Gene Therapy: New Options for Hypertensive Treatment

Abstract

Hypertension is a chronic disease, of which patients have to take medication throughout life. The ineffectiveness of blood pressure control partly stems from patient compliance due to several drug uses and intolerable side effects. Recent advances in biotechnology and transgenic medicines make gene therapy a new· promising frontier in treatment of hypetiension. Two approaches have been under investigation: 1) Sense approach using gain-of-function strategy by inserting a vasodilator gene into host genomes and 2) Antisense approach using loss-of-function strategy by suppressing the expression of vasoconstrictor gene with antisense oligonucleotides. The potential therapeutic targets in antisense gene therapy include genes encoding proteins in the renin-angiotensin-aldosterone system and adrenoceptors, which are the current targets for antihypertensive drugs such as ACEis and β-blockers. Either nonviral vectors (e.g., liposome) or viral vectors (e.g., retrovirus, adenovirus, and adeno-associated virus) can be used to deliver therapeutic genes to the target cells if they are nonpathogenic, highly selective and specific to the target. The vector delivery system is a crucial factor determining an outcome of the therapy especially its influences on the duration of action. The viral based vectors produce a longer duration than the nonviral vectors do. The results of preclinical studies support the potential of gene therapy for future clinical use in treatment of hypertension.