USE OF VON-WILLEBRAND-FACTOR PROMOTER TO TRANSDUCE SUICIDAL GENE TO HUMAN ENDOTHELIAL-CELLS, HUVEC

Angiogenesis is an essential component of multifactorial carcinogenesi s and thus a potential target of therapeutic intervention, To develop a novel cancer gene therapy strategy based on suppression of tumor ang iogenesis, we examined the feasibility of targeting and preferential k illing of proliferating endothelial cells by use of the von Willebrand factor (vWf) promoter and herpes simplex virus thymidine kinase gene (HSV-TK). Based on previous reports on the vWf promoter, we tested two putative vWf promoter regions, The luciferase assay showed that the s horter region, which encompasses most of the first noncoding exon, had stronger activity in endothelial cells, Although the promoter activit y was low when employed as an internal promoter for retroviral and ade noviral vectors, endothelial cell specificity was suggested; the promo ter, when used to drive the HSV-TK gene, could preferentially suppress endothelial cell growth in the presence of prodrug ganciclovir, sugge sting the feasibility of designing an anti-angiogenesis gene therapy u sing the vWf promoter and the suicide gene/prodrug strategy.