Abstract: Provided are gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of mutations in the Eukaryotic Translation Initiation Factor 2B Subunit Epsilon (EIF2B5) gene. The EIF2B5 gene provides instructions for making one of five subunits of the elF2B protein, specifically the epsilon subunit of this protein. Such mutations are associated with a disease or disorder such as a leukoencephalopathy, a megalencephalic leukoencephalopathy, a leukodystrophy, a stroke, a migraine, epilepsy, multiple sclerosis (MS), Parkinson's disease (PD), Alzheimer's disease (AD), astrogliosis in aging, Huntington's Disease (HD), amyotrophic lateral sclerosis (ALS), Alexander disease, hepatic encephalopathy (HE), AicardinGoutieres syndrome, CLC-2-related disease, oculodentodigital dysplasia, and/or giant axonal neuropathy. Such leukoencephalopathies or leukodystrophies include, but are not limited to, Vanishing White Matter Disease (VWM).

Abstract: Provided are gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of mutations in the TCAP gene. Such mutations are also known as telethoninopathies and are associated with such disorders as autosomal recessive limb girdle muscular dystrophy type 2G (LGMD2G), autosomal dominant dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) or idiopathic cardiomyopathy (ICM). The disclosed gene therapy vectors provide a TCAP cDNA to a subject in need which results in expression of a wild type or functional TCAP or telethonin protein.

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: The disclosure relates to the field of gene therapy for the treatment of a muscular dystrophy including, but not limited to, Duchenne's muscular dystrophy (DMD), Becker's muscular dystrophy (BMD), or intermediate muscular dystrophy (IMD). More particularly, the disclosure provides nucleic acids, including nucleic acids comprising guide RNAs (gRNAs) and nucleic acids encoding gRNAs to be used with nucleic acids encoding clustered regularly-interspaced short palindromic repeat associated protein 9 (Cas9), and adeno-associated virus (AAV) comprising the nucleic acids to deliver nucleic acids encoding guide RNAs and Cas9 to correct single or multiple DMD exon duplication mutations for use in treating a muscular dystrophy including, but not limited to, DMD, BMD, or IMD, resulting from an exon duplication mutation amenable to CRISPR-Cas9 therapy of the DMD gene.

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: The present disclosure relates to methods of treating conditions associated with a need for Merlin protein, for example due to a defective Neurofibromin 2/Merlin (NF2) gene as in neurofibromatosis type 2 (NF2). In particular. the disclosure provides gene therapy vectors to specifically treat loss of expression of the Merlin protein or reduced Merlin protein levels.

Abstract: Disclosed herein are products, methods, and uses for a new gene therapy for treating, ameliorating, delaying the progression of, and/or preventing a muscular dystrophy involving a mutation amenable to DNA repair including, but not limited to, any mutation involving, surrounding, or affecting various regions of the DMD gene. Specifically, the disclosure provides products and methods for fixing diverse DMD mutations by replacement of large segments of the DMD gene comprising multiple exons, using CRISPR/Cas9 and Homology-Independent Targeted-Integration (HITI) to accomplish high efficiency knock-in or make large replacements using the non-homologous end-joining (NHEJ) DNA repair pathway, previously not achievable. In particular, the disclosure provides products, methods and uses for the replacement of DMD exons 1-19, 2-19, or 41-55.

Abstract: The present invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne Muscular Dystrophy.

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 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 invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne 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 invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne Muscular Dystrophy.

Abstract: The present invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne 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 invention relates to recombinant adeno-associated virus (rAAV) delivery of polynucleotides for treating Duchenne Muscular Dystrophy resulting from the duplication of DMD exon 2. The invention provides rAAV products and methods of using the rAAV in the treatment of Duchenne Muscular Dystrophy.

Abstract: A buffer accessible by an application executing under an application server in a first address space is managed by a database adapter executing in a second address space. A data request from the application executing in said first address space, comprising a buffer locator in the empty state, is received by the database adapter executing in the second address space. A buffer is allocated in the first address space and the address of this buffer is stored in the buffer locator. Data associated with the data request, received from a database subsystem, is copied to the buffer. Control is then transferred back to the application whereby the application utilizes the buffer locator to access the buffer and process the data contained therein. A database adapter automatically managing application buffers across address spaces in accordance with the present invention may be referred to as an “auto-buffer database adapter”.

Abstract: Disclosed is a Single Condition Amplification/Internal Primer (SCAIP) sequencing method which allows for the rapid, accurate, and economical analysis of any large multi-exon gene. The method can be used to detect genomic mutations in any large multi-exon gene including the dystrophin gene. In some forms, the method can rely on amplification of a large number of exons at a single set of PCR temperatures with a first set of amplification primers followed by sequencing without optimization of individual amplicon conditions, using a second, internal set of sequencing primers. The SCAIP method provides for the identification and analysis of specific individual genomic mutations such as deletions, point mutations, frameshifts, or combinations thereof, in gene complexes with multiple exons/introns spanning large genomic regions.

Abstract: A buffer accessible by an application executing under an application server in a first address space is managed by a database adapter executing in a second address space. A data request from the application executing in said first address space, comprising a buffer locator in the empty state, is received by the database adapter executing in the second address space. A buffer is allocated in the first address space and the address of this buffer is stored in the buffer locator. Data associated with the data request, received from a database subsystem, is copied to the buffer. Control is then transferred back to the application whereby the application utilizes the buffer locator to access the buffer and process the data contained therein.