Intravascular ultrasound mediated delivery of DNA via microbubble carriers to an injured porcine artery in vivo

Millions of stents are implanted worldwide each year in patients with atherosclerotic arteries. Safety concerns relating to drug eluting stents have spurred interest in alternative vessel therapies. We hypothesized that a reporter gene could be delivered to a porcine coronary artery via intravascular ultrasound (IVUS) and plasmid-coupled microbubbles. In vitro delivery resulted in 0.17% of cells exhibiting successful transfection. An anesthetized porcine underwent balloon angioplasty on a coronary artery. Microbubble injection and rupture were controlled at the injury site using a modified intravascular ultrasound catheter. At 3 days post-insonation, gene expression was localized at injured vessel sites in (23.3% of luminal cells) with minimal expression in control arteries (3.6% of luminal cells). Our results demonstrate that IVUS has promise for localized intra-vascular gene therapy and may potentially offer a novel method for preventing restenosis.