Abstract: In certain aspects, the disclosure relates to compositions comprising modified Ornithine transcarbamylase (OTC) polyribonucleotides and methods of use.

Abstract: Provided herein are methods and compositions for treating a subject in need thereof, such as a subject with deficient SYNGAP1 protein or SCN1A protein expression or a subject having AD mental retardation 5 or Dravet syndrome.

Abstract: The invention describes a novel system for identifying optimized gRNAs for use in CRISPR/Cas9 genome editing platforms. The invention allows for the determination of specific gene alterations rendered by a particular gRNA, thereby permitting the generation of optimized gRNA libraries.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the Patatin-Like Phospholipase Domain Containing 3 (PNPLA3) gene, and methods of using such RNAi agents to inhibit expression of a PNPLA3 gene and methods of treating subjects having Nonalcoholic Fatty Liver Disease (NAFLD) and/or a PNPLA3-associated disorder.

Abstract: The present invention relates to a pharmaceutical composition for treating or preventing hepatitis B, comprising: at least one oligonucleotide selected from the group consisting an oligonucleotide represented by a nucleic acid sequence of SEQ ID NO: 1, 2, or 6 or a nucleic acid sequence complementary thereto; and an oligonucleotide having at least one chemical modification on the oligonucleotide, as an active ingredient, and a method for screening a therapeutic agent for hepatitis B according to the formation of a G-quadruplex by HBV and a candidate material. The pharmaceutical composition forms a G-quadruplex with HBV and reduces cccDNA (covalently closed circular DNA) and thus can be used in the treatment or prevention of hepatitis B.

Abstract: The invention relates to iRNA agents, which preferably include a monomer in which the ribose moiety has been replaced by a moiety other than ribose that further includes a tether having one or more linking groups, in which at least one of the linking groups is a cleavable linking group. The tether in turn can be connected to a selected moiety, e.g., a ligand, e.g., a targeting or delivery moiety, or a moiety which alters a physical property. The cleavable linking group is one which is sufficiently stable outside the cell such that it allows targeting of a therapeutically beneficial amount of an iRNA agent (e.g., a single stranded or double stranded iRNA agent), coupled by way of the cleavable linking group to a targeting agent—to targets cells, but which upon entry into a target cell is cleaved to release the iRNA agent from the targeting agent.

Abstract: The present invention relates to a novel anti-miRNA single-stranded nucleic acid maleimide derivative, which comprises an anti-miRNA single-stranded nucleic acid having a nucleic acid sequence complementary to a nucleic acid sequence of an miRNA. Further, the present invention provides an anti-miRNA single-stranded nucleic acid-serum albumin conjugate in which serum albumin is covalently bonded to the anti-miRNA single-stranded nucleic acid maleimide derivative via the maleimide group.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 214.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 214.

Abstract: In certain aspects, provided herein are RNA complexes (e.g., asymmetric RNA complexes, such as asiRNAs or cell penetrating asiRNAs) that inhibit IL4R?, TRPA1, and/or F2RL1 expression and are therefore useful for treating atopic dermatitis or asthma.

Abstract: The invention provides nucleic acid therapeutics and methods for using these nucleic acid therapeutics in the treatment of complement-related disorders.

Abstract: Provided herein are oligonucleotide compositions that inhibit ANGPTL7 and reduce intraocular pressure when administered to an eye. The oligonucleotide compositions contain nucleoside modifications.

Abstract: The invention relates to antisense oligonucleotides that are capable of bringing about specific editing of a target nucleotide (adenosine) in a target RNA sequence in a eukaryotic cell, wherein said oligonucleotide does not, in itself, form an intramolecular hairpin or stem-loop structure, and wherein said oligonucleotide comprises a non-complementary nucleotide in a position opposite to the nucleotide to be edited in the target RNA sequence.

Abstract: Immunogenic modulators and compositions comprising oligonucleotide agents capable of inhibiting suppression of immune response by reducing expression of one or more gene involved with an immune suppression mechanism.

