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GalNAc-Inhbe siRNA
- Development stage
- Preclinical
- Lead developer
- AstraZeneca
- Modality
- Chemically Modified siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Conjugated siRNA → Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Subcutaneous
01
Overview
GalNAc-Inhbe siRNA is an investigational, liver-targeted, N-acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) designed to silence the expression of the INHBE (inhibin subunit beta E) gene in hepatocytes. INHBE encodes the hepatokine Activin E, which is secreted by the liver and acts on adipose tissue to inhibit lipolysis and promote lipid storage. By silencing INHBE, GalNAc-Inhbe siRNA reduces Activin E levels, thereby promoting fat-selective weight loss, reducing visceral adiposity, and improving metabolic parameters such as liver lipidosis and adipose tissue inflammation while preserving lean muscle mass. Preclinical studies by AstraZeneca have demonstrated that GalNAc-Inhbe siRNA induces significant and durable body weight loss in diet-induced obese mice, and when combined with a GLP-1 receptor agonist (such as semaglutide), it potentiates weight loss and attenuates weight regain after treatment discontinuation.
- Other names
- GalNAc-conjugated Inhbe siRNAInhbe siRNAinhibin beta E siRNA
02
Targets
ACVR1C (Activin A Receptor Type 1C)ASGPR (Asialoglycoprotein Receptor 1)INHBE (Inhibin beta E chain)
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