Evaluation of Plasmid DNA for in Vivo Gene Therapy: Factors Affecting the Number of Transfected Fibers

Abstract

Gene transfer by intramuscular injection of plasmid DNA has potential application in gene therapy. We examined factors affecting the number of expressing fibers, in contrast to total expression, following injection of plasmid DNA. Barium chloride proved effective in inducing muscle necrosis and regeneration in mice, and this increased the number of fibers expressing a reporter gene. Coinjection of ion-channel modulators did not increase the number of positive fibers, but increasing dose and repeated administration of plasmid did. Importantly, the plasmid size (7–16 kb) did not affect the number of fibers expressing the transgene, in both normal and regenerating muscle.