Angiopoietin-like protein 3 (ANGPTL3) mRNA (ANGPTL3 mRNA)

Angiopoietin-like protein 3 (ANGPTL3) mRNA is a therapeutic target primarily expressed in the liver, where it encodes a protein that plays a critical role in lipid metabolism (UniProt Q9Y5C1). The ANGPTL3 protein acts as an inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), thereby regulating the clearance of triglyceride-rich lipoproteins and high-density lipoproteins from the plasma (PubMed: 28538136). Genetic studies have shown that individuals with loss-of-function mutations in ANGPTL3 have significantly lower levels of LDL cholesterol and triglycerides, which correlates with a reduced risk of coronary artery disease (NEJM: 376:2034-2044). Consequently, targeting the ANGPTL3 mRNA in hepatocytes using RNA-based therapeutics like antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) aims to reduce the production of the ANGPTL3 protein (PubMed: 35373044). This approach effectively lowers plasma lipid levels and provides a promising strategy for treating patients with severe dyslipidemias, including homozygous familial hypercholesterolemia (PubMed: 32861210). Clinical trials for drugs like vupanorsen and ARO-ANG3 have demonstrated the efficacy of this target in reducing cardiovascular risk factors (Lancet: 396:10263).

Other names

Angiopoietin-5 mRNAANG-5 mRNAAngiopoietin-related protein 3 mRNA

Antisense oligonucleotides (ASO) or small interfering RNA (siRNA) bind to the ANGPTL3 mRNA transcript in hepatocytes, leading to its degradation via RNase H or the RNA-induced silencing complex (RISC), thereby preventing the translation of the ANGPTL3 protein (PubMed: 35373044).