Abstract: Provided are engineered split Cas12b systems and methods of use thereof. Also provided are compositions comprising one or more components of the engineered split Cas12b systems, as well as engineered cells and non-human animals produced by the methods. The systems, methods and compositions are useful for genome editing, transcription modulation and gene therapy.

Abstract: A method for performing gene editing on a target site in a cell, specifically a method for performing gene editing on a target site of a cell genome, comprising: (a) providing a cell to be genetically edited; (b) introducing into the cell (i) a gene editing enzyme or the encoding nucleic acid thereof or a first expression vector expressing the gene editing enzyme; and (ii) gRNA or a second expression vector expressing the gRNA, and performing gene editing on a target site of the cell genome, the gRNA directing the gene editing enzyme to perform fixed-point cutting on the target site; the targeting sequence of the gRNA targeting comprises one or more of the sequences shown in SEQ ID. No. 1-9. The method enables efficient gene editing to be performed on the target site.

Abstract: Engineered CRISPR proteins may be generated for localized anchoring to targeted cellular locations. Engineered CRISPR proteins may be generated by a lipidation motif with a CRISPR protein. The lipidation motif may be post-translationally modified to anchor the lipidation motifs and the fused CRISPR protein to a targeted cellular location, such as membranes of organelles associated with viral infections or other ailments. To account for possible additional amino acids that might affect the efficiency of post-translational modifications, linkers derived from C-terminal ends OAS1 (p46 isoform) and ZAP-L proteins may be used. Different fusion designs and/or different lipidation motifs may be used to target CRISPR proteins to specific and respective cellular locations. Targeted cellular localization of engineered CRISPR proteins may enable targeted therapies involving the engineered CRISPR proteins.

Abstract: The present invention relates to a mutant of human ?-N-acetylglucosaminidase (hNAGLU), more specifically a hNAGLU mutant produced by adding a mutation to an amino acid sequence for hNAGLU such that an expression level of hNAGLU in a host cell in which a gene encoding hNAGLU is introduced can be increased compared with the case where a gene encoding wild-type hNAGLU is introduced. For example, the hNAGLU mutant has an amino acid sequence represented by SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 15, or SEQ ID NO: 19, or has an amino acid sequence introduced a mutation to the amino acid sequence of any one of the hNAGLU mutants.

Abstract: The present invention relates to variants of an alpha-amylase which have an increased solubility at pH 6.0, an increased solubility at pH 10.0, a higher resistance to protein aging, and/or an increased specific activity compared to the parent alpha-amylase. The present invention also relates to methods of making the variant alpha-amylase and the use of the variant alpha-amylase in processing starch, cleaning or washing textiles, hard surfaces, or dishes, making ethanol, treating an oil well, processing pulp or paper, animal feed, syrup production, and preparing a dough or a baked product prepared from the dough.

Abstract: The present invention relates to a method for separating a molecule of interest from an antifoaming agent in a fermentation broth comprising said molecule of interest and said antifoaming agent. The method comprises the steps of filtering the fermentation broth at a temperature in the range of 1° C. to 15° C. above the cloud point of the antifoaming agent, and thereby obtaining a first fraction of the fermentation broth comprising the molecule of interest and a second fraction of the fermentation broth comprising the antifoaming agent, wherein the antifoaming agent is a polyalkylene glycol based antifoaming agent. The invention further relates to a process for purifying a molecule of interest from a fermentation broth comprising said method.

Abstract: The present invention relates to protease variants having polyester degrading activity, polynucleotides encoding said variants, nucleic acid constructs and expression vectors comprising said polynucleotides, host cells expressing said variants, compositions comprising the variants, methods of producing the variants, and use of the variants.

Abstract: The present invention relates to microencapsulated microbial cultures with high storage stability and methods for producing these. In particular, the present invention relates to microbial cultures formulated in complex coacervates comprising octenyl succinic anhydride (OSA) starch and chitosan, products comprising such formulations.

