Myoblast-mediated ex vivo gene transfer to mature muscle

A major barrier to the application of gene therapy to skeletal muscle is the inability of viral vectors to efficiently transduce mature muscle fibers. Results from our laboratory and others have shown that adenovirus and herpes simplex virus efficiently infect neonatal muscle; however, within a few days of mouse development, the muscle is largely refractory to transduction with both viral vectors. The ex vivo technique has been investigated as an approach to achieve viral gene delivery to mature muscle fibers, since both viral vectors can efficiently transduce myoblasts, and myoblasts can fuse with mature muscle fibers. We demonstrated that myoblast-mediated gene transfer using both viral vectors has the ability to achieve an efficient gene transfer to mature skeletal muscle. In addition, the efficiency of gene transfer in mature muscle using both viral vectors in an ex vivo approach is higher than the direct injection of a similar amount of the virus. Our results suggest that the ex vivo approach may be an alternative method to achieve an efficient viral gene delivery to mature muscle and may contribute to eliminating one of the major hurdles facing the application of gene therapy to skeletal muscle.