Stent-based gene therapy.

Abstract

Delivery of gene therapy to inhibit intimal hyperplasia has been proposed to prevent postangioplasty restenosis. We sought to apply gene therapy by using a stent-based technique. There are several hurdles that must be overcome before gene-stent therapy can be applied successfully in clinical trials. These include increasing the efficiency of gene delivery through atherosclerotic plaque; increasing intramural retention times; preventing the inflammatory reaction that stents coated with biodegradable polymers can elicit; overcoming the risk of systemic gene delivery; and accessing the adventitia via percutaneous approach. We evaluated a gene-stent delivery mechanism based on microporous metal microneedles developed with nanotechnology in an attempt to overcome some of these problems. A novel approach to the transfection of genes by microfabricated technology was evaluated in smooth muscle cells in culture. We demonstrated that microneedles can deliver gene therapy to smooth muscle cells in culture and can produce controlled penetration of the IEL and intima. We conclude that taller microneedles need to be developed to reach the media in diseased human arteries and that this technology has the potential to be incorporated in a stent to deliver gene therapy in atherosclerotic plaque.