Abstract: Provided herein are oligomeric compounds with conjugate groups targeting apolipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and/or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Abstract: The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.

Abstract: The present invention relates to RNAi agents, e.g., double stranded RNAi agents, targeting the programmed cell death 1 ligand 1 (PD-L1) gene, and methods of using such RNAi agents to inhibit expression of a PD-L1 gene and methods of treating subjects having a PD-L1-associated disorder.

Abstract: The invention relates to double stranded ribonucleic acid (dsRNA) compositions targeting a glucokinase (GCK) gene, as well as methods of inhibiting expression of a glucokinase (GCK) gene, and methods of treating subjects having a glycogen storage disease (GSD), e.g., type Ia GSD.

Abstract: Provided herein are branched oligonucleotides exhibiting efficient and specific tissue distribution, cellular uptake, minimum immune response and off-target effects, without formulation.

Abstract: The present invention relates to an apparatus for inhibiting oncogene-induced malignant carcinogenesis, including an irradiation unit for applying low-dose radiation to a subject, and to a method of inhibiting oncogene-induced malignant carcinogenesis, including applying low-dose radiation to a subject, whereby oncogene-induced malignant carcinogenesis can be inhibited by means of the apparatus and method of the present invention.

Abstract: This disclosure relates to novel huntingtin targets. Novel oligonucleotides for the treatment of Huntington's disease are also provided.

Abstract: The present invention relates to methods for treating a tumor, including a metastatic tumor, with TLR9 agonist in combination with an immune checkpoint inhibitor therapy.

Abstract: Provided herein are hybrid oligonucleotides comprising a region that promotes cleavage of a nucleic acid and a region that protects a nucleic acid from exonuclease activity. Such hybrid oligonucleotides are useful for modulating the expression of genes. Related compositions and methods are also provided. In some embodiments, methods are provided for treating a disease, such as by administering a hybrid oligonucleotide.

Abstract: The present invention is directed to non-naturally occurring peptides containing a membrane-penetrating amino acid sequence and further at least one polycationic moiety or peptide sequence. The peptides are suitable for use in delivery a cargo to the interior of a cell. Suitable cargo includes nucleic acid molecules (including DNA, RNA or PNA), polypeptides, or other biologically active molecules. The present invention is further directed to transfection complexes containing the non-naturally occurring peptides of the present invention in non-covalent association with at least one cationic lipid and a cargo to be delivered to the interior of a cell. The invention further relates to methods for the preparation and use of the non-naturally occurring peptides for the formation of transfection complexes and the delivery of a cargo to the interior of a cell in culture, an animal or a human. The invention also relates to compositions and kits useful for transfecting cells.

Abstract: Disclosed herein are compounds, compositions and methods for modulating the expression of huntingtin in a cell, tissue or animal. Further provided are methods of slowing or preventing Huntington's disease progression using an antisense compound targeted to huntingtin. Additionally provided are methods of delaying or preventing the onset of Huntingtin's disease in an individual susceptible to Huntingtin's Disease. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders.

Abstract: The invention relates to antisense oligonucleotidic sequences (ODN) against Smad7 suitably modified, and their uses in medical field as therapeutic biological agents, in particular in the treatment of chronic inflammatory bowel disease, such as Crohn's disease and ulcerative colitis.

Abstract: Provided herein are, inter alia, nucleic acid compounds useful for targeting CTLA-4-expressing cells and modulating cell activity of the CTLA-4-expressing cells. The compositions provided herein may be part of pharmaceutical compositions and may be used for treatment of cancer, inflammatory diseases, infectious diseases or metabolic diseases.

Abstract: The present invention concerns methods and reagents useful in modulating gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to synthetic chemically modified small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules capable of mediating RNA interference (RNAi) against target nucleic acid sequences. The small nucleic acid molecules are useful in the treatment of any disease or condition that responds to modulation of gene expression or activity in a cell, tissue, or organism.

