Angiotensinogen is the sole precursor of angiotensin peptides and has a key role in the pathogenesis of hypertension.

Zilebesiran, an investigational RNA interference therapeutic agent with a prolonged duration of action, inhibits hepatic angiotensinogen synthesis.

Zilebesiran is a small interfering RNA that silences hepatic AGT expression leading to a decrease in  production of angiotensinogen protein and suppresses synthesis of angiotensin I, and angiotensin II, and consequent blood pressure lowering.

Dose-dependent decreases in serum angiotensinogen levels and 24-hour ambulatory blood pressure were sustained for up to 24 weeks after a single subcutaneous dose of zilebesiran of 200 mg or more; mild injection-site reactions were observed.

Subcutaneous, zilebesiran  of 150, 300, or 600 mg every six months or 300 mg every three months significantly decreases systolic blood pressure at three and six months versus placebo.

Zilebesiran is a siRNA that targets the AGT gene in the liver and post-transcriptionally silences its expression leading to a decreased production of angiotensinigen protein, suppressed synthesis of angiotensin I, and angiotensin II  and consequently blood pressure lowering.

Zilebesiran reduces hepatic angiotensinogen messenger RNA, resulting in reduction of angiotensinogen synthesis.

Zilebesiran given is a single subcutaneous dose of 200 mg or more induced dose dependent reductions in serum angiotensinogen and ambulatory blood pressure that is sustained for up to 24 weeks.

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