In vivo myocardial gene transfer: Optimization, evaluation and direct comparison of gene transfer vectors

The purpose was to determine the relative efficiency, toxicity and duration of expression following gene delivery by intramyocardial injection of nake d DNA, naked DNA complexed to cationic liposomes, naked DNA complexed to ca tionic liposomes with integrin-targetting peptide, recombinant (E1(-)/E3(-) ) adenovirus, recombinant adeno-associated virus and recombinant (ICP27(-)) herpes simplex virus. All vectors incorporated a LacZ reporter driven by a promoter containing the hCMV-IE promoter/enhancer, Efficiency was scored b y counting positive cells in five standard microscopic sections harvested f rom the left ventricular apex. Rabbit hearts (n = 100) were examined from 2 to 56 days after injection. Uncomplexed and complexed naked DNA were very inefficient with less than on e positive cell visible per heart. The viral vectors all resulted in robust gene expression with adenovirus being the most efficient by at least one o rder of magnitude before 21 days. However, despite disparate titres, the ef ficiency beyond 21 days of adenovirus and adeno-associated virus were compa rable. In contrast to adeno-associated virus, both adenovirus and herpes-si mplex virus were associated with a marked inflammatory response. Despite re porter gene activity appearing only after 21 days, adeno-associated virus s hows comparative promise as a myocardial gene delivery vector.