Adeno-Associated Virus Based Gene Therapy in Skeletal Muscle

Gene therapy, with the promise of symptomatic relief and curative potential, is being considered for a treatment of a wide variety of genetic and acquired diseases, with over 100 protocols approved by the National Institutes of Health since 1989. Skeletal muscle is an especially attractive target for gene therapy, because of its accessibility and capability to uptake, maintain, and express recombinant protein from plasmid DNA (1 –7 ). Transduction of muscle has been considered for systemic delivery of recombinant proteins for treatment of anemia, inherited coagulopathies, endocrinologic disorders, and metabolic storage diseases, as well as localized delivery to treat dystrophinopathies and cardiovascular disorders (6 –15 ). Numerous studies have already demonstrated expression in muscle of such transgenes as various reporter enzymes and relevant therapeutic proteins (1 ,3 –5 ,16 –18 ).