PLASMID DNA IS SUPERIOR TO VIRAL VECTORS FOR DIRECT GENE-TRANSFER INTO ADULT-MOUSE SKELETAL-MUSCLE

Direct gene transfer into skeletal muscle offers several therapeutic p ossibilities. We assessed direct intramuscular injection of recombinan t plasmids, adenovirus, or retrovirus in normal or regenerating muscle s of mice. The incorporation and expression of reporter genes introduc ed by any of these three vectors is greater in regenerating than in ma ture muscle. In regenerating muscle, pure DNA and adenovirus result in equivalent numbers of fibers expressing reporter gene (>10%), but ade novirus also induces considerable cellular infiltration. In mature mus cle, recombinant DNA is better than adenovirus. Retrovirus failed to i nfect mature muscle fibers and was less effective than plasmid DNA or adenovirus in regenerating muscle. The surprisingly high relative effi ciency of pure plasmid DNA suggests that this method will provide a si mple, safe and viable alternative for gene therapy involving muscle ti ssue.