Abstract: This invention provides plants having resistance to invertebrate pests. More specifically, this invention discloses a non-natural transgenic plant cell expressing at least one invertebrate miRNA in planta for suppression of a target gene of an invertebrate pest or of a symbiont associated with the invertebrate pest. Also provided are recombinant DNA constructs for expression of at least one invertebrate miRNA in planta, a non-natural transgenic plant containing the non-natural transgenic plant cell of this invention, a non-natural transgenic plant grown from the non-natural transgenic plant cell of this invention, and non-natural transgenic seed produced by the non-natural transgenic plants, as well as commodity products produced from a non-natural transgenic plant cell, plant, or seed of this invention.

Abstract: The present disclosure pertains generally to double-stranded small interfering RNAs that modulate gene expression for use in research, diagnostics, and/or therapeutics. In certain embodiments, the present disclosure provides double-stranded small interfering RNAs that modulate DUX4 gene expression. In certain embodiments, the present disclosure provides methods of inhibiting DUX4 gene expression by contacting a cell with double-stranded small interfering RNAs.

Abstract: The present invention provides an antiviral agent comprising an RNA oligonucleotide having a particular sequence and structure. Specifically, when a cell line is treated with an RNA oligonucleotide having specific sequence and helical bend structure according to the present invention, the expression of interferon-? or ISG56 is increased and anti-viral activating is exhibited. Thus, a composition comprising the RNA oligonucleotide can be used as an antiviral agent.

Abstract: The disclosure provides compositions and methods involving viral RNA segments for use in modulating immune responses, including inhibition inflammation related to pathogenic T-cell activation. In addition, modification of the viral sequences responsible for modulating immune response provides for improved vaccine formulations.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a Serum Amyloid A (SAA) gene, and methods of using the dsRNA to inhibit expression of SAA.

Abstract: This invention provides UNA oligomers for therapeutics having prolonged stability. The UNA oligomers can be composed of one or more 2?-3?-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used for therapeutics that target oligonucleotides, nucleic acids, or RNAs to reduce their activity.

Abstract: The present invention relates to oligomeric compounds and conjugates thereof that target Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) PCSK9 mRNA in a cell, leading to reduced expression of PCSK9. Reduction of PCSK9 expression is beneficial for a range of medical disorders, such as hypercholesterolemia and related disorders.

Abstract: The present embodiments provide methods, compounds, and compositions for treating, preventing, ameliorating, or slowing progression of retinitis pigmentosa (RP), such as autosomal dominant retinitis pigmentosa (AdRP) by administering a P23H rhodopsin specific inhibitor to a subject. The present embodiments provided herein are directed to compounds and compositions useful for treating, preventing, ameliorating, or slowing progression of retinitis pigmentosa (RP), such as autosomal dominant retinitis pigmentosa (AdRP). In certain embodiments, P23H rhodopsin inhibitors provided herein are allele-specific antisense compounds targeted to a P23H mutant allele that are capable of selectively inhibiting expression of P23H rhodopsin mutant protein to a greater extent than wild-type protein.

Abstract: This disclosure concerns nucleic acid molecules and methods of use thereof for control of pathogens through RNA interference-mediated inhibition of target coding and transcribed non-coding sequences in pathogens. The disclosure also concerns methods for applying dsRNA through formulations and/or transgenic plants that express nucleic acid molecules useful for the control of pathogens, and the plant cells and plants obtained thereby.

Abstract: The invention provides a double-stranded ribonucleic acid (dsRNA) having a chain length suitable for simultaneously showing low toxicity and high function in the use of an adjuvant and the like, and resisting variation of chain length even when subjected to a heating and cooling treatment, or a salt thereof; an immune potentiator, adjuvant, pharmaceutical product and the like containing the dsRNA and the like; and a production method of such dsRNA and the like. The invention is characterized in that the weight average chain length of two or more single-stranded ribonucleic acids (ssRNAs) constituting the first chain constituting dsRNA is not more than ½ of the weight average chain length of one ssRNA constituting the second chain.

