be selected such that the gRNAs are separated by, from about 0-50, 0-100, or 0-200 nucleotides. In an embodiment, there is no overlap between the target sequence that is complementary to the targeting domains of the two gRNAs. In an embodiment, the gRNAs do not overlap and are separated by as much as 50, 100, or 200 nucleotides. In an embodiment, the use of two gRNAs can increase specificity, e.g., by decreasing off-target binding (Ran et al., Cell 2013; 154(6):1380-1389).

In an embodiment, a single nick can be used to induce HDR. It is contemplated herein that a single nick can be used to increase the ratio of HR to NHEJ at a given cleavage site.

Placement of Double Strand or Single Strand Breaks Relative to the Target Position

The double strand break or single strand break in one of the strands should be sufficiently close to the target position such that correction occurs. In an embodiment, the distance is not more than 50, 100, 200, 300, 350 or 400 nucleotides. While not wishing to be bound by theory, it is believed that the break should be sufficiently close to the target sequence such that the break is within the region that is subject to exonuclease-mediated removal during end resection. If the distance between the target sequence and a break is too great, the mutation may not be included in the end resection and, therefore, may not be corrected, as donor sequence may only be used to correct sequence within the end resection region.

In an embodiment, in which a gRNA (unimolecular (or chimeric) or modular gRNA) and Cas9 nuclease induce a double strand break for the purpose of inducing HDR-mediated correction, the cleavage site is between 0 to 200 bp (e.g., 0 to 175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position. In an embodiment, the cleavage site is between 0 to 100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.

In an embodiment, in which two gRNAs (independently, unimolecular (or chimeric) or modular gRNA) complexing with Cas9 nickases induce two single strand breaks for the purpose of inducing HDR-mediated correction, the closer nick is between 0 to 200 bp (e.g., 0 to 175, 0 to 150, 0 to 125, 0 to 100, 0 to 75, 0 to 50, 0 to 25, 25 to 200, 25 to 175, 25 to 150, 25 to 125, 25 to 100, 25 to 75, 25 to 50, 50 to 200, 50 to 175, 50 to 150, 50 to 125, 50 to 100, 50 to 75, 75 to 200, 75 to 175, 75 to 150, 75 to 125, 75 to 100 bp) away from the target position and the two nicks will ideally be within 25 to 55 bp of each other (e.g., 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 30 to 55, 30 to 50, 30 to 45, 30 to 40, 30 to 35, 35 to 55, 35 to 50, 35 to 45, 35 to 40, 40 to 55, 40 to 50, 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20, 10 or 5 bp away from each other). In an embodiment, the cleavage site is between 0 to 100 bp (e.g., 0 to 75, 0 to 50, 0 to 25, 25 to 100, 25 to 75, 25 to 50, 50 to 100, 50 to 75 or 75 to 100 bp) away from the target position.

In one embodiment, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position. In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on either side of the target position. In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of the target position. The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp). In an embodiment, the gRNAs are configured to place a single strand break on either side of the target position. In an embodiment, the gRNAs are configured to place a single strand break on the same side (either 5′ or 3′) of the target position.

Regardless of whether a break is a double strand or a single strand break, the gRNA should be configured to avoid unwanted target chromosome elements, such as repeated elements, e.g., an Alu repeat, in the target domain. In addition, a break, whether a double strand or a single strand break, should be sufficiently distant from any sequence that should not be altered. For example, cleavage sites positioned within introns should be sufficiently distant from any intron/exon border, or naturally occurring splice signal, to avoid alteration of the exonic sequence or unwanted splicing events.

Length of the Homology Arms

The homology arm should extend at least as far as the region in which end resection may occur, e.g., in order to allow the resected single stranded overhang to find a complementary region within the donor template. The overall length could be limited by parameters such as plasmid size or viral packaging limits. In an embodiment, a homology arm does not extend into repeated elements, e.g., Alu repeats, LINE repeats.

Exemplary homology arm lengths include a least 50, 100, 250, 500, 750 or 1000 nucleotides.

Target position, as used herein, refers to a site on a target nucleic acid (e.g., the chromosome) that is modified by a Cas9 molecule-dependent process. For example, the target position can be a modified Cas9 molecule cleavage of the target nucleic acid and template nucleic acid directed modification, e.g., correction, of the target position. In an embodiment, a target position can be a site between two nucleotides, e.g., adjacent nucleotides, on the target nucleic acid into which one or more nucleotides is added. The target position may comprise one or more nucleotides that are altered, e.g., corrected, by a template nucleic acid. In an embodiment, the target position is within a target sequence (e.g., the sequence to which the gRNA binds). In an embodiment, a target position is upstream or downstream of a target sequence (e.g., the sequence to which the gRNA binds).

A template nucleic acid, as that term is used herein, refers to a nucleic acid sequence which can be used in conjunction with a Cas9 molecule and a gRNA molecule to alter the structure of a target position. In an embodiment, the target nucleic acid is modified to have the some or all of the sequence of the template nucleic acid, typically at or near cleavage site(s). In an embodiment, the template nucleic acid is single stranded. In an alternate embodiment, the template nucleic acid is double stranded. In an embodiment, the template nucleic acid is DNA, e.g., double stranded DNA. In an alternate embodiment, the template nucleic acid is single stranded DNA. In an embodiment, the template nucleic acid is encoded on the same vector backbone, e.g. AAV genome, plasmid DNA, as the Cas9 and gRNA. In an embodiment, the template nucleic acid is excised from a vector backbone in vivo, e.g., it is flanked by gRNA recognition sequences.

In an embodiment, the template nucleic acid alters the structure of the target position by participating in a homology directed repair event. In an embodiment, the template nucleic acid alters the sequence of the target position. In an embodiment, the template nucleic acid results in the incorporation of a modified, or non-naturally occurring base into the target nucleic acid.

Typically, the template sequence undergoes a breakage mediated or catalyzed recombination with the target sequence. In an embodiment, the template nucleic acid includes sequence that corresponds to a site on the target sequence that is cleaved by an eaCas9 mediated cleavage event. In an embodiment, the template nucleic acid includes sequence that corresponds to both, a first site on the target sequence that is cleaved in a first Cas9 mediated event, and a second site on the target sequence that is cleaved in a second Cas9 mediated event.

In an embodiment, the template nucleic acid can include sequence which results in an alteration in the coding sequence of a translated sequence, e.g., one which results in the substitution of one amino acid for another in a protein product, e.g., transforming a mutant allele into a wild type allele, transforming a wild type allele into a mutant allele, and/or introducing a stop codon, insertion of an amino acid residue, deletion of an amino acid residue, or a nonsense mutation.

In another embodiment, the template nucleic acid can include sequence which results in an alteration in a non-coding sequence, e.g., an alteration in an exon or in a 5′ or 3′ non-translated or non-transcribed region. Such alterations include an alteration in a control element, e.g., a promoter, enhancer, and an alteration in a cis-acting or trans-acting control element.

A template nucleic acid having homology with a target position in the CFTR gene can be used to alter the structure of a target sequence. The template sequence can be used to alter an unwanted structure, e.g., an unwanted or mutant nucleotide.

A template nucleic acid comprises the following components:

    • [5′ homology arm]-[replacement sequence]-[3′ homology arm].

The homology arms provide for recombination into the chromosome, thus replacing the undesired element, e.g., a mutation or signature, with the replacement sequence. In an embodiment, the homology arms flank the most distal cleavage sites.

In an embodiment, the 3′ end of the 5′ homology arm is the position next to the 5′ end of the replacement sequence. In an embodiment, the 5′ homology arm can extend at least 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 5′ from the 5′ end of the replacement sequence.

In an embodiment, the 5′ end of the 3′ homology arm is the position next to the 3′ end of the replacement sequence. In an embodiment, the 3′ homology arm can extend at least 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, or 2000 nucleotides 3′ from the 3′ end of the replacement sequence.

Exemplary Template Nucleic Acids

Exemplary template nucleic acids (also referred to herein as donor constructs) to correct a mutation, e.g., F508del target position in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(5′H arm) SEQ ID NO: 27266 AAAATACAAAAAATTAGCCAGACGTGATGGCGGGTGCCCGTAGTCCCAGC TACTCGGGAGGCTGAGGCAGGAGAATGGCGTGAACCCAGGAGGCAGAACT TGCAGTGAGCCGAGATCGCGCCACTGCACTCTAGCCTGGGTGACAGAGTG AGACTCTGTCTCTAAATAAATAAATAAATAAATAAATAAATAAATAAAAT CAGTGCTTTTTCTTCCTCTGCTACCTCCTTTCCTTCTACTCAGTTTTAGT CAGTAGTATTATCTTTTTTCAGATTTATCTTTGTATTGTTAAATCTGCTT ATGCTTCTATTACTTTATTTATTAGCTTTAAATGATACCTTTTGACTTTC AGCTTTTCTTAATAAAGCAATCAGCAAATTTCCTTTACACTCCACACTTA TACCCCATTTCCTTTGTTTGTTTATTTGGTTTTTACTTCTAACTTTTCTT ATTGTCAGGACATATAACATATTTAAACTTTGTTTTTCAACTCGAATTCT GCCATTAGTTTTAATTTTTGTTCACAGTTATATAAATCTTTGTTCACTGA TAGTCCTTTTGTACTATCATCTCTTAAATGACTTTATACTCCAAGAAAGG CTCATGGGAACAATATTACCTGAATATGTCTCTATTACTTAATCTGTACC TAATAATATGAAGGTAATCTACTTTGTAGGATTTCTGTGAAGATTAAATA AATTAATATAGTTAAAGCACATAGAACAGCACTCGACACAGAGTGAGCAC TTGGCAACTGTTAGCTGTTACTAACCTTTCCCATTCTTCCTCCAAACCTA TTCCAACTATCTGAATCATGTGCCCCTTCTCTGTGAACCTCTATCATAAT ACTTGTCACACTGTATTGTAATTGTCTCTTTTACTTTCCCTTGTATCTTT TGTGCATAGCAGAGTACCTGAAACAGGAAGTATTTTAAATATTTTGAATC AAATGAGTTAATAGAATCTTTACAAATAAGAATATACACTTCTGCTTAGG ATGATAATTGGAGGCAAGTGAATCCTGAGCGTGATTTGATAATGACCTAA TAATGATGGGTTTTATTTCCAGACTTCACTTCTAATGGTGATTATGGGAG AACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCATTC TGTTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCAT

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(3′H arm) SEQ ID NO: 27267 TGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGCC AACTAGAAGAGGTAAGAAACTATGTGAAAACTTTTTGATTATGCATATGA ACCCTTCACACTACCCAAATTATATATTTGGCTCCATATTCAATCGGTTA GTCTACATATATTTATGTTTCCTCTATGGGTAAGCTACTGTGAATGGATC AATTAATAAAACACATGACCTATGCTTTAAGAAGCTTGCAAACACATGAA ATAAATGCAATTTATTTTTTAAATAATGGGTTCATTTGATCACAATAAAT GCATTTTATGAAATGGTGAGAATTTTGTTCACTCATTAGTGAGACAAACG TCCTCAATGGTTATTTATATGGCATGCATATAAGTGATATGTGGTATCTT TTTAAAAGATACCACAAAATATGCATCTTTAAAAATATACTCCAAAAATT ATTAAGATTATTTTAATAATTTTAATAATACTATAGCCTAATGGAATGAG CATTGATCTGCCAGCAGAGAATTAGAGGGGTAAAATTGTGAAGATATTGT ATCCCTGGCTTTGAACAAATACCATATAACTTCTAGTGACTGCAATTCTT TGATGCAGAGGCAAAATGAAGATGATGTCATTACTCATTTCACAACAATA TTGGAGAATGAGCTAATTATCTGAAAATTACATGAAGTATTCCAAGAGAA ACCAGTATATGGATCTTGTGCTGTTCACTATGTAAATTGTGTGATGGTGG GTTCAGTAGTTATTGCTGTAAATGTTAGGGCAGGGAATATGTTACTATGA AGTTTATTGACAGTATACTCCAAATAGTGTTTGTGATTCAAAAGCAATAT CTTTGATAGTTGGCATTTGCAATTCCTTTATATAATCTTTTATGAAAAAA ATTGCAGAGAAAGTAAAATGTAGCTTAAAATACAGTATCCAAAAAAATGG AAAAGGGCAAACCGTGGATTAGATAGAAATGGCAATTCTTATAAAAAGGG TTGCATGCTTACATGAATGGCTTTCCATGTATATACTCAGTCATTCAACA GTTTTTTTTTTAGAGCCCCATTCTTATTTTTTATACACTTTGAGAGCATA ATGAAAAGAAAAGCTACCTGCAAAAGTTTTGGACTTACCTCAAAGAGGAT ATACTTCATTCCTCAAAAGGCCTTCTTCCAGGAATAGTATTTCATAACCT

In an embodiment, the replacement sequence comprises or consists of CTT residues.

In an embodiment, to correct a mutation, e.g., F508del target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 1; SEQ ID NO: 27268) AAAATACAAAAAATTAGCCAGACGTGATGGCGGGTGCCCGTAGTCCCAGC TACTCGGGAGGCTGAGGCAGGAGAATGGCGTGAACCCAGGAGGCAGAACT TGCAGTGAGCCGAGATCGCGCCACTGCACTCTAGCCTGGGTGACAGAGTG AGACTCTGTCTCTAAATAAATAAATAAATAAATAAATAAATAAATAAAAT CAGTGCTTTTTCTTCCTCTGCTACCTCCTTTCCTTCTACTCAGTTTTAGT CAGTAGTATTATCTTTTTTCAGATTTATCTTTGTATTGTTAAATCTGCTT ATGCTTCTATTACTTTATTTATTAGCTTTAAATGATACCTTTTGACTTTC AGCTTTTCTTAATAAAGCAATCAGCAAATTTCCTTTACACTCCACACTTA TACCCCATTTCCTTTGTTTGTTTATTTGGTTTTTACTTCTAACTTTTCTT ATTGTCAGGACATATAACATATTTAAACTTTGTTTTTCAACTCGAATTCT GCCATTAGTTTTAATTTTTGTTCACAGTTATATAAATCTTTGTTCACTGA TAGTCCTTTTGTACTATCATCTCTTAAATGACTTTATACTCCAAGAAAGG CTCATGGGAACAATATTACCTGAATATGTCTCTATTACTTAATCTGTACC TAATAATATGAAGGTAATCTACTTTGTAGGATTTCTGTGAAGATTAAATA AATTAATATAGTTAAAGCACATAGAACAGCACTCGACACAGAGTGAGCAC TTGGCAACTGTTAGCTGTTACTAACCTTTCCCATTCTTCCTCCAAACCTA TTCCAACTATCTGAATCATGTGCCCCTTCTCTGTGAACCTCTATCATAAT ACTTGTCACACTGTATTGTAATTGTCTCTTTTACTTTCCCTTGTATCTTT TGTGCATAGCAGAGTACCTGAAACAGGAAGTATTTTAAATATTTTGAATC AAATGAGTTAATAGAATCTTTACAAATAAGAATATACACTTCTGCTTAGG ATGATAATTGGAGGCAAGTGAATCCTGAGCGTGATTTGATAATGACCTAA TAATGATGGGTTTTATTTCCAGACTTCACTTCTAATGGTGATTATGGGAG AACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCATTC TGTTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCAT cttTGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCAT GCCAACTAGAAGAGGTAAGAAACTATGTGAAAACTTTTTGATTATGCATA TGAACCCTTCACACTACCCAAATTATATATTTGGCTCCATATTCAATCGG TTAGTCTACATATATTTATGTTTCCTCTATGGGTAAGCTACTGTGAATGG ATCAATTAATAAAACACATGACCTATGCTTTAAGAAGCTTGCAAACACAT GAAATAAATGCAATTTATTTTTTAAATAATGGGTTCATTTGATCACAATA AATGCATTTTATGAAATGGTGAGAATTTTGTTCACTCATTAGTGAGACAA ACGTCCTCAATGGTTATTTATATGGCATGCATATAAGTGATATGTGGTAT CTTTTTAAAAGATACCACAAAATATGCATCTTTAAAAATATACTCCAAAA ATTATTAAGATTATTTTAATAATTTTAATAATACTATAGCCTAATGGAAT GAGCATTGATCTGCCAGCAGAGAATTAGAGGGGTAAAATTGTGAAGATAT TGTATCCCTGGCTTTGAACAAATACCATATAACTTCTAGTGACTGCAATT CTTTGATGCAGAGGCAAAATGAAGATGATGTCATTACTCATTTCACAACA ATATTGGAGAATGAGCTAATTATCTGAAAATTACATGAAGTATTCCAAGA GAAACCAGTATATGGATCTTGTGCTGTTCACTATGTAAATTGTGTGATGG TGGGTTCAGTAGTTATTGCTGTAAATGTTAGGGCAGGGAATATGTTACTA TGAAGTTTATTGACAGTATACTCCAAATAGTGTTTGTGATTCAAAAGCAA TATCTTTGATAGTTGGCATTTGCAATTCCTTTATATAATCTTTTATGAAA AAAATTGCAGAGAAAGTAAAATGTAGCTTAAAATACAGTATCCAAAAAAA TGGAAAAGGGCAAACCGTGGATTAGATAGAAATGGCAATTCTTATAAAAA GGGTTGCATGCTTACATGAATGGCTTTCCATGTATATACTCAGTCATTCA ACAGTTTTTTTTTTAGAGCCCCATTCTTATTTTTTATACACTTTGAGAGC ATAATGAAAAGAAAAGCTACCTGCAAAAGTTTTGGACTTACCTCAAAGAG GATATACTTCATTCCTCAAAAGGCCTTCTTCCAGGAATAGTATTTCATAA CCT

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct F508del mutation in the CFTR gene, the 5′ homology arm may be shortened less than 500 nucleotides, e.g., approximately 450 nucleotides, e.g., 428 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 2; SEQ ID NO: 27269) AACCTTTCCCATTCTTCCTCCAAACCTATTCCAACTATCTGAATCATGTG CCCCTTCTCTGTGAACCTCTATCATAATACTTGTCACACTGTATTGTAAT TGTCTCTTTTACTTTCCCTTGTATCTTTTGTGCATAGCAGAGTACCTGAA ACAGGAAGTATTTTAAATATTTTGAATCAAATGAGTTAATAGAATCTTTA CAAATAAGAATATACACTTCTGCTTAGGATGATAATTGGAGGCAAGTGAA TCCTGAGCGTGATTTGATAATGACCTAATAATGATGGGTTTTATTTCCAG ACTTCACTTCTAATGGTGATTATGGGAGAACTGGAGCCTTCAGAGGGTAA AATTAAGCACAGTGGAAGAATTTCATTCTGTTCTCAGTTTTCCTGGATTA TGCCTGGCACCATTAAAGAAAATATCATcttTGGTGTTTCCTATGATGAA TATAGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAGGTAAGAAA CTATGTGAAAACTTTTTGATTATGCATATGAACCCTTCACACTACCCAAA TTATATATTTGGCTCCATATTCAATCGGTTAGTCTACATATATTTATGTT TCCTCTATGGGTAAGCTACTGTGAATGGATCAATTAATAAAACACATGAC CTATGCTTTAAGAAGCTTGCAAACACATGAAATAAATGCAATTTATTTTT TAAATAATGGGTTCATTTGATCACAATAAATGCATTTTATGAAATGGTGA GAATTTTGTTCACTCATTAGTGAGACAAACGTCCTCAATGGTTATTTATA TGGCATGCATATAAGTGATATGTGGTATCTTTTTAAAAGATACCACAAAA TATGCATCTTTAAAAATATACTCCAAAAATTATTAAGATTATTTTAATAA TTTTAATAATACTATAGCCTAATGGAATGAGCATTGATCTGCCAGCAGAG AATTAGAGGGGTAAAATTGTGAAGATATTGTATCCCTGGCTTTGAACAAA TACCATATAACTTCTAGTGACTGCAATTCTTTGATGCAGAGGCAAAATGA AGATGATGTCATTACTCATTTCACAACAATATTGGAGAATGAGCTAATTA TCTGAAAATTACATGAAGTATTCCAAGAGAAACCAGTATATGGATCTTGT GCTGTTCACTATGTAAATTGTGTGATGGTGGGTTCAGTAGTTATTGCTGT AAATGTTAGGGCAGGGAATATGTTACTATGAAGTTTATTGACAGTATACT CCAAATAGTGTTTGTGATTCAAAAGCAATATCTTTGATAGTTGGCATTTG CAATTCCTTTATATAATCTTTTATGAAAAAAATTGCAGAGAAAGTAAAAT GTAGCTTAAAATACAGTATCCAAAAAAATGGAAAAGGGCAAACCGTGGAT TAGATAGAAATGGCAATTCTTATAAAAAGGGTTGCATGCTTACATGAATG GCTTTCCATGTATATACTCAGTCATTCAACAGTTTTTTTTTTAGAGCCCC ATTCTTATTTTTTATACACTTTGAGAGCATAATGAAAAGAAAAGCTACCT GCAAAAGTTTTGGACTTACCTCAAAGAGGATATACTTCATTCCTCAAAAG GCCTTCTTCCAGGAATAGTATTTCATAACCT

In an embodiment, to correct F508del mutation in the CFTR gene, the 5′ homology arm may be shortened to approximately 500 nucleotides. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 3; SEQ ID NO: 27270) AATTAATATAGTTAAAGCACATAGAACAGCACTCGACACAGAGTGAGCAC TTGGCAACTGTTAGCTGTTACTAACCTTTCCCATTCTTCCTCCAAACCTA TTCCAACTATCTGAATCATGTGCCCCTTCTCTGTGAACCTCTATCATAAT ACTTGTCACACTGTATTGTAATTGTCTCTTTTACTTTCCCTTGTATCTTT TGTGCATAGCAGAGTACCTGAAACAGGAAGTATTTTAAATATTTTGAATC AAATGAGTTAATAGAATCTTTACAAATAAGAATATACACTTCTGCTTAGG ATGATAATTGGAGGCAAGTGAATCCTGAGCGTGATTTGATAATGACCTAA TAATGATGGGTTTTATTTCCAGACTTCACTTCTAATGGTGATTATGGGAG AACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTGGAAGAATTTCATTC TGTTCTCAGTTTTCCTGGATTATGCCTGGC cttTGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCAT GCCAACTAGAAGAGGTAAGAAACTATGTGAAAACTTTTTGATTATGCATA TGAACCCTTCACACTACCCAAATTATATATTTGGCTCCATATTCAATCGG TTAGTCTACATATATTTATGTTTCCTCTATGGGTAAGCTACTGTGAATGG ATCAATTAATAAAACACATGACCTATGCTTTAAGAAGCTTGCAAACACAT GAAATAAATGCAATTTATTTTTTAAATAATGGGTTCATTTGATCACAATA AATGCATTTTATGAAATGGTGAGAATTTTGTTCACTCATTAGTGAGACAA ACGTCCTCAATGGTTATTTATATGGCATGCATATAAGTGATATGTGGTAT CTTTTTAAAAGATACCACAAAATATGCATCTTTAAAAATATACTCCAAAA ATTATTAAGATTATTTTAATAATTTTAATAATACTATAGCCTAATGGAAT GAG

It is contemplated herein that, in an embodiment, template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., F508del target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the F508del mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 4; SEQ ID NO: 27271) TAAGCACAGTGGAAGAATTTCATTCTGTTCTCAGTTTTCCTGGATTATGC CTGGCACCATTAAAGAAAATATCATcttTGGTGTTTCCTATGATGAATAT AGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAGGTAAGAAACTA TGT

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., G542X target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(5′H arm) SEQ ID NO: 27272 TGTCCATATGGTAGATAAATGGAACAAATGAATAACAGAAGTAACCATTT TGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAAGAA GAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGG AGGTGGAAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTT TTTTTTTTTAAGGCGAGAGTTTACTACCTATCTAACTCTTCGCATTCTTG AAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAGGGTATTCTATC TATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAA CTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTAT TTAGCTTTCTCCAGGATTATGACTTACCTTCTAAATTAGACATACAATGC CTAGGAGTCAAGGACTATTTTGCATAAATTCCAGTCTTCTTTTACAATGC CTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAGGATGA CAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGG ATGGACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCA TGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTTAGAT CCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTT GTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAA AGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATG GATGATCTACACATATTTATATACCCATAAATATACACATATTTTAATTT TTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAAT TACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACT AAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACT GTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGC CTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATT TTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTT

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(3′H arm) SEQ ID NO: 27273 GAGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTA GCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTC ATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTT CTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCAC ATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTAT GGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCC TCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATAC TGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCAC TCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATT TTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGAT GTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCAT TAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAG CATTTTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGGA GAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTGA CTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCAC TTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTT GGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAAC TAACCCTAACTGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCATGTGT GTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAAGAATTG TTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATG TTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACC AGGTCCTTTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATACA CTGTAAGGCAATAAATCAATAGATACGGATAATTCACAGGCTTCTAAATA AATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTAA

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., G542X target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 5; SEQ ID NO: 27274) TGTCCATATGGTAGATAAATGGAACAAATGAATAACAGAAGTAACCATTT TGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAAGAA GAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGG AGGTGGAAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTT TTTTTTTTTAAGGCGAGAGTTTACTACCTATCTAACTCTTCGCATTCTTG AAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAGGGTATTCTATC TATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAA CTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTAT TTAGCTTTCTCCAGGATTATGACTTACCTTCTAAATTAGACATACAATGC CTAGGAGTCAAGGACTATTTTGCATAAATTCCAGTCTTCTTTTACAATGC CTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAGGATGA CAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGG ATGGACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCA TGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTTAGAT CCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTT GTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAA AGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATG GATGATCTACACATATTTATATACCCATAAATATACACATATTTTAATTT TTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAAT TACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACT AAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACT GTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGC CTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATT TTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTT gGAGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTT AGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGT CATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTT TCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCA CATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTA TGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGC CTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATA CTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCA CTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACAT TTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGA TGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCA TTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAA GCATTTTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGG AGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTG ACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCA CTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTT TGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAA CTAACCCTAACTGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCATGTG TGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAAGAATT GTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGAT GTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAAC CAGGTCCTTTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATAC ACTGTAAGGCAATAAATCAATAGATACGGATAATTCACAGGCTTCTAAAT AAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTA A

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct G542X mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 6; SEQ ID NO: 27275) CCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTT GTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAA AGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATG GATGATCTACACATATTTATATACCCATAAATATACACATATTTTAATTT TTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAAT TACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACT AAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACT GTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGC CTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATT TTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTT gGAGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTT AGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGT CATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTT TCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCA CATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTA TGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGC CTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATA CTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCA CTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACAT TTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGA T

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., G542X target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the G542X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 7; SEQ ID NO: 27276) AAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTT TGCAGAGAAAGACAATATAGTTCTTgGAGAAGGTGGAATCACACTGAGTG GAGGTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGG T

It is contemplated herein that, in an embodiment, a Cas9 molecule could potentially cleave donor constructs either prior to or following homology directed repair (e.g., homologous recombination), resulting in a possible non-homologous-end-joining event and further DNA sequence mutation at the chromosomal locus of interest. Therefore, to avoid cleavage of the donor sequence before and/or after Cas9-mediated homology directed repair, alternate versions of the donor sequence may be used where silent mutations are introduced. These silent mutations may disrupt Cas9 binding and cleavage, but not disrupt the amino acid sequence of the repaired gene. For example, mutations may include those made to a donor sequence to repair the CFTR gene, the mutant form which can cause CF or CF-like disease. In an embodiment, a silent mutation that disrupts Cas9 binding and cleavage, but does not disrupt the amino acid sequence of the repaired gene, is a sense mutation.

In an embodiment, to correct a mutation, e.g., G542X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 8; SEQ ID NO: 27277) TGTCCATATGGTAGATAAATGGAACAAATGAATAACAGAAGTAACCATTT TGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAAGAA GAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGG AGGTGGAAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTT TTTTTTTTTAAGGCGAGAGTTTACTACCTATCTAACTCTTCGCATTCTTG AAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAGGGTATTCTATC TATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAA CTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTAT TTAGCTTTCTCCAGGATTATGACTTACCTTCTAAATTAGACATACAATGC CTAGGAGTCAAGGACTATTTTGCATAAATTCCAGTCTTCTTTTACAATGC CTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAGGATGA CAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGG ATGGACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCA TGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTTAGAT CCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTT GTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAA AGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATG GATGATCTACACATATTTATATACCCATAAATATACACATATTTTAATTT TTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAAT TACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACT AAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACT GTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGC CTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATT TTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTa gGtGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTT AGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGT CATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTT TCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCA CATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTA TGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGC CTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATA CTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCA CTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACAT TTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGA TGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCA TTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAA GCATTTTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGG AGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTG ACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCA CTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTT TGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAA CTAACCCTAACTGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCATGTG TGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAAGAATT GTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGAT GTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAAC CAGGTCCTTTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATAC ACTGTAAGGCAATAAATCAATAGATACGGATAATTCACAGGCTTCTAAAT AAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTA A

In an embodiment, to correct a mutation, e.g., G542X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 9; SEQ ID NO: 27278) CCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTT GTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAA AGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATG GATGATCTACACATATTTATATACCCATAAATATACACATATTTTAATTT TTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAAT TACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACT AAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACT GTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGC CTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATT TTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTa gGtGAAGGTGGAATCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTT AGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGT CATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTT TCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCA CATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTA TGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGC CTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATA CTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCA CTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACAT TTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGA T

In an embodiment, an ssODN may be to correct a mutation, e.g., G542X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 10; SEQ ID NO: 27279) AAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTT TGCAGAGAAAGACAATATAGTTCTagGtGAAGGTGGAATCACACTGAGTG GAGGTCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGG T

The underlined A has been changed from a T to A at that position and the underlined T has been changed from an A to T at that position so that wild-type CFTR is still transcribed, but the PAM sequence AGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., G551D target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(5′H arm) SEQ ID NO: 27280 TGAATAACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGA TTATTTCTGGATTGTGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTT TTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACGAATGTACAAGGATGGGA GGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGTTTACTACC TATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTG AAAGCCTCTAGGGTATTCTATCTATTGTATACTTCTGTTATGTACAAAAT TAATTTGCCAATTAATTGTGAACTGTTTTATAAACTATCTTAAAATGGTT AGTTAAATCTTTGGGATAGTATTTAGCTTTCTCCAGGATTATGACTTACC TTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATAAA TTCCAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATT CATTACCTGGGAGAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGAGG TCGTGAGAATGAGGTGCTGAGGATGGACGAGGAAGAAAGCTGTTTTAGTT GGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCCATGGA AGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTT AGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAA GAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAACATTT GAATTTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCAT AAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGA TCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCA GCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGA TGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGA TTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAA AGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGC AGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAG

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27281 (3′H arm) TCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTG TAAATGTCATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAA TTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAAT GGTATAGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTC AGTGTATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAAT ACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACAC ACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCA TAACAAAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGG ACAAATGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATT TTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAA CTGTAACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCT GAACAAAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATG TTTTGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAAC TGAGCACCTGCAATTGCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCC CTTACAGCTCTGCAAAGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGA GGCTGTTAGATGTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAG GTCCTTTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAAT CAATAGATACGGATAATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGC CAAAGTAAGACTTATTCTAAGAATTCCACAAATTTAGATAAGATAGAG

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., G551D target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, codon 551 is shown as underlined sequence, the inserted base to correct the G551D mutation is shown as non-bold and boxed sequence, and the 3′ homology arm is shown as no emphasis sequence.

(Template Construct 11; SEQ ID NO: 27282) TGAATAACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTG TGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGG AAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGT TTACTACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCC TCTAGGGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTG AACTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCC AGGATTATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATA AATTCCAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGA GAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGG ACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTG GACCCATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTT TCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGA GAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTAC ACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTA ATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGT TTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGT GGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATT GAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAG AGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAG  TCAACGAGCAAGAAT TTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATG TAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGG GGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGA TTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGC CTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGA TGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTT CTIGGTATAGATAAACATACATITICAAAATITTICATCATAATTTTCATAACAAAATAGGAAG GCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACA TTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAG AGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTT TAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCT CACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCC CTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATT GCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAA AGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTA ACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTT TACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATAGATACGGATA ATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTAT TCTAAGAATTCCACAAATTTAGATAAGATAGAG

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct G551D mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., approximately 750 nucleotides, e.g., 724 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, codon 551 is shown as underlined sequence, the inserted base to correct the G551D mutation is shown as non-bold and boxed sequence, and the 3′ homology arm is shown as no emphasis sequence.

