VEGF Gene Transfer to the Utero-Placental Circulation of Pregnant Guinea Pigs to Enhance Fetal Growth.

Abstract

In this chapter, we describe a novel method of adenoviral gene transfer to the uterine and radial arteries of pregnant guinea pigs to improve fetal growth. Adenoviruses encoding VEGF-A165 or a reporter gene β-galactosidase were reconstituted in pluronic gel and applied topically to the exposed uterine and radial arteries following laparotomy. Pluronic gel is a thermosensitive gel that is liquid at 4 °C, but becomes solid as soon as it comes in contact with body temperature. It thereby acts as a slow-release vehicle for viral vectors to the target tissue and also facilitates closer contact of the viruses with the host tissue. Our studies have shown that adenoviral gene delivery using pluronic gel resulted in the highest transduction efficiency compared to intra-arterial administration or external administration in PBS as a vehicle, when measured by X-gal staining, immunohistochemistry, or Western blotting.