Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nuclear RNAs to induce DUX4 exon-skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

Abstract: Products and methods for treating or preventing muscular dystrophies in patients with duplications of exon (2) in their DMD gene or DMD mutations of any class that maintain a functional IRES sequence within exon (5), and an open reading frame from exon (6) though the end of the DMD gene are provided. Gene therapy vectors, such as adeno-associated virus (AAV) vectors and methods of using these vectors to express DMD are provided. The products and methods are used for treating and/or preventing muscular dystrophies, such as Duchenne Muscular Dystrophy or Becker Muscular Dystrophy.

Abstract: Products and methods for treating or preventing muscular dystrophies in patients with mutations in the 5? end of their DMD gene are provided. In some aspects, oligonucleotides, antisense phosphorodiamidate morpholino oligomers (PMO), and antisense cell penetrating peptide-conjugated PMOs (PPMOs) are provided for skipping exon 2 of the DMD gene. These oligonucleotides and oligomers can selectively suppress mutant forms of the dystrophin protein while allowing a functional form of the dystrophin protein to be expressed in sufficient quantity to retain its function in the cell. The oligonucleotides or oligomers can regulate or restore expression of transcripts of the DMD gene and a functional form of the dystrophin protein. Methods comprising administering the oligonucleotides. PMO, and PPMO targeting the DMD gene are provided. The products and methods are used for treating, ameliorating and/or preventing muscular dystrophies, such as Duchenne Muscular Dystrophy or Becker Muscular Dystrophy.

Abstract: Products and methods for treating or preventing muscular dystrophies in patients with mutations in any of exons 6, 7, 8, or 9 in their DMD gene are provided. Gene therapy vectors, such as adeno-associated virus (AAV) vectors, and methods of using these vectors to deliver nucleic acids comprising DMD antisense sequences in regulating or restoring expression of transcripts of the DMD gene and a functional form of the dystrophin protein are provided. The products and methods are used for treating, ameliorating and/or preventing muscular dystrophies, such as Duchenne Muscular Dystrophy or Becker Muscular Dystrophy.

Abstract: Disclosed herein are products, methods, and uses for treating, ameliorating, udaying the progression of, and/or preventing a muscular dystrophy or a cancer including, but not limited to, facioscapulohumeral muscular dystrophy (FSHD) or a sarcoma. More particularly, disclosed herein are RNA interference-based products, methods, and uses for inhibiting or downregulating the expression of double homeobox 4 (DUX4). Even more particularly, the disclosure provides nucleic acids comprising U7 DUX4 antisense sequences for inhibiting or downregulating the expression of DUX4 and methods of using said antisense sequences to inhibit or downregulate DUX4 expression in cells and/or in cells of a subject having a muscular dystrophy or a cancer including, but not limited to, FSHD or a cancer.

Abstract: The disclosure provides gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of an Interferon regulatory factor 2 binding protein like (IRF2BPL) disorder.

Abstract: The disclosure relates to the field of gene therapy for the treatment of a muscular dystrophy including, but not limited to, Duchenne Muscular Dystrophy (DMD). More particularly, the disclosure provides nucleic acids, including nucleic acids encoding U7-based small nuclear ribonucleic acids (RNAs) (snRNAs), U7-based snRNAs, and recombinant adeno-associated virus (rAAV) comprising the nucleic acid molecules to deliver nucleic acids encoding U7-based snRNAs to induce exon-skipping for use in treating a muscular dystrophy including, but not limited to, DMD, resulting from a mutation amenable to skipping exon 44 of the DMD gene (DMD exon 44) including, but not limited to, any mutation involving, surrounding, or affecting DMD exon 44.

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nucle-ar RNAs to induce DUX4 exon- skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

Abstract: The present invention relates to the delivery of oligomers for treating patients with a 5? mutation in their DMD gene other than a DMD exon 2 duplication. The invention provides methods and materials for activating an internal ribosome entry site in exon 5 of the DMD gene resulting in translation of a functional truncated isoform of dystrophin. The methods and materials can be used for the treatment of muscular dystrophies arising from 5? mutations in the DMD gene such as Duchenne Muscular Dystrophy or Becker Muscular Dystrophy.

Abstract: The present disclosure relates to RNA interference-based methods for inhibiting the expression of the dystrophia myotonia protein kinase (DMPK) gene. Recombinant adeno-associated viruses of the disclosure deliver DNAs encoding inhibitory RNAs that knock down the expression of DMPK or interfere with the expression of the CTG repeat associated with myotonic dystrophy type-1 (DM1). The methods have application in the treatment of myotonic dystrophies, including DM1, and other disorders associated with aberrant DMPK expression.