Abstract: Materials and methods for regulating gene expression using nanoparticles functionalized with antisense oligonucleotides are provided.

Abstract: In certain embodiments, the present disclosure provides compounds and methods for increasing the antisense activity of an antisense compound in a cell. In certain embodiments, the present disclosure provides methods for identifying antisense compounds having high activity. In certain embodiments, the present disclosure provides methods for identifying antisense compounds that bind to enhancer or repressor proteins.

Abstract: The present invention relates to antisense-oligonucleotides having a length of at least 10 nucleotides, wherein at least two of the nucleotides are LNAs, their use as inhibitors of TGF-R signaling, pharmaceutical compositions containing such antisense-oligonucleotides and the use for prophylaxis and treatment of neurological, neurodegenerative, fibrotic and hyperproliferative diseases.

Abstract: In certain aspects, provided herein are RNA complexes (e.g., asymmetric RNA complexes, such as asiRNAs or cell penetrating asiRNAs) that inhibit IL4R?, TRPA1, and/or F2RL1 expression and are therefore useful for treating atopic dermatitis or asthma.

Abstract: The present disclosure relates to compositions and methods for treating cancers using antisense (AS) nucleic acids directed against Insulin-like Growth Factor 1 Receptor (IGF-1R). The AS may be administered to the patients systemically, or may be used to produce an autologous cancer cell vaccine. In embodiments, the AS are provided in an implantable irradiated biodiffusion chamber comprising tumor cells and an effective amount of the AS. The chambers are irradiated and implanted in the abdomen of subjects and stimulate an immune response that attacks tumors distally. The compositions and methods disclosed herein may be used to treat many different kinds of cancer, for example glioblastoma.

Abstract: The present invention relates to a pharmaceutical composition for inhibiting cancer cell metastasis, the pharmaceutical composition including at least one of: (1) si-rpS3/203 binding to a 203rd base sequence of rpS3 mRNA; (2) si-rpS3/635 binding to a base sequence corresponding to a position 635 of the rpS3 mRNA; (3) si-rpS3/747 binding to a base sequence corresponding to a position 747 of the rpS3 mRNA; and (4) si-rpS3/766 binding to a base sequence corresponding to a position 766 of the rpS3 mRNA.

Abstract: Provided are a cationic lipid which facilitates the introduction of a nucleic acid into, for example, a cell or the like; a composition containing the cationic lipid and a nucleic acid; a method for introducing a nucleic acid into a cell by using a composition containing the cationic lipid and the nucleic acid; and the like. The cationic lipid is, for example, a cationic lipid represented by formula (A): formula (A): (wherein R1 is alkenyl or the like, R2 is alkenyl or the like, R3 and R4 are each alkyl, or are combined together to form alkylene, or R3 and R5 are combined together to form alkylene, R5 is a hydrogen atom or the like, or is combined together with R3 to form alkylene, X1 is alkylene, and X2 is a single bond or alkylene).

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the ANGPTL3 gene, as well as methods of inhibiting expression of ANGPTL3 and methods of treating subjects having a disorder of lipid metabolism, such as hyperlipidemia or hypertriglyceridemia, using such dsRNA compositions.

Abstract: The present disclosure provides a pharmaceutical composition for treating cancer comprising an RNA oligonucleotide having a particular sequence and structure. Specifically, when a cell line is treated with an RNA oligonucleotide having specific sequence and helical bend structure according to the present disclosure, the expression of ISG56 is increased and apoptosis of cancer cells is induced. Thus, a composition comprising the RNA oligonucleotide can be used as an anticancer agent.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

Abstract: Antisense molecules capable of binding to a selected target site in the dystrophin gene to induce exon skipping are described.