Transplantation of retroviral producer cells for in vivo gene transfer into mouse skeletal muscle.

We describe a new strategy for efficient in vivo gene transfer into skeletal muscle using retroviral vectors. Recombinant retroviral producer cells, previously treated with the cytostatic drug mitomycin C, were injected into regenerating muscle of adult nude, nude/mdx, and C57BL/10 mice. Using LacZ reporter gene activity, we detected efficient transduction in all mouse strains (Nude, mean 11%, range 4.2-21%; C57BL/10, mean 12%, range 3.4-20%; Nude mdx, mean 4.3%, range 2.1-7% at 4 weeks post-injection and 6.6%, range 1.3-12% at 12 weeks post-injection). Foreign gene expression was sustained at high levels for at least 3 months. This strategy allows muscle satellite cells to be transfected in vivo, forming a reservoir of the transgene for incorporation into new myofibers in subsequent rounds of degeneration and regeneration. Because of its efficiency and potentially broad application, this procedure represents a new strategy for in vivo genetic transfer in skeletal muscle and potentially in other tissues.