The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The disclosure relates, in some aspects, to compositions and methods for treatment of diseases associated with aberrant lysosomal function, for example Parkinson's disease (PD) and Gaucher disease. In some embodiments, the disclosure provides expression constructs comprising a transgene encoding beta-Glucocerebrosidase (GBA) or a portion thereof alone or in combination with one or more PD-associated genes. In some embodiments, the disclosure provides methods of Parkinson's disease by administering such expression constructs to a subject in need thereof.

The present invention relates to a Pde6b-deficient animal model of retinal degeneration produced by engineered endonucleases, and a method for producing the same. In the animal model of retinal degeneration according to the present invention, only a specific target gene can be removed using engineered endonucleases, so that mutagenesis can be stably achieved. In addition, it is possible to produce a congenital animal model through genetic manipulation at the embryonic stage rather than through acquired factors, which allows for production of an animal model that uniformly exhibits symptoms of the disease in question without being influenced by other factors.

Compositions and regimens useful in treating Wilson's Disease are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human ATP7B.

Provided herein are methods for treating a lysosomal transmembrane protein disease or disorder through ex vivo introduction of a nucleic acid molecule into hematopoietic stem and progenitor cells (HSPCs) followed by transplantation of the HSPCs into a subject in need of treatment. Also provided are vectors containing the nucleic acid molecule.

Provided herein are methods and compositions for treating an eye disorder, for example cone-rod dystrophy type 6 (CORD6). In certain aspects, a therapeutically effective amount of a composition comprising nucleic acids is administered to a subject to treat an autosomal dominant disorder or condition, such as a condition associated with a dominant mutation in a guanylate cyclase 2D (GUCY2D) gene, such as knocking out a dominant mutant form of the gene in the subject. Further provided herein are recombinant AAV particles that comprise one or more recombinant AAV genomes comprising nucleic acids that encode a guide RNA that targets a GUCY2D gene and/or an RNA-guided endonuclease.

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.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

Disclosed herein are methods of using probes for high-throughput screening of guide RNA (gRNA) efficiency for Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRiSPR-associated (Cas)-based genome editing systems. Further disclosed herein is a humanized transgenic mouse model that recapitulates the severe DMD pathology of human patients. The mouse model may be used for determining the feasibility of CRISPR-based therapies for the correction of the human dystrophin gene by gene editing and methods of use.

The invention provides for AAV vectors expressing the ANO5 gene and antioxidant therapy as methods of inducing muscle regeneration and a method of treating muscular dystrophy.