In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia

There is an unmet therapeutic goal in the treatment of critical limb ischemia (CLI). Various clinical trials have applied therapeutic angiogenesis to induce neovascularization in CLI by administering proangiogenic cytokines, their associated genes, or cells. However, the results have shown limited efficacy. One of the limiting factors in this strategy is the lack of a targeted gene delivery method that introduces the gene encoding the cytokine of interest in a specific vascular bed - a delivery modality that is noninvasive, nonviral-based, and is associated with few side effects. Using a mouse model of limb ischemia, we report that in vivo electroporation of hypoxia-inducible factor-1 alpha plasmid DNA enhances neovascularization and that this modality may be applied as a noninvasive, nonviral, and targeted gene delivery method in the treatment of CLI.