Angiotensinogen mRNA (AGT mRNA) (AGT mRNA)

Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides within the renin-angiotensin-aldosterone system (RAAS), a critical pathway for blood pressure and fluid homeostasis (UniProt P01019). It is primarily synthesized and secreted by hepatocytes in the liver. Targeting the mRNA of AGT in hepatocytes using RNA interference (RNAi) or antisense oligonucleotides (ASOs) allows for the specific knockdown of AGT production at its source (Desai et al., NEJM 2023). This strategy effectively lowers the levels of circulating AGT, thereby reducing the formation of angiotensin I and angiotensin II, leading to sustained blood pressure reduction. Investigational drugs like Zilebesiran utilize N-acetylgalactosamine (GalNAc) conjugation to ensure targeted delivery to hepatocytes, minimizing systemic off-target effects (Bakris et al., JAMA 2024). This approach is being evaluated for the treatment of hypertension, particularly in patients with high cardiovascular risk or resistant hypertension (Mueller et al., Hypertension 2021). By suppressing the RAAS at its most upstream point, these therapies offer the potential for infrequent dosing and improved long-term blood pressure control compared to traditional oral medications.

Other names

AGT mRNASerpin A8 mRNAAngiotensinogen messenger RNA

RNA interference (RNAi) or antisense-mediated degradation of mRNA to inhibit protein synthesis in hepatocytes (Desai et al., NEJM 2023).