Electroporation based gene therapy - from the bench to the bedside

A critical aspect of gene transfer is effective delivery of the transgene to the appropriate target. Electrically mediated delivery (electroporation) of plasmid DNA has been accepted as a viable approach to achieve effective delivery. One promising area is delivering plasmid DNA to skin. Gene transfer to the skin with electroporation is currently being evaluated for its potential for inducing angiogenesis for wound healing and for delivering DNA vaccines to the skin. Experiments utilizing a plasmid encoding for vascular endothelial growth factor has demonstrated how wound healing could be accelerated. In another study, delivery of a plasmid encoding Hepatitis B surface antigen have demonstrated that high antibody titers can be induced after two applications (prime/boost). Our laboratory has also examined the use of electroporation to delivery plasmid DNA encoding various cytokines as a potential therapy for melanoma. The plasmid is injected directly into the tumor followed by the administration of electroporation. Extensive preclinical work provided the rationale for a Phase I proof of concept first in human trial in patients with accessible cutaneous melanoma metastases. Biopsies of treated lesions showed significant necrosis of melanoma cells within the tumor as well as IL-12 expression. Lymphocytic infiltrate was observed in biopsies from patients in several cohorts. Clinical evidence of responses in untreated lesions suggested there was a systemic response following therapy was observed. Since this trial several other clinical studies utilizing electroporation to deliver plasmid DNA have been initiated. It is clear that this delivery approach has tremendous potential to facilitate the translation of gene transfer protocols from the bench to the bedside.