In vivo suppression of injury-induced vascular smooth muscle cell accumulation using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene.

Abstract

Restenosis, a process characterized in part by excessive smooth muscle cell (SMC)

Effect of percutaneous adenovirus-mediated Gax gene delivery to the arterial wall in double-injured atheromatous stented rabbit iliac arteries

“…22,61,62 In contrast to the Ad-Gaxtreated arteries, no discernible difference was seen in the extent of neointima formation between the Ad-CMVluctreated and saline-treated arteries in the control group of animals. The ability of Gax overexpression to inhibit neointima formation compares favorably with previous recent results reported by other groups using adenovirusencoded genes for wild-type and mutant form of RB in rat and porcine models, 46,63 the herpes simplex virus thymidine kinase gene in rat, rabbit and porcine models, 26,27,55,56 p21 53 in the rat model and hirudin in the rat model. 54 Overall, the reduction in intima/media ratio achieved with these agents ranged from 35 to 50%.…”

“…Gene Therapy products acting locally (eg herpes simplex virus 1 thymidine kinase, NO synthase, cytosine deaminase), 26,27,[55][56][57][58][59] have been developed with adenoviral vectors designed to optimize transfection efficiency. A previous report has demonstrated that gene transfer to the neointima 1 month after stent implantation was feasible.…”

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis

“…13 Other pro-death strategies have demonstrated efficacy in post-angioplasty restenosis models by overexpression of thymidine kinase. [16][17][18] Wildtype p53 (wt p53) has been shown to promote SMC apoptosis 19 and modulate SMC proliferation, 20 phenotypes that may be beneficial for prevention of neointimal hyperplasia by gene therapy. In this study we document the effect of wt p53 overexpression on human saphenous vein SMC in isolated culture and in an organ culture model of human vein graft neointimal thickening.…”

Spine fusion by gene therapy

“…One must consider the safety profile of the vector at the dose that would be required for the particular gene candidate. 59 In one sense, the least risky vectors are DNA, 60 followed by nonintegrating viruses such as adenovirus, [61][62][63] and lastly by integrating viruses such as adeno-associated virus 64 and lentivirus. 65,66 Another factor in safety is related to the immune response generated by the vector.…”