The present invention concerns methods and compositions for gene therapy, in particular in vivo gene therapy for delivery of bioactive glial derived neurotrophic factor (GDNF) for the treatment of Parkinson's Disease. The invention also concerns mammalian cells capable of producing GDNF in increased amounts as well as the use of these cells for recombinant production of bioactive GDNF and for therapeutic use. The invention also includes a device that may be implanted in the cochlear of a patient that is capable of secreting GDNF.

The present disclosure provides compositions and methods of restoring or enhancing visual function in an individual by administering to the individual a pharmaceutical composition comprising a recombinant adeno-associated viral (rAAV) vector having a polynucleotide sequence that encodes a medium wavelength cone opsin (MW-opsin). The MW-opsin is expressed in a retinal cell in the individual, thereby restoring or enhancing visual function.

A rAAV vector is described herein which has an AAVhu68 capsid and at least one expression cassette in the capsid. The at least one expression cassette comprises nucleic acid sequences encoding a functional SMN protein and expression control sequences that direct expression of the SMN sequences in a host cell. Also provided are compositions containing this rAAVhu68.SMN vector and methods of using same for spinal muscular atrophy in a patient.

Compositions for CDKL5 gene therapy are provided, as well as recombinant CDKL5 proteins. Such CDKL5 gene therapy compositions and/or recombinant CDKL5 proteins may incorporate cell-penetrating polypeptides and/or leader signal polypeptides. Also provided are methods of producing such gene therapy compositions and recombinant CDKL5 proteins, as well as pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and recombinant CDKL5 proteins.

This invention relates to polynucleotides encoding mini-dystrophin proteins, viral vectors comprising the same, and methods of using the same for delivery of mini-dystrophin to a cell or a subject.

Engineered CRISPR-Cas9 nucleases with altered and improved PAM specificities and their use in genomic engineering, epigenomic engineering, and genome targeting.

An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes arc alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.

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.

The present invention relates to an engineered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) system comprising engineered dual guide nucleic acids (e.g., RNAs) capable of activating a CRISPR-Associated (Cas) nuclease, such as a type V-A Cas nuclease. Also provided are methods of targeting, editing, and/or modifying a nucleic acid using the engineered CRISPR system, and compositions and cells comprising the engineered CRISPR system.

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.