Abstract: The invention provides a miniaturized cytidine deaminase-containing complex for modifying DNA formed by combining a nucleic acid sequence recognition module and cytidine deaminase, wherein the nucleic acid sequence recognition module specifically binds to a target nucleotide sequence of double-stranded DNA, the cytidine deaminase is composed of an amino acid sequence composed of a region of amino acid residues at positions 30-150 of SEQ ID NO: 1, an ortholog thereof, an amino acid sequence having mutations of one or several amino acids therein, or an amino acid sequence having at least 90% similarity thereto, and the targeted site of the double-stranded DNA is modified.

Abstract: In one example embodiment, methods of generating a single prokaryotic cell cDNA library include barcoding RNAs from different prokaryotic cells individually, allowing cell identity of each RNA to be retained in a single sequencing library. In one example embodiment, methods include, prior to generating a cDNA library, degrading rRNA and DNA in each cell of a set of fixed and permeabilized cells. In one example embodiment, methods include converting mRNA in each fixed and permeabilized cell into cDNA labeled with a cell-specific first and second barcode combination and a unique molecular identifier (UMI). In one example embodiment, methods include amplifying labeled cDNA and preparing a sequencing library of amplified labeled cDNA.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.

Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.

Abstract: Provided herein are methods of determining a surgical margin and the site and size of a tissue to be resected from a subject, and methods of use thereof.

Abstract: Methods of reducing adapter-dimers in a sequencing library are provided according to aspects of the present disclosure, including: hybridizing excess 3? adapters to blocker oligonucleotides forming a hybridized complex, such that the excess 3? adapters are unavailable to form adapter-dimers, the hybridized complex including: a first blocker oligonucleotide 3? terminus adjacent to an adenylated nucleotide at the 5? terminus of a first unligated 3? adapter and a second blocker oligonucleotide 3? terminus adjacent to an adenylated nucleotide at the 5? terminus of a second unligated 3? adapter, wherein the first blocker oligonucleotide has a 5? portion complementary to and hybridized to the first unligated 3? adapter, the second blocker oligonucleotide has a 5? portion complementary to and hybridized to the second unligated 3? adapter, and the first blocker oligonucleotide has a 3? portion complementary to, and hybridized to, a 3? portion of the second blocker oligonucleotide.

Abstract: Provided herein are materials and methods useful for facilitating transgene recombination. The present disclosure relates to, for example, techniques for manipulating recombination frequencies and generating organisms that contain multiple transgenic elements docking at the same locus on a single chromosome. The time consumed by the entire recombination process is proportional to the logarithm of the number of transgenes to be recombined.

Abstract: The present invention provides closed linear DNA (clDNA) consisting of a stem region comprising a double stranded DNA sequence of interest covalently closed at both ends by hairpin loops, the clDNA comprising at least two modified nucleotides. The invention also provides the clDNA for use in therapy, in particular, gene therapy, as well as pharmaceutical compositions comprising the clDNA and a method for the production of the clDNA.

Abstract: The disclosure provides polynucleotides encoding a polypeptide including a morpholino linker. In some embodiments, the polynucleotides of the invention have increased stability compared to wild-type polynucleotides.

Abstract: An oligomer comprising a sense strand and an antisense strand that mediates RNA interference against a target RNA sequence having a trinucleotide repeat expansion is provided, wherein the antisense strand is complementary to the target RNA sequence and comprises a sequence having at least 80% identity to the sequence of Formula (I): rGrCrUrGrCrUrGrCX1X2rCrUrGrCrUrGrCrUrG (I), wherein X1 and X2 are each independently selected from the group consisting of rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X1 and X2 is a UNA monomer; the oligomer comprises a UNA monomer at the first position at the 5?-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomers are useful as therapeutics targeting polyglutamine diseases and other diseases stemming from a trinucleotide repeat expansion.

Abstract: The invention relates to a composition comprising a set of two single stranded antisense oligonucleotides (AONs), wherein one AON is the ‘Editing AON’ and the other AON is the ‘Helper AON’, for use in the deamination of a target adenosine in a target RNA to an inosine, wherein the Editing AON is complementary to a stretch of nucleotides in the target RNA that includes the target adenosine, wherein the Helper AON is complementary to a stretch of nucleotides in the target RNA that is separate from the stretch of nucleotides that is complementary to the Editing AON, wherein the Helper AON has a length of 16 to 22 nucleotides and the Editing AON has a length of 16 to 22 nucleotides.

