The present invention provides a method for the treatment of autosomal dominant Catecholaminergic Polymorphic Ventricular Tachycardia associated with mutations in the cardiac ryanodine receptor type 2 (RYR2) gene, by the use of an AAV mediated RNA interference approach to induce allele specific silencing of mutant mRNA.

The present invention provides an isolated nucleic acid molecule comprising, or consisting of, the nucleic acid sequence of SEQ ID NO:1 or a nucleic acid sequence of at least 400 bp having at least 80% identity to said sequence of SEQ ID NO:1, wherein said isolated nucleic acid molecule specifically leads to the expression in rod photoreceptors of a gene when operatively linked to a nucleic acid sequence coding for said gene.

Provided are compositions and methods for stabilizing a transfection cocktail containing DNA-cationic polymer complexes for an extended time, while maintaining high transfection efficiency. Such stabilized transfection cocktail can be used to generate transfected cells that can produce, for example, rAAV vectors on a large scale without impacting the key attributes of the virus production, such as, titer, DNA packaged rAAV particle fraction, and rAAV vector purification profile.

Provided herein are compositions and methods for the design of synthetic regulatory sequences and for subsequent modulation of neural pathways.

Provided herein are Class 2 Type V CRISPR:gNA systems comprising Class 2 Type V CRISPR polypeptides (e.g. CasX), guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a RHO gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the rhodopsin protein. Also provided are methods of using such systems to modify cells having such mutations and utility in methods of treatment of a subject with a RHO-related disease, such as retinitis pigmentosa.

Provided herein are Class 2 Type V CRISPR:gNA systems comprising Class 2 Type V CRISPR polypeptides (e.g. CasX), guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a RHO gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the rhodopsin protein. Also provided are methods of using such systems to modify cells having such mutations and utility in methods of treatment of a subject with a RHO-related disease, such as retinitis pigmentosa.

The present disclosure provides zinc finger fusion proteins that inhibit expression of alpha-synuclein in the nervous system, and methods of using the proteins to treat Parkinson's disease, Lewy body dementia, multiple system atrophy, Alzheimer's disease, and other neurodegenerative diseases.

Aspects of the disclosure relate to compositions and methods for expressing one or more anti-Vascular endothelial cell growth factor (VEGF) agents in a cell or subject. In some embodiments, the disclosure provides isolated nucleic acids and rAAVs comprising a transgene encoding an anti-VEGF agent (e.g., KH902) and one or more regulatory sequences. In some embodiments, compositions described herein are useful for treating subjects having diseases associated with angiogenesis or aberrant VEGF activity/signaling.

An isolated recombinant parvovirus vector comprising a synthetic enhancer comprising plurality of enhancer sequences operably linked to a promoter, and methods of using the vector, are provided.

The present disclosure provides genome editing systems, compositions and methods. The genome editing system comprises at least one nuclease that generates blunt-ended DNA breaks in a sequence-specific manner, wherein the genome editing system is configured to form a first and a second blunt-ended double strand break in an intron of a gene, wherein the intron comprises a splice donor site mutation that alters splice site recognition, thereby excising a segment of the intron and simultaneously joining DNA ends flanking the excised segment of the intron to constitute a functional donor splice site.