793-3 Percutaneous Arterial Gene Transfer to the Media Using Hydrogel-Coated Balloon Delivery of Plasmld-Polylysine Complexes and Chloroquine

Abstract

Gene therapy for restenosis requires efficient and safe percutaneous gene transfer to medial cells, Adenoviral vectors may not be absolutely safe, and, most non-viral methods (such as direct DNA transfer or liposomes) for arterial gene transfer have a very low efficiency. We sought to determine whether the use of plasmid-polylysine complexes, associated with treatments designed to prevent lysosomal degradation (such as chloroquine) could be used for percutaneous local arterial gene transfer to the media using hydrogel-coated balloons. 16 rabbits underwent iliac transluminal angioplasty using a 3.0 mm hydrogel-coated balloon, with a 30 min inflation, The hydrogel had been coated with 25 μ l of a plasmid-polylysine complex (containing 5 μ g DNA of the β galactosidase reporter gene driven by the SV40 promoter) and with chloroquine (100 μ M). Rabbits were sacrificed at 3 days, and arteries (and other organs) assayed for reporter gene expression by X-gal staining. In all the animals, expression of the transgene was visible on macro and microscopic examinations. It was strictly confined to the media in the target arterial segment. Percutaneous site-specific arterial gene transfer to the media can be achieved using plasmid-polylysine complexes and chloroquine delivered via a hydrogel-coated angioplasty balloon.