Abstract: Disclosed are RNA-targeting gene therapy compositions and methods for destroying or blocking toxic target CUG repeat RNA and treating DM1.

Abstract: Disclosed are methods and compositions for promoting trans-splicing. In some embodiments, the composition comprises an engineered small nuclear RNA that promotes trans-splicing of a target RNA molecule. The composition may further comprise an RNA donor molecule.

Abstract: Disclosed are RNA-targeting gene therapy compositions and methods for destroying or blocking toxic target CAG repeat RNA and treating CAG repeat disorders such as Huntington's Disease (HD) and Spinocerebellar Ataxia Type 1 (SCA1).

Abstract: Cas9 polypeptides which target RNA and methods of using them are provided.

Abstract: Disclosed are compositions comprising: a trans-splicing nucleic acid comprising (a) one or more replacement domains that encode a therapeutic sequence; and (b) one or more intronic domains that promote RNA splicing of the replacement domain primarily in a specific tissue or cell type; and (c) one or more antisense domains that promote binding to a target RNA molecule, wherein an RNA trans-splicing reaction promotes insertion of the replacement domain into a target RNA. Methods of making and methods of using compositions of the disclosure are also provided, including but not limited to compositions of the disclosure that may be used in the treatment of a disease or disorder in a patient or subject. Example disease or disorders of the disclosure include genetic and epigenetic diseases or disorders.

Abstract: Cas9 polypeptides which target RNA and method of using them are provided.

Abstract: Provided herein are methods of identifying a cell uptake modulator of a molecule that include (a) contacting a plurality of cells of a cell-containing biological sample with a plurality of gene-editing agents, wherein a gene-editing agent from the plurality of gene-editing agents recognizes and alters a target gene of at least one cell of the plurality of cells; (b) contacting the plurality of cells with a plurality of molecules, wherein at least one molecule of the plurality of molecules is transported into at least one cell of the plurality of cells; and (c) detecting a presence of the at least one molecule in the plurality of cells, thereby identifying the cell uptake modulator of the molecule.

Abstract: Disclosed herein is a technology to perform programmable RNA editing at single-nucleotide resolution using RNA-targeting CRISPR/Cas9. This approach, which Applicants have termed “Cas9-directed RNA editing” or “CREDIT,” provides a means to reversibly alter genetic information in a temporal manner, unlike traditional CRISPR/Cas9 driven genomic engineering which relies on permanently altering DNA sequence.

Abstract: Disclosed herein is a technology to perform programmable RNA editing at single-nucleotide resolution using RNA-targeting CRISPR/Cas9. This approach, which Applicants have termed “Cas9-directed RNA editing” or “CREDIT,” provides a means to reversibly alter genetic information in a temporal manner, unlike traditional CRISPR/Cas9 driven genomic engineering which relies on permanently altering DNA sequence.

Abstract: Disclosed are compositions comprising a sequence encoding a non-self polypeptide of interest (POI), and a sequence encoding a non-cleavable FASL, wherein expression of the non-cleavable FASL in the presence of IL-6 or TNF-alpha eliminates WIC-mediated immunogenic peptides and helper T cells specific to the expression of the POI. Methods of making and methods of using compositions of the disclosure are also provided. For example, compositions of the disclosure may be used in the combined treatment of a disease or disorder in a subject and immune masking activity specific to the treatment. Exemplary disease or disorders of the disclosure include genetic and epigenetic diseases or disorders.

Abstract: Disclosed are compositions comprising: (a) a sequence comprising a guide RNA (gRNA) that specifically binds a target sequence within an RNA molecule and (b) a sequence encoding a fusion protein, the sequence comprising a sequence encoding a first RNA-binding polypeptide and a sequence encoding a second RNA-binding polypeptide, wherein neither the first RNA-binding polypeptide nor the second RNA-binding polypeptide comprises a significant DNA-nuclease activity, wherein the first RNA-binding polypeptide and the second RNA-binding polypeptide are not identical, and wherein the second RNA-binding polypeptide comprises an RNA-nuclease activity. Methods of making and methods of using compositions of the disclosure are also provided. For example, compositions of the disclosure may be used in the treatment of a disease or disorder in a subject. Exemplary disease or disorders of the disclosure include genetic and epigenetic diseases or disorders.

