In vivo skin-targeted gene delivery by pulsed electric fields

The skin is an especially attractive target for gene therapy. In particular, the ability to target genes to the epidermis of the skin could be used to correct skin-specific disorders as well as for the production of proteins secreted into the skin and the circulatory system to correct certain systemic diseases (1-3). For example, genes expressing cytokines, interferons, or other biologically active molecules could be used to treat skin tumors or other lesions. In addition, keratinocytes and fibroblasts in the skin may secrete protein factors to treat systemic conditions such as hemophilia (4). In other words, this technology for skin-targeted gene therapy would be useful not only for treating local indications, but also for treating systemic diseases by exploiting the secretory capability of the epidermal keratinocytes (5). It is reasonable to believe that skin-targeted gene delivery has great potential and is biologically sound as is indicated by the substantial in vitro and ex vivo data (6,7). However, despite the clear potential in using skin as a target for gene therapy, the major technical problem of an in vivo method of gene delivery remains mostly unresolved. Since the stratum corneum (SC) acts as a significant physical barrier against molecular transfer into the skin, the technical problem of how to deliver molecules as large as genes through this layer still persists. This chapter describes an in vivo method using pulsed electric fields to deliver naked reporter genes into the skin as "proof of principle."