Gene Therapy for Muscular Dystrophy

Gene therapy for muscular dystrophies will require that most if not all muscle fibers receive the appropriate gene to correct the underlying genetic defect. Non-specific gene delivery into non-muscle cells increases the chances of side effects that may or may not be revealed until these promiscuous vectors are used in humans. Furthermore, the use of large amounts of promiscuous vector increases the amounts of vector antigens and transgene product antigens that are delivered to immune cells which may enhance T cell responses in humans that limit gene therapy. Given these problems, approaches need to be developed to physically target vectors to muscle while detargeting them from non-target and immune cells. This project applies technologies developed in the our laboratory for vector targeting and vector detargeting to improve the pharmacology of both adenovirus and adeno-associated virus (AAV) vectors for muscle gene therapy.