(Template Construct 12; SEQ ID NO: 27283) AATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAGGATGACAGGAGGGGCAGAATGAA TGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAGGAAGAAAGCTGTTTTAGTTGGGA GGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCCATGGAAGCCCAGTGAAGATACTT AGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCTTCTTAGGAGGTTTGTTCATTTTG GGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAAGTACATTTTAGTATGTTGATAAC ATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATATTTATATACCCATAAATATACAC ATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGATCATTCATGACATTTTAAAAATTA CAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTGACCAACTAAATAAATTGCATTTG AAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTAAAGCAATAGTGTGATATATGATT ACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCATACTAAAAGTGACTCTCTAATTT TCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGG TGGAATCACACTGAGTGGAG  TCAACGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTAT TGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAAAAATTACAGACATTTCTCTATTG CTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCA CATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAAT CTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAA AACTCTAGGATTCTGCATAATACTGGACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGA CCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAA AATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCT ATAATATTTAAAATAAACAGGACAAATGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGA AACACICTIGGTCCAAGCATITTAAAGCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAA GGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCA AATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGA AATCACATTGACTCATTGATGTTTTGGCTCCTTTCCCTTACTTTCTGTTGCTTTCCAAAAGCTG AGACAGGA

In an embodiment, to correct G551D mutation in the CFTR gene, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 13; SEQ ID NO: 27284) AGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAAT TGGAGAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGAT CTACACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTA TTTAATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATG TTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAA CTGTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCA GATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTT GCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAGgTCAACGAGCAA GAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATT CATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATC CTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATC CAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGT TTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAG AAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAG GCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAG GAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTT

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., G551D target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the G542X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 14; SEQ ID NO: 27285) GGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAG TTCTTGGAGAAGGTGGAATCACACTGAGTGGAGgTCAACGAG CAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTA GCAAGCATTTGCTGTAAATGTCATT

In an embodiment, to correct a mutation, e.g., G551D target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 15; SEQ ID NO: 27286) TGAATAACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTG TGAAAGAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGG AAACGAATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGT TTACTACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCC TCTAGGGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTG AACTGTTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCC AGGATTATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATA AATTCCAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGA GAAAGGATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGG ACGAGGAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTG GACCCATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTT TCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGA GAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTAC ACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTA ATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGT TTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGT GGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATT GAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAG AGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGtcTGGAGgTCAACGAGCAAGAAT TTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATG TAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGG GGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGA TTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGC CTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGA TGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTT CTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAG GCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACA TTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAG AGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTT TAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCT CACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCC CTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATT GCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAA AGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTA ACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTT TACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATAGATACGGATA ATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTAT TCTAAGAATTCCACAAATTTAGATAAGATAGAG

In an embodiment, to correct a mutation, e.g., G551D target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 16; SEQ ID NO: 27287) AGTTTCTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAAT TGGAGAAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGAT CTACACATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTA TTTAATGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATG TTGTTTTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAA CTGTGGTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCA GATTGAGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTT GCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGtcTGGAGgTCAACGAGCAA GAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATT CATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATC CTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATC CAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGT TTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAG AAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAG GCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAG GAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTT

In an embodiment, an ssODN may be to correct a mutation, e.g., G551D target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the G551D mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 18; SEQ ID NO: 27288) GGTAATAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTT CTTGGAGAAGGTGGAATCACACTGtcTGGAGgTCAACGAGCAAG AATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGC ATTTGCTGTAAATGTCATT

The underlined T has been changed from a A to T at that position and the underlined C has been changed from an G to C at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., N1303K target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27289 (5′H arm) GTTTCTGAGACATTTGACAACAACTTTTTCTTTAAGTCATCAGTTATGCCCCGGGGTATGAAAT TTCTAACATGATCCTCAGTAAACTTGGCTGCCTTGCTGAGGATACTCTCCATCTGCCTGAGAGA CACAGACACCATTAATTGGGAATTGACTTGACTTGTGTGGTTCCTTGTGGACCAGATGGCCACT AAATATTCTCATTTCAAGGCAATTGGTAAAAACTACACTTCAAGAAATTTCATTCTTAATTCCC CTTAGTGGATGTTATTAACCAAAGGCAAAAGAAAAAAAGGGTTAAAAAAATATTCTAAATGTTA ATATCAAAAATATTATTTTTCATTCACCCCAGGCACAGAGAACTAAGTATTATTATTGCTATTG CACCGGCATTCCCCAATGAGACAGTGATTTTCTTTTAAGACATTTTTAAATAATATAGGCAGAA TTAAGTAGACGGTGATCTGGTAAGTAGATGTTTCAGGGTAACAGCTGTGCAATGCTCCATGCAG GGAATTAGATTGTCATTTTATTCCTTACCAGGAACATACATTCAGTTAAACAATTATTTGACTT CTGCTCTTCCACTGATTTCTAAGTTGAGGCTCTCTCTTGTGCCTGTCTGATCAGATAAGTAGAG TTGTGCCTTGGTTTATAGATGAGATAAATGTGTATTTGAATAAGCATAAGTTAAAGAAATTTTA AAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGGAATT TGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTATATT ACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAACAAT TATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCAAATA TTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAATTTG AGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAAATAT TTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCTTTTC TTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAA

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence.

SEQ ID NO: 27290 (3′H arm) TTGGATCCCTATGAACAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGC TAACTGAAATGATTTTGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCA TTCTACACACTTTGTGTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACC TGGAGCAACAGGTACTTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTC ATACCAACACAAATGGTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTG TGCACAACTTCAAAATGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTA CTTCTCTCCTCACTGGTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAA ATAAAATACCAAAGACTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAGTCAAAGATCAAG GTGCCAGCAGGTTTGCTGTCTCGTGAGAGCATACTTCCTGGTTCATTGATGGTGCTTTCTTGCT GTGTCCTCACATAATGGAAAGGGCAAGACCTCTCTGGTGTCTCTTTTACAATGGCACTAATCCC ATCATGAGGGCTTTGTTCTCATGACCTAATCACCTCCCACATGTCCTACATTCTAATACTATCA CCTTGGGGGTTAGGATTTTAACATATGAATTTGAGGAGGTGGCGGGGGGGACACAAATATTTAG ACCATAGCATTTCACTCCTGACCTCCAAAGTTCATGTCTTCTTCACATGCAAAATACATTCATT CCATCCCAATAGCCCCCAAAGTCTTAACTTGTTCCAGCATCAACTTACAAGGCTAAAGTCCAAG GTTTCATCTAAATATCAGCTAAATCAGCACAAACAGCTAAATCAGGTAGAGTGGGACTTAAGGT GTGATTCCTCTTTAGGCAGATTGCTCTCCAACTATGAAATTGTGAAATCAAACCTATTATGTAC TTTCAAAATAAAATGGTGAAACAGGCACAGGCTAGACAGTCCCATTTCAAAAAAGAGAAATAGA AAAGAAAAAAGGAGTGACAGGTCTCTATAAGTCTAAAACTTTAAGGCTTGAGAATAATTTGCTT TGCTTTGCCTCCAGGCTCACTGGGGTGGTGTCTTACCTCTGGACACAC

In an embodiment, the replacement sequence comprises or consists of a Cytosine (C) residue.

In an embodiment, to correct a mutation, e.g., N1303K target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the G542X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 19; SEQ ID NO: 27291) GTTTCTGAGACATTTGACAACAACTTTTTCTTTAAGTCATCAGTTATGCCCCGGGGTATGAAAT TTCTAACATGATCCTCAGTAAACTTGGCTGCCTTGCTGAGGATACTCTCCATCTGCCTGAGAGA CACAGACACCATTAATTGGGAATTGACTTGACTTGTGTGGTTCCTTGTGGACCAGATGGCCACT AAATATTCTCATTTCAAGGCAATTGGTAAAAACTACACTTCAAGAAATTTCATTCTTAATTCCC CTTAGTGGATGTTATTAACCAAAGGCAAAAGAAAAAAAGGGTAAAAAAAATATTCTAAATGTTA ATATCAAAAATATTATTTTCAATTCACCCCAGGCACAGAGAACTAAGTATTATTATTGCTATTG CACCGGCATTCCCCAATGAGACAGTGATTTTCTTTTAAGACATTTTTAAATAATATAGGCAGAA TTAAGTAGACGGTGATCTGGTAAGTAGATGTTTCAGGGTAACAGCTGTGCAATGCTCCATGCAG GGAATTAGATTGTCATTTTATTCCTTACCAGGAACATACATTCAGTTAAACAATTATTTGACTT CTGCTCTTCCACTGATTTCTAAGTTGAGGCTCTCTCTTGTGCCTGTCTGATCAGATAAGTAGAG TTGTGCCTTGGTTTATAGATGAGATAAATGTGTATTTGAATAAGCATAAGTTAAAGAAATTTTA AAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGGAATT TGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTATATT ACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAACAAT TATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCAAATA TTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAATTTG AGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAAATAT TTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCTTTTC TTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAcTTGGATCCCTATGAA CAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGCTAACTGAAATGATTT TGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCATTCTACACACTTTGT GTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACCTGGAGCAACAGGTAC TTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTCATACCAACACAAATG GTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTGTGCACAACTTCAAAA TGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTACTTCTCTCCTCACTG GTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAAATAAAATACCAAAGA CTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAGTCAAAGATCAAGGTGCCAGCAGGTTTG CTGTCTCGTGAGAGCATACTTCCTGGTTCATTGATGGTGCTTTCTTGCTGTGTCCTCACATAAT GGAAAGGGCAAGACCTCTCTGGTGTCTCTTTTACAATGGCACTAATCCCATCATGAGGGCTTTG TTCTCATGACCTAATCACCTCCCACATGTCCTACATTCTAATACTATCACCTTGGGGGTTAGGA TTTTAACATATGAATTTGAGGAGGTGGCGGGGGGGACACAAATATTTAGACCATAGCATTTCAC TCCTGACCTCCAAAGTTCATGTCTTCTTCACATGCAAAATACATTCATTCCATCCCAATAGCCC CCAAAGTCTTAACTTGTTCCAGCATCAACTTACAAGGCTAAAGTCCAAGGTTTCATCTAAATAT CAGCTAAATCAGCACAAACAGCTAAATCAGGTAGAGTGGGACTTAAGGTGTGATTCCTCTTTAG GCAGATTGCTCTCCAACTATGAAATTGTGAAATCAAACCTATTATGTACTTTCAAAATAAAATG GTGAAACAGGCACAGGCTAGACAGTCCCATTTCAAAAAAGAGAAATAGAAAAGAAAAAAGGAGT GACAGGTCTCTATAAGTCTAAAACTTTAAGGCTTGAGAATAATTTGCTTTGCTTTGCCTCCAGG CTCACTGGGGTGGTGTCTTACCTCTGGACACAC

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct N1303K mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 20; SEQ ID NO: 27292) TTTAAAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGG AATTTGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTA TATTACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAA CAATTATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCA AATATTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAA TTTGAGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAA ATATTTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCT TTTCTTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAcTTGGATCCCTA TGAACAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGCTAACTGAAATG ATTTTGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCATTCTACACACT TTGTGTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACCTGGAGCAACAG GTACTTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTCATACCAACACA AATGGTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTGTGCACAACTTC AAAATGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTACTTCTCTCCTC ACTGGTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAAATAAAATACCA AAGACTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAG

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., N1303K target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the N1303K mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 21; SEQ ID NO: 27293) AGTTATTCATACTTTCTTCTTCTTTTCTTTTTTGCTATAGAAAGTAT TTATTTTTTCTGGAACATTTAGAAAAAAcTTGGATCCCTATGAACAG TGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGCT AACTGAAATG

In an embodiment, to correct a mutation, e.g., N1303K target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 22; SEQ ID NO: 27294) GTTTCTGAGACATTTGACAACAACTTTTTCTTTAAGTCATCAGTTATGCCCCGGGGTATGAAAT TTCTAACATGATCCTCAGTAAACTTGGCTGCCTTGCTGAGGATACTCTCCATCTGCCTGAGAGA CACAGACACCATTAATTGGGAATTGACTTGACTTGTGTGGTTCCTTGTGGACCAGATGGCCACT AAATATTCTCATTTCAAGGCAATTGGTAAAAACTACACTTCAAGAAATTTCATTCTTAATTCCC CTTAGTGGATGTTATTAACCAAAGGCAAAAGAAAAAAAGGGTAAAAAAAATATTCTAAATGTTA ATATCAAAAATATTATTTTCAATTCACCCCAGGCACAGAGAACTAAGTATTATTATTGCTATTG CACCGGCATTCCCCAATGAGACAGTGATTTTCTTTTAAGACATTTTTAAATAATATAGGCAGAA TTAAGTAGACGGTGATCTGGTAAGTAGATGTTTCAGGGTAACAGCTGTGCAATGCTCCATGCAG GGAATTAGATTGTCATTTTATTCCTTACCAGGAACATACATTCAGTTAAACAATTATTTGACTT CTGCTCTTCCACTGATTTCTAAGTTGAGGCTCTCTCTTGTGCCTGTCTGATCAGATAAGTAGAG TTGTGCCTTGGTTTATAGATGAGATAAATGTGTATTTGAATAAGCATAAGTTAAAGAAATTTTA AAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGGAATT TGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTATATT ACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAACAAT TATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCAAATA TTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAATTTG AGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAAATAT TTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCTTTTC TTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAccTcGATCCCTATGAA CAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGCTAACTGAAATGATTT TGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCATTCTACACACTTTGT GTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACCTGGAGCAACAGGTAC TTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTCATACCAACACAAATG GTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTGTGCACAACTTCAAAA TGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTACTTCTCTCCTCACTG GTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAAATAAAATACCAAAGA CTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAGTCAAAGATCAAGGTGCCAGCAGGTTTG CTGTCTCGTGAGAGCATACTTCCTGGTTCATTGATGGTGCTTTCTTGCTGTGTCCTCACATAAT GGAAAGGGCAAGACCTCTCTGGTGTCTCTTTTACAATGGCACTAATCCCATCATGAGGGCTTTG TTCTCATGACCTAATCACCTCCCACATGTCCTACATTCTAATACTATCACCTTGGGGGTTAGGA TTTTAACATATGAATTTGAGGAGGTGGCGGGGGGGACACAAATATTTAGACCATAGCATTTCAC TCCTGACCTCCAAAGTTCATGTCTTCTTCACATGCAAAATACATTCATTCCATCCCAATAGCCC CCAAAGTCTTAACTTGTTCCAGCATCAACTTACAAGGCTAAAGTCCAAGGTTTCATCTAAATAT CAGCTAAATCAGCACAAACAGCTAAATCAGGTAGAGTGGGACTTAAGGTGTGATTCCTCTTTAG GCAGATTGCTCTCCAACTATGAAATTGTGAAATCAAACCTATTATGTACTTTCAAAATAAAATG GTGAAACAGGCACAGGCTAGACAGTCCCATTTCAAAAAAGAGAAATAGAAAAGAAAAAAGGAGT GACAGGTCTCTATAAGTCTAAAACTTTAAGGCTTGAGAATAATTTGCTTTGCTTTGCCTCCAGG CTCACTGGGGTGGTGTCTTACCTCTGGACACAC

In an embodiment, to correct a mutation, e.g., N1303K target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 23; SEQ ID NO: 27295) TTTAAAATCCCTTAGGAAGCTAGGCTTATCAGAGAAATCCAAGGAAATACATTAACAAACTAGG AATTTGTTCTAACAGGTTAATTATAACTCATAAACTTATTGGGTTTTTTTACCTTTTAATTTTA TATTACATTTGCTTATAATAAGGAATATTGCTAGGAATAAAATTTTTTAATATTCTACAATTAA CAATTATCTCAATTTCTTTATTCTAAAGACATTGGGATTAGAAAAATGTTCACAAGGGACTCCA AATATTGCTGTAGTATTTGTTTCTTAAAAGAATGATACAAAGCAGACATGATAAAATATTAAAA TTTGAGAGAACTTGATGGTAAGTACATGGGTGTTTCTTATTTTAAAATAATTTTTCTACTTGAA ATATTTTACAATACAATAAGGGAAAAATAAAAAGTTATTTAAGTTATTCATACTTTCTTCTTCT TTTCTTTTTTGCTATAGAAAGTATTTATTTTTTCTGGAACATTTAGAAAAAAccTcGATCCCTA TGAACAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAGGCTGCTAACTGAAATG ATTTTGAAAGGGGTAACTCATACCAACACAAATGGCTGATATAGCTGACATCATTCTACACACT TTGTGTGCATGTATGTGTGTGCACAACTTTAAAATGGAGTACCCTAACATACCTGGAGCAACAG GTACTTTTGACTGGACCTACCCCTAACTGAAATGATTTTGAAAGAGGTAACTCATACCAACACA AATGGTTGATATGGCTAAGATCATTCTACACACTTTGTGTGCATGTATTTCTGTGCACAACTTC AAAATGGAGTACCCTAAAATACCTGGCGCGACAAGTACTTTTGACTGAGCCTACTTCTCTCCTC ACTGGTATGGCTCCAACCATCAGGCCCTATCTTGGTCCATTTAGGCTGCTAAAATAAAATACCA AAGACTGAGCTGCTTATAAGCAATCTTTGGAGGCTGAGAAG

In an embodiment, an ssODN may be to correct a mutation, e.g., N1303K target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the N1303K mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 24; SEQ ID NO: 27296) AGTTATTCATACTTTCTTCTTCTTTTCTTTTTTGCTATAGAAAGT ATTTATTTTTTCTGGAACATTTAGAAAAAAccTcGATCCCTATGA ACAGTGGAGTGATCAAGAAATATGGAAAGTTGCAGATGAGGTAAG GCTGCTAACTGAAATG

The underlined C has been changed from a G to C so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., R117H target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27297(5′H arm) AACCCCTCAAATTAAGGGATGAGGCAGAATAATGCTTGGCAATACCAGGGGTAGGCTGCAGTCT TTCTTGGAAATATATATTTTAAATGGAACCAATTATCATAGCATCATTTCCTCTCAGGGTTACC CTCTGATCCCTATTTTACTAAATCGTTATAAAACAAAATGAGGAATTATGTGTCCTTCCCTTTT GAAGCCAATGTAACAAGATGGGTAAGAATTAGACCTCCTGAGTTCAAAATCCCTGGATTCAGAT CTATTCCTGTATATTCAGGAGAAGTGGTAATAAATTCGATGGACAATTTGGTTTAGTAGTCGAT TGAGGACCCTGATGAGGTATATTTGGGAAAACATAACTTCCGCTCTCTCTCATTGACTCACGGG CCTTTGAGGAGTCCAGGAGTCATTGGAATCTGGCCTGAGGTTGAGGCTGCTGGCAAAACTCCTT CCCCAAAGTCCATTCCTATTGCTGACTGAGAAGGGACTAGCATTGGAAGTGGCTGATTTTAAAT ACCGCTAGTGCTGGTGTGCTCCTCCCTCCCATTCCCAGCTCTGCTTTGTGTAGTTGCCTTGAGA AGCTAAGTTCATTCTGAAAATAATGCCATTGCACAAAACACTTTTGAAAGTTCTAGTTTGAAAT TACATCAGGTCACTTGGTCTGTGTGGCCTCAGTTTCTTCATCTGCCATGTGAAAATAATAATGC CTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCCTACTCTGATACTGAAAGT TGTTATGAAAAATAAAAAAGGGAAATGCTTTAGAAACTGTTAAGTGCTATGTAGATGTTACTAA TTAACAAACCATTTCAGAAACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAA ATACCTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTTATTTCAAAGT ACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGGTATGACCCTCTATATAAACTCATT TTAAGTCTCCTCTAAAGATGAAAAGTCTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAA ATGAAATTTAATTTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCTCT TACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAAC

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(3′H arm) SEQ ID NO: 27298 CTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGA GGACACTGCTCCTACACCCAGCCATTTTTGGCCTTCATCACATTGGAATG CAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGGTAATACTTCC TTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATGT CATAAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATTA ATTTAATATGCCTATTAAATAAATGGCAGGAATAATTAATGCTCTTAATT ATCCTTGATAATTTAATTGACTTAAACTGATAATTATTGAGTATCTTCTG TAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTATCATTT TTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAAA AGTAATTGACAAAATATCATCTTATAGTAAAATGCCACATATCTTTATGT TCAGCAAGAAGAGTATAATATATGATTGTTAATGATAACCCAAACAACAA AAGATTTCACCTTAACTGGTTGTCATAAGTAGTAGTATCCACCGCCTTAT TTTGAGTTGGATTTTTATCATCCTATGAGCCCTACAAATTTAAAGTTTTT GGAACAGCACGTGCATTGAACCCATAAGAACCTACTCTGCTTTTCTGCAT GTATTGTCCAGACAAGAGACCAAATTGCCGAGGCATCATTTAGGTGAATT CTAATTAACATTTAGCTACCTTACAACCACAATTCAAGGTTGTTTCAAAG GCATGTGCTTGCATCATCCTGATTCACTACCATGTGTTACTAACTTGGAT CTGCAAAGTCATTATAAAAAGCTGTTTTGATGGACTTATTTGGATATTGC TTTACCCTTCTTCTCTCTTTTCTTTTATCAATGTAAAAACATTATATGTT AAATACTTGGCTTTTAAGAGCATAGATCTGAAATCTGCCTCTAGCAAATA ACCCATAACACTTCTAAGATATACCTGCAAGGTCAATTGTGTTGTAAAAC CTTGATAACCATACTTTATTGTTCAAAAAAGCCTTTTATGAAGGCAGAAG TTAAAAAAAAAAAACAAAAAAAACAGAGTCCACAGTTATCACCTCAGCTA CAATCTCATCAGTTCACAAGTACCAGCAAAACATGTGATAAGTCAACAAA

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., R117H target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the R117H mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 25; SEQ ID NO: 27299) AACCCCTCAAATTAAGGGATGAGGCAGAATAATGCTTGGCAATACCAGGG GTAGGCTGCAGTCTTTCTTGGAAATATATATTTTAAATGGAACCAATTAT CATAGCATCATTTCCTCTCAGGGTTACCCTCTGATCCCTATTTTACTAAA TCGTTATAAAACAAAATGAGGAATTATGTGTCCTTCCCTTTTGAAGCCAA TGTAACAAGATGGGTAAGAATTAGACCTCCTGAGTTCAAAATCCCTGGAT TCAGATCTATTCCTGTATATTCAGGAGAAGTGGTAATAAATTCGATGGAC AATTTGGTTTAGTAGTCGATTGAGGACCCTGATGAGGTATATTTGGGAAA ACATAACTTCCGCTCTCTCTCATTGACTCACGGGCCTTTGAGGAGTCCAG GAGTCATTGGAATCTGGCCTGAGGTTGAGGCTGCTGGCAAAACTCCTTCC CCAAAGTCCATTCCTATTGCTGACTGAGAAGGGACTAGCATTGGAAGTGG CTGATTTTAAATACCGCTAGTGCTGGTGTGCTCCTCCCTCCCATTCCCAG CTCTGCTTTGTGTAGTTGCCTTGAGAAGCTAAGTTCATTCTGAAAATAAT GCCATTGCACAAAACACTTTTGAAAGTTCTAGTTTGAAATTACATCAGGT CACTTGGTCTGTGTGGCCTCAGTTTCTTCATCTGCCATGTGAAAATAATA ATGCCTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCC TACTCTGATACTGAAAGTTGTTATGAAAAATAAAAAAGGGAAATGCTTTA GAAACTGTTAAGTGCTATGTAGATGTTACTAATTAACAAACCATTTCAGA AACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAAATAC CTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTT ATTTCAAAGTACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGG TATGACCCTCTATATAAACTCATTTTAAGTCTCCTCTAAAGATGAAAAGT CTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAAATGAAATTTAAT TTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCT CTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAAC gCTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTG AGGACACTGCTCCTACACCCAGCCATTTTTGGCCTTCATCACATTGGAAT GCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGGTAATACTTC CTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATG TCATAAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATT AATTTAATATGCCTATTAAATAAATGGCAGGAATAATTAATGCTCTTAAT TATCCTTGATAATTTAATTGACTTAAACTGATAATTATTGAGTATCTTCT GTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTATCATT TTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAA AAGTAATTGACAAAATATCATCTTATAGTAAAATGCCACATATCTTTATG TTCAGCAAGAAGAGTATAATATATGATTGTTAATGATAACCCAAACAACA AAAGATTTCACCTTAACTGGTTGTCATAAGTAGTAGTATCCACCGCCTTA TTTTGAGTTGGATTTTTATCATCCTATGAGCCCTACAAATTTAAAGTTTT TGGAACAGCACGTGCATTGAACCCATAAGAACCTACTCTGCTTTTCTGCA TGTATTGTCCAGACAAGAGACCAAATTGCCGAGGCATCATTTAGGTGAAT TCTAATTAACATTTAGCTACCTTACAACCACAATTCAAGGTTGTTTCAAA GGCATGTGCTTGCATCATCCTGATTCACTACCATGTGTTACTAACTTGGA TCTGCAAAGTCATTATAAAAAGCTGTTTTGATGGACTTATTTGGATATTG CTTTACCCTTCTTCTCTCTTTTCTTTTATCAATGTAAAAACATTATATGT TAAATACTTGGCTTTTAAGAGCATAGATCTGAAATCTGCCTCTAGCAAAT AACCCATAACACTTCTAAGATATACCTGCAAGGTCAATTGTGTTGTAAAA CCTTGATAACCATACTTTATTGTTCAAAAAAGCCTTTTATGAAGGCAGAA GTTAAAAAAAAAAAACAAAAAAAACAGAGTCCACAGTTATCACCTCAGCT ACAATCTCATCAGTTCACAAGTACCAGCAAAACATGTGATAAGTCAACAA A

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct R117H mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the R117H mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 26; SEQ ID NO: 27300) ATGCCTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCC TACTCTGATACTGAAAGTTGTTATGAAAAATAAAAAAGGGAAATGCTTTA GAAACTGTTAAGTGCTATGTAGATGTTACTAATTAACAAACCATTTCAGA AACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAAATAC CTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTT ATTTCAAAGTACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGG TATGACCCTCTATATAAACTCATTTTAAGTCTCCTCTAAAGATGAAAAGT CTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAAATGAAATTTAAT TTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCT CTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAAC gCTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTG AGGACACTGCTCCTACACCCAGCCATTTTTGGCCTTCATCACATTGGAAT GCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGGTAATACTTC CTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATG TCATAAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATT AATTTAATATGCCTATTAAATAAATGGCAGGAATAATTAATGCTCTTAAT TATCCTTGATAATTTAATTGACTTAAACTGATAATTATTGAGTATCTTCT GTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTATCATT TTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAA AAGTAATTGACAAAATATCATCTTATAGTAAAATGCCACATATCTTTATG T

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., R117H target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the R117H mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 27; SEQ ID NO: 27301) AAGTCACCAAAGCAGTACAGCCTCTCTTACTGGGAAGAATCATAGCTTCC TATGACCCGGATAACAAGGAGGAACgCTCTATCGCGATTTATCTAGGCAT AGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCA T

In an embodiment, to correct a mutation, e.g., R117H target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the R117H mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 28; SEQ ID NO: 27302) AACCCCTCAAATTAAGGGATGAGGCAGAATAATGCTTGGCAATACCAGGG GTAGGCTGCAGTCTTTCTTGGAAATATATATTTTAAATGGAACCAATTAT CATAGCATCATTTCCTCTCAGGGTTACCCTCTGATCCCTATTTTACTAAA TCGTTATAAAACAAAATGAGGAATTATGTGTCCTTCCCTTTTGAAGCCAA TGTAACAAGATGGGTAAGAATTAGACCTCCTGAGTTCAAAATCCCTGGAT TCAGATCTATTCCTGTATATTCAGGAGAAGTGGTAATAAATTCGATGGAC AATTTGGTTTAGTAGTCGATTGAGGACCCTGATGAGGTATATTTGGGAAA ACATAACTTCCGCTCTCTCTCATTGACTCACGGGCCTTTGAGGAGTCCAG GAGTCATTGGAATCTGGCCTGAGGTTGAGGCTGCTGGCAAAACTCCTTCC CCAAAGTCCATTCCTATTGCTGACTGAGAAGGGACTAGCATTGGAAGTGG CTGATTTTAAATACCGCTAGTGCTGGTGTGCTCCTCCCTCCCATTCCCAG CTCTGCTTTGTGTAGTTGCCTTGAGAAGCTAAGTTCATTCTGAAAATAAT GCCATTGCACAAAACACTTTTGAAAGTTCTAGTTTGAAATTACATCAGGT CACTTGGTCTGTGTGGCCTCAGTTTCTTCATCTGCCATGTGAAAATAATA ATGCCTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCC TACTCTGATACTGAAAGTTGTTATGAAAAATAAAAAAGGGAAATGCTTTA GAAACTGTTAAGTGCTATGTAGATGTTACTAATTAACAAACCATTTCAGA AACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAAATAC CTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTT ATTTCAAAGTACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGG TATGACCCTCTATATAAACTCATTTTAAGTCTCCTCTAAAGATGAAAAGT CTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAAATGAAATTTAAT TTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCT CTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAAtAAaGAaGAAC gCTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTG AGGACACTGCTCCTACACCCAGCCATTTTTGGCCTTCATCACATTGGAAT GCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGGTAATACTTC CTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATG TCATAAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATT AATTTAATATGCCTATTAAATAAATGGCAGGAATAATTAATGCTCTTAAT TATCCTTGATAATTTAATTGACTTAAACTGATAATTATTGAGTATCTTCT GTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTATCATT TTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAA AAGTAATTGACAAAATATCATCTTATAGTAAAATGCCACATATCTTTATG TTCAGCAAGAAGAGTATAATATATGATTGTTAATGATAACCCAAACAACA AAAGATTTCACCTTAACTGGTTGTCATAAGTAGTAGTATCCACCGCCTTA TTTTGAGTTGGATTTTTATCATCCTATGAGCCCTACAAATTTAAAGTTTT TGGAACAGCACGTGCATTGAACCCATAAGAACCTACTCTGCTTTTCTGCA TGTATTGTCCAGACAAGAGACCAAATTGCCGAGGCATCATTTAGGTGAAT TCTAATTAACATTTAGCTACCTTACAACCACAATTCAAGGTTGTTTCAAA GGCATGTGCTTGCATCATCCTGATTCACTACCATGTGTTACTAACTTGGA TCTGCAAAGTCATTATAAAAAGCTGTTTTGATGGACTTATTTGGATATTG CTTTACCCTTCTTCTCTCTTTTCTTTTATCAATGTAAAAACATTATATGT TAAATACTTGGCTTTTAAGAGCATAGATCTGAAATCTGCCTCTAGCAAAT AACCCATAACACTTCTAAGATATACCTGCAAGGTCAATTGTGTTGTAAAA CCTTGATAACCATACTTTATTGTTCAAAAAAGCCTTTTATGAAGGCAGAA GTTAAAAAAAAAAAACAAAAAAAACAGAGTCCACAGTTATCACCTCAGCT ACAATCTCATCAGTTCACAAGTACCAGCAAAACATGTGATAAGTCAACAA A

In an embodiment, to correct a mutation, e.g., R117H target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the R117H mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 29; SEQ ID NO: 27303) ATGCCTACTCTGTAGCAAAGAAAGTCTCTATAGTAAACAAAAAAAAAGCC TACTCTGATACTGAAAGTTGTTATGAAAAATAAAAAAGGGAAATGCTTTA GAAACTGTTAAGTGCTATGTAGATGTTACTAATTAACAAACCATTTCAGA AACTATACTTTTTATTTTATGGCCACTATTCACTGTTTAACTTAAAATAC CTCATATGTAAACTTGTCTCCCACTGTTGCTATAACAAATCCCAAGTCTT ATTTCAAAGTACCAAGATATTGAAAATAGTGCTAAGAGTTTCACATATGG TATGACCCTCTATATAAACTCATTTTAAGTCTCCTCTAAAGATGAAAAGT CTTGTGTTGAAATTCTCAGGGTATTTTATGAGAAATAAATGAAATTTAAT TTCTCTGTTTTTCCCCTTTTGTAGGAAGTCACCAAAGCAGTACAGCCTCT CTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAAtAAaGAaGAAC gCTCTATCGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTG AGGACACTGCTCCTACACCCAGCCATTTTTGGCCTTCATCACATTGGAAT GCAGATGAGAATAGCTATGTTTAGTTTGATTTATAAGAAGGTAATACTTC CTTGCACAGGCCCCATGGCACATATATTCTGTATCGTACATGTTTTAATG TCATAAATTAGGTAGTGAGCTGGTACAAGTAAGGGATAAATGCTGAAATT AATTTAATATGCCTATTAAATAAATGGCAGGAATAATTAATGCTCTTAAT TATCCTTGATAATTTAATTGACTTAAACTGATAATTATTGAGTATCTTCT GTAAACTGCCTCTGTTGTAGTTTTTTTTTTCTCCTAATCATGTTATCATT TTTTTGGAATCCATGGTTTCCTGTTAAGATGACTCACACAGCCTACATAA AAGTAATTGACAAAATATCATCTTATAGTAAAATGCCACATATCTTTATG T

In an embodiment, an ssODN may be to correct a mutation, e.g., R117H target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the R117H mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 30; SEQ ID NO: 27304) AAGTCACCAAAGCAGTACAGCCTCTCTTACTGGGAAGAATCATAGCTTCC TATGACCCGGATAAtAAaGAaGAACgCTCTATCGCGATTTATCTAGGCAT AGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCAGCCA T

