The present invention discloses platforms for chemically modify AAV capsids with control over site and stoichiometry. An AAV packaging system is described that allows the introduction of site-directed natural and unnatural amino acid mutations into any subset of the three capsid proteins. These engineered residues can be subsequently used to chemically functionalize the resulting capsids with precise control over site and stoichiometry. Such controlled modification strategy can be used to attach a wide variety of entities to AAV capsids to engineer its tropism, immunogenicity, etc.

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides encoding AADC for the treatment of Parkinson's Disease.

Adeno-associated virus rh.10 sequences, vectors containing same, and methods of use are provided.

The present disclosure relates to recombinant nucleic acids and gene therapy vectors comprising a modified nucleic acid encoding aspartoacylase (ASPA), and variants thereof, for use in the treatment of diseases and disorders associated with a deficiency or dysfunction of ASPA, and in particular, Canavan disease.

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of modulatory polynucleotides.

The invention relates to isolated nucleic acids and rAAV-based compositions, methods and kits useful for treating genetic diseases (e.g., alpha-1 antitrypsin deficiency).

The teachings herein are generally directed to a method of enhancing the genetic stability of parvovirus vectors. The stability of conventional ss or dsAAV vector constructs can be enhanced, for example, to obtain a concurrent increase in vector titer and purity, as well as an improvement in vector safety, due at least in part to the elimination of stuffer DNA from the AAV vector. The method is broadly applicable to all gene transfer/therapy applications, such as those requiring delivery of foreign DNA containing recombinant gene expression cassettes. Such foreign DNA can range, for example, from about 0.2 up to about 5.2 kb in length. The enhanced vector constructs are highly flexible, user-friendly, and can be easily modified (via routine DNA cloning) and utilized (via standard AAV vector technology) by anyone skilled in the art.

Adeno-associated virus rh.20 sequences, vectors containing same, and methods of use are provided.

Recombinant viral vectors such as AAV vectors designed with expression cassettes that approach the natural packaging capacity of the virus, such as AAV are provided. The recombinant viral vectors reduce residual plasmid DNA impurities.