Compositions and methods are provided for the inhibition, treatment and/or prevention of Huntington's disease and related disorders.

The present application provides materials and methods for treating a patient with a titin-based myopathy, particularly a titin-based cardiomyopathy, and/or other titinopathy. In addition, the present application provides materials and methods for editing the titin gene in a cell by genome editing.

Compositions and methods are provided for treating Leber congenital amaurosis (LCA) in a subject. In one aspect, a recombinant adeno-associated viral vector is provided which includes a nucleic acid molecule comprising a sequence encoding Lebercilin. In another aspect, Lebercilin has an amino acid sequence of SEQ ID NO: 1. In yet another aspect, the nucleic acid molecule has a sequence of SEQ ID NO: 3 or a variant thereof. In desired embodiments, the subject is human, cat, dog, sheep, or non-human primate.

Provided herein are improved gene therapy vectors and methods of use, in some embodiments, comprising sequences for improved expression and cellular targeting of a therapeutic protein.

The present invention relates to regulatory nucleic acid sequences, in particular muscle-specific promoters, elements thereof, and other such nucleic acid sequences, that are capable of enhancing muscle-specific expression of genes. The invention also relates to expression constructs, vectors and cells comprising such muscle-specific regulatory nucleic acid sequences, and to methods of their use. The regulatory nucleic acid sequences are of particular utility for gene therapy applications, but also find utility in other areas such as bioprocessing and biotechnology.

An invention provides a chimeric antigen receptor. The chimeric antigen receptor includes an extracellular domain including a heavy chain variable region, a light chain variable region of a single chain antibody fragment and CD8 hinge region; a transmembrane domain including an immune co-stimulator transmembrane domain; and an intracellular domain including an immune co-stimulator intracellular segment and CD3ζ chain. According to the embodiments of the invention, the chimeric antigen receptor can specifically recognize the tumor cells expressing the specific antigen and achieve the specific killing effect against the tumor cells expressing the high specific antigen.

The present invention includes methods and compositions for elimination of polyomaviruses, such as John Cunningham Virus (JVC), from host cells, and the treatment of polyomavirus related diseases, such as progressive multifocal leukoencephalopathy (PML). The compositions include isolated nucleic acid sequences comprising an CRISPR-associated endonuclease and a guide RNA, wherein the guide RNA is complementary to a target sequence in a polyomavirus.

The invention provides for recombinant AAV vectors comprising a polynucleotide sequence comprising the guide strand of miR-29c and methods of using the recombinant vectors to reduce or prevent fibrosis in subjects suffering from muscular dystrophy.

Disclosed are compositions and methods of treating a neurodegenerative disease in an individual. The methods disclose administration of an Integrin α4β1, Very Late Antigen-4 positive neural precursor cell (“VLA4+NPC”) transfected with a lentivirus overexpressing wild type GCase to an individual having a neurodegenerative disorder. The neurodegenerative disease may include lipid storage diseases, for example Gaucher disease, Parkinson's disease (PD), Dementia with Lewy bodies.

The present invention relates to chimeric receptors (e.g. CARs including both single chain and multichain CARs) that bind to TREM2 ligands and their use in therapy. In particular, the invention provides a chimeric receptor comprising: (a) an exodomain comprising the ligand binding domain of TREM2 or a functional variant thereof, optionally wherein said exodomain is resistant to cleavage by a sheddase; (b) a transmembrane domain; and (c) an endodomain comprising an intracellular signalling domain.