Angiotensinogen (AGT)

Class

Antisense oligonucleotide (AGT-lowering)

Angiotensinogen (AGT) is a protein made mainly by the liver and released into the bloodstream, where it serves as the sole precursor substrate for the renin-angiotensin system (RAS), a hormonal cascade that regulates blood pressure, fluid balance, and vascular tone. The enzyme renin cleaves circulating AGT to generate angiotensin I, which is then converted to angiotensin II, the active hormone that constricts blood vessels and promotes sodium and water retention. Because AGT sits at the very top of this cascade, reducing its production lowers the raw material available for the entire downstream pathway, rather than blocking a single receptor or enzyme further along, as older RAS-targeting drugs do. This approach is being explored as a way to achieve durable, sustained reduction in angiotensin II generation, primarily for chronic hypertension and conditions where excessive RAS activity contributes to organ damage, such as kidney disease. Newer therapeutic modalities silence AGT production directly at the genetic level, offering the possibility of infrequent dosing compared to daily oral RAS-pathway drugs. The broad relevance of this mechanism spans blood pressure disorders and cardiovascular and renal conditions where excess angiotensin II signaling drives disease progression.