Targeting angiotensinogen with RNA-based therapeutics

Curr Opin Nephrol Hypertens. 2020 Mar;29(2):180-189. doi: 10.1097/MNH.0000000000000586.

Abstract

Purpose of review: To summarize all available data on targeting angiotensinogen with RNA-based therapeutics as a new tool to combat cardiovascular diseases.

Recent findings: Liver-targeted, stable antisense oligonucleotides and small interfering RNA targeting angiotensinogen are now available, and may allow treatment with at most a few injections per year, thereby improving adherence. Promising results have been obtained in hypertensive animal models, as well as in rodent models of atherosclerosis, polycystic kidney disease and pulmonary fibrosis. The next step will be to evaluate the optimal degree of suppression, synergy with existing renin-angiotensin-aldosterone system blockers, and to determine harmful effects of suppressing angiotensinogen in the context of common comorbidities, such as heart failure and chronic kidney disease.

Summary: Targeting angiotensinogen with RNA-based therapeutics is a promising new tool to treat hypertension and diseases beyond. Their long-lasting effects are particularly exciting, and if translated to a clinical application of at most a few administrations per year, may help to eliminate nonadherence.

Publication types

  • Review

MeSH terms

  • Angiotensinogen / antagonists & inhibitors*
  • Angiotensinogen / genetics
  • Animals
  • Humans
  • Hypertension / drug therapy*
  • Oligonucleotides, Antisense / therapeutic use
  • RNA, Small Interfering / therapeutic use
  • Renin-Angiotensin System / drug effects

Substances

  • Oligonucleotides, Antisense
  • RNA, Small Interfering
  • Angiotensinogen