ANGPTL3 gene (hepatocyte genomic DNA)

Class

In vivo CRISPR adenine base-editing therapeutic (lipid nanoparticle-delivered)

Pathway

Base-edits and permanently inactivates the ANGPTL3 gene in hepatocytes, lowering circulating LDL-C and triglycerides

ANGPTL3 (angiopoietin-like 3) is a protein secreted by liver cells that inhibits two enzymes, lipoprotein lipase and endothelial lipase, which break down triglyceride-rich particles and certain lipoproteins in the bloodstream. By suppressing these enzymes, ANGPTL3 raises circulating triglycerides and LDL-cholesterol (LDL-C), the lipid most strongly linked to atherosclerotic cardiovascular disease. People who naturally carry loss-of-function mutations in the ANGPTL3 gene have lifelong low lipid levels and reduced cardiovascular risk without apparent harm, making the gene an attractive target for therapies aimed at durably lowering cholesterol and triglycerides. This approach uses CRISPR base editing delivered to liver cells via lipid nanoparticles to chemically alter a single DNA letter within the ANGPTL3 gene, permanently disabling it in a manner intended to mimic these protective natural mutations. Because ANGPTL3 acts independently of the LDL receptor, this pathway can lower lipids even in situations where receptor-based approaches, such as statins, are less effective. The broader relevance spans familial hypercholesterolemia, mixed dyslipidemia, and general cardiovascular risk reduction, wherever sustained lipid lowering is desired without reliance on repeated dosing.