Small Interfering RNA Therapy for the Management and Prevention of Hypertension

Purpose of review: To review currently existing knowledge on a new type of antihypertensive treatment, small interfering RNA (siRNA) targeting hepatic angiotensinogen.

Recent findings: Targeting angiotensinogen synthesis in the liver with siRNA allows reaching a suppression of renin-angiotensin system (RAS) activity for up to 6 months after 1 injection. This might revolutionize antihypertensive treatment, as it could overcome non-adherence, the major reason for inadequate blood pressure control. Animal data support that its effects on blood pressure and end-organ damage are fully comparable to those of classical RAS blockers, and phase I and II clinical trials confirm its antihypertensive effectiveness and long-term action. Although its side effect profile is placebo-like, its long-term effects also pose a threat in patients who require immediate restoration of RAS activity, like in shock. Here tools are being developed, called REVERSIR, that allow immediate annihilation of the siRNA effect in the liver. One subcutaneous injection of angiotensinogen siRNA lowers blood pressure for 6 months without severe side effects. The decrease in angiotensinogen and blood pressure can be reversed with a drug called REVERSIR if needed.