AAV-directed muscular dystrophy gene therapy.
BACKGROUND
Muscle-directed gene therapy for genetic muscle diseases can be performed by the recombinant adeno-associated viral (rAAV) vector delivery system to achieve long-term therapeutic gene transfer in all affected muscles.


METHODS
Recent progress in rAAV-vector-mediated muscle-directed gene transfer and associated techniques for the treatment of muscular dystrophies (MD). The review covers literature from the past 2 - 3 years.


RESULTS
rAAV-directed muscular dystrophy gene therapy can be achieved by mini-dystrophin replacement and exon-skipping strategies. The additional strategies of enhancing muscle regeneration and reducing inflammation in the muscle micro-environment should be useful to optimize therapeutic efficacy. This review compares the merits and shortcomings of different administration methods, promoters and experimental animals that will guide the choice of the appropriate strategy for clinical trials.


CONCLUSIONS
Restoration of muscle histopathology and function has been performed using rAAV systemic gene delivery. In addition, the combination of gene replacement and adjuvant therapies in the future may be beneficial with regard to improving muscle regeneration and decreasing myofiber necrosis. The challenges faced by large animal model studies and in human trials arise from gene transfer efficiency and immune response, which may be overcome by optimizing the rAAV vectors utilized and the administration methods.
University of Pittsburgh, Department of Orthopaedic Surgery, Pittsburgh, PA 15261, USA.
Ying
Y
Tang
James
J
Cummins
Johnny
J
Huard
Bing
B
Wang
D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009136:Muscular Dystrophies / Q000628:therapy*; D011995:Recombination, Genetic