The underlined T has been changed from an A to T at that position and each underlined A has been changed from a T to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., W1282X target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(5′H arm) SEQ ID NO: 27305 TTTTTATTATATATTTTTGAAGTATTGATATGTAGTGAATTAGAAATTTA AAAAGAAAACAAAACTGTCCTTCACTACAGATTGAAAAGCATTATACTAA AAGACCATTTGCTCAGTTATAGTATATAAAGGCCAAATGACTTAAAAACA AATTATGTAAGGAGAAGGAAACAACCATTTATTCAGTGCCACTAACTGTC AGCCAGTTTTTTCAGTGGTCAGTTAATGACTGCAGTAGTGTTCTACCTTG CTCAAAGCACCCTCCTCAAGTTCTGGCATCTAAGCTGACATCAGAACACA GAGTTGGGGCTCTCTGTGGGTCACCTCTAGCACTTGATCTCCTCATGCAG TGCATGGTGCTCTCACGTCTATGCTATGTTCTTATGGTCTTTAGGTAACA AGAATAATTTTCTTTCTTTTCCTTACTATACATTTTGCTTTCTGAAATTC CCTTCTCGCCAATCCAGGTGAATGTCAGAATGTGATTTGACAACTGTCCA AAGTACTCATTCACTGAGGAGTGGTAAGGCCTTCGCCCAACCTGCCTTCT CTGGGAATATACTGCTGCCTGAACATATCATTGTTTATTGCCAGGCTTGA ACTTCACCAAATTAATTTATTAGGGTCAACATCTAAATATTAGAACTATT TCAGATTAATTTTTAAGTCGTATCCACTTTGGGTACTAGATCAAATTGCA GGTCTCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGA CACTCTTTGCTTTTCCTTTATGCAAAATGGGCATTTTCAATCTTTTTGTC ATTAGTAAAGGTCAGTGATAAAGGAAGTCTGCATCAGGGGTCCAATTCCT TATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATATATCA ACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAA AATCTTCCACTGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGT ACAATACTGAATTATGTTTATGGCATGGTACCTATATGTCACAGAAGTGA TCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAAGAACTGGATCAG GGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGA GAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTG

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

(3′H arm) SEQ ID NO: 27306 AGGAAAGCCTTTGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAGA AAAAAGGCAACTAAATTATATTTTTTACTGCTATTTGATACTTGTACTCA AGAAATTCATATTACTCTGCAAAATATATTTGTTATGCATTGCTGTCTTT TTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTTT GGAATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTTT TTCAGAAGACCAAATTTACAGTGGGAGCCTTGGGCTTTTGTTTTTTAACA GCTCTTTTTTGTTCCTGCTTCAGTGGCCTGACCTCCAAGTTAGCAATCGC CAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAATAACAA ACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGATT GTTTTTTGTTATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACTA TTTTTTTTTAATGTCACTCTGATTTGGTCACAAAGGATCTCTAGTCTCAT TGCCTTAGTATCATTCTACGAATTAGAATGTGTTACTGTGTAAGAGCACT TCTTGTATATGAGAGAAATAGCAACAGTTCCAGTTTAAAGTGATATAAAT GGAAACCAAGAAATGTCTTTACTGGGACCAAATCTGGACAGCATTTACTG TATTTTTGCTGGTATTTTCTCTAGTCTTTCCGGGTATATTCACATTTAAT GATCACTTTTCTCCCTTTGTGCTAATGGACACTGAATCCATTCCACTACC ATAGTTCTTGCTAATACTACTCTACTTTTTACACAAAATTAAAATGCCAG GAGCACCTCCAGGTAGACTGACTATAAATCTAGACTGAAAAAAAAGCTTG TATTTCTTAACAGATTACCTTGTGGAACATTTGCTCCTTTCAACTAATGA GGCACTAAATATTGTAACTGCTCAACTGGTGCTTTTAATTTATTTGTCTA GACTTTGTCATGTTGCCAGAAGCTTTATCCTGGTTGGAGTTTTGAAAACA GTATTGTTTCTTCAGAAAGAAAAAAGGGATTGTCAGATGATCTAAAAATA AAGAAACACTGGAAATACAAGTATCCCAAGGTGATAGCATTAGGCAAGAT AAAAATGTTGAAAAGCGAAAAAGAACTGGTTGATAGAGAAGTGTTGTTAT

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., W1282X target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 31; SEQ ID NO: 27307) TTTTTATTATATATTTTTGAAGTATTGATATGTAGTGAATTAGAAATTTA AAAAGAAAACAAAACTGTCCTTCACTACAGATTGAAAAGCATTATACTAA AAGACCATTTGCTCAGTTATAGTATATAAAGGCCAAATGACTTAAAAACA AATTATGTAAGGAGAAGGAAACAACCATTTATTCAGTGCCACTAACTGTC AGCCAGTTTTTTCAGTGGTCAGTTAATGACTGCAGTAGTGTTCTACCTTG CTCAAAGCACCCTCCTCAAGTTCTGGCATCTAAGCTGACATCAGAACACA GAGTTGGGGCTCTCTGTGGGTCACCTCTAGCACTTGATCTCCTCATGCAG TGCATGGTGCTCTCACGTCTATGCTATGTTCTTATGGTCTTTAGGTAACA AGAATAATTTTCTTTCTTTTCCTTACTATACATTTTGCTTTCTGAAATTC CCTTCTCGCCAATCCAGGTGAATGTCAGAATGTGATTTGACAACTGTCCA AAGTACTCATTCACTGAGGAGTGGTAAGGCCTTCGCCCAACCTGCCTTCT CTGGGAATATACTGCTGCCTGAACATATCATTGTTTATTGCCAGGCTTGA ACTTCACCAAATTAATTTATTAGGGTCAACATCTAAATATTAGAACTATT TCAGATTAATTTTTAAGTCGTATCCACTTTGGGTACTAGATCAAATTGCA GGTCTCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGA CACTCTTTGCTTTTCCTTTATGCAAAATGGGCATTTTCAATCTTTTTGTC ATTAGTAAAGGTCAGTGATAAAGGAAGTCTGCATCAGGGGTCCAATTCCT TATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATATATCA ACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAA AATCTTCCACTGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGT ACAATACTGAATTATGTTTATGGCATGGTACCTATATGTCACAGAAGTGA TCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAAGAACTGGATCAG GGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGA GAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTG gAGGAAAGCCTTTGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAG AAAAAAGGCAACTAAATTATATTTTTTACTGCTATTTGATACTTGTACTC AAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCATTGCTGTCTT TTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTT TGGAATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTT TTTCAGAAGACCAAATTTACAGTGGGAGCCTTGGGCTTTTGTTTTTTAAC AGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGACCTCCAAGTTAGCAATCG CCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAATAACA AACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGAT TGTTTTTTGTTATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACT ATTTTTTTTTAATGTCACTCTGATTTGGTCACAAAGGATCTCTAGTCTCA TTGCCTTAGTATCATTCTACGAATTAGAATGTGTTACTGTGTAAGAGCAC TTCTTGTATATGAGAGAAATAGCAACAGTTCCAGTTTAAAGTGATATAAA TGGAAACCAAGAAATGTCTTTACTGGGACCAAATCTGGACAGCATTTACT GTATTTTTGCTGGTATTTTCTCTAGTCTTTCCGGGTATATTCACATTTAA TGATCACTTTTCTCCCTTTGTGCTAATGGACACTGAATCCATTCCACTAC CATAGTTCTTGCTAATACTACTCTACTTTTTACACAAAATTAAAATGCCA GGAGCACCTCCAGGTAGACTGACTATAAATCTAGACTGAAAAAAAAGCTT GTATTTCTTAACAGATTACCTTGTGGAACATTTGCTCCTTTCAACTAATG AGGCACTAAATATTGTAACTGCTCAACTGGTGCTTTTAATTTATTTGTCT AGACTTTGTCATGTTGCCAGAAGCTTTATCCTGGTTGGAGTTTTGAAAAC AGTATTGTTTCTTCAGAAAGAAAAAAGGGATTGTCAGATGATCTAAAAAT AAAGAAACACTGGAAATACAAGTATCCCAAGGTGATAGCATTAGGCAAGA TAAAAATGTTGAAAAGCGAAAAAGAACTGGTTGATAGAGAAGTGTTGTTA T

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct W1282X mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 32; SEQ ID NO: 27308) GGTCTCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGA CACTCTTTGCTTTTCCTTTATGCAAAATGGGCATTTTCAATCTTTTTGTC ATTAGTAAAGGTCAGTGATAAAGGAAGTCTGCATCAGGGGTCCAATTCCT TATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATATATCA ACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAA AATCTTCCACTGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGT ACAATACTGAATTATGTTTATGGCATGGTACCTATATGTCACAGAAGTGA TCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAAGAACTGGATCAG GGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGA GAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTG gAGGAAAGCCTTTGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAG AAAAAAGGCAACTAAATTATATTTTTTACTGCTATTTGATACTTGTACTC AAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCATTGCTGTCTT TTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTT TGGAATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTT TTTCAGAAGACCAAATTTACAGTGGGAGCCTTGGGCTTTTGTTTTTTAAC AGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGACCTCCAAGTTAGCAATCG CCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAATAACA AACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGAT TGTTTTTTGTTATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACT A

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., W1282X target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the W1282X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 33; SEQ ID NO: 27309) TTTGAGACTACTGAACACTGAAGGAGAAATCCAGATCGATGGTGTGTCTT GGGATTCAATAACTTTGCAACAGTGgAGGAAAGCCTTTGGAGTGATACCA CAGGTGAGCAAAAGGACTTAGCCAGAAAAAAGGCAACTAAATTATATTTT

In an embodiment, to correct a mutation, e.g., W1282X target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 34; SEQ ID NO: 27310) TTTTTATTATATATTTTTGAAGTATTGATATGTAGTGAATTAGAAATTTA AAAAGAAAACAAAACTGTCCTTCACTACAGATTGAAAAGCATTATACTAA AAGACCATTTGCTCAGTTATAGTATATAAAGGCCAAATGACTTAAAAACA AATTATGTAAGGAGAAGGAAACAACCATTTATTCAGTGCCACTAACTGTC AGCCAGTTTTTTCAGTGGTCAGTTAATGACTGCAGTAGTGTTCTACCTTG CTCAAAGCACCCTCCTCAAGTTCTGGCATCTAAGCTGACATCAGAACACA GAGTTGGGGCTCTCTGTGGGTCACCTCTAGCACTTGATCTCCTCATGCAG TGCATGGTGCTCTCACGTCTATGCTATGTTCTTATGGTCTTTAGGTAACA AGAATAATTTTCTTTCTTTTCCTTACTATACATTTTGCTTTCTGAAATTC CCTTCTCGCCAATCCAGGTGAATGTCAGAATGTGATTTGACAACTGTCCA AAGTACTCATTCACTGAGGAGTGGTAAGGCCTTCGCCCAACCTGCCTTCT CTGGGAATATACTGCTGCCTGAACATATCATTGTTTATTGCCAGGCTTGA ACTTCACCAAATTAATTTATTAGGGTCAACATCTAAATATTAGAACTATT TCAGATTAATTTTTAAGTCGTATCCACTTTGGGTACTAGATCAAATTGCA GGTCTCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGA CACTCTTTGCTTTTCCTTTATGCAAAATGGGCATTTTCAATCTTTTTGTC ATTAGTAAAGGTCAGTGATAAAGGAAGTCTGCATCAGGGGTCCAATTCCT TATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATATATCA ACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAA AATCTTCCACTGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGT ACAATACTGAATTATGTTTATGGCATGGTACCTATATGTCACAGAAGTGA TCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAAGAACTGGATCAG GGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGA GAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTG gAGaAAAGCCTTTGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAG AAAAAAGGCAACTAAATTATATTTTTTACTGCTATTTGATACTTGTACTC AAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCATTGCTGTCTT TTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTT TGGAATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTT TTTCAGAAGACCAAATTTACAGTGGGAGCCTTGGGCTTTTGTTTTTTAAC AGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGACCTCCAAGTTAGCAATCG CCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAATAACA AACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGAT TGTTTTTTGTTATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACT ATTTTTTTTTAATGTCACTCTGATTTGGTCACAAAGGATCTCTAGTCTCA TTGCCTTAGTATCATTCTACGAATTAGAATGTGTTACTGTGTAAGAGCAC TTCTTGTATATGAGAGAAATAGCAACAGTTCCAGTTTAAAGTGATATAAA TGGAAACCAAGAAATGTCTTTACTGGGACCAAATCTGGACAGCATTTACT GTATTTTTGCTGGTATTTTCTCTAGTCTTTCCGGGTATATTCACATTTAA TGATCACTTTTCTCCCTTTGTGCTAATGGACACTGAATCCATTCCACTAC CATAGTTCTTGCTAATACTACTCTACTTTTTACACAAAATTAAAATGCCA GGAGCACCTCCAGGTAGACTGACTATAAATCTAGACTGAAAAAAAAGCTT GTATTTCTTAACAGATTACCTTGTGGAACATTTGCTCCTTTCAACTAATG AGGCACTAAATATTGTAACTGCTCAACTGGTGCTTTTAATTTATTTGTCT AGACTTTGTCATGTTGCCAGAAGCTTTATCCTGGTTGGAGTTTTGAAAAC AGTATTGTTTCTTCAGAAAGAAAAAAGGGATTGTCAGATGATCTAAAAAT AAAGAAACACTGGAAATACAAGTATCCCAAGGTGATAGCATTAGGCAAGA TAAAAATGTTGAAAAGCGAAAAAGAACTGGTTGATAGAGAAGTGTTGTTA T

In an embodiment, to correct a mutation, e.g., W1282X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

GGTCTCTGCTTCTGGCTTGAGCCTATGTTTAGAGATGATGTGCATGAAGA CACTCTTTGCTTTTCCTTTATGCAAAATGGGCATTTTCAATCTTTTTGTC ATTAGTAAAGGTCAGTGATAAAGGAAGTCTGCATCAGGGGTCCAATTCCT TATGGCCAGTTTCTCTATTCTGTTCCAAGGTTGTTTGTCTCCATATATCA ACATTGGTCAGGATTGAAAGTGTGCAACAAGGTTTGAATGAATAAGTGAA AATCTTCCACTGGTGACAGGATAAAATATTCCAATGGTTTTTATTGAAGT ACAATACTGAATTATGTTTATGGCATGGTACCTATATGTCACAGAAGTGA TCCCATCACTTTTACCTTATAGGTGGGCCTCTTGGGAAGAACTGGATCAG GGAAGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGA GAAATCCAGATCGATGGTGTGTCTTGGGATTCAATAACTTTGCAACAGTG gAGaAAAGCCTTTGGAGTGATACCACAGGTGAGCAAAAGGACTTAGCCAG AAAAAAGGCAACTAAATTATATTTTTTACTGCTATTTGATACTTGTACTC AAGAAATTCATATTACTCTGCAAAATATATTTGTTATGCATTGCTGTCTT TTTTCTCCAGTGCAGTTTTCTCATAGGCAGAAAAGATGTCTCTAAAAGTT TGGAATTCTCAAATTCTGGTTATTGAAATGTTCATAGCTTTGATAGTGTT TTTCAGAAGACCAAATTTACAGTGGGAGCCTTGGGCTTTTGTTTTTTAAC AGCTCTTTTTTGTTCCTGCTTCAGTGGCCTGACCTCCAAGTTAGCAATCG CCAGGTTGAGAAATGCTTTGCGAGACATAACAGATGCTCCTGAAATAACA AACACTTGGAATCATGAGGTAGTGGAATTGAAAATAGAAAGTGTAGTGAT TGTTTTTTGTTATTTGGATGGGATGAACAATGTCAGATTAGTCTGTAACT A

In an embodiment, an ssODN may be to correct a mutation, e.g., W1282X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the W1282X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 35; SEQ ID NO: 27311) TTTGAGACTACTGAACACTGAAGGAGAAATCCAGATCGATGGTGTGTCTT GGGATTCAATAACTTTGCAACAGTGgAGaAAAGCCTTTGGAGTGATACCA CAGGTGAGCAAAAGGACTTAGCCAGAAAAAAGGCAACTAAATTATATTTT

The underlined A has been changed from a T to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence AGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., R553X target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27312 (5'H arm) AACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAA GAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACG AATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGTTTACT ACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAG GGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAACTG TTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCCAGGAT TATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATAAATTC CAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAG GATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAG GAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCC ATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCT TCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAA GTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATA TTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGAT CATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTG ACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTA AAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCA TACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAA GACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAGGTCAA

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27313 (3'H arm) GAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAAT GTCATTCATGTAAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAA AAAATCCTGGGGTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTAT AGTATCCAGATTTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGT ATTTGTTTGCCTCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGG ACAGAGAAGATGTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAG CTTTAGGCTTCTTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACA AAATAGGAAGGCAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAA TGCATTAACATTGTTGGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAA GCTGTCAAAGAGATGTAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTA ACTTTCAGTTTAAACAATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACA AAATTCTTCTCACTTTGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTG GCTCCITTCCCTTACTTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGC ACCTGCAATTGCCTGGTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTAC AGCTCTGCAAAGTAAGAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTG TTAGATGTTAACTTGCCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCT TTTGATTCTTTACATTAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATA GATACGGATAATTCACAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAG TAAGACTTATTCTAAGAATTCCACAAATTTAGATAAGATAGAGTATAT

In an embodiment, the replacement sequence comprises or consists of a Cytosine (C) residue.

In an embodiment, to correct a mutation, e.g., R553X target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 36; SEQ ID NO: 27314) AACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAA GAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACG AATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGTTTACT ACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAG GGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAACTG TTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCCAGGAT TATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATAAATTC CAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAG GATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAG GAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCC ATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCT TCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAA GTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATA TTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGAT CATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTG ACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTA AAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCA TACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAA GACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAGGTCAAcGAGCAAGAATTTCTT TAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAA AAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTT TATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGG TAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCAT AGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGATGTAA ATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGG TATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAA TGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACATTGTT GGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAGAGATG TAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAAC AATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCACTT TGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCCCTTAC TTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATTGCCTG GTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAA GAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTAACTTG CCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTTTACAT TAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATAGATACGGATAATTCA CAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTAA GAATTCCACAAATTTAGATAAGATAGAGTATAT

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct R553X mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 37; SEQ ID NO: 27315) CTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAG AAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACA CATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAA TGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTT TTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTG GTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTG AGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGA GAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTGGAGGTCAAcGAGCAAGAATT TCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGT AAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGG GTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGAT TTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCC TCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGAT GTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTC TTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGG CAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAAT

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., R553X target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the R553X mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 38; SEQ ID NO: 27316) TAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGA GTGGAGGTCAAcGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCA TTTGCTGTAAATGTCATTCATGT

In an embodiment, to correct a mutation, e.g., R553X target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 39; SEQ ID NO: 27317) AACAGAAGTAACCATTTTGATACTTTAGATATAGATAATATTGGATTATTTCTGGATTGTGAAA GAAGAAGGAAGAAGCATATGGAAGAGAAGTTTTAGTAGAGGGGAGGAAGGAGGAGGTGGAAACG AATGTACAAGGATGGGAGGAGAAAAGGGAGAGAGACTTTTTTTTTTTTAAGGCGAGAGTTTACT ACCTATCTAACTCTTCGCATTCTTGAAGTCTCAGACCAAATCCCATCGGTTTGAAAGCCTCTAG GGTATTCTATCTATTGTATACTTCTGTTATGTACAAAATTAATTTGCCAATTAATTGTGAACTG TTTTATAAACTATCTTAAAATGGTTAGTTAAATCTTTGGGATAGTATTTAGCTTTCTCCAGGAT TATGACTTACCTTCTAAATTAGACATACAATGCCTAGGAGTCAAGGACTATTTTGCATAAATTC CAGTCTTCTTTTACAATGCCTAGAATGATTGTTACCACAGAAATATTCATTACCTGGGAGAAAG GATGACAGGAGGGGCAGAATGAATGGAGAGAGGTCGTGAGAATGAGGTGCTGAGGATGGACGAG GAAGAAAGCTGTTTTAGTTGGGAGGATAGGTGACAGAAGCATGGAAAGGAATTGCCTTGGACCC ATGGAAGCCCAGTGAAGATACTTAGATCCTGCAGGGGTGTGAATAATGTTCTTTTAGTTTCTCT TCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAGAAAA GTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACACATA TTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAATGAT CATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTTTTTG ACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTGGTTA AAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTGAGCA TACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGAGAAA GACAATATAGTTCTTGGAGAAGGTGGAATCACACTGtcaGGAGGTCAAcGAGCAAGAATTTCTT TAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGTAAAA AAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGGGTTT TATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGATTTGG TAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCCTCAT AGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGATGTAA ATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTCTTGG TATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGGCAAA TGATGTCACTTGGCTTAAAATCTATAATATTTAAAATAAACAGGACAAATGCATTAACATTGTT GGGGGAGGAGGTCCCTTAGTAGAAACACTCTTGGTCCAAGCATTTTAAAGCTGTCAAAGAGATG TAAATATAGATAATGTATGTCAAGGAGAGAGCTTTGTGGTTAAACTGTAACTTTCAGTTTAAAC AATTATTGGTGACTCTGATGTCAAATGTTTCTCAAGCTTTATCTGAACAAAATTCTTCTCACTT TGTTGCCAAAGTCGTTAACAAGAAATCACATTGACTCATTGATGTTTTGGCTCCTTTCCCTTAC TTTCTGTTGCTTTCCAAAAGCTGAGACAGGAAACTAACCCTAACTGAGCACCTGCAATTGCCTG GTAGTATTCTAGTCATGTGTGTACTTTTGTGTGTATGTAATCCCCTTACAGCTCTGCAAAGTAA GAATTGTTCTCCCTGCTTTACAGAAGAGATCATAAGATAATTGAGGCTGTTAGATGTTAACTTG CCAAAAGCCATACAGGAAAATGGTAGAGTCACAGTTTGAACCAGGTCCTTTTGATTCTTTACAT TAAACCATGCTTTGATCTTGGAAATACACTGTAAGGCAATAAATCAATAGATACGGATAATTCA CAGGCTTCTAAATAAATGGAAGTTGATTGTTTTTATCTGTGAGCCAAAGTAAGACTTATTCTAA GAATTCCACAAATTTAGATAAGATAGAGTATAT

In an embodiment, to correct a mutation, e.g., R553X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 40; SEQ ID NO: 27318) CTCTTCTTAGGAGGTTTGTTCATTTTGGGAGATTTCTTTTGAAAAGAGTGAACTTAAATTGGAG AAAAGTACATTTTAGTATGTTGATAACATTTGAATTTGTAAAATGGACCTATGGATGATCTACA CATATTTATATACCCATAAATATACACATATTTTAATTTTTGGTATTTTATAATTATTATTTAA TGATCATTCATGACATTTTAAAAATTACAGAAAAATTTACATCTAAAATTTCAGCAATGTTGTT TTTGACCAACTAAATAAATTGCATTTGAAATAATGGAGATGCAATGTTCAAAATTTCAACTGTG GTTAAAGCAATAGTGTGATATATGATTACATTAGAAGGAAGATGTGCCTTTCAAATTCAGATTG AGCATACTAAAAGTGACTCTCTAATTTTCTATTTTTGGTAATAGGACATCTCCAAGTTTGCAGA GAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGtcaGGAGGTCAAcGAGCAAGAATT TCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCATTTGCTGTAAATGTCATTCATGT AAAAAAATTACAGACATTTCTCTATTGCTTTATATTCTGTTTCTGGAATTGAAAAAATCCTGGG GTTTTATGGCTAGTGGGTTAAGAATCACATTTAAGAACTATAAATAATGGTATAGTATCCAGAT TTGGTAGAGATTATGGTTACTCAGAATCTGTGCCCGTATCTTGGTGTCAGTGTATTTGTTTGCC TCATAGTATAGTTTACTACAAATGGAAAACTCTAGGATTCTGCATAATACTGGACAGAGAAGAT GTAAATATCTGTTAGTTCCATCATAGACCCTGCCACTCCAATGTACACACCAGCTTTAGGCTTC TTGGTATAGATAAACATACATTTTCAAAATTTTTCATCATAATTTTCATAACAAAATAGGAAGG CAAATGATGTCACTTGGCTTAAAATCTATAATATTTAAAAT

In an embodiment, an ssODN may be to correct a mutation, e.g., R553X target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the R553X mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 41; SEQ ID NO: 27319) TAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGt caGGAGGTCAAcGAGCAAGAATTTCTTTAGCAAGGTGAATAACTAATTATTGGTCTAGCAAGCA TTTGCTGTAAATGTCATTCATGT

The underlined T has been changed from an A to T at that position, the underlined C has been changed from a G to C at that position, and the underlined A has been changed from a T to A at that position, so that wild-type CFTR is still transcribed, but the PAM sequence AGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., an intronic 2789+5bp (G→A) target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27320 (5'H arm) TTTTTCTGTTTCATTCTGTGGTAAAGGTATCATTTGGCTAATTGTATAATTTCAGTGTCATTTC TAATATTCCAATTGTGATAGTATCAACACAAGATTAAATTTCTCTACATGGTTTATGAGAATGG AATGCCAAATTGAAATAGAACAGAGCACAGATGATCTAAATATAAAAAGAACTACAAAAATCAC AGTTGTTTAAAAAGGTTTTTTGTTTGTTTATATATGGTGCAGAACATTTGTTCCTTAGCCAAAT GTTTCCACCTTGAGAAAGCTATAGAGATTCTATGTAGTCCTAGTACCAATAATATGTTTTAACC TGAATGTACCTTATCTTTATTCATAAACTGTGACTTTTTACACTGCTGAAACTTTTTTTTTTAA GACAATCTCACTCTGTCGTCCAGTCTGGAGTGCAGCAGTGGTGTGATCTTGGCTCACTGCAACC TCTACCTTCTGTGTTCAAGCAATTCTGGTGCCTCGGCCACCTGAGTAGTTGGGATCACAGGTGT ACACCACCAGGCCTGGCTAATAGTTTTTGATATTTCTAGTAGAGATGAGTTTTGCCACATTGGC CAGGCTGGCCTGAAACTCCTGGCCTCAAGTGATCTGCCTGCCTTGGCCTCCCAAAGTGTTGGTA TTACAAGTGTGAGCCACTGTGCCTGGCCTGAAACTCATAATTCATTTCCATTAATATTAATCTC ACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCTAATA AAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAAAAAT GTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCTATTG AGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAATGTG GTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACAAAGC AAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTGAATT TAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGTTCCA TTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGA

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27321 (3'H arm) TATTCCATGTCCTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTAT GTTTGTATGTATTGTAATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAA GGTTTTTTGTTTAAATGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCC TCCACAGGCTGACGCAGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATT GTGAGTAGCCACCGCACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAA ATAAAATGAATAAATTGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCA GTTTCTGTGAAACACAATAAAAATATTTGAAATAACATTACATATTTAGGGTTTTCTTCAAATT TTTTAATTTAATAAAGAACAACTCAATCTCTATCAATAGTGAGAAAACATATCTATTTTCTTGC AATAATAGTATGATTTTGAGGTTAAGGGTGCATGCTCTTCTAATGCAAAATATTGTATTTATTT AGACTCAAGTTTAGTTCCATTTACATGTATTGGAAATTCAGTAAGTAACTTTGGCTGCCAAATA ACGATTTCCTATTTGCTTTACAGCACTCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAA ATAACAGCTATGCAGTGATTATCACCAGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGG AGTAGCCGACACTTTGCTTGCTATGGGATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATC ACAGTGTCGAAAATTTTACACCACAAAATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCC TCAACACGTTGAAAGCAGGTACTTTACTAGGTCTAAGAAATGAAACTGCTGATCCACCATCAAT AGGGCCTGTGGTTTTGTTGGTTTTCTAATGGCAGTGCTGGCTTTTGCACAGAGGCATGTGCCCT TTGTTGAACCTCCATTTGACTGGCATGCACATGTCTCAGATATTATAGGTTATCATATATTGTT GCTCCTAATATTTCTGTGTTAGATAATTAGAGTAGCTTGGTTTGTAAGAATGTGATGTTGGTGG GACTGTAGCAGAACAAGAAGGCCCTTATGGGTCAGTCATACCTCTCTT

In an embodiment, the replacement sequence comprises or consists of a Guanine (G) residue.

In an embodiment, to correct a mutation, e.g., an intronic 2789+5bp (G→A) target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G→A) mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 42; SEQ ID NO: 27322) TTTTTCTGTTTCATTCTGTGGTAAAGGTATCATTTGGCTAATTGTATAATTTCAGTGTCATTTC TAATATTCCAATTGTGATAGTATCAACACAAGATTAAATTTCTCTACATGGTTTATGAGAATGG AATGCCAAATTGAAATAGAACAGAGCACAGATGATCTAAATATAAAAAGAACTACAAAAATCAC AGTTGTTTAAAAAGGTTTTTTGTTTGTTTATATATGGTGCAGAACATTTGTTCCTTAGCCAAAT GTTTCCACCTTGAGAAAGCTATAGAGATTCTATGTAGTCCTAGTACCAATAATATGTTTTAACC TGAATGTACCTTATCTTTATTCATAAACTGTGACTTTTTACACTGCTGAAACTTTTTTTTTTAA GACAATCTCACTCTGTCGTCCAGTCTGGAGTGCAGCAGTGGTGTGATCTTGGCTCACTGCAACC TCTACCTTCTGTGTTCAAGCAATTCTGGTGCCTCGGCCACCTGAGTAGTTGGGATCACAGGTGT ACACCACCAGGCCTGGCTAATAGTTTTTGATATTTCTAGTAGAGATGAGTTTTGCCACATTGGC CAGGCTGGCCTGAAACTCCTGGCCTCAAGTGATCTGCCTGCCTTGGCCTCCCAAAGTGTTGGTA TTACAAGTGTGAGCCACTGTGCCTGGCCTGAAACTCATAATTCATTTCCATTAATATTAATCTC ACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCTAATA AAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAAAAAT GTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCTATTG AGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAATGTG GTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACAAAGC AAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTGAATT TAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGTTCCA TTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTATTCCATGTCCTAT TGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGITTGTATGTATTGT AATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTTTAAA TGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTGACGC AGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCACCGC ACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAATAAAT TGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAAACAC AATAAAAATATTTGAAATAACATTACATATTTAGGGTTTTCTTCAAATTTTTTAATTTAATAAA GAACAACTCAATCTCTATCAATAGTGAGAAAACATATCTATTTTCTTGCAATAATAGTATGATT TTGAGGTTAAGGGTGCATGCTCTTCTAATGCAAAATATTGTATTTATTTAGACTCAAGTTTAGT TCCATTTACATGTATTGGAAATTCAGTAAGTAACTTTGGCTGCCAAATAACGATTTCCTATTTG CTTTACAGCACTCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAG TGATTATCACCAGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTT GCTTGCTATGGGATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATT TTACACCACAAAATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAG CAGGTACTTTACTAGGTCTAAGAAATGAAACTGCTGATCCACCATCAATAGGGCCTGTGGTTTT GTTGGTTTTCTAATGGCAGTGCTGGCTTTTGCACAGAGGCATGTGCCCTTTGTTGAACCTCCAT TTGACTGGCATGCACATGTCTCAGATATTATAGGTTATCATATATTGTTGCTCCTAATATTTCT GTGTTAGATAATTAGAGTAGCTTGGTTTGTAAGAATGTGATGTTGGTGGGACTGTAGCAGAACA AGAAGGCCCTTATGGGTCAGTCATACCTCTCTT

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct an intronic 2789+5bp (G→A) mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G→A) mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 43; SEQ ID NO: 27323) TCTCACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCT AATAAAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAA AAATGTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCT ATTGAGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAA TGTGGTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACA AAGCAAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTG AATTTAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGT TCCATTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTATTCCATGTC CTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGTTTGTATGTA TTGTAATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTT TAAATGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTG ACGCAGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCA CCGCACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAAT AAATTGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAA ACACAATAAAAATATTTGAAATAACATTACATATTTAGGGTTTTCTTCAAATTTTTTAATTTAA TAAAGAACAACTCAATCTCTATCAATAGTGAGAAAACATAT

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., an intronic 2789+5bp (G→A) target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the intronic 2789+5bp (G→A) mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 44; SEQ ID NO: 27324) AAAAAAAATCAACTGTGTCTTGTTCCATTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCC TTGGAAAGTGAgTATTCCATGTCCTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATT GTAATCCACTATGTTTGTATGTA

In an embodiment, to correct a mutation, e.g., an intronic 2789+5bp (G→A) target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G→A) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 45; SEQ ID NO: 27325) TTTTTCTGTTTCATTCTGTGGTAAAGGTATCATTTGGCTAATTGTATAATTTCAGTGTCATTTC TAATATTCCAATTGTGATAGTATCAACACAAGATTAAATTTCTCTACATGGTTTATGAGAATGG AATGCCAAATTGAAATAGAACAGAGCACAGATGATCTAAATATAAAAAGAACTACAAAAATCAC AGTTGTTTAAAAAGGTTTTTTGTTTGTTTATATATGGTGCAGAACATTTGTTCCTTAGCCAAAT GTTTCCACCTTGAGAAAGCTATAGAGATTCTATGTAGTCCTAGTACCAATAATATGTTTTAACC TGAATGTACCTTATCTTTATTCATAAACTGTGACTTTTTACACTGCTGAAACTTTTTTTTTTAA GACAATCTCACTCTGTCGTCCAGTCTGGAGTGCAGCAGTGGTGTGATCTTGGCTCACTGCAACC TCTACCTTCTGTGTTCAAGCAATTCTGGTGCCTCGGCCACCTGAGTAGTTGGGATCACAGGTGT ACACCACCAGGCCTGGCTAATAGTTTTTGATATTTCTAGTAGAGATGAGTTTTGCCACATTGGC CAGGCTGGCCTGAAACTCCTGGCCTCAAGTGATCTGCCTGCCTTGGCCTCCCAAAGTGTTGGTA TTACAAGTGTGAGCCACTGTGCCTGGCCTGAAACTCATAATTCATTTCCATTAATATTAATCTC ACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCTAATA AAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAAAAAT GTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCTATTG AGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAATGTG GTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACAAAGC AAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTGAATT TAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGTTCCA TTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTATTggATGTCCTAT TGTGTAGATTGTGTTTTATTICTGTTGATTAAATATTGTAATCCACTATGTTTGTATGTATTGT AATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTTTAAA TGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTGACGC AGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCACCGC ACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAATAAAT TGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAAACAC AATAAAAATATTTGAAATAACATTACATATTTAGGGTTTTCTTCAAATTTTTTAATTTAATAAA GAACAACTCAATCTCTATCAATAGTGAGAAAACATATCTATTTTCTTGCAATAATAGTATGATT TTGAGGTTAAGGGTGCATGCTCTTCTAATGCAAAATATTGTATTTATTTAGACTCAAGTTTAGT TCCATTTACATGTATTGGAAATTCAGTAAGTAACTTTGGCTGCCAAATAACGATTTCCTATTTG CTTTACAGCACTCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAG TGATTATCACCAGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTT GCTTGCTATGGGATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATT TTACACCACAAAATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAG CAGGTACTTTACTAGGTCTAAGAAATGAAACTGCTGATCCACCATCAATAGGGCCTGTGGTTTT GTTGGTTTTCTAATGGCAGTGCTGGCTTTTGCACAGAGGCATGTGCCCTTTGTTGAACCTCCAT TTGACTGGCATGCACATGTCTCAGATATTATAGGTTATCATATATTGTTGCTCCTAATATTTCT GTGTTAGATAATTAGAGTAGCTTGGTTTGTAAGAATGTGATGTTGGTGGGACTGTAGCAGAACA AGAAGGCCCTTATGGGTCAGTCATACCTCTCTT

In an embodiment, to correct a mutation, e.g., an intronic 2789+5bp (G→A) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G→A) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 46; SEQ ID NO: 27326) TCTCACCTTTTCCAATAATTAATTGATTTCACAAGTATTAGTCCCCTATAATCATTGAATGGCT AATAAAATTATTTATAGCAAACAGATTAATTATCTGCCAGCAGTCTGAGATTAGTTTCTTTAAA AAATGTTTATTATTTAAAACATTCAGCTGTGATCTTGGCTTTCTTGTGAGGTTCAATAGTTTCT ATTGAGTAAAGGAGAGAAATGGCAGAGAATTTACTTCAGTGAAATTTGAATTCCATTAACTTAA TGTGGTCTCATCACAAATAATAGTACTTAGAACACCTAGTACAGCTGCTGGACCCAGGAACACA AAGCAAAGGAAGATGAAATTGTGTGTACCTTGATATTGGTACACACATCAAATGGTGTGATGTG AATTTAGATGTGGGCATGGGAGGAATAGGTGAAGATGTTAGAAAAAAAATCAACTGTGTCTTGT TCCATTCCAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAAGTGAgTATTggATGTC CTATTGTGTAGATTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGTTTGTATGTA TTGTAATCCACTTTGTTTCATTTCTCCCAAGCATTATGGTAGTGGAAAGATAAGGTTTTTTGTT TAAATGATGACCATTAGTTGGGTGAGGTGACACATTCCTGTAGTCCTAGCTCCTCCACAGGCTG ACGCAGGAGGATCACTTGAGCCCAGGAGTTCAGGGCTGTAGTGTTGTATCATTGTGAGTAGCCA CCGCACTCCAGCCTGGACAATATAGTGAGATCCTATATCTAAAATAAAATAAAATAAAATGAAT AAATTGTGAGCATGTGCAGCTCCTGCAGTTTCTAAAGAATATAGTTCTGTTCAGTTTCTGTGAA ACACAATAAAAATATTTGAAATAACATTACATATTTAGGGTTTTCTTCAAATTTTTTAATTTAA TAAAGAACAACTCATCTCTATCAATAGTGAGAAAACATAT

In an embodiment, an ssODN may be to correct a mutation, e.g., an intronic 2789+5bp (G→A) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 2789+5bp (G→A) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 47; SEQ ID NO: 27327) AAAAAAAATCAACTGTGTCTTGTTCCATTCCAGGTGGCTGCTTCTTTGG TTGTGCTGTGGCTCCTTGGAAAGTGAgTATTggATTCCTATTGTGTAGA TTGTGTTTTATTTCTGTTGATTAAATATTGTAATCCACTATGTTTGTAT GTA

The underlined G has been changed from a C to G at that position, so that wild-type CFTR is still transcribed, but the PAM sequence CCA has been modified to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template nucleic acids (also referred to herein as donor constructs) to correction a mutation, e.g., an intronic 3272-26bp (A→G) target site in the CFTR gene, are provided.

