Gene therapy for hypertension: antisense inhibition with adeno-associated viral vector delivery targeting angiotensin II type 1 receptor messenger ribonucleic acid

Abstract

The goal of gene therapy for hypertension is to provide treatment that decreases blood pressure for much longer than can be achieved using a single dose of currently available pharmacologic agents and with an equivalent or improved side-effects profile. Although many risk factors for the development of hypertension have been identified, the exact pathophysiologic mechanisms remain largely undefined. Hypertension is known to be a multifactorial disorder that is likely to involve a wide array of genes. Candidate genes that make attractive targets for investigation of potential therapeutic intervention include those regulating vasoconstrictors, such as renin–angiotensin, adrenergic, endothelin, and neuropeptide Y genes, and those regulating vasodilators, including genes for kallikrein, atrial natriuretic peptide, nitric oxide (NO), and calcitonin gene-related peptide. We have performed several studies to assess the potential for gene therapy targeting the renin–angiotensin system.