Adenovirus-Mediated Gene Transfer In Vivo An Approach to Reduce Oxidative Stress

Replication-deficient adenoviruses are used as vectors to study function of genes and to treat hypertension and cardiovascular diseases in preclinical studies. The purpose of this chapter is to provide an example of applications of the “first-generation,” E1-deleted and partially E3-deleted, human adenovirus type 5 vector, to test the hypothesis that gene transfer of a primary antioxidant enzyme, human extracellular superoxide dismutase (ECSOD), reduces arterial pressure in a genetic animal model of hypertension. Two concepts in application of gene transfer in vascular biology are illustrated. First, the liver, by iv injection of an adenoviral vector, can function as the source for abundant amounts of a transgene product, with profound vascular effects, when the transgene encodes a secreted protein. Second, the specific function of a domain of the transgene product can be studied by preparation and injection of isogenic vectors that express the identical product with or without a domain.