IN-VIVO GENE-TRANSFER AND GENE MODULATION IN HYPERTENSION RESEARCH

Transgenic technologies and homologous recombination approaches have b een useful for studying the roles of specific genes in systemic hypert ension. Recently, me and others have introduced the use of in vivo gen e transfer to study the effects of local gene overexpression or inacti vation in hypertension. Using in vivo gene transfer for the blood vess el, we have documented the direct hypertrophic action of local angiote nsin and the growth-inhibitory effect of nitric oxide. In vivo gene tr ansfer is also an effective method for discovering the unknown functio ns of a newly cloned gene. Using this approach, we identified the in v ivo growth-inhibitory action of the angiotensin II type 2 receptor. In addition, we have developed a novel strategy using transcriptional fa ctor ''decoy'' oligonucleotides to regulate the interaction of cis- an d trans-acting factors involved in the modulation of gene expression i n vivo. Thus, the decoy approach can ''switch'' on or off specific gen es in selective tissues in vivo, thereby influencing local gene expres sion and tissue function. For example, using decoy oligonucleotides, w e have ''turned on'' renin gene expression in the rat liver, in which it is usually not expressed, resulting in increased hepatic and plasma renin levels. Thus, in vivo gene transfer technology provides us with a new tool for in vivo characterization of genes involved in hyperten sion that has potential application in human therapy.