Suitable sequence for the 5′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27328(5′H arm) GTGCACATGTACCCTAAAACTTAAAGTATAATAAAAAAAATAAAAAAAAGTTTGAGGTGTTTAA AGTATGCAAAAAAAAAAAAAGAAATAAATCACTGACACACTTTGTCCACTTTGCAATGTGAAAA TGTTTACTCACCAACATGTTTTCTTTGATCTTACAGTTGTTATTAATTGTGATTGGAGCTATAG CAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTAT TATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTCAAACAACTGGAATCTGAAGGTATG ACAGTGAATGTGCGATACTCATCTTGTAAAAAAGCTATAAGAGCTATTTGAGATTCTTTATTGT TAATCTACTTAAAAAAAATTCTGCTTTTAAACTTTTACATCATATAACAATAATTTTTTTCTAC ATGCATGTGTATATAAAAGGAAACTATATTACAAAGTACACATGGATTTTTTTTCTTAATTAAT GACCATGTGACTTCATTTTGGTTTTAAAATAGGTATATAGAATCTTACCACAGTTGGTGTACAG GACATTCATTTATAATAAACTTATATCAGTCAAATTAAACAAGGATAGTGCTGCTATTACTAAA GGTTTCTCTGGGTTCCCAAATGATACTTGACCAAATTTGTCCCTTTGGCTTGTTGTCTTCAGAC ACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGTTAGG GAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAGTATA TTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACTTGAA AAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACTCCCA GTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGTAGCC AAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGGCACC AGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCTTTTT CAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCA

Suitable sequence for the 3′ homology arm can be selected from (e.g., includes a portion of) or include the following sequence:

SEQ ID NO: 27329(3′H arm) TGTTTTCTATGGAAATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAA AAGGACTATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGC TCTGAATTTACATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGA ATAGAAATGATTTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTA CTATGAACTCATTAACTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCA TTCTATAGGTTATCAATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATT ATTGAACAAGTGATTTCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAAT CGGATATATATATATATATGTATATATATATATATATATATATATATATACATATATATATATA GTATTATCCCTGTTTTCACAGTTTTAAAAACCGATGCACACAGATTGTCAGATAGCAATTCTGT GATTGAAGGGGAAATATGTCACCTCTTCATACTCATATTGGTGAAGGGTCCTAGCTTCAAAATT AATAGATTCCTAAAGAGGGGAAATGAAACATCCGCATTTACACACACACACACACACACACACA CAGAGTTCCTCTTGTCGGTAAGTTTTGTTTTTTTTAAATCTCTACTAGATAAAATTTGTTATCT AATTGTGAGTTTTACACAAAGAAAAACTGTCACAGAAAAGAAAGACAGTGTCACATTTTTCAAA AGAAAAAGAAGAAAAGAAAGTGCCATGTTTTTCAAATACAAATGTTCTGGATTGATTTTAGGAT CTTTAGTGAAAAACAAAGTATTTCATAATAAGTAAAATAAAAATCTATGTAGGTAAATTTGTTT CTCTAATTTAAGAATTTGAATTTCTGAGTATTTATGATAAGTGTTGAAATAACTTCTTATATGT GACAGTGAATACTGGCAGAGCAAATGCCAAATCAATGCCAAATCTGTAGGATCATTTGATTGTA GGAACAGAATTCTACTCAAACCGAAAGCAGGCATTTGCTGGAGTTACAGAAAGGCCTCATGGAA CACCGAGAAGGTGGTGCCATTCGACTCTTAAAGAAGCTGCAACAGGCA

In an embodiment, the replacement sequence comprises or consists of an Adenine (A) residue.

In an embodiment, to correct a mutation, e.g., an intronic 3272-26bp (A→G) target site in the CFTR gene, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A→G) mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 48; SEQ ID NO: 27330) GTGCACATGTACCCTAAAACTTAAAGTATAATAAAAAAAATAAAAAAAAGTTTGAGGTGTTTAA AGTATGCAAAAAAAAAAAAAGAAATAAATCACTGACACACTTTGTCCACTTTGCAATGTGAAAA TGTTTACTCACCAACATGTTTTCTTTGATCTTACAGTTGTTATTAATTGTGATTGGAGCTATAG CAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTAT TATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTCAAACAACTGGAATCTGAAGGTATG ACAGTGAATGTGCGATACTCATCTTGTAAAAAAGCTATAAGAGCTATTTGAGATTCTTTATTGT TAATCTACTTAAAAAAAATTCTGCTTTTAAACTTTTACATCATATAACAATAATTTTTTTCTAC ATGCATGTGTATATAAAAGGAAACTATATTACAAAGTACACATGGATTTTTTTTCTTAATTAAT GACCATGTGACTTCATTTTGGTTTTAAAATAGGTATATAGAATCTTACCACAGTTGGTGTACAG GACATTCATTTATAATAAACTTATATCAGTCAAATTAAACAAGGATAGTGCTGCTATTACTAAA GGTTTCTCTGGGTTCCCAAATGATACTTGACCAAATTTGTCCCTTTGGCTTGTTGTCTTCAGAC ACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGTTAGG GAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAGTATA TTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACTTGAA AAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACTCCCA GTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGTAGCC AAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGGCACC AGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCTTTTT CAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCAaTGTTTTCTATGGAAA TATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGACTATGGACAC TTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAATTTACATAC TGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAAATGATTTTT GTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTACTATGAACTCATTAA CTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCATTCTATAGGTTATCA ATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACAAGTGATT TCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAATCGGATATATATATAT ATATGTATATATATATATATATATATATATATATACATATATATATATAGTATTATCCCTGTTT TCACAGTTTTAAAAACCGATGCACACAGATTGTCAGATAGCAATTCTGTGATTGAAGGGGAAAT ATGTCACCTCTTCATACTCATATTGGTGAAGGGTCCTAGCTTCAAAATTAATAGATTCCTAAAG AGGGGAAATGAAACATCCGCATTTACACACACACACACACACACACACACAGAGTTCCTCTTGT CGGTAAGTTTTGTTTTTTTTAAATCTCTACTAGATAAAATTTGTTATCTAATTGTGAGTTTTAC ACAAAGAAAAACTGTCACAGAAAAGAAAGACAGTGTCACATTTTTCAAAAGAAAAAGAAGAAAA GAAAGTGCCATGTTTTTCAAATACAAATGTTCTGGATTGATTTTAGGATCTTTAGTGAAAAACA AAGTATTTCATAATAAGTAAAATAAAAATCTATGTAGGTAAATTTGTTTCTCTAATTTAAGAAT TTGAATTTCTGAGTATTTATGATAAGTGTTGAAATAACTTCTTATATGTGACAGTGAATACTGG CAGAGCAAATGCCAAATCAATGCCAAATCTGTAGGATCATTTGATTGTAGGAACAGAATTCTAC TCAAACCGAAAGCAGGCATTTGCTGGAGTTACAGAAAGGCCTCATGGAACACCGAGAAGGTGGT GCCATTCGACTCTTAAAGAAGCTGCAACAGGCA

As described below in Table 49, shorter homology arms, e.g., 5′ and/or 3′ homology arms may be used.

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to correct an intronic 3272-26bp (A→G) mutation in the CFTR gene, the 5′ homology arm may be shortened less than 1000 nucleotides, e.g., e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A→G) mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 49; SEQ ID NO: 27331) AGACACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCA AACTCTACTTGAGCTGTTAGGGAATCACATTTTGCAGTGACAGCCTT AGTGTGGGTGCATTTTCAGGCAATACTTTTTCAGTATATTTCTGCTT TGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGA TACTTGAAAAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAA TTTAGAATTAGCCAGAAAACTCCCAGTGGTAGCCAAGAAAGAGGAAT AAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGTAGCCAAGTA AAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCA AAGAATGGCACCAGTGTGAAAAAAAGCTTTTTAACCAATGACATTTG TGATATGATTATTCTAATTTAGTCTTTTTCAGGTACAAGATATTATG AAATTACATTTTGTGTTTATGTTATTTGCAaTGTTTTCTATGGAAAT ATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTA AAAGGACTATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGA AACTCTGTTCCACAAAGCTCTGAATTTACATACTGCCAACTGGTTCT TGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAAATGATT TTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAAC AGGTACTATGAACTCATTAACTTTAGCTAAGCATTTAAGTAAAAAAT TTTCAATGAATAAAATGCTGCATTCTATAGGTTATCAATTTTTGATA TCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACA AGTGATTTCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTT CCTTGAAATCGGATATATATATATATATGTATATATATATATATATA TATATATATATACA

It is contemplated herein that template nucleic acids for correcting a mutation may designed for use as a single-stranded oligonucleotide (ssODN). When using a ssODN, 5′ and 3′ homology arms may range up to about 200 base pairs (bp) in length, e.g., at least 25, 50, 75, 100, 125, 150, 175, or 200 bp in length. Longer homology arms are also contemplated for ssODNs as improvements in oligonucleotide synthesis continue to be made.

In an embodiment, an ssODN may be used to correct a mutation, e.g., an intronic 3272-26bp (A→G) target site in the CFTR gene. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted bases to correct the intronic 3272-26bp (A→G) mutation is shown as lower case sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 50; SEQ ID NO: 27332) ATATGATTATTCTAATTTAGTCTTTTTCAGGTACAAGATATTATGAA ATTACATTTTGTGTTTATGTTATTTGCAaTGTTTTCTATGGAAATAT TTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAA AGGACTATGG

In an embodiment, to correct a mutation, e.g., an intronic 3272-26bp (A→G) target site in the CFTR gene, and concomitantly introduce a silent sense mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A→G) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 51; SEQ ID NO: 27333) GTGCACATGTACCCTAAAACTTAAAGTATAATAAAAAAAATAAAAAAAAGTTTGAGGTGTTTAA AGTATGCAAAAAAAAAAAAAGAAATAAATCACTGACACACTTTGTCCACTTTGCAATGTGAAAA TGTTTACTCACCAACATGTTTTCTTTGATCTTACAGTTGTTATTAATTGTGATTGGAGCTATAG CAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTAT TATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTCAAACAACTGGAATCTGAAGGTATG ACAGTGAATGTGCGATACTCATCTTGTAAAAAAGCTATAAGAGCTATTTGAGATTCTTTATTGT TAATCTACTTAAAAAAAATTCTGCTTTTAAACTTTTACATCATATAACAATAATTTTTTTCTAC ATGCATGTGTATATAAAAGGAAACTATATTACAAAGTACACATGGATTTTTTTTCTTAATTAAT GACCATGTGACTTCATTTTGGTTTTAAAATAGGTATATAGAATCTTACCACAGTTGGTGTACAG GACATTCATTTATAATAAACTTATATCAGTCAAATTAAACAAGGATAGTGCTGCTATTACTAAA GGTTTCTCTGGGTTCCCAAATGATACTTGACCAAATTTGTCCCTTTGGCTTGTTGTCTTCAGAC ACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGTTAGG GAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAGTATA TTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACTTGAA AAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACTCCCA GTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGTAGCC AAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGGCACC AGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCTTTTT CAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCAaTGTTTTCTATccAAA TATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGACTATGGACAC TTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAATTTACATAC TGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAAATGATTTTT GTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTACTATGAACTCATTAA CTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCATTCTATAGGTTATCA ATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACAAGTGATT TCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAATCGGATATATATATAT ATATGTATATATATATATATATATATATATATATACATATATATATATAGTATTATCCCTGTTT TCACAGTTTTAAAAACCGATGCACACAGATTGTCAGATAGCAATTCTGTGATTGAAGGGGAAAT ATGTCACCTCTTCATACTCATATTGGTGAAGGGTCCTAGCTTCAAAATTAATAGATTCCTAAAG AGGGGAAATGAAACATCCGCATTTACACACACACACACACACACACACACAGAGTTCCTCTTGT CGGTAAGTTTTGTTTTTTTTAAATCTCTACTAGATAAAATTTGTTATCTAATTGTGAGTTTTAC ACAAAGAAAAACTGTCACAGAAAAGAAAGACAGTGTCACATTTTTCAAAAGAAAAAGAAGAAAA GAAAGTGCCATGTTTTTCAAATACAAATGTTCTGGATTGATTTTAGGATCTTTAGTGAAAAACA AAGTATTTCATAATAAGTAAAATAAAAATCTATGTAGGTAAATTTGTTTCTCTAATTTAAGAAT TTGAATTTCTGAGTATTTATGATAAGTGTTGAAATAACTTCTTATATGTGACAGTGAATACTGG CAGAGCAAATGCCAAATCAATGCCAAATCTGTAGGATCATTTGATTGTAGGAACAGAATTCTAC TCAAACCGAAAGCAGGCATTTGCTGGAGTTACAGAAAGGCCTCATGGAACACCGAGAAGGTGGT GCCATTCGACTCTTAAAGAAGCTGCAACAGGCA

In an embodiment, to correct a mutation, e.g., an intronic 3272-26bp (A→G) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the 5′ homology arm may be shortened less than 750 nucleotides, e.g., 500 nucleotides, to avoid inclusion of a LINE repeat element in the 5′ homology arm. The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A→G) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 52; SEQ ID NO: 27334) AGACACCCTTTCTTCATGTGTTGGAGCTGCCATTTCGTGTGCCCCCAAACTCTACTTGAGCTGT TAGGGAATCACATTTTGCAGTGACAGCCTTAGTGTGGGTGCATTTTCAGGCAATACTTTTTCAG TATATTTCTGCTTTGTAGATTATTAGCTAAATCAAGTCACATAAACTTCCTTAATTTAGATACT TGAAAAAATTGTCTTAAAAGAAAATTTTTTTAGTAAGAATTAATTTAGAATTAGCCAGAAAACT CCCAGTGGTAGCCAAGAAAGAGGAATAAATATTGGTGGTAATTTTTTAAGTTCCCATCTCTGGT AGCCAAGTAAAAAAAGAGGGTAACTCATTAATAAAATAACAAATCATATCTATTCAAAGAATGG CACCAGTGTGAAAAAAAGCTTTTTAACCAATGACATTTGTGATATGATTATTCTAATTTAGTCT TTTTCAGGTACAAGATATTATGAAATTACATTTTGTGTTTATGTTATTTGCAaTGTTTTCTATc cAAATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGACTATGG ACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAATTTAC ATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAAATGAT TTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGTACTATGAACTCA TTAACTTTAGCTAAGCATTTAAGTAAAAAATTTTCAATGAATAAAATGCTGCATTCTATAGGTT ATCAATTTTTGATATCTTTAGAGTTTAGTAATTAACAAATTTGTTGGTTTATTATTGAACAAGT GATTTCTTTGAATTTCCATTGTTTTATTGTTAAACAAATAATTTCCTTGAAATCGGATATATAT ATATATATGTATATATATATATATATATATATATATATACA

In an embodiment, an ssODN may be to correct a mutation, e.g., an intronic 3272-26bp (A→G) target site in the CFTR gene, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage. For example, the ssODN may include 5′ and 3′ homology arms as shown below. The 5′ homology arm is shown as bold sequence, the inserted base to correct the intronic 3272-26bp (A→G) mutation is shown as lower case sequence, the silent sense mutation is shown as lower case underlined and italicized sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(Template Construct 53; SEQ ID NO: 27335) ATATGATTATTCTAATTTAGTCTTTTTCAGGTACAAGATATTATG AAATTACATTTTGTGTTTATGTTATTTGCAaTGTTTTCTATccAA ATATTTCACAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAG CTTAAAAGGACTATGG

The underlined C has been changed from a G to C at that position, so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to reduce or eliminate Cas9 cleavage at that locus.

Table 49 below provides exemplary template nucleic acids. In an embodiment, the template nucleic acid includes the 5′ homology arm and the 3′ homology arm of a row from Table 49. In other embodiments, a 5′ homology arm from the first column can be combined with a 3′ homology arm from Table 49. In each embodiment, a combination of the 5′ and 3′ homology arms include a replacement sequence, e.g., Cytosine-Thymine-Thymine (CTT) residues or a Guanine (G) residue.

TABLE 49 5′ homology arm 3′ homology arm (the number of (the number of nucleotides from nucleotides from SEQ ID NO: 5′H, SEQ ID NO: 3′H, beginning at Replacement beginning at the 3′ end of Sequence = CT the 5′ end of SEQ ID NO: 5′H) T or G SEQ ID NO: 3′H)   10 or more   10 or more   20 or more   20 or more   50 or more   50 or more  100 or more  100 or more  150 or more  150 or more  200 or more  200 or more  250 or more  250 or more  300 or more  300 or more  350 or more  350 or more  400 or more  400 or more  450 or more  450 or more  500 or more  500 or more  550 or more  550 or more  600 or more  600 or more  650 or more  650 or more  700 or more  700 or more  750 or more  750 or more  800 or more  800 or more  850 or more  850 or more  900 or more  900 or more 1000 or more 1000 or more 1100 or more 1100 or more 1200 or more 1200 or more 1300 or more 1300 or more 1400 or more 1400 or more 1500 or more 1500 or more 1600 or more 1600 or more 1700 or more 1700 or more 1800 or more 1800 or more 1900 or more 1900 or more 1200 or more 1200 or more At least 50 but not At least 50 but not long enough to long enough to include a include a repeated element. repeated element. At least 100 but At least 100 but not long enough to not long enough to include a include a repeated element. repeated element. At least 150 but At least 150 but not long enough to not long enough to include a include a repeated element. repeated element.    5 to 100 nucleotides    5 to 100 nucleotides   10 to 150 nucleotides   10 to 150 nucleotides   20 to 150 nucleotides   20 to 150 nucleotides Template Construct No. 1 Template Construct No. 2 Template Construct No. 3 Template Construct No. 4

In an embodiment, a single or dual nickase eaCas9 is used to cleave the target DNA near the site of the mutation, or signature, to be modified, e.g., replaced. While not wishing to be bound by theory, in an embodiment, it is believed that the Cas9 mediated break induces HDR with the template nucleic acid to replace the target DNA sequence with the template sequence.

Targeted Knockin by cDNA Insertion

In an embodiment, homology-directed repair of the CFTR gene is used to target an intronic region between exons X and Y, wherein exons X and Y are any exons between exon 1 and exon 27, given that exon X and exon Y are adjacent and exon X has a lower number than exon Y, and deliver a Cas9 molecule, CRIPSR-gRNAs, and homology-directed repair templates that include homology arms, splice acceptor, contiguous coding sequence of exons (X+1) through exon 27 of CFTR gene and polyadenylation signal.

In an embodiment, one single strand break, two single strand breaks, one double strand break or two double strand breaks are introduced (e.g., positioned by one, two, three, or four gRNA molecule/s) at or in close proximity to a CF target knockin position in the CFTR gene. The CF target knockin position is the intronic region between CFTR exons X and Y. Altering the CF target knockin position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of contiguous exons (X+1) through exon 27 of CFTR gene. Targeted knockin of CFTR cDNA leads to the cessation of production of mutant or truncated CFTR protein and results in the production of wild-type CFTR protein. Targeted knockin of CFTR cDNA prevents the development or progression of lung, gastrointestinal and/or reproductive disease in a subject due to the cessation of production of mutant CFTR protein and restoration of wild-type CFTR protein production. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exon (X+1) through exon 27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is after intron X.

In an embodiment, homology-directed repair of the CFTR gene in any subject with CF mutations in exons 3 through 27 and introns 2 through 26 by targeting intronic region between exons 2 and 3 and with delivery of a homology-directed repair template including homology arms, splice acceptor, coding sequence of contiguous exons 3-27 of CFTR gene and polyadenylation signal. The CF target position is the intronic region between exons 2 and 3. Altering the CF target position refers to homology-directed repair of genomic sequence including the delivery of cDNA template of exons 3-27 of CFTR gene. This approach cures and/or prevents the progression of lung, gastrointestinal and/or reproductive disease in any subject with CF or CF-like disease deficiency who has a mutation in exons 3-27 of the CFTR gene, or in any subject who has a mutation in an intronic or exonic region of the CFTR gene that is on or after the second intron, including but not limited to the following mutations: e.g., F508del, G551D, G542X, N1303K, R117H, W1282X, R553X, c.3717+12191C>T, 2657+5G>A, or c.3140-26A>G.

In an embodiment, a cDNA insert construct comprises a 5′ homology arm, a splice acceptor, a cDNA insert (e.g., CFTR exons 3 to 27, e.g., CFTR exons 11 to 27), a 3′ homology arm, and a polyadenylation signal. Splice acceptors and polyadenylation signals are well known to one of skill in the art.

It is contemplated herein that, in an embodiment, a Cas9 molecule could potentially cleave cDNA insert constructs either prior to or following homology directed repair (e.g., homologous recombination), resulting in a possible non-homologous-end-joining event and further DNA sequence mutation at the chromosomal locus of interest. Therefore, to avoid cleavage of the cDNA insert sequence before and/or after Cas9-mediated homology directed repair, alternate versions of the homology arms may be used where silent mutations are introduced into a PAM. These silent mutations may disrupt Cas9 binding and cleavage, but not disrupt the amino acid sequence of the cDNA insert.

Exemplary template cDNA (also referred to herein as cDNA inserts) to introduce wild-type sequence, e.g., exons 3 to 27 of the CFTR gene, are provided. In an embodiment, the CRISPR-Cas9 binding site is CTCAAGTGATCTGCCCACCTTGG (SEQ ID NO: 27336) (PAM is underlined TGG).

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 3 to 27) into intron 2, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(SEQ ID NO: 27337) CAATCAAAAGGTTAGGATCCTTTTGATTGCCAGTGACAGAAACCCAATTTACTAGCTTAAGTAA ATAAAAGGAACGAATTTATTGGCTCATGAAGCCTGAACTATGTGAAGACCTAGGTGGAGAACTG GCCTTAGGAACTCAATGGGACCAAGGACTCAAATGCCACCTGGTGGCATTTGCCTTATGCTGGT TTTATTTTCTCAGACCGGACCAGCTTTCTACATAAAGTGGGTCCCTGGTTAGAACTCTTTGCTC CTATCTTTAAGGACCACGAAAGAAGGAGCCCTTTGTCCTTGGCTAAATGTGAAAAATCCCAGAG ACTCTTGAGTCATAGTGCTTACCCCTTGGGCCACTCATAGTCTAGAATGAACTAGGCTGAGTCT CGTGCCAACAGCACAGGCCTGATGCCAGATAAAAGGGTGAGTGAAGGGGGATAAAAAATAAGAC ATAGCTACTAAATTATTGCACCAAAGTAAAAACATTGAGTTGACTTGCAATTTGTTTCTTTTAA TTAAATTCATTTCCTTTTTTTGGCATTTTGAAGGCAAAGTAAGATATTAAACTTTATTTTTATT GATTTTATTCAAAGAATTAAGCTAGTGGGAGTAGCAGATTCACACTTCTAAGATCAAGGGCCAG CTTCTATTATTGAACACTTGGTGTGTGCAAATGCCATGAGGTAGGGATACTTTGTTTTGTTTTT TATTTTTTATTGGGTTCGATCTCTTTTGTTTATGATGTATCCCCAAGTGCCTAGAATAGGGCCT GGCATATGGTATATACTCAATAAATATTTGTTGAATGAATCCATGATGGAATGTGAAATGGCTA GCATTACATAGAAACCTGTAGCATTGCTGGAGAGATAAAATATATAAACATAATCCATTGCAGG TATATTGACAAGTTCAAAATAATATAATGGGTATTGAATATCTAAATGTTTGTTGTTGTTGTTG CTGTTGTTTTTGAGACAGAGTCTTGCTCTGTTGCCCAGGCTGGAGTGTAATGGTGCAATTTTGG CTCACTGCAAACTTCGTCTCCTGGGTTCAAGTGATTCTCCTGCCTCAGCCTCTCGAGTAGCTGG GTTTACAGGCACTCGCCACAATGCCTGGCTAATTTTTGTATTTTAGTAGATGTGGAGTTTCGCC ATGTTGGCCAGGCTGGTCTTGAACTCCTGACCTCAAGTGATCTGCCCACCTTaaCCTCCCAAAA TGCTGGGATTATAGGTGTGAGCCACTATGCCCAGCTTTGAATATCTAAGTTTTAATTGGATGCT GAGGGAATGATTAATCAGAGTAGGGCTGGGTTAATTGAAAAATGTGATACATTTGTATTTATGG CCAGATAGAGAACATGAATCTGAATTTGCAGAATTATCTGGCTTAACATTTTTTTCTTTCCAGT TTTCACTGTATCCCCCATGTTGATTCAATTTAAAAAATATACCTATTTTACTTCAATTCAACAA TGCTATGCCAGTACAAACCCATACGTTCTATTATTTTTGTTTTGTTTTGTTTTTGTATCTCCAC CCTGTTACTTCTTTTCTTATAAAATTGGTATTTGAAATTTATTGAAATATTTTGGAAGAGTGAC ATACCATTTTTGGTACTTTGTACCTCTGCACCCTTGGGAAGTGACCCTGGCTTCACATTTCATA ACTGCCTTGTGACCATGGCCCTCAAGTGGTTGCCAGATGGTTGAAGAACATTAACCTATCTGGC TCAATTTTGTGACCATGGATTGAATCCTCTACATAACTGCAGTGTGCAAACCACACATCCGTTC CAAGATTGTAGTCAGGATATGAACTTTTTAAGAATAAAACTTCTTCCCTTCTGATCTGGGCCTG GTATGTGGTCCTACTAGAACCACATCACCTACTCTTGGTGCTAACAATTTGTGGCACCAAGTTG TTCAAGTTTCACCCATTAAAGAAATTCCCCGACCTTGCCTTCTCCTCAGGTAACTACCCCATTC TATTTTTTCTTTCATAGCTAACATTCTCTGCTCTCCTGGTCTCTCTACTTCACTTTCATTTACA TCTCAGCTCCTGAAGTATGGTTTCCACCATGTTCCTAAAACTACATTGCCCAGGGTCACTAGAG ACCTCTTATGAAATATAACAACACCTTTCTACATTACTTCCGTGTGGACCACTTTTTCACATTG AACCCATTTTGTTGGTTTATGTACACACCCCTTCCTTGGCTTTCCCATCTGATCCATTTCTCCT TTGATGGAGAAGGTGAGTCTGCTCCATATTTAGCTTCTTACTCTGAGTAACCAAATGTTATGGA TGGGAGGTTAGCTCTGTGTGTGAGAGAAAGGTGGAGAAGCATGTGGGGAGGGAAATAGATGGGA AAAGGTAATTAGGCTTTATAGAAGGGCTCTCA

The underlined A has been changed from a G to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to TAA to reduce or eliminate Cas9 cleavage at that locus.