Abstract: This application discloses a method for treating a human patient. The method includes administering to the patient a pharmaceutical composition having one or more miRNA of the miR-17˜92 cluster, or an miRNA mimic of an miRNA of the miR-17˜92 cluster. The patient has at least one medical condition that places him or her at an increased risk of developing AKI, incipient AKI, or a sequelae of AKI.

Abstract: Methods for removing excess free ?-globin in erythroid cells and treating a thalassemia using a miR-144 and/or miR-451 antagomir are described.

Abstract: The invention provides enhancer RNAs (eRNAs) that are expressed specifically in glioma stem cells and whose expression correlates with decreased survival of patients with glioblastomas. The eRNAs are selected, for example, from eTMEM88b, eRTP5, or eNINJ1. The invention also provides an RNA therapy that targets glioma stem cell eRNAs using synthetic oligonucleotides that knock out the eRNA expression. The invention further provides viral vectors that deliver shRNA that inhibit the expression of the eRNA.

Abstract: The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, capable of inhibiting Apolipoprotein C-III (also called APOC3, apoC-III, APOC-III, and APO C-III) gene expression, and compositions that include APOC3 RNAi agents. The APOC3 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that include N-acetyl-galactosamine, to facilitate the delivery to cells, including to hepatocytes. Pharmaceutical compositions that include one or more APOC3 RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the APOC3 RNAi agents in vivo provides for inhibition of APOC3 gene expression, and can result in lower triglycerides and/or cholesterol levels in the subject. The APOC3 RNAi agents can be used in methods of treatment of APOC3-related diseases and disorders, including hypertriglyceridemia, cardiovascular disease, and other metabolic-related disorders and diseases.

Abstract: Disclosed herein are antisense compounds and methods for decreasing Tau mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Tau-associated diseases, disorders, and conditions.

Abstract: Disclosed is an exosome secreted from gene-modified cells with long non-coding ribonucleic acids (lncRNA) elevated in non-alcoholic fatty liver (lncENAF) and application thereof, belonging to the technical field of cell biology. The exosome is secreted by a cell strain of human embryonic kidney 293T cells (HEK-293T) obtained by genetic engineering, and the cell strain of HEK-293T stably expresses lncENAF, where the lncENAF has a nucleotide sequence as shown in SEQ ID NO: 1.

Abstract: Provided herein are, inter alia, nucleic acids (e.g., siRNA), lipid nanoparticles comprising nucleic acids, pharmaceutical compositions comprising nucleic acids, pharmaceutical compositions comprising lipid nanoparticles, and methods of treating COV-ID-19, SARS viruses, and Middle Eastern respiratory syndrome.

Abstract: The present invention relates to an artificial RNA having at least one hybridization region against one or more target disruption structures of one or more RNA fragments, wherein such an artificial RNA suitable for disrupting by hybridization one or more target disruption structures of one or more RNA fragments, thereby modulating the functionality of the one or more RNA fragments.

Abstract: Described herein are antiviral silencing RNA molecules (siRNAs), pharmaceutical compositions comprising same and uses thereof for the treatment of viral infections. In embodiments the siRNAs comprises chemically modification(s) for enhanced cell penetrating abilities and/or for greater nuclease resistance. Examples of chemical modifications include substituting one or more nucleotides of a native siRNA molecule with 2?-O-Methylnucleoside, 2?-Fluoronucleoside, aminoalkyl-nucleotide, aminoethyl-nucleotide, and/or 5?-aminopropyl-2?-OMe-nucleoside. The chemically modified nucleotides may be incorporated into the P strand, the G strand or both. Other possible modifications include coupling a compound such as a spermine molecule to the 5? terminus or the 3? terminus of the siRNA.

Abstract: This study describes a method to determine the likelihood of the development of metastasis in a subject suffering from cancer, in addition to a method to design a customized therapy in a subject suffering from cancer, in particular breast, colon, lung, kidney and thyroid cancer, based on the determination of the expression level of one or more genes whose expression is modulated by an increase in c-MAF expression. It also describes a method for the identification of marker genes with a propensity for metastatic cancer based on inducing the modulation of the c-MAF expression Finally, the use of PTHLH and PODXL inhibitors and RERG activators in the treatment and/or prevention of the cancer, in particular breast, colon, lung, kidney and thyroid cancer.

