Zilebesiran (AD-85481; ALN-AGT) sodium is a long-acting liver-targeted small interfering RNA (siRNA) antihypertensive agent. Zilebesiran sodium binds to the hepatic asialoglycoprotein receptor ( ASGPR ), activates the RNA-induced silencing complex to degrade hepatic angiotensinogen mRNA, thereby inhibiting the gene expression and synthesis of angiotensinogen. Zilebesiran sodium dose-dependently reduces serum angiotensinogen levels and 24-hour ambulatory blood pressure, with its effect persisting throughout the circadian cycle. Zilebesiran sodium is applicable to research related to hypertension [1] [2].
In Vivo, AGT siRNA (analog of Zilebesiran) (10 mg/kg; s.c.; once every 2 weeks for a total of 4 weeks) sodium exerts significant hypotensive effects in spontaneously hypertensive rats, 5/6 nephrectomized chronic kidney disease rats, and streptozotocin (STZ) -induced diabetic rats[2].
References:
[1]. Desai AS, Webb DJ, Taubel J, et al. Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension. N Engl J Med. 2023;389(3):228-238. doi:10.1056/NEJMoa2208391
[2]. Dudzicz-Gojowy S, et al. Zilebesiran-Small Interfering RNAs as Prospective New Drug in the Treatment of Hypertension. J Clin Med. 2025;14(20):7365. Published 2025 Oct 17.
In Vivo, AGT siRNA (analog of Zilebesiran) (10 mg/kg; s.c.; once every 2 weeks for a total of 4 weeks) sodium exerts significant hypotensive effects in spontaneously hypertensive rats, 5/6 nephrectomized chronic kidney disease rats, and streptozotocin (STZ) -induced diabetic rats[2].
References:
[1]. Desai AS, Webb DJ, Taubel J, et al. Zilebesiran, an RNA Interference Therapeutic Agent for Hypertension. N Engl J Med. 2023;389(3):228-238. doi:10.1056/NEJMoa2208391
[2]. Dudzicz-Gojowy S, et al. Zilebesiran-Small Interfering RNAs as Prospective New Drug in the Treatment of Hypertension. J Clin Med. 2025;14(20):7365. Published 2025 Oct 17.