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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.