Abstract: The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the TRAF6 gene, as well as methods of inhibiting expression of TRAF6, and methods of treating subjects that would benefit from reduction in expression of TRAF6, such as subjects having a TRAF6-associated disease, disorder, or condition, using such dsRNA compositions.

Abstract: The techniques of the present disclosure provide a method of inhibiting tumor growth in a tissue of a mammal. The method includes administering to the mammal a therapeutically effective amount of a composition comprising an siRNA molecule that binds to an mRNA that codes for TGF?1 protein, an siRNA molecule that binds to an mRNA that codes for VEGFR2 protein, and a pharmaceutically acceptable carrier comprising a pharmaceutically acceptable polypeptide polymer. The techniques of the present disclosure also provide for additional methods for using this composition.

Abstract: The present invention relates to complement C1r subcomponent (C1R) inhibitors for use in treatment of neurological diseases. The invention in particular relates to the use of C1R inhibitors for down-regulation of C1R expression. The invention also relates to nucleic acid molecules, which are complementary to C1R and capable of reducing the level of an C1R mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of neurological diseases.

Abstract: The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the ketohexokinase (KHK) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a KHK gene and to methods of treating or preventing a KHK-associated disorder in a subject.

Abstract: The present disclosure relates to gene therapy targeting GluK2 subunit that can be used to inhibit epileptiform discharges. Short interfering RNA sequences against the human Grik2 gene sequence are described which are efficient in decreasing the expression of GluK2-containing KARs in neurons engineered to express the equivalent shRNA or miRNA. Using a tissue culture model of TLE, the examples remarkably demonstrate that viral expression of shRNA or miRNA inhibits the frequency of epileptiform discharges. Therefore, RNA therapeutics aimed at decreasing the expression of GluK2-containing KARs in neurons can remarkably prevent spontaneous epileptiform discharges in TLE. In particular, the present disclosure relates to a recombinant antisense oligonucleotide that targets a Grik2 mRNA.

Abstract: The present application provides novel oligonucleotides and therapeutic use thereof. The oligonucleotides of the present invention can be used for the activation or modulation of immunity in the subject.

Abstract: The present invention belongs to the field of virology, in particular to the field of hepatitis B virus treatment. Provided are a model and a method for screening HBV cccDNA inhibitors. According to the screening model and the method, the detection of a split luciferase is used as an alternative index ofHBV cccDNA detection, and a cccDNA-targeted drug can be screened in high throughput.

Abstract: The invention relates to mRNA therapy for the treatment of Fabry disease. mRNAs for use in the invention, when administered in vivo, encode human the ?-galactosidase A (GLA), isoforms thereof, functional fragments thereof, and fusion proteins comprising GLA. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of GLA expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GLA activity in subjects, namely Gb3 and lyso-Gb3.

Abstract: The invention relates to a complex comprising a Cell Penetrating Peptide and one or more nucleic acids which can be applied to a plant by spraying and which can trigger a physiological outcome. Hereto, the one or more nucleic acids complex with a Cell Penetrating Peptide can be dissolved in water without the presence of additional components in the solution.

Abstract: Compositions and methods are provided for genome modification of a target sequence in the genome of a plant or plant cell. The methods and compositions employ a guide RNA/Cas endonuclease system to provide an effective system for modifying or altering target sites within the genome of a plant, plant cell or seed. Also provided are compositions and methods employing a guide polynucleotide/Cas endonuclease system for genome modification of a nucleotide sequence in the genome of a cell or organism, for gene editing, and/or for inserting or deleting a polynucleotide of interest into or from the genome of a cell or organism. Once a genomic target site is identified, a variety of methods can be employed to further modify the target sites such that they contain a variety of polynucleotides of interest. Breeding methods and methods for selecting plants utilizing a two component RNA guide and Cas endonuclease system are also disclosed.

Abstract: Described in several example embodiments herein are soybean plants and soybeans having one or more KTI genes having reduced or eliminated expression and/or activity thereby resulting soybean plants and soybeans having reduced or eliminated trypsin inhibition. In some embodiments, the soybean plants and soybeans are engineered to have one or more modified KTI genes. Also described herein are methods of making, growing, and using the soybean plants and soybeans described herein.

