AGT-siRNA

**AGT-siRNA** (angiotensinogen small interfering RNA) is a target-specific generic descriptor for a class of RNA interference (RNAi) therapeutics designed to target and silence the mRNA of angiotensinogen (AGT) in the liver. By inhibiting hepatic AGT expression, these agents block the renin-angiotensin-aldosterone system (RAAS) at its source, leading to sustained reductions in circulating AGT and blood pressure. This approach is primarily developed for the treatment of hypertension, offering the potential for quarterly or twice-yearly dosing to improve patient adherence and reduce blood pressure variability. Preclinical studies, notably conducted by Alnylam and Erasmus MC, have utilized rodent-specific AGT-siRNA to demonstrate long-lasting antihypertensive effects that can be rapidly reversed using complementary REVERSIR oligonucleotides (such as AGT-RVR). In clinical development, several specific AGT-targeting siRNAs are being evaluated, including Alnylam's zilebesiran (ALN-AGT01) and Leaderna Therapeutics' LDR2402, the latter of which demonstrated a favorable safety profile and potent, sustained blood pressure reduction in a Phase I trial conducted at the Sichuan Academy of Medical Sciences.

Other names

AGT siRNAangiotensinogen siRNAsiRNA targeting angiotensinogen