Percutaneous Adenoviral Gene Transfer into Porcine Coronary Arteries: Is Catheter-Based Gene Delivery Adapted to Coronary Circulation?

Abstract

Recombinant adenoviral (Ad) vectors represent an efficient gene transfer system for targeting the cardiovascular system. Phenotypic modulation of coronary vascular cells in vivo is, however, critically dependent on the efficacy of local delivery devices. Four local drug delivery catheters were tested for intracoronary gene transfer efficiency: the Infiltrator (INF, n = 10), the Crescendo (CRE, n = 10), the Infusasleeve (SLE, n = 8), and the Remedy balloon (channel balloon [CHA], n = 8). After balloon injury of the LAD, Ad vector containing the firefly luciferase cDNA (AdCMVluc, 1.5 X 1010 plaque-forming units) was administered at the site of injury. On day 4, tissue samples from different regions in the heart and from the liver were assayed for luciferase activity to evaluate local and systemic gene transfer. INF, CRE, and SLE catheters showed higher transduction levels of the target LAD segment than did the CHA catheter (median luciferase activity = 4.2 X 10 6, 11 X 10 6, and 1.3 X 10 6 light units [LU]/vessel versus 0.09 X 10 6 LU/vessel, respectively, p < 0.05). Luciferase activity was occasionally observed in nontarget tissues (right and left ventricular free wall, distal LAD, and liver) and was not significantly different between groups. The viral circulatory half-life was similar for the four groups (<1 min). Gene transfer efficiency was positively correlated with the degree of injury for the intralumenal catheters (CRE, SLE, and CHA) but was independent of the vessel wall injury for the intramural INF. Local drug delivery catheters enable efficient vascular gene transfer in balloon-injured coronary arteries, a prerequisite for further development of intracoronary gene therapy for restenosis.