Targeting of the renin-angiotensin system by antisense gene therapy: a possible strategy for the long-term control of hypertension

Traditional pharmacological agents have been successfully used for the trea tment of hypertension for a number of decades. However, this therapeutic re gimen has reached a conceptual plateau and a cure for the disease is far fr om appearing on the horizon. With this in mind, and recent advances in stat e of the art gene delivery system coupled with the anticipated completion o f the human genome project, it is timely to think about the possibility of treating and/or curing hypertension using genetic means. In this review, we discuss the role of renin-angiotensin system (RAS) in hypertension; the cu rrent gene delivery/gene transfer systems and the RAS as a target for gene therapy to treat hypertension; the successful use of retroviral vectors to deliver antisense to the AT(1) receptor (AT(1)-AS) to prevent the developme nt of hypertension and cardiovascular pathophysiology; the potential use of the viral vectors for the reversal of hypertension; and the future of anti sense gene therapy and potential advantages and limitations of this regimen in the treatment and/or control of hypertension. J Hypertens 2000, 18:353- 362 (C) Lippincott Williams & Wilkins.