Summary
A CRISPR base-editing approach targeting ANGPTL3 reduced LDL cholesterol and triglycerides in mouse and nonhuman-primate models. In primates, ANGPTL3 protein reductions lasted up to three years after one dose.
A study published in Nature on 6 November 2026 reports that a single dose of an in vivo CRISPR base-editing treatment targeting ANGPTL3 produced durable reductions in the protein in nonhuman primates and lowered blood lipids in animal models. The findings are preclinical: the paper says they provided the scientific foundation for an ongoing first-in-human trial in patients with refractory hyperlipidemia syndromes.
ANGPTL3 is a liver-produced protein that contributes to higher LDL cholesterol (LDL-C) and triglyceride concentrations. Both are risk factors for atherosclerotic cardiovascular disease. The study explores whether inactivating the gene that encodes ANGPTL3 could offer a single-course alternative to lipid-lowering treatments taken over time.
How the treatment targets ANGPTL3
The researchers delivered guide RNA and messenger RNA encoding a CRISPR adenine base editor in a GalNAc–lipid nanoparticle infusion. The guide RNA directs the editor to the intended DNA sequence; the editor makes a targeted base-pair change intended to inactivate ANGPTL3. Base editing alters DNA at a chosen site rather than relying on a conventional double-strand cut. In this study, the treatment was designed to act in the liver.
In human liver cells tested in vitro, the researchers confirmed editing at the ANGPTL3 target. They reported no detectable off-target editing at approximately 3,000 candidate sites and no treatment-related structural variants in those analyses.
What the animal studies found
In nonhuman primates, ANGPTL3 inactivation was reported as well-tolerated and produced a mean reduction of more than 90% in circulating ANGPTL3 protein. The reduction remained durable for up to three years after a single dose. In mouse and nonhuman-primate models of hyperlipidemia, the gene inactivation was associated with LDL-C reductions of approximately 40–50% and triglyceride reductions of 50–70%.
Those lipid changes were measured in animal models, while the human liver-cell work tested editing in a laboratory setting. The paper does not report clinical lipid or cardiovascular outcomes in people. Its findings instead mark a step toward testing whether the approach can work in patients: the authors say they formed the scientific basis for an ongoing first-in-human clinical trial. Whether the animal results translate into comparable effects and durability in people is now a question for clinical testing.