Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus

Abstract

The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this report, we demonstrate that catheter-mediated infusion of replication-defective adenovirus into the coronary arterial circulation in vivo represents a novel and efficient method for the induction of recombinant gene expression in both the coronary arteries and the myocardium. A single intracoronary infusion of 2 x 10(9) - 1 x 10(10) p.f.u. of adenovirus resulted in high level recombinant gene expression in both the coronary arteries and surrounding myocardium of adult rabbits for at least 2 weeks. No inflammatory response or myocardial necrosis was observed following the adenovirus infusions. The polymerase chain reaction (PCR) was used to assess the tissue distribution of infection following intracoronary infusion of adenovirus. Adenovirus DNA was detected by PCR in the livers, kidneys, lungs, brains and testes of animals 5 days after virus infusion. Percutaneous transluminal gene transfer (PTGT) into the heart by intracoronary infusion of replication-defective adenovirus represents a relatively non-invasive and efficient method of inducing recombinant gene expression both in the coronary arterial wall and in the surrounding myocardium.