In an embodiment, suitable sequence for the cDNA insert of CFTR exons 3 to 27, can be selected from (e.g., includes a portion of) or include the following sequence:

(SEQ ID NO: 27338) AGAATGGGATAGAGAGCTGGCTTCAAAGAAAAATCCTAAACTCATTAATGCCCTTCGGCGATGT TTTTTCTGGAGATTTATGTTCTATGGAATCTTTTTATATTTAGGGGAAGTCACCAAAGCAGTAC AGCCTCTCTTACTGGGAAGAATCATAGCTTCCTATGACCCGGATAACAAGGAGGAACGCTCTAT CGCGATTTATCTAGGCATAGGCTTATGCCTTCTCTTTATTGTGAGGACACTGCTCCTACACCCA GCCATTTTTGGCCTTCATCACATTGGAATGCAGATGAGAATAGCTATGTTTAGTTTGATTTATA AGAAGACTTTAAAGCTGTCAAGCCGTGTTCTAGATAAAATAAGTATTGGACAACTTGTTAGTCT CCTTTCCAACAACCTGAACAAATTTGATGAAGGACTTGCATTGGCACATTTCGTGTGGATCGCT CCTTTGCAAGTGGCACTCCTCATGGGGCTAATCTGGGAGTTGTTACAGGCGTCTGCCTTCTGTG GACTTGGTTTCCTGATAGTCCTTGCCCTTTTTCAGGCTGGGCTAGGGAGAATGATGATGAAGTA CAGAGATCAGAGAGCTGGGAAGATCAGTGAAAGACTTGTGATTACCTCAGAAATGATTGAAAAT ATCCAATCTGTTAAGGCATACTGCTGGGAAGAAGCAATGGAAAAAATGATTGAAAACTTAAGAC AAACAGAACTGAAACTGACTCGGAAGGCAGCCTATGTGAGATACTTCAATAGCTCAGCCTTCTT CTTCTCAGGGTTCTTTGTGGTGTTTTTATCTGTGCTTCCCTATGCACTAATCAAAGGAATCATC CTCCGGAAAATATTCACCACCATCTCATTCTGCATTGTTCTGCGCATGGCGGTCACTCGGCAAT TTCCCTGGGCTGTACAAACATGGTATGACTCTCTTGGAGCAATAAACAAAATACAGGATTTCTT ACAAAAGCAAGAATATAAGACATTGGAATATAACTTAACGACTACAGAAGTAGTGATGGAGAAT GTAACAGCCTTCTGGGAGGAGGGATTTGGGGAATTATTTGAGAAAGCAAAACAAAACAATAACA ATAGAAAAACTTCTAATGGTGATGACAGCCTCTTCTTCAGTAATTTCTCACTTCTTGGTACTCC TGTCCTGAAAGATATTAATTTCAAGATAGAAAGAGGACAGTTGTTGGCGGTTGCTGGATCCACT GGAGCAGGCAAGACTTCACTTCTAATGGTGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAA TTAAGCACAGTGGAAGAATTTCATTCTGTTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAA AGAAAATATCATCTTTGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGC CAACTAGAAGAGGACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAA TCACACTGAGTGGAGGTCAACGAGCAAGAATTTCTTTAGCAAGAGCAGTATACAAAGATGCTGA TTTGTATTTATTAGACTCTCCTTTTGGATACCTAGATGTTTTAACAGAAAAAGAAATATTTGAA AGCTGTGTCTGTAAACTGATGGCTAACAAAACTAGGATTTTGGTCACTTCTAAAATGGAACATT TAAAGAAAGCTGACAAAATATTAATTTTGCATGAAGGTAGCAGCTATTTTTATGGGACATTTTC AGAACTCCAAAATCTACAGCCAGACTTTAGCTCAAAACTCATGGGATGTGATTCTTTCGACCAA TTTAGTGCAGAAAGAAGAAATTCAATCCTAACTGAGACCTTACACCGTTTCTCATTAGAAGGAG ATGCTCCTGTCTCCTGGACAGAAACAAAAAAACAATCTTTTAAACAGACTGGAGAGTTTGGGGA AAAAAGGAAGAATTCTATTCTCAATCCAATCAACTCTATACGAAAATTTTCCATTGTGCAAAAG ACTCCCTTACAAATGAATGGCATCGAAGAGGATTCTGATGAGCCTTTAGAGAGAAGGCTGTCCT TAGTACCAGATTCTGAGCAGGGAGAGGCGATACTGCCTCGCATCAGCGTGATCAGCACTGGCCC CACGCTTCAGGCACGAAGGAGGCAGTCTGTCCTGAACCTGATGACACACTCAGTTAACCAAGGT CAGAACATTCACCGAAAGACAACAGCATCCACACGAAAAGTGTCACTGGCCCCTCAGGCAAACT TGACTGAACTGGATATATATTCAAGAAGGTTATCTCAAGAAACTGGCTTGGAAATAAGTGAAGA AATTAACGAAGAAGACTTAAAGGAGTGCTTTTTTGATGATATGGAGAGCATACCAGCAGTGACT ACATGGAACACATACCTTCGATATATTACTGTCCACAAGAGCTTAATTTTTGTGCTAATTTGGT GCTTAGTAATTTTTCTGGCAGAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAACAC TCCTCTTCAAGACAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAGTGATTATCACC AGCACCAGTTCGTATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTTGCTTGCTATGG GATTCTTCAGAGGTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATTTTACACCACAA AATGTTACATTCTGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAGCAGGTGGGATT CTTAATAGATTCTCCAAAGATATAGCAATTTTGGATGACCTTCTGCCTCTTACCATATTTGACT TCATCCAGTTGTTATTAATTGTGATTGGAGCTATAGCAGTTGTCGCAGTTTTACAACCCTACAT CTTTGTTGCAACAGTGCCAGTGATAGTGGCTTTTATTATGTTGAGAGCATATTTCCTCCAAACC TCACAGCAACTCAAACAACTGGAATCTGAAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAA GCTTAAAAGGACTATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCA CAAAGCTCTGAATTTACATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAA ATGAGAATAGAAATGATTTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAA CAGGAGAAGGAGAAGGAAGAGTTGGTATTATCCTGACTTTAGCCATGAATATCATGAGTACATT GCAGTGGGCTGTAAACTCCAGCATAGATGTGGATAGCTTGATGCGATCTGTGAGCCGAGTCTTT AAGTTCATTGACATGCCAACAGAAGGTAAACCTACCAAGTCAACCAAACCATACAAGAATGGCC AACTCTCGAAAGTTATGATTATTGAGAATTCACACGTGAAGAAAGATGACATCTGGCCCTCAGG GGGCCAAATGACTGTCAAAGATCTCACAGCAAAATACACAGAAGGTGGAAATGCCATATTAGAG AACATTTCCTTCTCAATAAGTCCTGGCCAGAGGGTGGGCCTCTTGGGAAGAACTGGATCAGGGA AGAGTACTTTGTTATCAGCTTTTTTGAGACTACTGAACACTGAAGGAGAAATCCAGATCGATGG TGTGTCTTGGGATTCAATAACTTTGCAACAGTGGAGGAAAGCCTTTGGAGTGATACCACAGAAA GTATTTATTTTTTCTGGAACATTTAGAAAAAACTTGGATCCCTATGAACAGTGGAGTGATCAAG AAATATGGAAAGTTGCAGATGAGGTTGGGCTCAGATCTGTGATAGAACAGTTTCCTGGGAAGCT TGACTTTGTCCTTGTGGATGGGGGCTGTGTCCTAAGCCATGGCCACAAGCAGTTGATGTGCTTG GCTAGATCTGTTCTCAGTAAGGCGAAGATCTTGCTGCTTGATGAACCCAGTGCTCATTTGGATC CAGTAACATACCAAATAATTAGAAGAACTCTAAAACAAGCATTTGCTGATTGCACAGTAATTCT CTGTGAACACAGGATAGAAGCAATGCTGGAATGCCAACAATTTTTGGTCATAGAAGAGAACAAA GTGCGGCAGTACGATTCCATCCAGAAACTGCTGAACGAGAGGAGCCTCTTCCGGCAAGCCATCA GCCCCTCCGACAGGGTGAAGCTCTTTCCCCACCGGAACTCAAGCAAGTGCAAGTCTAAGCCCCA GATTGCTGCTCTGAAAGAGGAGACAGAAGAAGAGGTGCAAGATACAAGGCTTTAG

It is contemplated herein that one or both homology arms may be shortened to avoid including certain sequence repeat elements, e.g., Alu repeats, LINE elements. For example, a 5′ homology arm may be shortened to avoid a sequence repeat element. In other embodiments, a 3′ homology arm may be shortened to avoid a sequence repeat element. In some embodiments, both the 5′ and the 3′ homology arms may be shortened to avoid including certain sequence repeat elements.

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 3 to 27) into intron 2, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may be shorted to approximately 500 bp. The 5′ homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(SEQ ID NO: 27339) TTTTTATTTTTTATTGGGTTCGATCTCTTTTGTTTATGATGTATCCCCAAGTGCCTAGAATAGG GCCTGGCATATGGTATATACTCAATAAATATTTGTTGAATGAATCCATGATGGAATGTGAAATG GCTAGCATTACATAGAAACCTGTAGCATTGCTGGAGAGATAAAATATATAAACATAATCCATTG CAGGTATATTGACAAGTTCAAAATAATATAATGGGTATTGAATATCTAAATGTTTGTTGTTGTT GTTGCTGTTGTTTTTGAGACAGAGTCTTGCTCTGTTGCCCAGGCTGGAGTGTAATGGTGCAATT TTGGCTCACTGCAAACTTCGTCTCCTGGGTTCAAGTGATTCTCCTGCCTCAGCCTCTCGAGTAG CTGGGTTTACAGGCACTCGCCACAATGCCTGGCTAATTTTTGTATTTTAGTAGATGTGGAGTTT CGCCATGTTGGCCAGGCTGGTCTTGAACTCCTGACCTCAAGTGATCTGCCCACCTTaaCCTCCC AAAATGCTGGGATTATAGGTGTGAGCCACTATGCCCAGCTTTGAATATCTAAGTTTTAATTGGA TGCTGAGGGAATGATTAATCAGAGTAGGGCTGGGTTAATTGAAAAATGTGATACATTTGTATTT ATGGCCAGATAGAGAACATGAATCTGAATTTGCAGAATTATCTGGCTTAACATTTTTTTCTTTC CAGTTTTCACTGTATCCCCCATGTTGATTCAATTTAAAAAATATACCTATTTTACTTCAATTCA ACAATGCTATGCCAGTACAAACCCATACGTTCTATTATTTTTGTTTTGTTTTGTTTTTGTATCT CCACCCTGTTACTTCTTTTCTTATAAAATTGGTATTTGAAATTTATTGAAATATTTTGGAAGAG TGACATACCATTTTTGGTACTTTGTACCTCTGCACCCTTGGGAAGTGACCCTGGCTTCACATTT CATAACTGCCTTGTGACCATGGCCCTCAAGTGGTTGCCAG

The underlined A has been changed from a G to A at that position so that wild-type CFTR is still transcribed, but the PAM sequence TGG has been modified to TAA to reduce or eliminate Cas9 cleavage at that locus.

Exemplary template cDNA (also referred to herein as cDNA inserts) to introduce wild-type sequence, e.g., exons 11 to 27 of the CFTR gene, are provided. In an embodiment, the CRISPR-Cas9 binding site is AGTGAATGAATGTGGTATCCCGG (SEQ ID NO: 27340) (PAM is underlined CGG).

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 11 to 27) into intron 10, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may each comprise about 1000 base pairs (bp) of sequence flanking the most distal gRNAs (e.g., 1200 bp of sequence on either side of the mutation). The 5′ homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(SEQ ID NO: 27341) CTAAATAGAGTGCTGATTTCCCCACAGCATTACTAACAGATGATATTATCTAATTTAAAAAGTT TCTCATCTTATAGGGAAAATAGTATGTCAATGTATTCTTAACTTGCATTTCTTTTATTATAAGT AGTGTAAAATATCATTTCAACTTATACACAGGAGGAATTTCTCTCTATATAAAGTGATCCTAGA ATCATAATGAAAAATATCACCAACTCATTAGGAAAATGTACAAAGGATTGAATAGATATCTCAT CAAAAATAAAAATATAAGTGGCCTTTAAACATTGAAAGGTAACATTTGAACAAAGACTTGCAGG AGGTGAGGGATTAGGGAATGCAGACTCTGGGAAGAGTCTTCCAAGTAGCAGGTGAAGCAAGTGC AAAGCTTTCAGATGGGACTGACTATACCTGTCTGGTTTGAAGAACAGTAAGGAGGTCACTGAGG CTGGCATAGAGTAAGACAGGGAGGGTAGAATACTGTCAGAGAAGTAATCGGCGGTGGAGGTAGG GGGTAAACCATAAAGTGCTCGTAAAGACTAAGGCTTATTTCTCTGGGTGAGATTAGAGGCCACT GGAGAGTTTTAAACAGAAGTAACAGGGCCACTTTGGCTAATGTTTTTAGGCTATTCTGTAGGGA GACAAGGGAGGAAGCAAGGAGATGAGTTAGGAGTCTATTGTGCCAGTTCAGGCAAGTGATGATG GTGGCTTGATCCAGGTAGTAGTGGAAGTAGTATAGTAGGAAGTGATCAGATTCAGGACATGCTT TGAAGGAAGATCCAATAGGATTAATGGATAAGTTGAACAATGGCATATGAGAAAAGTCACAGAG GAGTCAAAGATGATTCCAAGCTTTCTGGACTGAGTAACTGGAAGGATAAATGTGCCGTTTACTA GAAAGATAATGGGAGAAACAGGTTTTGGATGGAGCTTGGTTTGGGAATATTAAGTTTGAAATGC CTATTTGACATCCAAATAGAGATGTTAGTTGGATGTACAAGTCTAGTTTCAAGGAAGAGGGGGC TGGTAGTGTGAAGATGGGGCTGGATAAGATTCTAAAGGAAAGAGGGTTGATAAGAAGAGAAAGG GGTGTAGGGGTTAGCCTAAGGGCATTCTAAGTATTAGAGGTTAAGGAGGTGGGTGAAGAAAACC CAATAAAATAAAAGTCTGAGAAGACAAAGCTAGTGAATGAATGTGGTATCCCttAACCCAACTG ATGTCAAGCAGAAGGGTGTTATCAACTAGGTCAAATGCTCATTCATCAAGTAAGATGAAACTGT TATAATTAACCGGTGTCTTCTGAAATACGGAGATAACTCGTGACTTAATGAAAGCAATAGTAGA GAAGGTCAAACTTGACCAGAATGAAATTAGAAAGAATAAGAGGAAAGAAAAGACCAAATACAGA CAACCATTGATGCCTTATTCTTTTGATATACTCCTGGAGTCCACTTGCTAATACAATTGACCCT TAAACAATACAGGCTTGAACTGCATGGGTCCACTTATTTGTGAATTTTTTTTCAGTTAATACAT TGGAAAATTTTTGGGGTTTTTTGACAATTTGAAAAAACTCACAAACTGTCTAGCCTAGAAATAC CGAGAAAATTAAGAAAAAGTAAGATATGCCATGAATGCATAAAATATATGTAGACACTAGCCTA TTTTATCATTTGCTACTATAAAATATACACAATCTATTATAAAAAGTTAAAATTTATCAAAACT TAACACACACTAACACCTACCCTACCTGGCACCATTCACAGTAAAGAGAAATGTAAATAAACAT AAAAATGTAGTATTAAACCATAATGGCATAAAACTAATTGTAGTACATATGGTACTACTGTAAT AATTTGGAAGCCACTTCCTGTTGCTATTACGGTAAGCTCAAGCATTGTGGATAGCCATTTAAAA CACCACGTGATGCTAATCATCTCCGTGTGAGCAGTTCTCTCTCCAGTAAATTGCATATTGCAGT AAAAAGTGATCTCTAGTGGTTCTCGCATATTTTTCATCATGTTTAGTGCAATGCCATAAACCTT GAATAACATCAAGCAATCCATACAAAGTGCCACTAGTGATGCACGGAAAAGTTGTAACAGTACA AGAAAAAAGTTGAGTTGCTTGGTATTTACCATATATTGAGGTCTGCAGCTACAGTTGCCTGCAA TTTCGAGATAAATGAACCCAGTATAAAGACTGTTGTAACAAAAGAAAAGAAAATGTGAAACCAT CAGTGCAGCTATGCCAGCAGGTGTGAAGTCTTGCACTTTTTGCAAAATACAAAATATGAAATAT GTGTTAATTGACTGTTTATGTTATCTGTAAGGTTTCCACTCAACAATAGGCTATTAGTAGTTAA GTTTTTGTGGAGTCAAAAATTATACGTGGATT

The underlined T has been changed from a G to T at that position so that wild-type CFTR is still transcribed, but the PAM sequence CGG has been modified to CTT to reduce or eliminate Cas9 cleavage at that locus.

In an embodiment, suitable sequence for the cDNA insert of CFTR exons 11 to 27, can be selected from (e.g., includes a portion of) or include the following sequence:

(SEQ ID NO: 27342) ACTTCACTTCTAATGGTGATTATGGGAGAACTGGAGCCTTCAGAGGGTAAAATTAAGCACAGTG GAAGAATTTCATTCTGTTCTCAGTTTTCCTGGATTATGCCTGGCACCATTAAAGAAAATATCAT CTTTGGTGTTTCCTATGATGAATATAGATACAGAAGCGTCATCAAAGCATGCCAACTAGAAGAG GACATCTCCAAGTTTGCAGAGAAAGACAATATAGTTCTTGGAGAAGGTGGAATCACACTGAGTG GAGGTCAACGAGCAAGAATTTCTTTAGCAAGAGCAGTATACAAAGATGCTGATTTGTATTTATT AGACTCTCCTTTTGGATACCTAGATGTTTTAACAGAAAAAGAAATATTTGAAAGCTGTGTCTGT AAACTGATGGCTAACAAAACTAGGATTTTGGTCACTTCTAAAATGGAACATTTAAAGAAAGCTG ACAAAATATTAATTTTGCATGAAGGTAGCAGCTATTTTTATGGGACATTTTCAGAACTCCAAAA TCTACAGCCAGACTTTAGCTCAAAACTCATGGGATGTGATTCTTTCGACCAATTTAGTGCAGAA AGAAGAAATTCAATCCTAACTGAGACCTTACACCGTTTCTCATTAGAAGGAGATGCTCCTGTCT CCTGGACAGAAACAAAAAAACAATCTTTTAAACAGACTGGAGAGTTTGGGGAAAAAAGGAAGAA TTCTATTCTCAATCCAATCAACTCTATACGAAAATTTTCCATTGTGCAAAAGACTCCCTTACAA ATGAATGGCATCGAAGAGGATTCTGATGAGCCTTTAGAGAGAAGGCTGTCCTTAGTACCAGATT CTGAGCAGGGAGAGGCGATACTGCCTCGCATCAGCGTGATCAGCACTGGCCCCACGCTTCAGGC ACGAAGGAGGCAGTCTGTCCTGAACCTGATGACACACTCAGTTAACCAAGGTCAGAACATTCAC CGAAAGACAACAGCATCCACACGAAAAGTGTCACTGGCCCCTCAGGCAAACTTGACTGAACTGG ATATATATTCAAGAAGGTTATCTCAAGAAACTGGCTTGGAAATAAGTGAAGAAATTAACGAAGA AGACTTAAAGGAGTGCTTTTTTGATGATATGGAGAGCATACCAGCAGTGACTACATGGAACACA TACCTTCGATATATTACTGTCCACAAGAGCTTAATTTTTGTGCTAATTTGGTGCTTAGTAATTT TTCTGGCAGAGGTGGCTGCTTCTTTGGTTGTGCTGTGGCTCCTTGGAAACACTCCTCTTCAAGA CAAAGGGAATAGTACTCATAGTAGAAATAACAGCTATGCAGTGATTATCACCAGCACCAGTTCG TATTATGTGTTTTACATTTACGTGGGAGTAGCCGACACTTTGCTTGCTATGGGATTCTTCAGAG GTCTACCACTGGTGCATACTCTAATCACAGTGTCGAAAATTTTACACCACAAAATGTTACATTC TGTTCTTCAAGCACCTATGTCAACCCTCAACACGTTGAAAGCAGGTGGGATTCTTAATAGATTC TCCAAAGATATAGCAATTTTGGATGACCTTCTGCCTCTTACCATATTTGACTTCATCCAGTTGT TATTAATTGTGATTGGAGCTATAGCAGTTGTCGCAGTTTTACAACCCTACATCTTTGTTGCAAC AGTGCCAGTGATAGTGGCTTTTATTATGTTGAGAGCATATTTCCTCCAAACCTCACAGCAACTC AAACAACTGGAATCTGAAGGCAGGAGTCCAATTTTCACTCATCTTGTTACAAGCTTAAAAGGAC TATGGACACTTCGTGCCTTCGGACGGCAGCCTTACTTTGAAACTCTGTTCCACAAAGCTCTGAA TTTACATACTGCCAACTGGTTCTTGTACCTGTCAACACTGCGCTGGTTCCAAATGAGAATAGAA ATGATTTTTGTCATCTTCTTCATTGCTGTTACCTTCATTTCCATTTTAACAACAGGAGAAGGAG AAGGAAGAGTTGGTATTATCCTGACTTTAGCCATGAATATCATGAGTACATTGCAGTGGGCTGT AAACTCCAGCATAGATGTGGATAGCTTGATGCGATCTGTGAGCCGAGTCTTTAAGTTCATTGAC ATGCCAACAGAAGGTAAACCTACCAAGTCAACCAAACCATACAAGAATGGCCAACTCTCGAAAG TTATGATTATTGAGAATTCACACGTGAAGAAAGATGACATCTGGCCCTCAGGGGGCCAAATGAC TGTCAAAGATCTCACAGCAAAATACACAGAAGGTGGAAATGCCATATTAGAGAACATTTCCTTC TCAATAAGTCCTGGCCAGAGGGTGGGCCTCTTGGGAAGAACTGGATCAGGGAAGAGTACTTTGT TATCAGCTTTTTTGAGACTACTGAACACTGAAGGAGAAATCCAGATCGATGGTGTGTCTTGGGA TTCAATAACTTTGCAACAGTGGAGGAAAGCCTTTGGAGTGATACCACAGAAAGTATTTATTTTT TCTGGAACATTTAGAAAAAACTTGGATCCCTATGAACAGTGGAGTGATCAAGAAATATGGAAAG TTGCAGATGAGGTTGGGCTCAGATCTGTGATAGAACAGTTTCCTGGGAAGCTTGACTTTGTCCT TGTGGATGGGGGCTGTGTCCTAAGCCATGGCCACAAGCAGTTGATGTGCTTGGCTAGATCTGTT CTCAGTAAGGCGAAGATCTTGCTGCTTGATGAACCCAGTGCTCATTTGGATCCAGTAACATACC AAATAATTAGAAGAACTCTAAAACAAGCATTTGCTGATTGCACAGTAATTCTCTGTGAACACAG GATAGAAGCAATGCTGGAATGCCAACAATTTTTGGTCATAGAAGAGAACAAAGTGCGGCAGTAC GATTCCATCCAGAAACTGCTGAACGAGAGGAGCCTCTTCCGGCAAGCCATCAGCCCCTCCGACA GGGTGAAGCTCTTTCCCCACCGGAACTCAAGCAAGTGCAAGTCTAAGCCCCAGATTGCTGCTCT GAAAGAGGAGACAGAAGAAGAGGTGCAAGATACAAGGCTTTAG

In an embodiment, to insert CFTR cDNA (e.g., CFTR exons 11 to 27) into intron 10, and concomitantly introduce a silent mutation to disrupt subsequent Cas9 binding and cleavage, the homology arms, e.g., the 5′ and 3′ homology arms, may be shorted to approximately 500 bp. The 5′ homology arm is shown as bold sequence, the CRISPR-Cas9 binding site is shown as italicized sequence, the PAM site is underlined, the silent sense mutation in the PAM is shown as lower case underlined sequence, and the 3′ homology arm is shown as no emphasis capitalized sequence.

(SEQ ID NO: 27343) GATGGTGGCTTGATCCAGGTAGTAGTGGAAGTAGTATAGTAGGAAGTGATCAGATTCAGGACAT GCTTTGAAGGAAGATCCAATAGGATTAATGGATAAGTTGAACAATGGCATATGAGAAAAGTCAC AGAGGAGTCAAAGATGATTCCAAGCTTTCTGGACTGAGTAACTGGAAGGATAAATGTGCCGTTT ACTAGAAAGATAATGGGAGAAACAGGTTTTGGATGGAGCTTGGTTTGGGAATATTAAGTTTGAA ATGCCTATTTGACATCCAAATAGAGATGTTAGTTGGATGTACAAGTCTAGTTTCAAGGAAGAGG GGGCTGGTAGTGTGAAGATGGGGCTGGATAAGATTCTAAAGGAAAGAGGGTTGATAAGAAGAGA AAGGGGTGTAGGGGTTAGCCTAAGGGCATTCTAAGTATTAGAGGTTAAGGAGGTGGGTGAAGAA AACCCAATAAAATAAAAGTCTGAGAAGACAAAGCTAGTGAATGAATGTGGTATCCCttAACCCA ACTGATGTCAAGCAGAAGGGTGTTATCAACTAGGTCAAATGCTCATTCATCAAGTAAGATGAAA CTGTTATAATTAACCGGTGTCTTCTGAAATACGGAGATAACTCGTGACTTAATGAAAGCAATAG TAGAGAAGGTCAAACTTGACCAGAATGAAATTAGAAAGAATAAGAGGAAAGAAAAGACCAAATA CAGACAACCATTGATGCCTTATTCTTTTGATATACTCCTGGAGTCCACTTGCTAATACAATTGA CCCTTAAACAATACAGGCTTGAACTGCATGGGTCCACTTATTTGTGAATTTTTTTTCAGTTAAT ACATTGGAAAATTTTTGGGGTTTTTTGACAATTTGAAAAAACTCACAAACTGTCTAGCCTAGAA ATACCGAGAAAATTAAGAAAAAGTAAGATATGCCATGAATGCATAAAATATATGTAGACACTAG CCTATTTTATCATTTGCTACTATAAAATATACACAATCTA

The underlined T has been changed from a G to T at that position so that wild-type CFTR is still transcribed, but the PAM sequence CGG has been modified to CTT to reduce or eliminate Cas9 cleavage at that locus.

V.2 NHEJ Approaches for Gene Targeting

As described herein, nuclease-induced non-homologous end-joining (NHEJ) can be used to target gene-specific knockouts. Nuclease-induced NHEJ can also be used to remove (e.g., delete) sequence insertions in a gene of interest.

While not wishing to be bound by theory, it is believed that, in an embodiment, the genomic alterations associated with the methods described herein rely on nuclease-induced NHEJ and the error-prone nature of the NHEJ repair pathway. NHEJ repairs a double-strand break in the DNA by joining together the two ends; however, generally, the original sequence is restored only if two compatible ends, exactly as they were formed by the double-strand break, are perfectly ligated. The DNA ends of the double-strand break are frequently the subject of enzymatic processing, resulting in the addition or removal of nucleotides, at one or both strands, prior to rejoining of the ends. This results in the presence of insertion and/or deletion (indel) mutations in the DNA sequence at the site of the NHEJ repair. Two-thirds of these mutations typically alter the reading frame and, therefore, produce a non-functional protein. Additionally, mutations that maintain the reading frame, but which insert or delete a significant amount of sequence, can destroy functionality of the protein. This is locus dependent as mutations in critical functional domains are likely less tolerable than mutations in non-critical regions of the protein.

The indel mutations generated by NHEJ are unpredictable in nature; however, at a given break site certain indel sequences are favored and are over represented in the population, likely due to small regions of microhomology. The lengths of deletions can vary widely; most commonly in the 1-50 bp range, but they can easily reach greater than 100-200 bp. Insertions tend to be shorter and often include short duplications of the sequence immediately surrounding the break site. However, it is possible to obtain large insertions, and in these cases, the inserted sequence has often been traced to other regions of the genome or to plasmid DNA present in the cells.

Because NHEJ is a mutagenic process, it can also be used to delete small sequence motifs as long as the generation of a specific final sequence is not required. If a double-strand break is targeted near to a short target sequence, the deletion mutations caused by the NHEJ repair often span, and therefore remove, the unwanted nucleotides. For the deletion of larger DNA segments, introducing two double-strand breaks, one on each side of the sequence, can result in NHEJ between the ends with removal of the entire intervening sequence. Both of these approaches can be used to delete specific DNA sequences; however, the error-prone nature of NHEJ may still produce indel mutations at the site of repair.

Both double strand cleaving eaCas9 molecules and single strand, or nickase, eaCas9 molecules can be used in the methods and compositions described herein to generate NHEJ-mediated indels. NHEJ-mediated indels targeted to the gene, e.g., a coding region, e.g., an early coding region of a gene of interest can be used to knockout (i.e., eliminate expression of) a gene of interest. For example, early coding region of a gene of interest includes sequence immediately following a transcription start site, within a first exon of the coding sequence, or within 500 bp of the transcription start site (e.g., less than 500, 450, 400, 350, 300, 250, 200, 150, 100 or 50 bp).

Placement of Double Strand or Single Strand Breaks Relative to the Target Position

In an embodiment, in which a gRNA and Cas9 nuclease generate a double strand break for the purpose of inducing NHEJ-mediated indels, a gRNA, e.g., a unimolecular (or chimeric) or modular gRNA molecule, is configured to position one double-strand break in close proximity to a nucleotide of the target position. In an embodiment, the cleavage site is between 0-30 bp away from the target position (e.g., less than 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 bp from the target position).

In an embodiment, in which two gRNAs complexing with Cas9 nickases induce two single strand breaks for the purpose of inducing NHEJ-mediated indels, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position two single-strand breaks to provide for NHEJ repair a nucleotide of the target position. In an embodiment, the gRNAs are configured to position cuts at the same position, or within a few nucleotides of one another, on different strands, essentially mimicking a double strand break. In an embodiment, the closer nick is between 0-30 bp away from the target position (e.g., less than 30, 25, 20, 15, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 bp from the target position), and the two nicks are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp). In an embodiment, the gRNAs are configured to place a single strand break on either side of a nucleotide of the target position.

Both double strand cleaving eaCas9 molecules and single strand, or nickase, eaCas9 molecules can be used in the methods and compositions described herein to generate breaks both sides of a target position. Double strand or paired single strand breaks may be generated on both sides of a target position to remove the nucleic acid sequence between the two cuts (e.g., the region between the two breaks in deleted). In one embodiment, two gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double-strand break on both sides of a target position. In an alternate embodiment, three gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to position a double strand break (i.e., one gRNA complexes with a cas9 nuclease) and two single strand breaks or paired single stranded breaks (i.e., two gRNAs complex with Cas9 nickases) on either side of the target position. In another embodiment, four gRNAs, e.g., independently, unimolecular (or chimeric) or modular gRNA, are configured to generate two pairs of single stranded breaks (i.e., two pairs of two gRNAs complex with Cas9 nickases) on either side of the target position. The double strand break(s) or the closer of the two single strand nicks in a pair will ideally be within 0-500 bp of the target position (e.g., no more than 450, 400, 350, 300, 250, 200, 150, 100, 50 or 25 bp from the target position). When nickases are used, the two nicks in a pair are within 25-55 bp of each other (e.g., between 25 to 50, 25 to 45, 25 to 40, 25 to 35, 25 to 30, 50 to 55, 45 to 55, 40 to 55, 35 to 55, 30 to 55, 30 to 50, 35 to 50, 40 to 50, 45 to 50, 35 to 45, or 40 to 45 bp) and no more than 100 bp away from each other (e.g., no more than 90, 80, 70, 60, 50, 40, 30, 20 or 10 bp).

V.3 Single-Strand Annealing

Single strand annealing (SSA) is another DNA repair process that repairs a double-strand break between two repeat sequences present in a target nucleic acid. Repeat sequences utilized by the SSA pathway are generally greater than 30 nucleotides in length. Resection at the break ends occurs to reveal repeat sequences on both strands of the target nucleic acid. After resection, single strand overhangs containing the repeat sequences are coated with RPA protein to prevent the repeats sequences from inappropriate annealing, e.g., to themselves. RAD52 binds to and each of the repeat sequences on the overhangs and aligns the sequences to enable the annealing of the complementary repeat sequences. After annealing, the single-strand flaps of the overhangs are cleaved. New DNA synthesis fills in any gaps, and ligation restores the DNA duplex. As a result of the processing, the DNA sequence between the two repeats is deleted. The length of the deletion can depend on many factors including the location of the two repeats utilized, and the pathway or processivity of the resection.

In contrast to HDR pathways, SSA does not require a template nucleic acid to alter or correct a target nucleic acid sequence. Instead, the complementary repeat sequence is utilized.

V.4 Other DNA Repair Pathways

SSBR (Single Strand Break Repair)

Single-stranded breaks (SSB) in the genome are repaired by the SSBR pathway, which is a distinct mechanism from the DSB repair mechanisms discussed above. The SSBR pathway has four major stages: SSB detection, DNA end processing, DNA gap filling, and DNA ligation. A more detailed explanation is given in Caldecott, Nature Reviews Genetics 9, 619-631 (August 2008), and a summary is given here.

In the first stage, when a SSB forms, PARP1 and/or PARP2 recognize the break and recruit repair machinery. The binding and activity of PARP1 at DNA breaks is transient and it seems to accelerate SSBr by promoting the focal accumulation or stability of SSBr protein complexes at the lesion. Arguably the most important of these SSBr proteins is XRCC1, which functions as a molecular scaffold that interacts with, stabilizes, and stimulates multiple enzymatic components of the SSBr process including the protein responsible for cleaning the DNA 3′ and 5′ ends. For instance, XRCC1 interacts with several proteins (DNA polymerase beta, PNK, and three nucleases, APE1, APTX, and APLF) that promote end processing. APE1 has endonuclease activity. APLF exhibits endonuclease and 3′ to 5′ exonuclease activities. APTX has endonuclease and 3′ to 5′ exonuclease activity.

This end processing is an important stage of SSBR since the 3′- and/or 5′-termini of most, if not all, SSBs are ‘damaged’. End processing generally involves restoring a damaged 3′-end to a hydroxylated state and and/or a damaged 5′ end to a phosphate moiety, so that the ends become ligation-competent. Enzymes that can process damaged 3′ termini include PNKP, APE1, and TDP1. Enzymes that can process damaged 5′ termini include PNKP, DNA polymerase beta, and APTX. LIG3 (DNA ligase III) can also participate in end processing. Once the ends are cleaned, gap filling can occur.

At the DNA gap filling stage, the proteins typically present are PARP1, DNA polymerase beta, XRCC1, FEN1 (flap endonuclease 1), DNA polymerase delta/epsilon, PCNA, and LIG1. There are two ways of gap filling, the short patch repair and the long patch repair. Short patch repair involves the insertion of a single nucleotide that is missing. At some SSBs, “gap filling” might continue displacing two or more nucleotides (displacement of up to 12 bases have been reported). FEN1 is an endonuclease that removes the displaced 5′-residues. Multiple DNA polymerases, including Pol β, are involved in the repair of SSBs, with the choice of DNA polymerase influenced by the source and type of SSB.

In the fourth stage, a DNA ligase such as LIG1 (Ligase I) or LIG3 (Ligase III) catalyzes joining of the ends. Short patch repair uses Ligase III and long patch repair uses Ligase I.

Sometimes, SSBR is replication-coupled. This pathway can involve one or more of CtIP, MRN, ERCC1, and FEN1. Additional factors that may promote SSBR include: aPARP, PARP1, PARP2, PARG, XRCC1, DNA polymerase b, DNA polymerase d, DNA polymerase e, PCNA, LIG1, PNK, PNKP, APE1, APTX, APLF, TDP1, LIG3, FEN1, CtIP, MRN, and ERCC1.

MMR (Mismatch Repair)

Cells contain three excision repair pathways: MMR, BER, and NER. The excision repair pathways hace a common feature in that they typically recognize a lesion on one strand of the DNA, then exo/endonucleaseases remove the lesion and leave a 1-30 nucleotide gap that is sub-sequentially filled in by DNA polymerase and finally sealed with ligase. A more complete picture is given in Li, Cell Research (2008) 18:85-98, and a summary is provided here.

