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GalNAc-siRNA targeting ANGPTL4
- Development stage
- Preclinical
- Lead developer
- Leaderna Therapeutics
- 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-siRNA targeting ANGPTL4 is an investigational RNA interference (RNAi) therapeutic designed to silence the expression of angiopoietin-like protein 4 (ANGPTL4) in the liver. The molecule consists of a small interfering RNA (siRNA) sequence specific to the ANGPTL4 mRNA, conjugated to N-acetylgalactosamine (GalNAc) to enable targeted delivery to hepatocytes via the asialoglycoprotein receptor (ASGPR). ANGPTL4 is a hepatokine that inhibits lipoprotein lipase (LPL) and endothelial lipase, thereby increasing circulating triglyceride levels. Beyond its role in lipid metabolism, recent preclinical evidence suggests that ANGPTL4 also modulates vascular tone through integrin signaling (specifically α5β1 integrin). Silencing of ANGPTL4 has been shown to enhance vasoconstriction in hypertensive models, indicating a potential compensatory role in blood pressure regulation and suggesting that ANGPTL4 bioavailability may be a target for managing vascular resistance.
- Other names
- ANGPTL4 siRNAANGPTL-4 siRNAANGPTL 4 siRNAGalNAc-conjugated ANGPTL4 siRNA
02
Targets
ANGPTL4 (Angiopoietin-like 4)ASGPR (Asialoglycoprotein Receptor 1)AGO2 (Argonaute RISC catalytic component 2)
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