Adult form glycogen storage disease type III (GSD III) is an orphan neuromuscular disorder caused by a deficiency of glycogen debranching enzyme. Long-term complications include progressive liver fibrosis, hepatic failure, and end-stage liver cirrhosis, and progressive muscle myopathy. Presently, there are no clinically approved therapies or cures for GSD III. Disclosed herein are compositions for and methods of treating and/or preventing GSD III disease progression.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3(SCA3).

The present invention relates to a hemophilia B rat and a method of producing the hemophilia B rat. More particularly, the present invention relates to a hemophilia B rat having F9 factor knocked-down or knocked-out and a method of producing the hemophilia B rat.

Disclosed herein are CRISPR/Cas-based genome editing compositions and methods for treating Duchenne Muscular Dystrophy by restoring dystrophin function.

Methods and compositions for increasing neurogenesis and for preventing or treating diseases, disorders or conditions associated with neurodegeneration, are provided herein.

A recombinant adeno-associated virus (rAAV) useful for treating type II glycogen storage disease (Pompe) disease is provided. The rAAV comprises an AAV capsid which targets cells of at least one of muscle, heart, kidney, and the central nervous system and which has packaged therein a vector genome comprising a nucleic acid sequence encoding a a chimeric fusion protein comprising a signal peptide and a vIGF2 peptide fused to a human acid-α-glucosidase hGAA780I protein under the control of regulatory sequences which direct its expression. Also provided are methods of making and using this rAAV.

A recombinant adeno-associated virus (AAV) vector that carries a nucleic acid sequence encoding the retinal transcription factor cone-rod homeobox (CRX) for its use in treating CRX-associated IRDs in a subject in need thereof or for use in treating inherited retinal dystrophies caused by hypomorphic mutations in the CRX target genes.

The present disclosure provides short enhanced human opsin promoters for rod-specific expression that satisfy a need in the art for promoters that are able to control transgene expression both efficiently and selectively in rod cells, with little to no off-target expression in other photoreceptor cells. The disclosure provides vector constructs comprising transgenes operably controlled by this enhanced human opsin promoter that may be delivered and targeted with high specificity to rod cells. The disclosure also provides compositions comprising these vector constructs and methods for administration of these compositions to subjects in need thereof.

Aspects of the disclosure relate to compositions and methods useful for delivering minigenes to a subject. Accordingly, the disclosure is based, in part, on isolated nucleic acids and gene therapy vectors, such as viral (e.g., rAAV) vectors, comprising one or more gene fragments encoding a therapeutic gene product, such as a protein or peptide (e.g. a minigene). In some embodiments, the disclosure relates to gene therapy vectors encoding a USH1B protein (e.g. the gene product of USH1B, also referred to as MY07A) or a portion thereof. In some embodiments, compositions described by the disclosure are useful for treating diseases associated with mutations in the USH1B (MY07A) gene, for example Usher Syndrome.

Provided herein is a gene therapy for PKP2 (Plakophilin-2), e.g. using an adeno-associated virus (AAV) vector. The promoter of the vector may be a MHCK7 promoter or a cardiac troponin T (HTNNT2) promoter. The capsid may be an AAV9 or AAVrh74 capsid or a functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intravenous, intracoronary, intracarotid or intracardiac administration of the rAAV vector, and other compositions and methods.