Mismatch repair (MMR) operates on mispaired DNA bases.

The MSH2/6 or MSH2/3 complexes both have ATPases activity that plays an important role in mismatch recognition and the initiation of repair. MSH2/6 preferentially recognizes base-base mismatches and identifies mispairs of 1 or 2 nucleotides, while MSH2/3 preferentially recognizes larger ID mispairs.

hMLH1 heterodimerizes with hPMS2 to form hMutL a which possesses an ATPase activity and is important for multiple steps of MMR. It possesses a PCNA/replication factor C (RFC)-dependent endonuclease activity which plays an important role in 3′ nick-directed MMR involving EXO1. (EXO1 is a participant in both HR and MMR.) It regulates termination of mismatch-provoked excision. Ligase I is the relevant ligase for this pathway. Additional factors that may promote MMR include: EXO1, MSH2, MSH3, MSH6, MLH1, PMS2, MLH3, DNA Pol d, RPA, HMGB1, RFC, and DNA ligase I.

Base Excision Repair (BER)

The base excision repair (BER) pathway is active throughout the cell cycle; it is responsible primarily for removing small, non-helix-distorting base lesions from the genome. In contrast, the related Nucleotide Excision Repair pathway (discussed in the next section) repairs bulky helix-distorting lesions. A more detailed explanation is given in Caldecott, Nature Reviews Genetics 9, 619-631 (August 2008), and a summary is given here.

Upon DNA base damage, base excision repair (BER) is initiated and the process can be simplified into five major steps: (a) removal of the damaged DNA base; (b) incision of the subsequent a basic site; (c) clean-up of the DNA ends; (d) insertion of the correct nucleotide into the repair gap; and (e) ligation of the remaining nick in the DNA backbone. These last steps are similar to the SSBR.

In the first step, a damage-specific DNA glycosylase excises the damaged base through cleavage of the N-glycosidic bond linking the base to the sugar phosphate backbone. Then AP endonuclease-1 (APE1) or bifunctional DNA glycosylases with an associated lyase activity incised the phosphodiester backbone to create a DNA single strand break (SSB). The third step of BER involves cleaning-up of the DNA ends. The fourth step in BER is conducted by Pol R that adds a new complementary nucleotide into the repair gap and in the final step XRCC1/Ligase III seals the remaining nick in the DNA backbone. This completes the short-patch BER pathway in which the majority (80%) of damaged DNA bases are repaired. However, if the 5′-ends in step 3 are resistant to end processing activity, following one nucleotide insertion by Pol β there is then a polymerase switch to the replicative DNA polymerases, Pol δ/ε, which then add ˜2-8 more nucleotides into the DNA repair gap. This creates a 5′-flap structure, which is recognized and excised by flap endonuclease-1 (FEN-1) in association with the processivity factor proliferating cell nuclear antigen (PCNA). DNA ligase I then seals the remaining nick in the DNA backbone and completes long-patch BER. Additional factors that may promote the BER pathway include: DNA glycosylase, APE1, Polb, Pold, Pole, XRCC1, Ligase III, FEN-1, PCNA, RECQL4, WRN, MYH, PNKP, and APTX.

Nucleotide Excision Repair (NER)

Nucleotide excision repair (NER) is an important excision mechanism that removes bulky helix-distorting lesions from DNA. Additional details about NER are given in Marteijn et al., Nature Reviews Molecular Cell Biology 15, 465-481 (2014), and a summary is given here. NER a broad pathway encompassing two smaller pathways: global genomic NER (GG-NER) and transcription coupled repair NER (TC-NER). GG-NER and TC-NER use different factors for recognizing DNA damage. However, they utilize the same machinery for lesion incision, repair, and ligation.

Once damage is recognized, the cell removes a short single-stranded DNA segment that contains the lesion. Endonucleases XPF/ERCC1 and XPG (encoded by ERCC5) remove the lesion by cutting the damaged strand on either side of the lesion, resulting in a single-strand gap of 22-30 nucleotides. Next, the cell performs DNA gap filling synthesis and ligation. Involved in this process are: PCNA, RFC, DNA Pol δ, DNA Pol ε or DNA Pol κ, and DNA ligase I or XRCC1/Ligase III. Replicating cells tend to use DNA pol ε and DNA ligase I, while non-replicating cells tend to use DNA Pol δ, DNA Pol κ, and the XRCC1/Ligase III complex to perform the ligation step.

NER can involve the following factors: XPA-G, POLH, XPF, ERCC1, XPA-G, and LIG1. Transcription-coupled NER (TC-NER) can involve the following factors: CSA, CSB, XPB, XPD, XPG, ERCC1, and TTDA. Additional factors that may promote the NER repair pathway include XPA-G, POLH, XPF, ERCC1, XPA-G, LIG1, CSA, CSB, XPA, XPB, XPC, XPD, XPF, XPG, TTDA, UVSSA, USP7, CETN2, RAD23B, UV-DDB, CAK subcomplex, RPA, and PCNA.

Interstrand Crosslink (ICL)

A dedicated pathway called the ICL repair pathway repairs interstrand crosslinks. Interstrand crosslinks, or covalent crosslinks between bases in different DNA strand, can occur during replication or transcription. ICL repair involves the coordination of multiple repair processes, in particular, nucleolytic activity, translesion synthesis (TLS), and HDR. Nucleases are recruited to excise the ICL on either side of the crosslinked bases, while TLS and HDR are coordinated to repair the cut strands. ICL repair can involve the following factors: endonucleases, e.g., XPF and RAD51C, endonucleases such as RAD51, translesion polymerases, e.g., DNA polymerase zeta and Rev1), and the Fanconi anemia (FA) proteins, e.g., FancJ.

Other Pathways

Several other DNA repair pathways exist in mammals.

Translesion synthesis (TLS) is a pathway for repairing a single stranded break left after a defective replication event and involves translesion polymerases, e.g., DNA pol□ and Rev1.

Error-free postreplication repair (PRR) is another pathway for repairing a single stranded break left after a defective replication event.

V.5 Targeted Knockdown

Unlike CRISPR/Cas-mediated gene knockout, which permanently eliminates expression by mutating the gene at the DNA level, CRISPR/Cas knockdown allows for temporary reduction of gene expression through the use of artificial transcription factors. Mutating key residues in both DNA cleavage domains of the Cas9 protein (e.g. the D10A and H840A mutations) results in the generation of a catalytically inactive Cas9 (eiCas9 which is also known as dead Cas9 or dCas9) molecule. A catalytically inactive Cas9 complexes with a gRNA and localizes to the DNA sequence specified by that gRNA's targeting domain, however, it does not cleave the target DNA. Fusion of the dCas9 to an effector domain, e.g., a transcription repression domain, enables recruitment of the effector to any DNA site specified by the gRNA. Although an enzymatically inactive (eiCas9) Cas9 molecule itself can block transcription when recruited to early regions in the coding sequence, more robust repression can be achieved by fusing a transcriptional repression domain (for example KRAB, SID or ERD) to the Cas9 and recruiting it to the target knockdown position, e.g., within 1000 bp of sequence 3′ of the start codon or within 500 bp of a promoter region 5′ of the start codon of a gene. It is likely that targeting DNAseI hypersensitive sites (DHSs) of the promoter may yield more efficient gene repression or activation because these regions are more likely to be accessible to the Cas9 protein and are also more likely to harbor sites for endogenous transcription factors. Especially for gene repression, it is contemplated herein that blocking the binding site of an endogenous transcription factor would aid in downregulating gene expression. In an embodiment, one or more eiCas9 molecules may be used to block binding of one or more endogenous transcription factors. In another embodiment, an eiCas9 molecule can be fused to a chromatin modifying protein. Altering chromatin status can result in decreased expression of the target gene. One or more eiCas9 molecules fused to one or more chromatin modifying proteins may be used to alter chromatin status.

In an embodiment, a gRNA molecule can be targeted to a known transcription response elements (e.g., promoters, enhancers, etc.), a known upstream activating sequences (UAS), and/or sequences of unknown or known function that are suspected of being able to control expression of the target DNA.

CRISPR/Cas-mediated gene knockdown can be used to reduce expression of an unwanted allele or transcript. Contemplated herein are scenarios wherein permanent destruction of the gene is not ideal. In these scenarios, site-specific repression may be used to temporarily reduce or eliminate expression. It is also contemplated herein that the off-target effects of a Cas-repressor may be less severe than those of a Cas-nuclease as a nuclease can cleave any DNA sequence and cause mutations whereas a Cas-repressor may only have an effect if it targets the promoter region of an actively transcribed gene. However, while nuclease-mediated knockout is permanent, repression may only persist as long as the Cas-repressor is present in the cells. Once the repressor is no longer present, it is likely that endogenous transcription factors and gene regulatory elements would restore expression to its natural state.

V.6 Examples of gRNAs in Genome Editing Methods

gRNA molecules as described herein can be used with Cas9 molecules that generate a double strand break or a single strand break to alter the sequence of a target nucleic acid, e.g., a target position or target genetic signature. gRNA molecules useful in these methods are described below.

In an embodiment, the gRNA, e.g., a chimeric gRNA, is configured such that it comprises one or more of the following properties;

    • a) it can position, e.g., when targeting a Cas9 molecule that makes double strand breaks, a double strand break (i) within 50, 100, 150 or 200 nucleotides of a target position, or (ii) sufficiently close that the target position is within the region of end resection;
    • b) it has a targeting domain of at least 17 nucleotides, e.g., a targeting domain of (i) 17, (ii) 18, or (iii) 20 nucleotides; and
    • c)
      • (i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; or, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom; or
      • (v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain.

In an embodiment, the gRNA is configured such that it comprises properties: a and b(i).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(ii).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(iii).

In an embodiment, the gRNA is configured such that it comprises properties: a and c.

In an embodiment, the gRNA is configured such that in comprises properties: a, b, and c.

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(ii).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(ii).

In an embodiment, the gRNA, e.g., a chimeric gRNA, is configured such that it comprises one or more of the following properties;

    • a) it can position, e.g., when targeting a Cas9 molecule that makes single strand breaks, a single strand break (i) within 50, 100, 150 or 200 nucleotides of a target position, or (ii) sufficiently close that the target position is within the region of end resection;
    • b) it has a targeting domain of at least 17 nucleotides, e.g., a targeting domain of (i) 17, (ii) 18, or (iii) 20 nucleotides; and
    • c)
      • (i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; or, a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom; or
      • (v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain.

In an embodiment, the gRNA is configured such that it comprises properties: a and b(i).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(ii).

In an embodiment, the gRNA is configured such that it comprises properties: a and b(iii).

In an embodiment, the gRNA is configured such that it comprises properties: a and c.

In an embodiment, the gRNA is configured such that in comprises properties: a, b, and c.

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(i), and c(ii).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(i).

In an embodiment, the gRNA is configured such that in comprises properties: a(i), b(iii), and c(ii).

In an embodiment, the gRNA is used with a Cas9 nickase molecule having HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D10, e.g., the D10A mutation.

In an embodiment, the gRNA is used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at H840, e.g., a H840A.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at N863, e.g., an N863A mutation.

In an embodiment, a pair of gRNAs, e.g., a pair of chimeric gRNAs, comprising a first and a second gRNA, is configured such that they comprises one or more of the following properties;

    • a) one or both of the gRNAs can position, e.g., when targeting a Cas9 molecule that makes single strand breaks, a single strand break within (i) 50, 100, 150 or 200 nucleotides of a target position, or (ii) sufficiently close that the target position is within the region of end resection;
    • b) one or both have a targeting domain of at least 17 nucleotides, e.g., a targeting domain of (i) 17 or (ii) 18 nucleotides;
    • c) for one or both:
      • (i) the proximal and tail domain, when taken together, comprise at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail and proximal domain, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (ii) there are at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides 3′ to the last nucleotide of the second complementarity domain, e.g., at least 15, 18, 20, 25, 30, 31, 35, 40, 45, 49, 50, or 53 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (iii) there are at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides 3′ to the last nucleotide of the second complementarity domain that is complementary to its corresponding nucleotide of the first complementarity domain, e.g., at least 16, 19, 21, 26, 31, 32, 36, 41, 46, 50, 51, or 54 nucleotides from the corresponding sequence of a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis gRNA, or a sequence that differs by no more than 1, 2, 3, 4, 5; 6, 7, 8, 9 or 10 nucleotides therefrom;
      • (iv) the tail domain is at least 10, 15, 20, 25, 30, 35 or 40 nucleotides in length, e.g., it comprises at least 10, 15, 20, 25, 30, 35 or 40 nucleotides from a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain; or, or a sequence that differs by no more than 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 nucleotides therefrom; or
      • (v) the tail domain comprises 15, 20, 25, 30, 35, 40 nucleotides or all of the corresponding portions of a naturally occurring tail domain, e.g., a naturally occurring S. pyogenes, S. thermophilus, S. aureus, or N. meningitidis tail domain;
    • d) the gRNAs are configured such that, when hybridized to target nucleic acid, they are separated by 0-50, 0-100, 0-200, at least 10, at least 20, at least 30 or at least 50 nucleotides;
    • e) the breaks made by the first gRNA and second gRNA are on different strands; and
    • f) the PAMs are facing outwards.

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(i).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(ii).

In an embodiment, one or both of the gRNAs is configured such that it comprises properties: a and b(iii).

In an embodiment, one or both of the gRNAs configured such that it comprises properties: a and c.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a, b, and c.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), and c(i).

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), c, and d.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), c, and e.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(i), c, d, and e.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), and c(i).

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), and c(ii).

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), c, and d.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), c, and e.

In an embodiment, one or both of the gRNAs is configured such that in comprises properties: a(i), b(iii), c, d, and e.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having HNH activity, e.g., a Cas9 molecule having the RuvC activity inactivated, e.g., a Cas9 molecule having a mutation at D10, e.g., the D10A mutation.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at H840, e.g., a H840A.

In an embodiment, the gRNAs are used with a Cas9 nickase molecule having RuvC activity, e.g., a Cas9 molecule having the HNH activity inactivated, e.g., a Cas9 molecule having a mutation at N863, e.g., a N863A mutation.

VI. Target Cells

Cas9 molecules, gRNA molecules (e.g., a Cas9 molecule/gRNA molecule complex), and donor nucleic acids can be used to manipulate a cell, e.g., to edit a target nucleic acid, in a wide variety of cells.

In an embodiment, a cell is manipulated by editing (e.g., correcting or introducing a mutation in) the CFTR and/or SCNN1A target genes, e.g., as described herein. In an embodiment, the expression of the CFTR and/or SCNN1A target genes is modulated, e.g., in vivo.

In another embodiment, the expression of the CFTR and/or SCNN1A target genes is modulated, e.g., ex vivo.

The Cas9 and gRNA molecules described herein can be delivered to a target cell. Methods and compositions discussed herein, provide for treating or delaying the onset or progression of diseases of the lung and airways, including the nose, trachea, bronchus, bronchioles, alveoli, submucosal ducts and submucosal glands. In an embodiment, the target cell is an airway cell, e.g., a nasal epithelial cell, e.g., a tracheal epithelial cell. In an embodiment, the target cell is a lung epithelial cell, e.g., a bronchial epithelial cell, e.g., a proximal bronchial epithelial cell, e.g., a bronchiolar epithelial cell, e.g., an alveolar epithelial cell, e.g., a clara cell, e.g., a ciliated cell, e.g., a goblet cell, e.g., a basal cell, e.g., an acinus cell. Methods and compositions discussed herein, provide for treating or delaying the onset or progression of diseases of the gastrointestinal tract, including pancreas, bile ducts, gallbladder, small intestine, large intestine and salivary glands. In an embodiment, the target cell is a gastrointestinal epithelial cell. In an embodiment, the target cell is a biliary epithelial cell. In an embodiment, the target cell is a pancreatic ductal epithelial cell. In an embodiment, the target cell is a gastrointestinal cell, e.g., an enteroendocrine cell, e.g., a Brunner's gland cell. In an embodiment, the target cell is a hepatobiliary epithelial cell. In an embodiment, the target cell is a gallbladder epithelial cell. In an embodiment, the target cell is a large intestine epithelial cell. In an embodiment, the target cell is a small intestine epithelial cell. In an embodiment, the target cell is a jejunum epithelial cell. In an embodiment, the target cell is an epithelial cell of the iluem. In an embodiment, the target cell is a duodenum epithelial cell. Methods and compositions discussed herein, provide for treating or delaying the onset or progression of diseases of the reproductive tract, including the epididymis. In an embodiment, the target cell is a reproductive epithelial cell, e.g. an epididymal epithelial cell. In an embodiment, the target cell is a pulmonary stem cell. In an embodiment, the target cell is a gastrointestinal stem cell.

In an embodiment, the target cell is manipulated ex vivo by editing (e.g., correcting or introducing a mutation in) the CFTR and/or SCNN1A target genes and/or modulating the expression of the CFTR and/or SCNN1A target genes, and administered to the subject. A suitable cell for such manipulation can include a stem cell such as, by way of example, an embryonic stem cell, an induced pluripotent stem cell, a pulmonary stem cell, a gastrointestinal stem cell and a mesenchymal stem cell. In an embodiment, the cell is an induced pluripotent stem cell (iPS) cell or a cell derived from an iPS cell, e.g., an iPS cell generated from the subject, modified to correct or introduce the mutation and differentiated into a clinically relevant cell such as a pulmonary stem cell, a gastrointestinal stem cell, a pulmonary epithelial cell, a bronchial epithelial cell, a proximal bronchial epithelial cell, a bronchiolar epithelial cell, an alveolar epithelial cell, a clara cell, a ciliated cell, a goblet cell, a basal cell, an acinus cell, a gastrointestinal epithelial cell, a biliary epithelial cell, a pancreatic ductal epithelial cell, a hepatobiliary epithelial cell, an enteroendocrine cell, a Brunner's gland cell, a reproductive epithelial cell, or an epididymal epithelial cell.

VII. Delivery, Formulations and Routes of Administration

The components, e.g., a Cas9 molecule and gRNA molecule (e.g., a Cas9 molecule/gRNA molecule complex), and a donor template nucleic acid can be delivered or formulated in a variety of forms, see, e.g., Tables 56-57. In an embodiment, one Cas9 molecule and two or more (e.g., 2, 3, 4, or more) different gRNA molecules are delivered, e.g., by an AAV vector. In an embodiment, the sequence encoding the Cas9 molecule and the sequence(s) encoding the two or more (e.g., 2, 3, 4, or more) different gRNA molecules are present on the same nucleic acid molecule, e.g., an AAV vector. When a Cas9 or gRNA component is encoded as DNA for delivery, the DNA will typically but not necessarily include a control region, e.g., comprising a promoter, to effect expression. Useful promoters for Cas9 molecule sequences include CMV, EFS, EF-1a, MSCV, PGK, CAG control promoters. In an embodiment, the promoter is a constitutive promoter. In another embodiment, the promoter is a tissue specific promoter. Useful promoters for gRNAs include H1, 7SK, tRNA and U6 promoters. Promoters with similar or dissimilar strengths can be selected to tune the expression of components. Sequences encoding a Cas9 molecule can comprise a nuclear localization signal (NLS), e.g., an SV40 NLS. In an embodiment, the sequence encoding a Cas9 molecule comprises at least two nuclear localization signals. In an embodiment a promoter for a Cas9 molecule or a gRNA molecule can be, independently, inducible, tissue specific, or cell specific.

Table 56 provides examples of how the components can be formulated, delivered, or administered.

TABLE 56 Elements Donor Cas9 gRNA Template Molecule(s) Molecule(s) Nucleic Acid Comments DNA DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, and a gRNA are transcribed from DNA. In this embodiment, they are encoded on separate molecules. In this embodiment, the donor template is provided as a separate DNA molecule. DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, and a gRNA are transcribed from DNA. In this embodiment, they are encoded on separate molecules. In this embodiment, the donor template is provided on the same DNA molecule that encodes the gRNA. DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, and a gRNA are transcribed from DNA, here from a single molecule. In this embodiment, the donor template is provided as a separate DNA molecule. DNA DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, and a gRNA are transcribed from DNA. In this embodiment, they are encoded on separate molecules. In this embodiment, the donor template is provided on the same DNA molecule that encodes the Cas9. DNA RNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is transcribed from DNA, and a gRNA is provided as in vitro transcribed or synthesized RNA. In this embodiment, the donor template is provided as a separate DNA molecule. DNA RNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is transcribed from DNA, and a gRNA is provided as in vitro transcribed or synthesized RNA. In this embodiment, the donor template is provided on the same DNA molecule that encodes the Cas9. mRNA RNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is translated from in vitro transcribed mRNA, and a gRNA is provided as in vitro transcribed or synthesized RNA. In this embodiment, the donor template is provided as a DNA molecule. mRNA DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is translated from in vitro transcribed mRNA, and a gRNA is transcribed from DNA. In this embodiment, the donor template is provided as a separate DNA molecule. mRNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is translated from in vitro transcribed mRNA, and a gRNA is transcribed from DNA. In this embodiment, the donor template is provided on the same DNA molecule that encodes the gRNA. Protein DNA DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is provided as a protein, and a gRNA is transcribed from DNA. In this embodiment, the donor template is provided as a separate DNA molecule. Protein DNA In this embodiment, a Cas9 molecule, typically an eaCas9 molecule, is provided as a protein, and a gRNA is transcribed from DNA. In this embodiment, the donor template is provided on the same DNA molecule that encodes the gRNA. Protein RNA DNA In this embodiment, an eaCas9 molecule is provided as a protein, and a gRNA is provided as transcribed or synthesized RNA. In this embodiment, the donor template is provided as a DNA molecule.

Table 57 summarizes various delivery methods for the components of a Cas system, e.g., the Cas9 molecule component and the gRNA molecule component, as described herein.

TABLE 57 Delivery into Non- Duration Type of Delivery Dividing of Genome Molecule Vector/Mode Cells Expression Integration Delivered Physical (eg, YES Transient NO Nucleic electroporation, Acids particle gun, Calcium and Phosphate transfection, Proteins cell compression or squeezing)) Viral Retrovirus NO Stable YES RNA Lentivirus YES Stable YES/NO with RNA modifications Adenovirus YES Transient NO DNA Adeno- YES Stable NO DNA Associated Virus (AAV) Vaccinia YES Very NO DNA Virus Transient Herpes YES Stable NO DNA Simplex Virus Non-Viral Cationic YES Transient Depends on Nucleic Liposomes what is Acids delivered and Proteins Polymeric YES Transient Depends on Nucleic Nanoparticles what is Acids delivered and Proteins Biological Attenuated YES Transient NO Nucleic Non-Viral Bacteria Acids Delivery Engineered YES Transient NO Nucleic Vehicles Bacterio- Acids phages Mammalian YES Transient NO Nucleic Virus-like Acids Particles Biological YES Transient NO Nucleic liposomes: Acids Erythrocyte Ghosts and Exosomes

DNA-Based Delivery of a Cas9 Molecule and/or One or More gRNA Molecule

Nucleic acids encoding Cas9 molecules (e.g., eaCas9 molecules), gRNA molecules, a donor template nucleic acid, or a combination thereof, can be administered to subjects or delivered into cells by art-known methods or as described herein. For example, Cas9-encoding and/or gRNA-encoding DNA, as well as donor nucleic acids can be delivered, e.g., by vectors (e.g., viral or non-viral vectors), non-vector based methods (e.g., using naked DNA or DNA complexes), or a combination thereof.

DNA encoding Cas9 molecules (e.g., eaCas9 molecules) and/or gRNA molecules, as well as template nucleic acids, can be conjugated to molecules (e.g., N-acetylgalactosamine), thereby promoting uptake by the target cells (e.g., the target cells described herein).

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a vector (e.g., viral vector/virus or plasmid). In some embodiments the donor nucleic acid is delivered by a vector (e.g., a viral vector/virus or plasmid).

A vector can comprise a sequence that encodes a Cas9 molecule and/or a gRNA molecule. A vector can comprise a donor nucleic acid. A vector can also comprise a sequence encoding a signal peptide (e.g., for nuclear localization, nucleolar localization, mitochondrial localization), fused, e.g., to a Cas9 molecule sequence. For example, ae vector can comprise a nuclear localization sequence (e.g., from SV40) fused to the sequence encoding the Cas9 molecule.

One or more regulatory/control elements, e.g., a promoter, an enhancer, an intron, a polyadenylation signal, a Kozak consensus sequence, internal ribosome entry sites (IRES), a 2A sequence, and splice acceptor or donor can be included in the vectors. In some embodiments, the promoter is recognized by RNA polymerase II (e.g., a CMV promoter). In other embodiments, the promoter is recognized by RNA polymerase III (e.g., a U6 promoter). In some embodiments, the promoter is a regulated promoter (e.g., inducible promoter). In other embodiments, the promoter is a constitutive promoter. In some embodiments, the promoter is a tissue specific promoter. In some embodiments, the promoter is a viral promoter. In other embodiments, the promoter is a non-viral promoter.

In some embodiments, the vector or delivery vehicle is a viral vector (e.g., for generation of recombinant viruses). In some embodiments, the virus is a DNA virus (e.g., dsDNA or ssDNA virus). In other embodiments, the virus is an RNA virus (e.g., an ssRNA virus). Exemplary viral vectors/viruses include, e.g., retroviruses, lentiviruses, adenovirus, adeno-associated virus (AAV), vaccinia viruses, poxviruses, and herpes simplex viruses.

In some embodiments, the virus infects dividing cells. In other embodiments, the virus infects non-dividing cells. In some embodiments, the virus infects both dividing and non-dividing cells. In some embodiments, the virus can integrate into the host genome. In some embodiments, the virus is engineered to have reduced immunity, e.g., in human. In some embodiments, the virus is replication-competent. In other embodiments, the virus is replication-defective, e.g., having one or more coding regions for the genes necessary for additional rounds of virion replication and/or packaging replaced with other genes or deleted. In some embodiments, the virus causes transient expression of the Cas9 molecule and/or the gRNA molecule. In other embodiments, the virus causes long-lasting, e.g., at least 1 week, 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 1 year, 2 years, or permanent expression, of the Cas9 molecule and/or the gRNA molecule. The packaging capacity of the viruses may vary, e.g., from at least about 4 kb to at least about 30 kb, e.g., at least about 5 kb, 10 kb, 15 kb, 20 kb, 25 kb, 30 kb, 35 kb, 40 kb, 45 kb, or 50 kb.

In an embodiment, the viral vector recognizes a specific cell type or tissue. For example, the viral vector can be pseudotyped with a different/alternative viral envelope glycoprotein; engineered with a cell type-specific receptor (e.g., genetic modification(s) of one or more viral envelope glycoproteins to incorporate a targeting ligand such as a peptide ligand, a single chain antibody, or a growth factor); and/or engineered to have a molecular bridge with dual specificities with one end recognizing a viral glycoprotein and the other end recognizing a moiety of the target cell surface (e.g., a ligand-receptor, monoclonal antibody, avidin-biotin and chemical conjugation).

Exemplary viral vectors/viruses include, e.g., retroviruses, lentiviruses, adenovirus, adeno-associated virus (AAV), vaccinia viruses, poxviruses, and herpes simplex viruses.

In some embodiments, the Cas9- and/or gRNA-encoding sequence is delivered by a recombinant retrovirus. In some embodiments, the donor nucleic acid is delivered by a recombinant retrovirus. In some embodiments, the retrovirus (e.g., Moloney murine leukemia virus) comprises a reverse transcriptase, e.g., that allows integration into the host genome. In some embodiments, the retrovirus is replication-competent. In other embodiments, the retrovirus is replication-defective, e.g., having one of more coding regions for the genes necessary for additional rounds of virion replication and packaging replaced with other genes, or deleted.

In some embodiments, the Cas9- and/or gRNA-encoding sequence is delivered by a recombinant lentivirus. In some embodiments, the donor nucleic acid is delivered by a recombinant lentivirus. For example, the lentivirus is replication-defective, e.g., does not comprise one or more genes required for viral replication.

In some embodiments, the Cas9- and/or gRNA-encoding sequence is delivered by a recombinant adenovirus. In some embodiments, the donor nucleic acid is delivered by a recombinant adenoviru. In some embodiments, the adenovirus is engineered to have reduced immunity in human.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a recombinant AAV. In some embodiments, the AAV does not incorporate its genome into that of a host cell, e.g., a target cell as describe herein. In some embodiments, the AAV can incorporate at least part of its genome into that of a host cell, e.g., a target cell as described herein. In some embodiments, the AAV is a self-complementary adeno-associated virus (scAAV), e.g., a scAAV that packages both strands which anneal together to form double stranded DNA. AAV serotypes that may be used in the disclosed methods, include AAV1, AAV2, modified AAV2 (e.g., modifications at Y444F, Y500F, Y730F and/or S662V), AAV3, modified AAV3 (e.g., modifications at Y705F, Y731F and/or T492V), AAV4, AAV5, AAV6, modified AAV6 (e.g., modifications at S663V and/or T492V), AAV8, AAV 8.2, AAV9, AAV rh 10, and pseudotyped AAV, such as AAV2/8, AAV2/5 and AAV2/6 can also be used in the disclosed methods. In an embodiment, an AAV capsid that can be used in the methods described herein is a capsid sequence from serotype AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV.rh8, AAV.rh10, AAV.rh32/33, AAV.rh43, AAV.rh64R1, or AAV7m8.

In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered in a re-engineered AAV capsid, e.g., with 50% or greater, e.g., 60% or greater, 70% or greater, 80% or greater, 90% or greater, or 95% or greater, sequence homology with a capsid sequence from serotypes AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV.rh8, AAV.rh10, AAV.rh32/33, AAV.rh43, or AAV.rh64R1.

In an embodiment, the Cas9- and/or gRNA-encoding DNA is delivered by a chimeric AAV capsid. In an embodiment, the donor nucleic acid is delivered by a chimeric AAV capsid. Exemplary chimeric AAV capsids include, but are not limited to, AAV9i1, AAV2i8, AAV-DJ, AAV2G9, AAV2i8G9, or AAV8G9.

In an embodiment, the AAV is a self-complementary adeno-associated virus (scAAV), e.g., a scAAV that packages both strands which anneal together to form double stranded DNA.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a hybrid virus, e.g., a hybrid of one or more of the viruses described herein. In an embodiment, the hybrid virus is hybrid of an AAV (e.g., of any AAV serotype), with a Bocavirus, B19 virus, porcine AAV, goose AAV, feline AAV, canine AAV, or MVM.

A Packaging cell is used to form a virus particle that is capable of infecting a target cell. Such a cell includes a 293 cell, which can package adenovirus, and a W2 cell or a PA317 cell, which can package retrovirus. A viral vector used in gene therapy is usually generated by a producer cell line that packages a nucleic acid vector into a viral particle. The vector typically contains the minimal viral sequences required for packaging and subsequent integration into a host or target cell (if applicable), with other viral sequences being replaced by an expression cassette encoding the protein to be expressed, eg. Cas9. For example, an AAV vector used in gene therapy typically only possesses inverted terminal repeat (ITR) sequences from the AAV genome which are required for packaging and gene expression in the host or target cell. The missing viral functions can be supplied in trans by the packaging cell line and/or plasmid containing E2A, E4, and VA genes from adenovirus, and plasmid encoding Rep and Cap genes from AAV, as described in “Triple Transfection Protocol.” Henceforth, the viral DNA is packaged in a cell line, which contains a helper plasmid encoding the other AAV genes, namely rep and cap, but lacking ITR sequences. In embodiment, the viral DNA is packaged in a producer cell line, which contains E1A and/or E1B genes from adenovirus. The cell line is also infected with adenovirus as a helper. The helper virus (e.g., adenovirus or HSV) or helper plasmid promotes replication of the AAV vector and expression of AAV genes from the helper plasmid with ITRs. The helper plasmid is not packaged in significant amounts due to a lack of ITR sequences. Contamination with adenovirus can be reduced by, e.g., heat treatment to which adenovirus is more sensitive than AAV.

In an embodiment, the viral vector has the ability of cell type and/or tissue type recognition. For example, the viral vector can be pseudotyped with a different/alternative viral envelope glycoprotein; engineered with a cell type-specific receptor (e.g., genetic modification of the viral envelope glycoproteins to incorporate targeting ligands such as a peptide ligand, a single chain antibodie, a growth factor); and/or engineered to have a molecular bridge with dual specificities with one end recognizing a viral glycoprotein and the other end recognizing a moiety of the target cell surface (e.g., ligand-receptor, monoclonal antibody, avidin-biotin and chemical conjugation).

In an embodiment, the viral vector achieves cell type specific expression. For example, a tissue-specific promoter can be constructed to restrict expression of the transgene (Cas 9 and gRNA) in only the target cell. The specificity of the vector can also be mediated by microRNA-dependent control of transgene expression. In an embodiment, the viral vector has increased efficiency of fusion of the viral vector and a target cell membrane. For example, a fusion protein such as fusion-competent hemagglutin (HA) can be incorporated to increase viral uptake into cells. In an embodiment, the viral vector has the ability of nuclear localization. For example, aviruse that requires the breakdown of the nuclear envelope (during cell division) and therefore will not infect a non-diving cell can be altered to incorporate a nuclear localization peptide in the matrix protein of the virus thereby enabling the transduction of non-proliferating cells.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a non-vector based method (e.g., using naked DNA or DNA complexes). For example, the DNA can be delivered, e.g., by organically modified silica or silicate (Ormosil), electroporation, transient cell compression or squeezing (e.g., as described in Lee, et al [2012] Nano Lett 12: 6322-27), gene gun, sonoporation, magnetofection, lipid-mediated transfection, dendrimers, inorganic nanoparticles, calcium phosphates, or a combination thereof.

