Electroporation-enhanced Delivery of Plasmid DNA for Gene Therapy and DNA Vaccines

Abstract

Due to its accessibility and regenerative capabilities, in vivo gene delivery to skin is attractive for a broad range of potential clinical purposes, including dermatological indications, DNA vaccination and systemic gene therapy. Respectively, Genetronics’ studies have been aimed at (i) examining the location of transgene expression in skin; (ii) determining the level of transgene expression and secretion of transgene products ad a result of injecting naked plasmid DNA into skin, followed by non-invasive in vivo electroporation (EP); (iii) comparing the characteristics of gene expression in skin and muscle; and (iv) evaluating the immune response elicited by transgene expression after delivering DNA into skin and muscle via electroporation. The correlation of betagal gene expression in mouse skin and human xenografts demonstrates the feasibility of epidermal targeted gene delivery. For local gene expression, EP revealed increases, by a level of two orders of magnitude, in terms of luciferase expression as opposed to injection alone. The same amount of SEAP plasmid DNA was delivered into mouse skin and muscle respectively. Electroporation in skin results in a short-term gene expression, which peaks at day 7. When a low amount of DNA is used, the skin is superior to muscle in inducing immune responses to a highly secreted antigen. In vivo electroporation dramatically improves DNA vaccine efficacy: IgG antibodies can be detected beginning three weeks after DNA has been delivered to the skin. Skin delivery evoked a mixed Th1/Th2 immune response. Genetronics’ results demonstrate that in vivo electroporation technology is a simple and extremely effective method for delivering naked DNA into both muscle and skin.