Vascular gene transfer driven by endoglin and ICAM-2 endothelial-specific promoters

The involvement of the vascular endothelium in a large number of diseases s upports the importance of vascular-specific gene delivery for their treatme nt. The hereditary hemorrhagic telangiectasia type 1 is an example of a vas cular inherited disease (OMIM 187300). This is an autosomal dominant vascul ar disorder originated by mutations in the endoglin gene and associated wit h frequent epistaxis, telangiectases, gastrointestinal bleedings, and arter iovenous malformations in brain, lung and liver. Here, we address for the f irst time the possibility of using in vivo gene transfer to target endoglin expression to the vasculature. The promoter of the endothelial gene, ICAM- 2 was used to generate transgenic animals which demonstrated endothelial ex pression of endoglin. Next, the promoters of the human endothelial genes, e ndoglin and ICAM-2, were inserted upstream of the human endoglin cDNA, and the resulting constructs were systemically or locally delivered, demonstrat ing endoglin expression in the vessel wails of liver, lung and skin. These gene transfer experiments represent an initial step in the treatment of the hereditary hemorrhagic telangiectasia type I by gene therapy, and suggest that endoglin and ICAM-2 promoters can be used to deliver other genes to th e endothelium specifically.