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zilebesiran + REVERSIR
- Development stage
- Unknown
- Lead developer
- Alnylam Pharmaceuticals
- Modality
- Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Modified DNA Oligonucleotides → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Single-strand DNA → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Subcutaneous
01
Overview
Zilebesiran + REVERSIR is an investigational therapeutic combination comprising zilebesiran, a small interfering RNA (siRNA), and REVERSIR, a specific antisense oligonucleotide antidote. Zilebesiran is designed to treat hypertension by inhibiting the hepatic synthesis of angiotensinogen (AGT), the primary precursor in the renin-angiotensin-aldosterone system (RAAS). By silencing AGT mRNA, zilebesiran provides a durable reduction in blood pressure with infrequent dosing. REVERSIR is a GalNAc-conjugated, single-stranded oligonucleotide that acts as a high-affinity antidote, binding to zilebesiran to rapidly reverse its RNAi activity and restore AGT production within 24 hours. This approach is intended to provide a safety mechanism for the long-acting siRNA therapy, allowing for rapid reversal in clinical situations such as acute hypotension or pregnancy. The combination is currently being evaluated in Phase 1 clinical trials by Alnylam Pharmaceuticals.
- Other names
- zilebesiran REVERSIR
02
Targets
AGT (O6-methylguanine-DNA methyltransferase)ASGPR (Asialoglycoprotein Receptor 1)
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