Arterial gene transfer of naked DNA for therapeutic angiogenesis: early clinical results.

Patients with critical limb ischemia constitute a potential target population for therapeutic angiogenesis. Because the growth of new collateral vessels can be achieved in a time interval of 1 month or less, these patients are suitable candidates for treatment with non-viral vectors intended to yield short-term gene expression. Accordingly, we applied naked plasmid DNA encoding for vascular endothelial growth factor, a secreted endothelial cell mitogen, to the hydrogel polymer coating of an angioplasty balloon. The balloon was then used to perform arterial gene transfer to the arterial circulation of the ischemic lower extremity. Using a dose-escalating strategy, it was possible to document that naked DNA was sufficient to generate evidence of new collateral growth by both magnetic resonance angiography and contrast angiography in the affected limb. These findings establish that the use of naked DNA may be suitable for gene therapy when the gene product is actively secreted from transfected cells.