ABSTRACT

Plasmid-DNA-based gene transfer is an elegant strategy for gene therapy because it suppresses the need for a biological (viral) vector, although its use is limited by the lack of e¤cient and safe delivery methods (Gill et al., 2009). When compared with viral vector, the advantages include the absence of immunogenicity and integration into the host genome (Gill et al., 2009). One physical method that has emerged as a way to improve the in vivo delivery of plasmid DNA is electropermeabilization (or electroporation). Since its rst demonstration 25 years ago (Neumann et al., 1982), this method is now routinely used for in vitro transfection (Esco re et al., 2009; Mir, 2009). e application of controlled electric pulses causes a transient permeabilization of the plasma membrane and thus allows exogenous molecules to enter the cells (Teissié et al., 2005; Esco re et al., 2009). In vivo, electropermeabilization is e¤cient for enhanced plasmid DNA delivery and expression (Heller et al., 1996; Rols et al., 1998). In vivo, electropermeabilization is e ective on many tissues: skeletal muscle (Aihara and Miyazaki, 1998; Mir et al., 1999), liver (Heller et al., 1996), skin (Vandermeulen et al., 2007), brain (Kondoh et al., 2000), testis (Huang et al., 2000), and tumor (Rols et al., 1998). e use of in vivo gene electrotransfer has seen tremendous growth, including the initiation of clinical trials (Daud et al., 2008; Horton et al., 2008; Gehl, 2008).