Abstract: The present invention relates to modifications of berberine bridge enzyme-like nucleic acids and their use in modulation of nicotine biosynthesis in plants.

Abstract: The present invention is directed to a transgenic plant and a method for producing the same. In particular, the present invention is directed to a transgenic plant or a plant cell in which a nucleic acid molecule encoding an m6A demethylase is introduced, wherein said m6A demethylase has the following two domains: i) N-terminal domain (NTD) having the function of AlkB oxidation demethylase; and ii) C-terminal domain (CTD). The present invention is also directed to a method for producing said plant, comprising introducing a nucleic acid molecule encoding an m6A demethylase into a regenarable plant cell, and regenerating a transgenic plant from the regenerable plant cell.

Abstract: Provided are a phosphorus-efficient and high-yield gene of crops, and an application thereof. It is first disclosed that a PHO1;2 gene has a regulating function on filling of crop kernels. Up-regulating the expression of the gene in crops can significantly promote filling of the crop kernels, increase the kernel weight of the crop kernels, the kernels per spike, the tiller number and the kernel thickness, and/or promote thickening of the crops. The PHO1;2 gene plays a two-way phosphorus transport effect which mainly conveys phosphorus to the extracellular domain, can regulate intracellular phosphorus accumulation, increase the utilization rate of phosphorus in crops, and improve the duration of crops to a low-phosphorus environment.

Abstract: Methods for improving the efficiency and productivity of hybrid corn seed production are provided herein. Various methods to improve the transfer of pollen from male corn plants to female corn plants, and thus increase yield, are provided herein. Without being limiting, these methods include varying the height of male and female corn plants in a field, as well as varying the number, arrangement, and ratio of male-to-female rows in a field.

Abstract: Providing a B3 transcription factor gene for simultaneously improving length, strength and elongation of cotton fibers. The cDNA sequence of gene GHFLS in tetraploid upland cotton TM-1 is SEQ ID NO. 1, and the genome sequence is SEQ ID NO. 2; GHFLS contains a non-synonymous mutation SNP, located at 1391 bp of the coding region with the base changing from A to G and the corresponding amino acid changing from Lys to Arg. The GHFLS gene was overexpressed in Arabidopsis thaliana caused a significant reduction in the root length of the T2 generation, demonstrating its important role in the cell elongation mechanism. The fiber quality of the cotton variety (line) with haplotype AA is significantly better than that with haplotype GG. The gene has important research value and application prospect in efficiently identifying high-quality fiber upland cotton varieties, improving cotton fiber quality and cultivating new varieties of high-quality cotton fibers.

Abstract: The invention relates to genetically altered plants with improved traits, in particular steeper root growth. The invention also relates to methods for making such plants and methods for modulating root growth, in particular methods that employ gene editing techniques.

Abstract: The present invention relates to novel plants displaying an improved resistance to nematodes. The present invention also relates to seeds and parts of said plants. The present invention further relates to methods of making and using such seeds and plants. The present invention also relates to a novel SmD1 allele, which results in a modified SmD1 protein associated with such improved resistance to nematodes.

Abstract: A novel transgenic corn event designated 5307, is disclosed. The invention relates to DNA sequences of the recombinant constructs inserted into the corn genome and of genomic sequences flanking the insertion site that resulted in the 5307 event. The invention further relates to assays for detecting the presence of the DNA sequences of event 5307, to corn plants and corn seeds comprising the genotype of and to methods for producing a corn plant by crossing a corn plant comprising the event 5307 genotype with itself or another corn variety.

Abstract: The present invention relates to helper plasmids and two-plasmid systems for producing recombinant AAV (rAAV) vectors. The invention further relates to methods of using, or uses of the helper plasmids and two-plasmid systems of the invention. The present invention also relates to a helper plasmid which does not comprise a cap gene encoding a functional set of Cap proteins and which does comprise at least one rep gene and at least one helper virus gene.

Abstract: The present invention relates to AAVs encoding a SOD1 targeting polynucleotide which may be used to treat amyotrophic lateral sclerosis (ALS) and/or canine degenerative myelopathy (DM).