Abstract: Disclosed are compositions and methods for specifically targeting and knocking down pathogenic RNA molecules which lead to toxic gain-or-loss-of-function mutations while also replacing the targeted, and knocked down, gene with a therapeutic replacement gene.

Abstract: Disclosed are compositions comprising: a sequence encoding a fusion protein, the sequence comprising a sequence encoding a first RNA-binding polypeptide and a sequence encoding a second RNA-binding polypeptide, wherein neither the first RNA-binding polypeptide nor the second RNA-binding polypeptide comprises a significant DNA-nuclease activity, wherein the first RNA-binding polypeptide and the second RNA-binding polypeptide are not identical, and wherein the second RNA-binding polypeptide comprises an RNA-nuclease activity. Methods of making and methods of using compositions of the disclosure are also provided. For example, compositions of the disclosure may be used in the treatment of a disease or disorder in a subject. Exemplary disease or disorders of the disclosure include genetic and epigenetic diseases or disorders.

Abstract: Cas9 polypeptides which target RNA and methods of using them are provided

Abstract: Disclosed are compositions comprising: (a) a sequence comprising a guide RNA (gRNA) that specifically binds a target sequence within an RNA molecule and (b) a sequence encoding a fusion protein, the sequence comprising a sequence encoding a first RNA-binding polypeptide and a sequence encoding a second RNA-binding polypeptide, wherein neither the first RNA-binding polypeptide nor the second RNA-binding polypeptide comprises a significant DNA-nuclease activity, wherein the first RNA-binding polypeptide and the second RNA-binding polypeptide are not identical, and wherein the second RNA-binding polypeptide comprises an RNA-nuclease activity. Methods of making and methods of using compositions of the disclosure are also provided. For example, compositions of the disclosure may be used in the treatment of a disease or disorder in a subject. Exemplary disease or disorders of the disclosure include genetic and epigenetic diseases or disorders.

Abstract: Disclosed are compositions comprising: (a) a sequence comprising a guide RNA (gRNA) that specifically binds a target sequence within an RNA molecule and (b) a sequence encoding a fusion protein, the sequence comprising a sequence encoding a first RNA-binding polypeptide and a sequence encoding a second RNA-binding polypeptide, wherein neither the first RNA-binding polypeptide nor the second RNA-binding polypeptide comprises a significant DNA-nuclease activity, wherein the first RNA-binding polypeptide and the second RNA-binding polypeptide are not identical, and wherein the second RNA-binding polypeptide comprises an RNA-nuclease activity. Methods of making and methods of using compositions of the disclosure are also provided. For example, compositions of the disclosure may be used in the treatment of a disease or disorder in a subject. Exemplary disease or disorders of the disclosure include genetic and epigenetic diseases or disorders.

Abstract: Disclosed are compositions and methods for simultaneously providing a gene therapy and preventing an adaptive immune response to a cell modified by the gene therapy by the immune system of a subject. In some embodiments, compositions of the disclosure modify a level of expression of an RNA molecule associated with a disease or disorder as well as inhibit expression or activity of a component of an adaptive immune response to mask the modified cell from a subject's immune system.

Abstract: Cas9 polypeptides which target RNA and methods of using them are provided.

Abstract: Disclosed herein is a technology to perform programmable RNA editing at single-nucleotide resolution using RNA-targeting CRISPR/Cas9. This approach, which Applicants have termed “Cas9-directed RNA editing” or “CREDIT,” provides a means to reversibly alter genetic information in a temporal manner, unlike traditional CRISPR/Cas9 driven genomic engineering which relies on permanently altering DNA sequence.

Abstract: Cas9 polypeptides which target RNA and methods of using them are provided.