In an embodiment, delivery via electroporation comprises mixing the cells with the Cas9- and/or gRNA-encoding DNA in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the Cas9- and/or gRNA-encoding DNA in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel.

In some embodiments, the Cas9- and/or gRNA-encoding DNA is delivered by a combination of a vector and a non-vector based method. In some embodiments, the donor nucleic acid is delivered by a combination of a vector and a non-vector based method. For example, a virosome comprises a liposome combined with an inactivated virus (e.g., HIV or influenza virus), which can result in more efficient gene transfer, e.g., in a respiratory epithelial cell than either a viral or a liposomal method alone.

In an embodiment, the delivery vehicle is a non-viral vector. In an embodiment, the non-viral vector is an inorganic nanoparticle. Exemplary inorganic nanoparticles include, e.g., magnetic nanoparticles (e.g., Fe3MnO2) or silica. The outer surface of the nanoparticle can be conjugated with a positively charged polymer (e.g., polyethylenimine, polylysine, polyserine) which allows for attachment (e.g., conjugation or entrapment) of payload. In an embodiment, the non-viral vector is an organic nanoparticle. Exemplary organic nanoparticles include, e.g., SNALP liposomes (e.g., SNALP liposomes that contain cationic lipids together with neutral helper lipids and polyethylene glycol (PEG)-conjugated lipids) and protamine-nucleic acid complexes, e.g., protamine-nucleic acid complexes coated with lipid coating.

Exemplary lipids for gene transfer are shown below in Table 58.

TABLE 58 Lipids Used for Gene Transfer Lipid Abbreviation Feature 1,2-Dioleoyl-sn-glycero-3-phosphatidylcholine DOPC Helper 1,2-Dioleoyl-sn-glycero-3-phosphatidyl- DOPE Helper ethanolamine Cholesterol Helper N-[1-(2,3-Dioleyloxy)proph- DOTMA Cationic yl]N,N,N-trimethylammonium chloride 1,2-Dioleoyloxy-3-trimethyl- DOTAP Cationic ammonium-propane Dioctadecylamidoglycylspermine DOGS Cationic N-(3-Aminopropyl)-N,N-dimeth- GAP-DLRIE Cationic yl-2,3-bis(dodecyloxy)-1-prop- anaminium bromide Cetyltrimethylammonium bromide CTAB Cationic 6-Lauroxyhexyl ornithinate LHON Cationic 1-(2,3-Dioleoyloxyprop- 2Oc Cationic yl)-2,4,6-trimethylpyridinium 2,3-Dioleyloxy-N-[2(sperminecarbox- DOSPA Cationic amido-ethyl]-N,N-dimethyl-1-prop- anaminium trifluoroacetate 1,2-Dioleyl-3-trimethylammonium-propane DOPA Cationic N-(2-Hydroxyethyl)-N,N-dimeth- MDRIE Cationic yl-2,3-bis(tetradecyloxy)-1-prop- anaminium bromide Dimyristooxypropyl dimethyl DMRI Cationic hydroxyethyl ammonium bromide 3β-[N-(N′,N′-Dimethylaminoeth- DC-Chol Cationic ane)-carbamoyl]cholesterol Bis-guanidium-tren-cholesterol BGTC Cationic 1,3-Diodeoxy-2-(6-carboxy-sperm- DOSPER Cationic yl)-propylamide Dimethyloctadecylammonium bromide DDAB Cationic Dioctadecylamidoglicylspermidin DSL Cationic rac-[(2,3-Dioctadecyloxypropyl)(2-hydroxy- CLIP-1 Cationic ethyl)]dimethylammonium chloride rac-[2(2,3-Dihexadecyloxypropyl- CLIP-6 Cationic oxymethyloxy)ethyl]trimethyl- ammonium bromide Ethyldimyristoylphosphatidylcholine EDMPC Cationic 1,2-Distearyloxy-N,N-dimeth- DSDMA Cationic yl-3-aminopropane 1,2-Dimyristoyl-trimethyl- DMTAP Cationic ammonium propane O,O′-Dimyristyl-N-lysyl aspartate DMKE Cationic 1,2-Distearoyl-sn-glycero-3-ethyl- DSEPC Cationic phosphocholine N-Palmitoyl D-erythro-sphingosyl CCS Cationic carbamoyl-spermine N-t-Butyl-N0-tetradecyl-3-tetradecyl- diC14-amidine Cationic aminopropionamidine Octadecenolyoxy[ethyl-2-heptadecen- DOTIM Cationic yl-3 hydroxyethyl] imidazolinium chloride N1-Cholesteryloxycarbon- CDAN Cationic yl-3,7-diazanonane-1,9-diamine 2-(3-[Bis(3-amino-propyl)-amino]propyl- RPR209120 Cationic amino)-N-ditetradecyl- carbamoylme-ethyl-acetamide 1,2-dilinoleyloxy-3-dimethylaminopropane DLinDMA Cationic 2,2-dilinoleyl-4-dimethylaminoeth- DLin-KC2- Cationic yl-[1,3]-dioxolane DMA dilinoleyl-methyl-4-dimethyl- DLin-MC3- Cationic aminobutyrate DMA

Exemplary polymers for gene transfer are shown below in Table 59.

TABLE 59 Polymers Used for Gene Transfer Polymer Abbreviation Poly(ethylene)glycol PEG Polyethylenimine PEI Dithiobis(succinimidylpropionate) DSP Dimethyl-3,3′-dithiobispropionimidate DTBP Poly(ethylene imine) biscarbamate PEIC Poly(L-lysine) PLL Histidine modified PLL Poly(N-vinylpyrrolidone) PVP Poly(propylenimine) PPI Poly(amidoamine) PAMAM Poly(amido ethylenimine) SS-PAEI Triethylenetetramine TETA Poly(β-aminoester) Poly(4-hydroxy-L-proline ester) PHP Poly(allylamine) Poly(α[4-aminobutyl]-L-glycolic acid) PAGA Poly(D,L-lactic-co-glycolic acid) PLGA Poly(N-ethyl-4-vinylpyridinium bromide) Poly(phosphazene)s PPZ Poly(phosphoester)s PPE Poly(phosphoramidate)s PPA Poly(N-2-hydroxypropylmethacrylamide) pHPMA Poly(2-(dimethylamino)ethyl methacrylate) pDMAEMA Poly(2-aminoethyl propylene phosphate) PPE-EA Chitosan Galactosylated chitosan N-Dodacylated chitosan Histone Collagen Dextran-spermine D-SPM

In an embodiment, the vehicle has targeting modifications to increase target cell update of nanoparticles and liposomes, e.g., cell specific antigens, monoclonal antibodies, single chain antibodies, aptamers, polymers, sugars, and cell penetrating peptides. In an embodiment, the vehicle uses fusogenic and endosome-destabilizing peptides/polymers. In an embodiment, the vehicle undergoes acid-triggered conformational changes (e.g., to accelerate endosomal escape of the cargo). In an embodiment, a stimuli-cleavable polymer is used, e.g., for release in a cellular compartment. For example, disulfide-based cationic polymers that are cleaved in the reducing cellular environment can be used.

In an embodiment, the delivery vehicle is a biological non-viral delivery vehicle. In an embodiment, the vehicle is an attenuated bacterium (e.g., naturally or artificially engineered to be invasive but attenuated to prevent pathogenesis and expressing the transgene (e.g., Listeria monocytogenes, certain Salmonella strains, Bifidobacterium longum, and modified Escherichia coli), bacteria having nutritional and tissue-specific tropism to target specific tissues, bacteria having modified surface proteins to alter target tissue specificity). In an embodiment, the vehicle is a genetically modified bacteriophage (e.g., engineered phages having large packaging capacity, less immunogenic, containing mammalian plasmid maintenance sequences and having incorporated targeting ligands). In an embodiment, the vehicle is a mammalian virus-like particle. For example, modified viral particles can be generated (e.g., by purification of the “empty” particles followed by ex vivo assembly of the virus with the desired cargo). The vehicle can also be engineered to incorporate targeting ligands to alter target tissue specificity. In an embodiment, the vehicle is a biological liposome. For example, the biological liposome is a phospholipid-based particle derived from human cells (e.g., erythrocyte ghosts, which are red blood cells broken down into spherical structures derived from the subject (e.g., tissue targeting can be achieved by attachment of various tissue or cell-specific ligands), or secretory exosomes—subject (i.e., patient) derived membrane-bound nanovesicle (30-100 nm) of endocytic origin (e.g., can be produced from various cell types and can therefore be taken up by cells without the need of for targeting ligands).

In an embodiment, the delivery vehicle is a powder comprising, e.g., calcium carbonate, sucrose, mannitol, dextrose, or lactose.

In an embodiment, components are delivered as an aerosol.

In an embodiment, one or more nucleic acid molecules (e.g., DNA molecules) other than the components of a Cas system, e.g., the Cas9 molecule component and/or the gRNA molecule component described herein, are delivered. In an embodiment, the nucleic acid molecule is delivered at the same time as one or more of the components of the Cas system are delivered. In an embodiment, the nucleic acid molecule is delivered before or after (e.g., less than about 30 minutes, 1 hour, 2 hours, 3 hours, 6 hours, 9 hours, 12 hours, 1 day, 2 days, 3 days, 1 week, 2 weeks, or 4 weeks) one or more of the components of the Cas system are delivered. In an embodiment, the nucleic acid molecule is delivered by a different means than one or more of the components of the Cas system, e.g., the Cas9 molecule component and/or the gRNA molecule component, are delivered. The nucleic acid molecule can be delivered by any of the delivery methods described herein. For example, the nucleic acid molecule can be delivered by a viral vector, e.g., an integration-deficient lentivirus, and the Cas9 molecule component and/or the gRNA molecule component can be delivered by electroporation, e.g., such that the toxicity caused by nucleic acids (e.g., DNAs) can be reduced. In an embodiment, the nucleic acid molecule encodes a therapeutic protein, e.g., a protein described herein. In an embodiment, the nucleic acid molecule encodes an RNA molecule, e.g., an RNA molecule described herein.

Delivery of RNA Encoding a Cas9 Molecule

RNA encoding Cas9 molecules (e.g., eaCas9 molecules or eiCas9 molecules) and/or gRNA molecules, can be delivered into cells, e.g., target cells described herein, by art-known methods or as described herein. For example, Cas9-encoding and/or gRNA-encoding RNA can be delivered, e.g., by microinjection, electroporation, transient cell compression or squeezing (e.g., as described in Lee, et al [2012] Nano Lett 12: 6322-27), lipid-mediated transfection, lipid-mediated transfection, peptide-mediated delivery, or a combination thereof. Cas9-encoding and/or gRNA-encoding RNA can be conjugated to molecules promoting uptake by the target cells (e.g., target cells described herein).

In an embodiment, delivery via electroporation comprises mixing the cells with the RNA encoding Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion proteins) and/or gRNA molecules, with or without donor nucleic acid molecules in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the RNA encoding Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion proteins) and/or gRNA molecules, with or without donor nucleic acid molecules in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel.

Delivery Cas9 Molecule Protein

Cas9 molecules (e.g., eaCas9 molecules or eiCas9 molecules) can be delivered into cells by art-known methods or as described herein. For example, Cas9 protein molecules can be delivered, e.g., by microinjection, electroporation, lipid-mediated transfection, peptide-mediated delivery, or a combination thereof. Delivery can be accompanied by DNA encoding a gRNA or by a gRNA. Cas9 protein can be conjugated to molecules promoting uptake by the target cells (e.g., target cells described herein).

In an embodiment, delivery via electroporation comprises mixing the cells with the Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion proteins) and/or gRNA molecules, with or without donor nucleic acid, in a cartridge, chamber or cuvette and applying one or more electrical impulses of defined duration and amplitude. In an embodiment, delivery via electroporation is performed using a system in which cells are mixed with the Cas9 molecules (e.g., eaCas9 molecules, eiCas9 molecules or eiCas9 fusion proteins) and/or gRNA molecules, with or without donor nucleic acid in a vessel connected to a device (eg, a pump) which feeds the mixture into a cartridge, chamber or cuvette wherein one or more electrical impulses of defined duration and amplitude are applied, after which the cells are delivered to a second vessel.

Route of Administration

Systemic modes of administration include oral and parenteral routes. Parenteral routes include, by way of example, intravenous, intra-arterial, intraosseous, intramuscular, intradermal, subcutaneous and intraperitoneal routes. Components administered systemically may be modified or formulated to target the components to specific cells, e.g., airway epithelial cells, pulmonary epithelial cells, gastrointestinal epithelial cells, biliary epithelial cells, pancreatic ductal epithelial cells, reproductive epithelial cells or pulmonary stem cells.

Local modes of administration include, by way of example, inhalation, intra-nasal instillation, and intraparenchymal injection, e.g., intraparenchymal injection into the lung, bronchial tree, liver, pancreas, pancreatic duct, bile duct, gastrointestinal tract or reproductive tract. In an embodiment, significantly smaller amounts of the components (compared with systemic approaches) may exert an effect when administered locally (for example, by inhalation) compared to when administered systemically (for example, intravenously). Local modes of administration can reduce or eliminate the incidence of potentially toxic side effects that may occur when therapeutically effective amounts of a component are administered systemically.

In an embodiment, components described herein are delivered by inhalation.

In an embodiment, nanoparticle or viral, e.g., AAV vector, delivery is via inhalation.

In an embodiment, subjects are treated with mucus loosening agents and/or chest physical therapy prior to administration of components by inhalation.

Administration may be provided as a periodic bolus or as continuous infusion from an internal reservoir or from an external reservoir (for example, from an intravenous bag). Components may be administered locally, for example, by continuous release from a sustained release drug delivery device.

In addition, components may be formulated to permit release over a prolonged period of time. A release system can include a matrix of a biodegradable material or a material which releases the incorporated components by diffusion. The components can be homogeneously or heterogeneously distributed within the release system. A variety of release systems may be useful, however, the choice of the appropriate system will depend upon rate of release required by a particular application. Both non-degradable and degradable release systems can be used. Suitable release systems include polymers and polymeric matrices, non-polymeric matrices, or inorganic and organic excipients and diluents such as, but not limited to, calcium carbonate and sugar (for example, trehalose). Release systems may be natural or synthetic. However, synthetic release systems are preferred because generally they are more reliable, more reproducible and produce more defined release profiles. The release system material can be selected so that components having different molecular weights are released by diffusion through or degradation of the material.

Representative synthetic, biodegradable polymers include, for example: polyamides such as poly(amino acids) and poly(peptides); polyesters such as poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid), and poly(caprolactone); poly(anhydrides); polyorthoesters; polycarbonates; and chemical derivatives thereof (substitutions, additions of chemical groups, for example, alkyl, alkylene, hydroxylations, oxidations, and other modifications routinely made by those skilled in the art), copolymers and mixtures thereof. Representative synthetic, non-degradable polymers include, for example: polyethers such as poly(ethylene oxide), poly(ethylene glycol), and poly(tetramethylene oxide); vinyl polymers-polyacrylates and polymethacrylates such as methyl, ethyl, other alkyl, hydroxyethyl methacrylate, acrylic and methacrylic acids, and others such as poly(vinyl alcohol), poly(vinyl pyrolidone), and poly(vinyl acetate); poly(urethanes); cellulose and its derivatives such as alkyl, hydroxyalkyl, ethers, esters, nitrocellulose, and various cellulose acetates; polysiloxanes; and any chemical derivatives thereof (substitutions, additions of chemical groups, for example, alkyl, alkylene, hydroxylations, oxidations, and other modifications routinely made by those skilled in the art), copolymers and mixtures thereof.

Poly(lactide-co-glycolide) microsphere can also be used for injection. Typically the microspheres are composed of a polymer of lactic acid and glycolic acid, which are structured to form hollow spheres. The spheres can be approximately 15-30 microns in diameter and can be loaded with components described herein.

Bi-Modal or Differential Delivery of Components

Separate delivery of the components of a Cas system, e.g., the Cas9 molecule component and the gRNA molecule component, and more particularly, delivery of the components by differing modes, can enhance performance, e.g., by improving tissue specificity and safety.

In an embodiment, the Cas9 molecule and the gRNA molecule are delivered by different modes, or as sometimes referred to herein as differential modes. Different or differential modes, as used herein, refer modes of delivery that confer different pharmacodynamic or pharmacokinetic properties on the subject component molecule, e.g., a Cas9 molecule, gRNA molecule, or template nucleic acid. For example, the modes of delivery can result in different tissue distribution, different half-life, or different temporal distribution, e.g., in a selected compartment, tissue, or organ.

Some modes of delivery, e.g., delivery by a nucleic acid vector that persists in a cell, or in progeny of a cell, e.g., by autonomous replication or insertion into cellular nucleic acid, result in more persistent expression of and presence of a component. Examples include viral, e.g., adeno-associated virus or lentivirus, delivery.

By way of example, the components, e.g., a Cas9 molecule and a gRNA molecule, can be delivered by modes that differ in terms of resulting half-life or persistent of the delivered component the body, or in a particular compartment, tissue or organ. In an embodiment, a gRNA molecule can be delivered by such modes. The Cas9 molecule component can be delivered by a mode which results in less persistence or less exposure to the body or a particular compartment or tissue or organ.

More generally, in an embodiment, a first mode of delivery is used to deliver a first component and a second mode of delivery is used to deliver a second component. The first mode of delivery confers a first pharmacodynamic or pharmacokinetic property. The first pharmacodynamic property can be, e.g., distribution, persistence, or exposure, of the component, or of a nucleic acid that encodes the component, in the body, a compartment, tissue or organ. The second mode of delivery confers a second pharmacodynamic or pharmacokinetic property. The second pharmacodynamic property can be, e.g., distribution, persistence, or exposure, of the component, or of a nucleic acid that encodes the component, in the body, a compartment, tissue or organ.

In an embodiment, the first pharmacodynamic or pharmacokinetic property, e.g., distribution, persistence or exposure, is more limited than the second pharmacodynamic or pharmacokinetic property.

In an embodiment, the first mode of delivery is selected to optimize, e.g., minimize, a pharmacodynamic or pharmacokinetic property, e.g., distribution, persistence or exposure.

In an embodiment, the second mode of delivery is selected to optimize, e.g., maximize, a pharmacodynamic or pharmcokinetic property, e.g., distribution, persistence or exposure.

In an embodiment, the first mode of delivery comprises the use of a relatively persistent element, e.g., a nucleic acid, e.g., a plasmid or viral vector, e.g., an AAV or lentivirus. As such vectors are relatively persistent product transcribed from them would be relatively persistent.

In an embodiment, the second mode of delivery comprises a relatively transient element, e.g., an RNA or protein.

In an embodiment, the first component comprises gRNA, and the delivery mode is relatively persistent, e.g., the gRNA is transcribed from a plasmid or viral vector, e.g., an AAV or lentivirus. Transcription of these genes would be of little physiological consequence because the genes do not encode for a protein product, and the gRNAs are incapable of acting in isolation. The second component, a Cas9 molecule, is delivered in a transient manner, for example as mRNA or as protein, ensuring that the full Cas9 molecule/gRNA molecule complex is only present and active for a short period of time.

Furthermore, the components can be delivered in different molecular form or with different delivery vectors that complement one another to enhance safety and tissue specificity.

Use of differential delivery modes can enhance performance, safety and efficacy. E.g., the likelihood of an eventual off-target modification can be reduced. Delivery of immunogenic components, e.g., Cas9 molecules, by less persistent modes can reduce immunogenicity, as peptides from the bacterially-derived Cas enzyme are displayed on the surface of the cell by MHC molecules. A two-part delivery system can alleviate these drawbacks.

Differential delivery modes can be used to deliver components to different, but overlapping target regions. The formation active complex is minimized outside the overlap of the target regions. Thus, in an embodiment, a first component, e.g., a gRNA molecule is delivered by a first delivery mode that results in a first spatial, e.g., tissue, distribution. A second component, e.g., a Cas9 molecule is delivered by a second delivery mode that results in a second spatial, e.g., tissue, distribution. In an embodiment, the first mode comprises a first element selected from a liposome, nanoparticle, e.g., polymeric nanoparticle, and a nucleic acid, e.g., viral vector. The second mode comprises a second element selected from the group. In an embodiment, the first mode of delivery comprises a first targeting element, e.g., a cell specific receptor or an antibody, and the second mode of delivery does not include that element. In embodiment, the second mode of delivery comprises a second targeting element, e.g., a second cell specific receptor or second antibody.

When the Cas9 molecule is delivered in a virus delivery vector, a liposome, or polymeric nanoparticle, there is the potential for delivery to and therapeutic activity in multiple tissues, when it may be desirable to only target a single tissue. A two-part delivery system can resolve this challenge and enhance tissue specificity. If the gRNA molecule and the Cas9 molecule are packaged in separated delivery vehicles with distinct but overlapping tissue tropism, the fully functional complex is only be formed in the tissue that is targeted by both vectors.

Ex Vivo Delivery

In some embodiments, components described in Table 56 are introduced into cells which are then introduced into the subject e.g., cells are removed from a subject, manipulated ex vivo and then introduced into the subject. Methods of introducing the components can include, e.g., any of the delivery methods described herein, e.g., any of the delivery methods described in Table 57.

VIII. Modified Nucleosides, Nucleotides, and Nucleic Acids

Modified nucleosides and modified nucleotides can be present in nucleic acids, e.g., particularly gRNA, but also other forms of RNA, e.g., mRNA, RNAi, or siRNA. As described herein, “nucleoside” is defined as a compound containing a five-carbon sugar molecule (a pentose or ribose) or derivative thereof, and an organic base, purine or pyrimidine, or a derivative thereof. As described herein, “nucleotide” is defined as a nucleoside further comprising a phosphate group.

Modified nucleosides and nucleotides can include one or more of:

    • (i) alteration, e.g., replacement, of one or both of the non-linking phosphate oxygens and/or of one or more of the linking phosphate oxygens in the phosphodiester backbone linkage;
    • (ii) alteration, e.g., replacement, of a constituent of the ribose sugar, e.g., of the 2′ hydroxyl on the ribose sugar;
    • (iii) wholesale replacement of the phosphate moiety with “dephospho” linkers;
    • (iv) modification or replacement of a naturally occurring nucleobase;
    • (v) replacement or modification of the ribose-phosphate backbone;
    • (vi) modification of the 3′ end or 5′ end of the oligonucleotide, e.g., removal, modification or replacement of a terminal phosphate group or conjugation of a moiety; and
    • (vii) modification of the sugar.

The modifications listed above can be combined to provide modified nucleosides and nucleotides that can have two, three, four, or more modifications. For example, a modified nucleoside or nucleotide can have a modified sugar and a modified nucleobase. In an embodiment, every base of a gRNA is modified, e.g., all bases have a modified phosphate group, e.g., all are phosphorothioate groups. In an embodiment, all, or substantially all, of the phosphate groups of a unimolecular or modular gRNA molecule are replaced with phosphorothioate groups.

In an embodiment, modified nucleotides, e.g., nucleotides having modifications as described herein, can be incorporated into a nucleic acid, e.g., a “modified nucleic acid.” In some embodiments, the modified nucleic acids comprise one, two, three or more modified nucleotides. In some embodiments, at least 5% (e.g., at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or about 100%) of the positions in a modified nucleic acid are a modified nucleotides.

Unmodified nucleic acids can be prone to degradation by, e.g., cellular nucleases. For example, nucleases can hydrolyze nucleic acid phosphodiester bonds. Accordingly, in one aspect the modified nucleic acids described herein can contain one or more modified nucleosides or nucleotides, e.g., to introduce stability toward nucleases.

In some embodiments, the modified nucleosides, modified nucleotides, and modified nucleic acids described herein can exhibit a reduced innate immune response when introduced into a population of cells, both in vivo and ex vivo. The term “innate immune response” includes a cellular response to exogenous nucleic acids, including single stranded nucleic acids, generally of viral or bacterial origin, which involves the induction of cytokine expression and release, particularly the interferons, and cell death. In some embodiments, the modified nucleosides, modified nucleotides, and modified nucleic acids described herein can disrupt binding of a major groove interacting partner with the nucleic acid. In some embodiments, the modified nucleosides, modified nucleotides, and modified nucleic acids described herein can exhibit a reduced innate immune response when introduced into a population of cells, both in vivo and ex vivo, and also disrupt binding of a major groove interacting partner with the nucleic acid.

Definitions of Chemical Groups

As used herein, “alkyl” is meant to refer to a saturated hydrocarbon group which is straight-chained or branched. Example alkyl groups include methyl (Me), ethyl (Et), propyl (e.g., n-propyl and isopropyl), butyl (e.g., n-butyl, isobutyl, t-butyl), pentyl (e.g., n-pentyl, isopentyl, neopentyl), and the like. An alkyl group can contain from 1 to about 20, from 2 to about 20, from 1 to about 12, from 1 to about 8, from 1 to about 6, from 1 to about 4, or from 1 to about 3 carbon atoms.

As used herein, “aryl” refers to monocyclic or polycyclic (e.g., having 2, 3 or 4 fused rings) aromatic hydrocarbons such as, for example, phenyl, naphthyl, anthracenyl, phenanthrenyl, indanyl, indenyl, and the like. In some embodiments, aryl groups have from 6 to about 20 carbon atoms.

As used herein, “alkenyl” refers to an aliphatic group containing at least one double bond.

As used herein, “alkynyl” refers to a straight or branched hydrocarbon chain containing 2-12 carbon atoms and characterized in having one or more triple bonds. Examples of alkynyl groups include, but are not limited to, ethynyl, propargyl, and 3-hexynyl.

As used herein, “arylalkyl” or “aralkyl” refers to an alkyl moiety in which an alkyl hydrogen atom is replaced by an aryl group. Aralkyl includes groups in which more than one hydrogen atom has been replaced by an aryl group. Examples of “arylalkyl” or “aralkyl” include benzyl, 2-phenylethyl, 3-phenylpropyl, 9-fluorenyl, benzhydryl, and trityl groups.

As used herein, “cycloalkyl” refers to a cyclic, bicyclic, tricyclic, or polycyclic non-aromatic hydrocarbon groups having 3 to 12 carbons. Examples of cycloalkyl moieties include, but are not limited to, cyclopropyl, cyclopentyl, and cyclohexyl.

As used herein, “heterocyclyl” refers to a monovalent radical of a heterocyclic ring system. Representative heterocyclyls include, without limitation, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl, piperidinyl, pyrrolinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, and morpholinyl.

As used herein, “heteroaryl” refers to a monovalent radical of a heteroaromatic ring system. Examples of heteroaryl moieties include, but are not limited to, imidazolyl, oxazolyl, thiazolyl, triazolyl, pyrrolyl, furanyl, indolyl, thiophenyl pyrazolyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, indolizinyl, purinyl, naphthyridinyl, quinolyl, and pteridinyl.

Phosphate Backbone Modifications

The Phosphate Group

In some embodiments, the phosphate group of a modified nucleotide can be modified by replacing one or more of the oxygens with a different substituent. Further, the modified nucleotide, e.g., modified nucleotide present in a modified nucleic acid, can include the wholesale replacement of an unmodified phosphate moiety with a modified phosphate as described herein. In some embodiments, the modification of the phosphate backbone can include alterations that result in either an uncharged linker or a charged linker with unsymmetrical charge distribution.

Examples of modified phosphate groups include, phosphorothioate, phosphoroselenates, borano phosphates, borano phosphate esters, hydrogen phosphonates, phosphoroamidates, alkyl or aryl phosphonates and phosphotriesters. In some embodiments, one of the non-bridging phosphate oxygen atoms in the phosphate backbone moiety can be replaced by any of the following groups: sulfur (S), selenium (Se), BR3 (wherein R can be, e.g., hydrogen, alkyl, or aryl), C (e.g., an alkyl group, an aryl group, and the like), H, NR2 (wherein R can be, e.g., hydrogen, alkyl, or aryl), or OR (wherein R can be, e.g., alkyl or aryl). The phosphorous atom in an unmodified phosphate group is achiral. However, replacement of one of the non-bridging oxygens with one of the above atoms or groups of atoms can render the phosphorous atom chiral; that is to say that a phosphorous atom in a phosphate group modified in this way is a stereogenic center. The stereogenic phosphorous atom can possess either the “R” configuration (herein Rp) or the “S” configuration (herein Sp).

Phosphorodithioates have both non-bridging oxygens replaced by sulfur. The phosphorus center in the phosphorodithioates is achiral which precludes the formation of oligoribonucleotide diastereomers. In some embodiments, modifications to one or both non-bridging oxygens can also include the replacement of the non-bridging oxygens with a group independently selected from S, Se, B, C, H, N, and OR (R can be, e.g., alkyl or aryl).

The phosphate linker can also be modified by replacement of a bridging oxygen, (i.e., the oxygen that links the phosphate to the nucleoside), with nitrogen (bridged phosphoroamidates), sulfur (bridged phosphorothioates) and carbon (bridged methylenephosphonates). The replacement can occur at either linking oxygen or at both of the linking oxygens.

Replacement of the Phosphate Group

The phosphate group can be replaced by non-phosphorus containing connectors. In some embodiments, the charge phosphate group can be replaced by a neutral moiety.

Examples of moieties which can replace the phosphate group can include, without limitation, e.g., methyl phosphonate, hydroxylamino, siloxane, carbonate, carboxymethyl, carbamate, amide, thioether, ethylene oxide linker, sulfonate, sulfonamide, thioformacetal, formacetal, oxime, methyleneimino, methylenemethylimino, methylenehydrazo, methylenedimethylhydrazo and methyleneoxymethylimino.

Replacement of the Ribophosphate Backbone

Scaffolds that can mimic nucleic acids can also be constructed wherein the phosphate linker and ribose sugar are replaced by nuclease resistant nucleoside or nucleotide surrogates. In some embodiments, the nucleobases can be tethered by a surrogate backbone. Examples can include, without limitation, the morpholino, cyclobutyl, pyrrolidine and peptide nucleic acid (PNA) nucleoside surrogates.

Sugar Modifications

The modified nucleosides and modified nucleotides can include one or more modifications to the sugar group. For example, the 2′ hydroxyl group (OH) can be modified or replaced with a number of different “oxy” or “deoxy” substituents. In some embodiments, modifications to the 2′ hydroxyl group can enhance the stability of the nucleic acid since the hydroxyl can no longer be deprotonated to form a 2′-alkoxide ion. The 2′-alkoxide can catalyze degradation by intramolecular nucleophilic attack on the linker phosphorus atom.

Examples of “oxy”-2′ hydroxyl group modifications can include alkoxy or aryloxy (OR, wherein “R” can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or a sugar); polyethyleneglycols (PEG), O(CH2CH2O)nCH2CH2OR wherein R can be, e.g., H or optionally substituted alkyl, and n can be an integer from 0 to 20 (e.g., from 0 to 4, from 0 to 8, from 0 to 10, from 0 to 16, from 1 to 4, from 1 to 8, from 1 to 10, from 1 to 16, from 1 to 20, from 2 to 4, from 2 to 8, from 2 to 10, from 2 to 16, from 2 to 20, from 4 to 8, from 4 to 10, from 4 to 16, and from 4 to 20). In some embodiments, the “oxy”-2′ hydroxyl group modification can include “locked” nucleic acids (LNA) in which the 2′ hydroxyl can be connected, e.g., by a C1-6 alkylene or C1-6 heteroalkylene bridge, to the 4′ carbon of the same ribose sugar, where exemplary bridges can include methylene, propylene, ether, or amino bridges; O-amino (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino) and aminoalkoxy, O(CH2)n-amino, (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino). In some embodiments, the “oxy”-2′ hydroxyl group modification can include the methoxyethyl group (MOE), (OCH2CH2OCH3, e.g., a PEG derivative).

“Deoxy” modifications can include hydrogen (i.e. deoxyribose sugars, e.g., at the overhang portions of partially ds RNA); halo (e.g., bromo, chloro, fluoro, or iodo); amino (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclyl, arylamino, diarylamino, heteroarylamino, diheteroarylamino, or amino acid); NH(CH2CH2NH)nCH2CH2-amino (wherein amino can be, e.g., as described herein), —NHC(O)R (wherein R can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar), cyano; mercapto; alkyl-thio-alkyl; thioalkoxy; and alkyl, cycloalkyl, aryl, alkenyl and alkynyl, which may be optionally substituted with e.g., an amino as described herein.

The sugar group can also contain one or more carbons that possess the opposite stereochemical configuration than that of the corresponding carbon in ribose. Thus, a modified nucleic acid can include nucleotides containing e.g., arabinose, as the sugar. The nucleotide “monomer” can have an alpha linkage at the 1′ position on the sugar, e.g., alpha-nucleosides. The modified nucleic acids can also include “abasic” sugars, which lack a nucleobase at C-1′. These abasic sugars can also be further modified at one or more of the constituent sugar atoms. The modified nucleic acids can also include one or more sugars that are in the L form, e.g. L-nucleosides.

Generally, RNA includes the sugar group ribose, which is a 5-membered ring having an oxygen. Exemplary modified nucleosides and modified nucleotides can include, without limitation, replacement of the oxygen in ribose (e.g., with sulfur (S), selenium (Se), or alkylene, such as, e.g., methylene or ethylene); addition of a double bond (e.g., to replace ribose with cyclopentenyl or cyclohexenyl); ring contraction of ribose (e.g., to form a 4-membered ring of cyclobutane or oxetane); ring expansion of ribose (e.g., to form a 6- or 7-membered ring having an additional carbon or heteroatom, such as for example, anhydrohexitol, altritol, mannitol, cyclohexanyl, cyclohexenyl, and morpholino that also has a phosphoramidate backbone). In some embodiments, the modified nucleotides can include multicyclic forms (e.g., tricyclo; and “unlocked” forms, such as glycol nucleic acid (GNA) (e.g., R-GNA or S-GNA, where ribose is replaced by glycol units attached to phosphodiester bonds), threose nucleic acid (TNA, where ribose is replaced with α-L-threofuranosyl-(3′→2′)).

