Percutaneous pulmonary artery gene transfer in pigs using naked plasmid DNA delivered during angioplasty

Gene transfer techniques are increasingly being used to study blood vessel biology and develop models for gene therapy. To date, there are no reports of pulmonary vascular gene transfer performed either without adjunctive agents or during angioplasty. We sought to demonstrate the feasibility of recombinant gene transfer to the pulmonary artery of juvenile pigs using naked plasmid DNA delivered via percutaneous angioplasty techniques. Plasmid DNA directing the expression of beta-galactosidase was used to transfect one pulmonary artery while the contralateral vessel served as an untreated control. One delivery technique used a standard angioplasty balloon coated with a DNA-heparin mixture. The second involved infusion of DNA between an angioplasty balloon and a surrounding, microporous balloon. Vessels were harvested 3 or 4 days following gene delivery. Protein expression was demonstrated by immunohistochemical staining in transfected but not control vessels in 9/9 pigs. Vascular wall expression was limited to endothelial cells. Pulmonary artery gene transfer using naked plasmid DNA delivered via percutaneous angioplasty techniques is feasible. Using naked plasmid DNA removes the potential for toxicity associated with adjunctive agents. The described techniques provide novel methods for studying pulmonary vascular biology in vivo and for developing future gene therapies.