Gene therapy, electroporation, and the future of wound-healing therapies

Chronic wounds are a major clinical problem with notable morbidity. Treatment is usually supportive and results in significant healthcare expenditures. It is estimated that 1.25 million people are burned each year in the United States and that 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus. Wound healing is a complex and lengthy process, often taking up to 12 months to complete. The cost of treating poorly healing foot wounds in the United States has been estimated at $1 billion per year. A number of topical commercial products have become available to provide an optimal environment for problematic open wounds. Topical platelet-derived growth factor (PDGF)-BB has proven effective in improving healing in impaired wounds but has the disadvantage of requiring large and repeated doses. More recently, investigators have focused on the possibility of inserting genes encoding for growth factors such as PDGF-BB into the cells participating in the wound-healing response. This approach offers the potential of single-dose growth factor treatment of chronic wounds. There are several approaches for gene insertion, including viral vectors, gene guns, and electroporation. This article reviews the strategies and potential of these approaches, with a focus on electroporation.