Periadventitial lacZ gene transfer to pig carotid arteries using a biodegradable collagen collar or a wrap of collagen sheet with adenoviruses and plasmid-liposome complexes

Background Periadventitial gene therapy is a promising alternative for the treatment of stenosis, vessel wall thickening and other complications in va scular surgery. Methods We compared lacZ gene transfer efficiency of DOTMA:DOPE (1.1 w/w) p lasmid/liposome complexes and adenoviruses in pig carotid arteries using pe rivascular delivery with either a collagen collar or a wrap of collagen she et. Safety of the gene transfer was studied by clinical chemistry, tissue p athology and PCR analysis of lung, liver, kidney, spleen, skeletal muscle a nd gonads. Results Gene transfer efficiency using the periadventitial collar was fourf old higher than using the collagen wrap with adenovirus at 7 days (10.22+/- 2.96 vs 2.78+/-1.28 positive cells/mm(2); p = 0.18) and 4.3-fold at 14 days (13.46+/-3.49 vs 3.11+/-0.88 positive cells/mm(2); p = 0.03). Gene transfe r efficiency at 7 days with adenovirus was fivefold higher than with the pl asmid/liposome complexes both using the collar (10.22+/-2.96 vs 2.07+/-0.95 positive cells/mm(2); p = 0.01) and the collagen wrap (2.78+/-1.28 vs 0.45 +/-0.35 positive cells/mm(2); p = 0.03). No lacZ activity was detected in p lasmid/liposome transfected arteries at 14 days. In spite of the local gene delivery methods a moderate systemic distribution of the transgene was det ected in the major organs by PCR analysis. Conclusions This study shows that: (i) adenovirus delivered with the periad ventitial collar or the collagen wrap is well tolerated and may become an e fficient new tool in vascular gene therapy, and (ii) gene transfer vector d elivered in the periadventitial collar reaches the target tissue more effic iently than the vector in the collagen wrap. Copyright (C) 2000 John Wiley & Sons, Ltd.