Spatial Distribution of Transgenic Protein After Gene Electrotransfer to Porcine Muscle

Abstract

Gene electrotransfer is an effective nonviral technique for delivery of plasmid DNA into tissues. From a clinical perspective, muscle is an attractive target tissue as long-term, high-level transgenic expression can be achieved. Spatial distribution of the transgenic protein following gene electrotransfer to muscle in a large animal model has not yet been investigated. In this study, 17 different doses of plasmid DNA (1–1500 μg firefly luciferase pCMV-Luc) were delivered in vivo to porcine gluteal muscle using electroporation. Forty-eight hours post treatment several biopsies were obtained from each transfection site in order to examine the spatial distribution of the transgenic product. We found a significantly higher luciferase activity in biopsies from the center of the transfection site compared to biopsies taken adjacent to the center, 1 and 2 cm along muscle fiber orientation (p<0.05 and p<0.0001, respectively). On average, 43% of the total luciferase activity was localized in the center biopsy. In conclusion, we found that gene electrotransfer to muscle in a large animal model led to localized gene expression corresponding to the area delineated by the electrodes. High doses of plasmid DNA did not lead to a larger area of the muscle expressing the transgenic protein.

Spanggaard and colleagues examine the spatial distribution of transgenic protein after plasmid DNA electrotransfer to muscle in a porcine animal model. They find that this approach leads to localized gene expression corresponding to the area delineated by the electrodes and that high doses of plasmid DNA do not lead to a larger area of muscle transduction.