GENE-TRANSFER INTO THE CAROTID-ARTERY USING AN ADVENTITIAL COLLAR - COMPARISON OF THE EFFECTIVENESS OF THE PLASMID-LIPOSOME COMPLEXES, RETROVIRUSES, PSEUDOTYPED RETROVIRUSES, AND ADENOVIRUSES

We studied the efficiency of plasmid/liposome complexes, Moloney murin e leukemia virus-derived (MMLV) retroviruses, pseudotyped vesicular st omatitis virus protein-G (VSV-G)-containing retroviruses, and adenovir uses in delivering genes into the rabbit carotid artery using a silast ic collar applied to the adventitia, This method was used for gene tra nsfer because (a) it provides a gene delivery reservoir; (b) no intral uminal manipulations are performed; (c) installation of the collar ind uces arterial smooth muscle cell (SMC) proliferation and enhances retr oviral gene transfer efficiency where target cell proliferation is req uired. The transfer of the beta-galactosidase (lacZ) marker gene to th e adventitia and media occurred with all gene transfer systems, Adenov iruses also transferred the beta-galactosidase gene to some endothelia l cells, After 5 days, adenoviral vectors produced the highest gene tr ansfer efficiency with up to 10% +/- 6% of cells showing beta-galactos idase activity, Pseudotyped VSV-G retroviruses were also effective in achieving gene transfer in 0.05% +/- 0.03% of cells in the adventitia and media, Plasmid/liposome complexes and MMLV retroviruses infected 0 .05% +/- 0.03% and <0.01% +/- 0.01% of cells, respectively. It is conc luded that replication-deficient adenoviruses, VSV-G pseudotyped retro viruses, and plasmid/liposome complexes can be used for gene transfer to the arterial wall using the collar method, Because the endothelium remains anatomically present throughout the experiments, the model may be useful for the gene transfer studies involving diffusible or secre ted gene products that primarily act on the endothelium, Effects on me dial SMC and even endothelium can be achieved from the adventitial sid e, suggesting an alternative route for the delivery of therapeutically useful genes into the arterial wall.