Modifications on the Nucleobase

The modified nucleosides and modified nucleotides described herein, which can be incorporated into a modified nucleic acid, can include a modified nucleobase. Examples of nucleobases include, but are not limited to, adenine (A), guanine (G), cytosine (C), and uracil (U). These nucleobases can be modified or wholly replaced to provide modified nucleosides and modified nucleotides that can be incorporated into modified nucleic acids. The nucleobase of the nucleotide can be independently selected from a purine, a pyrimidine, a purine or pyrimidine analog. In some embodiments, the nucleobase can include, for example, naturally-occurring and synthetic derivatives of a base.

Uracil

In some embodiments, the modified nucleobase is a modified uracil. Exemplary nucleobases and nucleosides having a modified uracil include without limitation pseudouridine (ψ), pyridin-4-one ribonucleoside, 5-aza-uridine, 6-aza-uridine, 2-thio-5-aza-uridine, 2-thio-uridine (s2U), 4-thio-uridine (s4U), 4-thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxy-uridine (ho5U), 5-aminoallyl-uridine, 5-halo-uridine (e.g., 5-iodo-uridine or 5-bromo-uridine), 3-methyl-uridine (m3U), 5-methoxy-uridine (mo5U), uridine 5-oxyacetic acid (cmo5U), uridine 5-oxyacetic acid methyl ester (mcmo5U), 5-carboxymethyl-uridine (cm5U), 1-carboxymethyl-pseudouridine, 5-carboxyhydroxymethyl-uridine (chm5U), 5-carboxyhydroxymethyl-uridine methyl ester (mchm5U), 5-methoxycarbonylmethyl-uridine (mcm5U), 5-methoxycarbonylmethyl-2-thio-uridine (mcm5s2U), 5-aminomethyl-2-thio-uridine (nm5s2U), 5-methylaminomethyl-uridine (mnm5U), 5-methylaminomethyl-2-thio-uridine (mnm5s2U), 5-methylaminomethyl-2-seleno-uridine (mnm5se2U), 5-carbamoylmethyl-uridine (ncm5U), 5-carboxymethylaminomethyl-uridine (cmnm5U), 5-carboxymethylaminomethyl-2-thio-uridine (cmnm5s2U), 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyl-uridine (τcm5U), 1-taurinomethyl-pseudouridine, 5-taurinomethyl-2-thio-uridine (τm5s2U), 1-taurinomethyl-4-thio-pseudouridine, 5-methyl-uridine (m5U, i.e., having the nucleobase deoxythymine), 1-methyl-pseudouridine (m1ψ), 5-methyl-2-thio-uridine (m5s2U), 1-methyl-4-thio-pseudouridine (m1s4ψ), 4-thio-1-methyl-pseudouridine, 3-methyl-pseudouridine (m3ψ), 2-thio-1-methyl-pseudouridine, 1-methyl-1-deaza-pseudouridine, 2-thio-1-methyl-1-deaza-pseudouridine, dihydrouridine (D), dihydropseudouridine, 5,6-dihydrouridine, 5-methyl-dihydrouridine (m5D), 2-thio-dihydrouridine, 2-thio-dihydropseudouridine, 2-methoxy-uridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, 4-methoxy-2-thio-pseudouridine, N1-methyl-pseudouridine, 3-(3-amino-3-carboxypropyl)uridine (acp3U), 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (acp3ψ), 5-(isopentenylaminomethyl)uridine (inm5U), 5-(isopentenylaminomethyl)-2-thio-uridine (inm5s2U), α-thio-uridine, 2′-O-methyl-uridine (Um), 5,2′-O-dimethyl-uridine (m5Um), 2′-O-methyl-pseudouridine (ψm), 2-thio-2′-O-methyl-uridine (s2Um), 5-methoxycarbonylmethyl-2′-O-methyl-uridine (mcm5Um), 5-carbamoylmethyl-2′-O-methyl-uridine (ncm5Um), 5-carboxymethylaminomethyl-2′-O-methyl-uridine (cmnm5Um), 3,2′-O-dimethyl-uridine (m3Um), 5-(isopentenylaminomethyl)-2′-O-methyl-uridine (inm5Um), 1-thio-uridine, deoxythymidine, 2′-F-ara-uridine, 2′-F-uridine, 2′-OH-ara-uridine, 5-(2-carbomethoxyvinyl) uridine, 5-[3-(1-E-propenylamino)uridine, pyrazolo[3,4-d]pyrimidines, xanthine, and hypoxanthine.

Cytosine

In some embodiments, the modified nucleobase is a modified cytosine. Exemplary nucleobases and nucleosides having a modified cytosine include without limitation 5-aza-cytidine, 6-aza-cytidine, pseudoisocytidine, 3-methyl-cytidine (m3C), N4-acetyl-cytidine (act), 5-formyl-cytidine (f5C), N4-methyl-cytidine (m4C), 5-methyl-cytidine (m5C), 5-halo-cytidine (e.g., 5-iodo-cytidine), 5-hydroxymethyl-cytidine (hm5C), 1-methyl-pseudoisocytidine, pyrrolo-cytidine, pyrrolo-pseudoisocytidine, 2-thio-cytidine (s2C), 2-thio-5-methyl-cytidine, 4-thio-pseudoisocytidine, 4-thio-1-methyl-pseudoisocytidine, 4-thio-1-methyl-1-deaza-pseudoisocytidine, 1-methyl-1-deaza-pseudoisocytidine, zebularine, 5-aza-zebularine, 5-methyl-zebularine, 5-aza-2-thio-zebularine, 2-thio-zebularine, 2-methoxy-cytidine, 2-methoxy-5-methyl-cytidine, 4-methoxy-pseudoisocytidine, 4-methoxy-1-methyl-pseudoisocytidine, lysidine (k2C), α-thio-cytidine, 2′-O-methyl-cytidine (Cm), 5,2′-O-dimethyl-cytidine (m5Cm), N4-acetyl-2′-O-methyl-cytidine (ac4Cm), N4,2′-O-dimethyl-cytidine (m4Cm), 5-formyl-2′-O-methyl-cytidine (f5Cm), N4,N4,2′-O-trimethyl-cytidine (m42Cm), 1-thio-cytidine, 2′-F-ara-cytidine, 2′-F-cytidine, and 2′-OH-ara-cytidine.

Adenine

In some embodiments, the modified nucleobase is a modified adenine. Exemplary nucleobases and nucleosides having a modified adenine include without limitation 2-amino-purine, 2,6-diaminopurine, 2-amino-6-halo-purine (e.g., 2-amino-6-chloro-purine), 6-halo-purine (e.g., 6-chloro-purine), 2-amino-6-methyl-purine, 8-azido-adenosine, 7-deaza-adenosine, 7-deaza-8-aza-adenosine, 7-deaza-2-amino-purine, 7-deaza-8-aza-2-amino-purine, 7-deaza-2,6-diaminopurine, 7-deaza-8-aza-2,6-diaminopurine, 1-methyl-adenosine (m1A), 2-methyl-adenosine (m2A), N6-methyl-adenosine (m6A), 2-methylthio-N6-methyl-adenosine (ms2 m6A), N6-isopentenyl-adenosine (i6A), 2-methylthio-N6-isopentenyl-adenosine (ms2i6A), N6-(cis-hydroxyisopentenyl)adenosine (io6A), 2-methylthio-N6-(cis-hydroxyisopentenyl)adenosine (ms2io6A), N6-glycinylcarbamoyl-adenosine (g6A), N6-threonylcarbamoyl-adenosine (t6A), N6-methyl-N6-threonylcarbamoyl-adenosine (m6t6A), 2-methylthio-N6-threonylcarbamoyl-adenosine (ms2g6A), N6,N6-dimethyl-adenosine (m62A), N6-hydroxynorvalylcarbamoyl-adenosine (hn6A), 2-methylthio-N6-hydroxynorvalylcarbamoyl-adenosine (ms2hn6A), N6-acetyl-adenosine (ac6A), 7-methyl-adenosine, 2-methylthio-adenosine, 2-methoxy-adenosine, α-thio-adenosine, 2′-O-methyl-adenosine (Am), N6,2′-O-dimethyl-adenosine (m6Am), N6-Methyl-2′-deoxyadenosine, N6,N6,2′-O-trimethyl-adenosine (m62Am), 1,2′-O-dimethyl-adenosine (m1Am), 2′-O-ribosyladenosine (phosphate) (Ar(p)), 2-amino-N6-methyl-purine, 1-thio-adenosine, 8-azido-adenosine, 2′-F-ara-adenosine, 2′-F-adenosine, 2′-OH-ara-adenosine, and N6-(19-amino-pentaoxanonadecyl)-adenosine.

Guanine

In some embodiments, the modified nucleobase is a modified guanine. Exemplary nucleobases and nucleosides having a modified guanine include without limitation inosine (I), 1-methyl-inosine (m1I), wyosine (imG), methylwyosine (mimG), 4-demethyl-wyosine (imG-14), isowyosine (imG2), wybutosine (yW), peroxywybutosine (o2yW), hydroxywybutosine (OHyW), undermodified hydroxywybutosine (OHyW*), 7-deaza-guanosine, queuosine (Q), epoxyqueuosine (oQ), galactosyl-queuosine (galQ), mannosyl-queuosine (manQ), 7-cyano-7-deaza-guanosine (preQo), 7-aminomethyl-7-deaza-guanosine (preQ1), archaeosine (G+), 7-deaza-8-aza-guanosine, 6-thio-guanosine, 6-thio-7-deaza-guanosine, 6-thio-7-deaza-8-aza-guanosine, 7-methyl-guanosine (m7G), 6-thio-7-methyl-guanosine, 7-methyl-inosine, 6-methoxy-guanosine, 1-methyl-guanosine (m′G), N2-methyl-guanosine (m2G), N2,N2-dimethyl-guanosine (m22G), N2,7-dimethyl-guanosine (m2,7G), N2, N2,7-dimethyl-guanosine (m2,2,7G), 8-oxo-guanosine, 7-methyl-8-oxo-guanosine, 1-methyl-6-thio-guanosine, N2-methyl-6-thio-guanosine, N2,N2-dimethyl-6-thio-guanosine, α-thio-guanosine, 2′-O-methyl-guanosine (Gm), N2-methyl-2′-O-methyl-guanosine (m2Gm), N2,N2-dimethyl-2′-O-methyl-guanosine (m22Gm), 1-methyl-2′-O-methyl-guanosine (m′Gm), N2,7-dimethyl-2′-O-methyl-guanosine (m2,7Gm), 2′-O-methyl-inosine (Im), 1,2′-O-dimethyl-inosine (m′Im), O6-phenyl-2′-deoxyinosine, 2′-O-ribosylguanosine (phosphate) (Gr(p)), 1-thio-guanosine, O6-methyl-guanosine, O6-Methyl-2′-deoxyguanosine, 2′-F-ara-guanosine, and 2′-F-guanosine.

Exemplary Modified gRNAs

In some embodiments, the modified nucleic acids can be modified gRNAs. It is to be understood that any of the gRNAs described herein can be modified in accordance with this section, including any gRNA that comprises a targeting domain from Tables 1A-1E, 2A-2E, 3A-3D, 4A-4D, 5A-5E, 6A-6C, 7A-7D, 8A-8E, 9A-9B, 10A-10C, 11A-11E, 12A-12C, 13A-13D, 14A-14E, 15A-15C, or 16A-16D, 17A-17E, 18A-18C, 19A-19D, 20A-20E, 21A-21B, 22A-22D, 23A-23E, 24A-24D, 25A-25D, 26A-26E, 27A-27D, 28A-28D, 29A-29E, 30A-30B, 31A-31D, 32A-32D, 33A-33B, 34A-34D, 35A-35D, 36A-36D, 37A-37D, 38A-38E, 39A-39D, 40A-40D, 41A-41E, 42A-42D, 43A-43E, 44A-44G, 45A-45E, 46A-46E, 47A-47G, or 48A-48E.

Through experimentation (results not shown) we have found that the guide RNA (gRNA) component of the CRISPR/Cas system is more efficient at editing genes in T cells when it has been modified at or near its 5′ end (e.g., when the 5′ end of a gRNA is modified by the inclusion of a eukaryotic mRNA cap structure or cap analog). While not wishing to be bound by theory it is believed that these and other modified gRNAs described herein elicit a reduced innate immune response from certain circulatory cell types (e.g., T cells) and that this might be responsible for the observed improvements. The present invention encompasses the realization that minimizing the innate immune response of circulating cells (e.g., T cells) to gRNAs could be advantageous when using gRNAs to edit circulating cells (whether ex vivo or in vivo) and could also be advantageous when using gRNAs to edit non-circulating cells, e.g., when a gRNA is administered systemically or locally for in vivo gene editing purposes. The present invention also encompasses the realization that the improvements observed with a 5′ capped gRNA can be extended to gRNAs that have been modified in other ways to achieve the same type of structural or functional result (e.g., by the inclusion of modified nucleosides or nucleotides, or when an in vitro transcribed gRNA is modified by treatment with a phosphatase such as calf intestinal alkaline phosphatase to remove the 5′ triphosphate group). While not wishing to be bound by theory, in some embodiments, the modified gRNAs described herein may contain one or more modifications (e.g., modified nucleosides or nucleotides) which introduce stability toward nucleases (e.g., by the inclusion of modified nucleosides or nucleotides and/or a 3′ polyA tract).

Thus, in one aspect, methods and compositions discussed herein provide methods and compositions for gene editing by using gRNAs which have been modified at or near their 5′ end (e.g., within 1-10, 1-5, or 1-2 nucleotides of their 5′ end). In an embodiment, the 5′ end of a gRNA is modified by the inclusion of a eukaryotic mRNA cap structure or cap analog (e.g., a G(5′)ppp(5′)G cap analog, a m7G(5′)ppp(5′)G cap analog, or a 3′-O-Me-m7G(5′)ppp(5′)G anti reverse cap analog (ARCA)). The cap or cap analog can be included during either chemical synthesis or in vitro transcription of the gRNA. In an embodiment, an in vitro transcribed gRNA is modified by treatment with a phosphatase (e.g., calf intestinal alkaline phosphatase) to remove the 5′ triphosphate group.

In another aspect, methods and compositions discussed herein provide methods and compositions for gene editing by using gRNAs which include one or more modified nucleosides or nucleotides that are described herein. In some embodiments, the inclusion of the one or more modified nucleosides or nucleotides causes the gRNA to elicit a reduced innate immune response in certain circulating cell types (e.g., T cells, macrophages, dendritic cells, and/or B cells) as compared to an otherwise unmodified gRNA.

While some of the exemplary modifications discussed in this section may be included at any position within the gRNA sequence, in some embodiments, a gRNA comprises a modification at or near its 5′ end (e.g., within 1-10, 1-5, or 1-2 nucleotides of its 5′ end). In some embodiments, a gRNA comprises a modification at or near its 3′ end (e.g., within 1-10, 1-5, or 1-2 nucleotides of its 3′ end). In some embodiments, a gRNA comprises both a modification at or near its 5′ end and a modification at or near its 3′ end.

In an embodiment, the 3′ end of a gRNA is modified by the addition of one or more (e.g., 25-200) adenine (A) residues. The polyA tract can be contained in the nucleic acid (e.g., plasmid, PCR product, viral genome) encoding the gRNA, or can be added to the gRNA during chemical synthesis, or following in vitro transcription using a polyadenosine polymerase (e.g., E. coli Poly(A)Polymerase).

In an embodiment, in vitro transcribed gRNA contains both a 5′ cap structure or cap analog and a 3′ polyA tract. In an embodiment, an in vitro transcribed gRNA is modified by treatment with a phosphatase (e.g., calf intestinal alkaline phosphatase) to remove the 5′ triphosphate group and comprises a 3′ polyA tract.

In some embodiments, gRNAs can be modified at a 3′ terminal U ribose. For example, the two terminal hydroxyl groups of the U ribose can be oxidized to aldehyde groups and a concomitant opening of the ribose ring to afford a modified nucleoside as shown below:

wherein “U” can be an unmodified or modified uridine.

In another embodiment, the 3′ terminal U can be modified with a 2′3′ cyclic phosphate as shown below:

wherein “U” can be an unmodified or modified uridine.

In some embodiments, the gRNA molecules may contain 3′ nucleotides which can be stabilized against degradation, e.g., by incorporating one or more of the modified nucleotides described herein. In this embodiment, e.g., uridines can be replaced with modified uridines, e.g., 5-(2-amino)propyl uridine, and 5-bromo uridine, or with any of the modified uridines described herein; adenosines, cytidines and guanosines can be replaced with modified adenosines, cytidines and guanosines, e.g., with modifications at the 8-position, e.g., 8-bromo guanosine, or with any of the modified adenosines, cytidines or guanosines described herein.

In some embodiments, sugar-modified ribonucleotides can be incorporated into the gRNA, e.g., wherein the 2′ OH-group is replaced by a group selected from H, —OR, —R (wherein R can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar), halo, —SH, —SR (wherein R can be, e.g., alkyl, cycloalkyl, aryl, aralkyl, heteroaryl or sugar), amino (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclylamino, arylamino, diarylamino, heteroarylamino, diheteroarylamino, or amino acid); or cyano (—CN). In some embodiments, the phosphate backbone can be modified as described herein, e.g., with a phosphothioate group. In some embodiments, one or more of the nucleotides of the gRNA can each independently be a modified or unmodified nucleotide including, but not limited to 2′-sugar modified, such as, 2′-O-methyl, 2′-O-methoxyethyl, or 2′-Fluoro modified including, e.g., 2′-F or 2′-O-methyl, adenosine (A), 2′-F or 2′-O-methyl, cytidine (C), 2′-F or 2′-O-methyl, uridine (U), 2′-F or 2′-O-methyl, thymidine (T), 2′-F or 2′-O-methyl, guanosine (G), 2′-O-methoxyethyl-5-methyluridine (Teo), 2′-O-methoxyethyladenosine (Aeo), 2′-O-methoxyethyl-5-methylcytidine (m5Ceo), and any combinations thereof.

In some embodiments, a gRNA can include “locked” nucleic acids (LNA) in which the 2′ OH-group can be connected, e.g., by a C1-6 alkylene or C1-6 heteroalkylene bridge, to the 4′ carbon of the same ribose sugar, where exemplary bridges can include methylene, propylene, ether, or amino bridges; O-amino (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclylamino, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino) and aminoalkoxy or O(CH2)n-amino (wherein amino can be, e.g., NH2; alkylamino, dialkylamino, heterocyclylamino, arylamino, diarylamino, heteroarylamino, or diheteroarylamino, ethylenediamine, or polyamino).

In some embodiments, a gRNA can include a modified nucleotide which is multicyclic (e.g., tricyclo; and “unlocked” forms, such as glycol nucleic acid (GNA) (e.g., R-GNA or S-GNA, where ribose is replaced by glycol units attached to phosphodiester bonds), or threose nucleic acid (TNA, where ribose is replaced with α-L-threofuranosyl-(3′→2′)).

Generally, gRNA molecules include the sugar group ribose, which is a 5-membered ring having an oxygen. Exemplary modified gRNAs can include, without limitation, replacement of the oxygen in ribose (e.g., with sulfur (S), selenium (Se), or alkylene, such as, e.g., methylene or ethylene); addition of a double bond (e.g., to replace ribose with cyclopentenyl or cyclohexenyl); ring contraction of ribose (e.g., to form a 4-membered ring of cyclobutane or oxetane); ring expansion of ribose (e.g., to form a 6- or 7-membered ring having an additional carbon or heteroatom, such as for example, anhydrohexitol, altritol, mannitol, cyclohexanyl, cyclohexenyl, and morpholino that also has a phosphoramidate backbone). Although the majority of sugar analog alterations are localized to the 2′ position, other sites are amenable to modification, including the 4′ position. In an embodiment, a gRNA comprises a 4′-S, 4′-Se or a 4′-C-aminomethyl-2′-O-Me modification.

In some embodiments, deaza nucleotides, e.g., 7-deaza-adenosine, can be incorporated into the gRNA. In some embodiments, O- and N-alkylated nucleotides, e.g., N6-methyl adenosine, can be incorporated into the gRNA. In some embodiments, one or more or all of the nucleotides in a gRNA molecule are deoxynucleotides.

miRNA Binding Sites

microRNAs (or miRNAs) are naturally occurring cellular 19-25 nucleotide long noncoding RNAs. They bind to nucleic acid molecules having an appropriate miRNA binding site, e.g., in the 3′ UTR of an mRNA, and down-regulate gene expression. While not wishing to be bound by theory it is believed that the down regulation is either by reducing nucleic acid molecule stability or by inhibiting translation. An RNA species disclosed herein, e.g., an mRNA encoding Cas9 can comprise an miRNA binding site, e.g., in its 3′UTR. The miRNA binding site can be selected to promote down regulation of expression is a selected cell type. By way of example, the incorporation of a binding site for miR-122, a microRNA abundant in liver, can inhibit the expression of the gene of interest in the liver.

EXAMPLES

The following Examples are merely illustrative and are not intended to limit the scope or content of the invention in any way.

Example 1: Evaluation of Candidate Guide RNAs (gRNAs)

The suitability of candidate gRNAs can be evaluated as described in this example. Although described for a chimeric gRNA, the approach can also be used to evaluate modular gRNAs.

Cloning gRNAs into Vectors

For each gRNA, a pair of overlapping oligonucleotides is designed and obtained. Oligonucleotides are annealed and ligated into a digested vector backbone containing an upstream U6 promoter and the remaining sequence of a long chimeric gRNA. Plasmid is sequence-verified and prepped to generate sufficient amounts of transfection-quality DNA. Alternate promoters maybe used to drive in vivo transcription (e.g. H1 promoter) or for in vitro transcription (e.g., a T7 promoter).

Cloning gRNAs in Linear dsDNA Molecule (STITCHR)

For each gRNA, a single oligonucleotide is designed and obtained. The U6 promoter and the gRNA scaffold (e.g. including everything except the targeting domain, e.g., including sequences derived from the crRNA and tracrRNA, e.g., including a first complementarity domain; a linking domain; a second complementarity domain; a proximal domain; and a tail domain) are separately PCR amplified and purified as dsDNA molecules. The gRNA-specific oligonucleotide is used in a PCR reaction to stitch together the U6 and the gRNA scaffold, linked by the targeting domain specified in the oligonucleotide. Resulting dsDNA molecule (STITCHR product) is purified for transfection. Alternate promoters may be used to drive in vivo transcription (e.g., H1 promoter) or for in vitro transcription (e.g., T7 promoter). Any gRNA scaffold may be used to create gRNAs compatible with Cas9s from any bacterial species.

Initial gRNA Screen

Each gRNA to be tested is transfected, along with a plasmid expressing Cas9 and a small amount of a GFP-expressing plasmid into human cells. In preliminary experiments, these cells can be immortalized human cell lines such as 293T, K562 or U2OS. Alternatively, primary human cells may be used. In this case, cells may be relevant to the eventual therapeutic cell target (for example, an erythroid cell). The use of primary cells similar to the potential therapeutic target cell population may provide important information on gene targeting rates in the context of endogenous chromatin and gene expression.

Transfection may be performed using lipid transfection (such as Lipofectamine or Fugene) or by electroporation (such as Lonza Nucleofection). Following transfection, GFP expression can be determined either by fluorescence microscopy or by flow cytometry to confirm consistent and high levels of transfection. These preliminary transfections can comprise different gRNAs and different targeting approaches (17-mers, 20-mers, nuclease, dual-nickase, etc.) to determine which gRNAs/combinations of gRNAs give the greatest activity.

Efficiency of cleavage with each gRNA may be assessed by measuring NHEJ-induced indel formation at the target locus by a T7E1-type assay or by sequencing. Alternatively, other mismatch-sensitive enzymes, such as Cell/Surveyor nuclease, may also be used.

For the T7E1 assay, PCR amplicons are approximately 500-700 bp with the intended cut site placed asymmetrically in the amplicon. Following amplification, purification and size-verification of PCR products, DNA is denatured and re-hybridized by heating to 95° C. and then slowly cooling. Hybridized PCR products are then digested with T7 Endonuclease I (or other mismatch-sensitive enzyme) which recognizes and cleaves non-perfectly matched DNA. If indels are present in the original template DNA, when the amplicons are denatured and re-annealed, this results in the hybridization of DNA strands harboring different indels and therefore lead to double-stranded DNA that is not perfectly matched. Digestion products may be visualized by gel electrophoresis or by capillary electrophoresis. The fraction of DNA that is cleaved (density of cleavage products divided by the density of cleaved and uncleaved) may be used to estimate a percent NHEJ using the following equation: % NHEJ=(1−(1−fraction cleaved)1/2). The T7E1 assay is sensitive down to about 2-5% NHEJ.

Sequencing may be used instead of, or in addition to, the T7E1 assay. For Sanger sequencing, purified PCR amplicons are cloned into a plasmid backbone, transformed, miniprepped and sequenced with a single primer. Sanger sequencing may be used for determining the exact nature of indels after determining the NHEJ rate by T7E1.

Sequencing may also be performed using next generation sequencing techniques. When using next generation sequencing, amplicons may be 300-500 bp with the intended cut site placed asymmetrically. Following PCR, next generation sequencing adapters and barcodes (for example Illumina multiplex adapters and indexes) may be added to the ends of the amplicon, e.g., for use in high throughput sequencing (for example on an Illumina MiSeq). This method allows for detection of very low NHEJ rates.

Example 2: Assessment of Gene Targeting by NHEJ

The gRNAs that induce the greatest levels of NHEJ in initial tests can be selected for further evaluation of gene targeting efficiency. In this case, cells are derived from disease subjects and, therefore, harbor the relevant mutation.

Following transfection (usually 2-3 days post-transfection) genomic DNA may be isolated from a bulk population of transfected cells and PCR may be used to amplify the target region. Following PCR, gene targeting efficiency to generate the desired mutations (either knockout of a target gene or removal of a target sequence motif) may be determined by sequencing. For Sanger sequencing, PCR amplicons may be 500-700 bp long. For next generation sequencing, PCR amplicons may be 300-500 bp long. If the goal is to knockout gene function, sequencing may be used to assess what percent of alleles have undergone NHEJ-induced indels that result in a frameshift or large deletion or insertion that would be expected to destroy gene function. If the goal is to remove a specific sequence motif, sequencing may be used to assess what percent of alleles have undergone NHEJ-induced deletions that span this sequence.

Example 3: Assessment of Gene Targeting by HDR

The gRNAs that induce the greatest levels of NHEJ in initial tests can be selected for further evaluation of gene targeting efficiency. In this case, cells are derived from disease subjects and, therefore, harbor the relevant mutation.

Following transfection (usually 2-3 days post-transfection) genomic DNA may be isolated from a bulk population of transfected cells and PCR may be used to amplify the target region. Following PCR, gene targeting efficiency can be determined by several methods.

Determination of gene targeting frequency involves measuring the percentage of alleles that have undergone homologous directed repair (HDR) with the donor template and which therefore have incorporated desired correction. If the desired HDR event creates or destroys a restriction enzyme site, the frequency of gene targeting may be determined by a RFLP assay. If no restriction site is created or destroyed, sequencing may be used to determine gene targeting frequency. If a RFLP assay is used, sequencing may still be used to verify the desired HDR event and ensure that no other mutations are present. At least one of the primers is placed in the endogenous gene sequence outside of the region included in the homology arms, which prevents amplification of donor template still present in the cells. Therefore, the length of the homology arms present in the donor template may affect the length of the PCR amplicon. PCR amplicons can either span the entire donor region (both primers placed outside the homology arms) or they can span only part of the donor region and a single junction between donor and endogenous DNA (one internal and one external primer). If the amplicons span less than entire donor region, two different PCRs should be used to amplify and sequence both the 5′ and the 3′ junction.

If the PCR amplicon is short (less than 600 bp) it is possible to use next generation sequencing. Following PCR, next generation sequencing adapters and barcodes (for example Illumina multiplex adapters and indexes) may be added to the ends of the amplicon, e.g., for use in high throughput sequencing (for example on an Illumina MiSeq). This method allows for detection of very low gene targeting rates.

If the PCR amplicon is too long for next generation sequencing, Sanger sequencing can be performed. For Sanger sequencing, purified PCR amplicons will be cloned into a plasmid backbone (for example, TOPO cloned using the LifeTech Zero Blunt® TOPO® cloning kit), transformed, miniprepped and sequenced.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

1. A method of altering a cystic fibrosis transmembrane conductance regulator (CFTR) gene in a cell, comprising administering to said cell:

(i) a CRISPR/Cas system comprising: (a) a gRNA molecule comprising a targeting domain that is complementary with a target sequence of a CFTR gene and (b) a Cas9 molecule; or
(ii) a nucleic acid composition comprising: (a) a first nucleotide sequence encoding a gRNA molecule comprising a targeting domain that is complementary with a target sequence of a CFTR gene and (b) a second nucleotide sequence encoding a Cas9 molecule.

2. The method of claim 1, wherein said alteration comprises correction of one or more mutations in said CFTR gene.

3. The method of claim 1, wherein said alteration of said CFTR gene results in restoration of a mutant CFTR gene to its wild type state thereby providing a functional CFTR protein.

4. The method of claim 1, wherein said cell is from a subject suffering from or at risk for Cystic Fibrosis (CF) and CF-like disease.

5. The method of claim 1, wherein said cell is from a subject having a mutation at a CF target mutant position.

6. The method of claim 1, wherein said cell is selected from the group consisting of an airway cell, an epithelial cell, and a stem cell.

7. The method of claim 6, wherein said epithelial cell is selected from the group consisting of a lung epithelial cell, a gastrointestinal epithelial cell, a biliary epithelial cell, a pancreatic ductal epithelial cell, a gastrointestinal cell, a hepatobiliary epithelial cell, a gallbladder epithelial cell, a large intestine epithelial cell, a small intestine epithelial cell, a jejunum epithelial cell, a epithelial cell of the ileum, a duodenum epithelial cell, and a reproductive epithelial cell; and said stem cell is selected from the group consisting of an embryonic stem cell, an induced pluripotent stem cell, a pulmonary stem cell, a gastrointestinal stem cell, and a mesenchymal stem cell.

8. The method of claim 1, wherein said targeting domain that is complementary with a target sequence of said CFTR gene comprises or consists of a nucleotide sequence that is the same as, or differs by no more than 3 nucleotides from, a nucleotide sequence set forth in SEQ ID NOs: 15101-27265.

9. A method of altering a sodium channel epithelial 1 alpha (SCNN1A) gene in a cell, comprising administering to said cell:

(i) a CRISPR/Cas system comprising: (a) a gRNA molecule comprising a targeting domain that is complementary with a target sequence of a SCNN1A gene and (b) a Cas9 molecule; or
(ii) a nucleic acid composition comprising: (a) a first nucleotide sequence encoding a gRNA molecule comprising a targeting domain that is complementary with a target sequence of a SCNN1A gene and (b) a second nucleotide sequence encoding a Cas9 molecule.

10. The method of claim 9, wherein said alteration comprises correction of one or more mutations in said SCNN1A gene, knockout of said SCNN1A gene, or knockdown of said SCNN1A gene.

11. The method of claim 9, wherein the alteration of said SCNN1A gene results in a reduction or elimination of expression of said SCNN1A gene.

12. The method of claim 9, wherein said cell is from a subject suffering from or at risk for Cystic Fibrosis (CF) and CF-like disease.

13. The method of claim 9, wherein said cell is from a subject having a mutation at a CF target mutant position, or from a subject who would benefit from having a mutation in said SCNN1A gene.

14. The method of claim 9, wherein the cell is selected from the group consisting of an airway cell, an epithelial cell, and a stem cell.

15. The method of claim 14, wherein said epithelial cell is selected from the group consisting of a lung epithelial cell, a gastrointestinal epithelial cell, a biliary epithelial cell, a pancreatic ductal epithelial cell, a gastrointestinal cell, a hepatobiliary epithelial cell, a gallbladder epithelial cell, a large intestine epithelial cell, a small intestine epithelial cell, a jejunum epithelial cell, a epithelial cell of the ileum, a duodenum epithelial cell, and a reproductive epithelial cell; and said stem cell is selected from the group consisting of an embryonic stem cell, an induced pluripotent stem cell, a pulmonary stem cell, a gastrointestinal stem cell, and a mesenchymal stem cell.

16. The method of claim 9, wherein said targeting domain that is complementary to a target sequence of said SCNN1A gene comprises or consists of a nucleotide sequence that is the same as, or differs by no more than 3 nucleotides from, a nucleotide sequence set forth in SEQ ID NOs: 497-654, 803-916, and 4176-15100.

Patent History
Publication number: 20210380987
Type: Application
Filed: Apr 30, 2021
Publication Date: Dec 9, 2021
Applicant: EDITAS MEDICINE, INC. (Cambridge, MA)
Inventors: Deepak Reyon (Malden, MA), Morgan L. Maeder (Jamaica Plain, MA), Ari E. Friedland (Boston, MA), G. Grant Welstead (Cambridge, MA), David A. Bumcrot (Blemont, MA)
Application Number: 17/246,081
Classifications
International Classification: C12N 15/113 (20060101); C12N 9/22 (20060101);