CRISPR base editing of ANGPTL3 lowers lipids in animal models

Researchers tested an infusion of guide RNA and mRNA encoding a CRISPR adenine base editor, delivered in a GalNAc–lipid nanoparticle, to inactivate hepatic ANGPTL3. The study included human liver cells in vitro and mouse and nonhuman-primate models; the authors say the findings provided the scientific basis for an ongoing first-in-human trial in patients with refractory hyperlipidemia syndromes.

In human liver cells, the editor changed the target DNA base pair, with no detectable off-target editing at approximately 3,000 candidate sites or treatment-related structural variants. In nonhuman primates, treatment was reported as well tolerated and reduced circulating ANGPTL3 protein by more than 90% on average, with the effect observed up to three years after a single dose. In hyperlipidemic mice and nonhuman primates, ANGPTL3 inactivation was associated with approximately 40–50% lower LDL cholesterol and 50–70% lower triglycerides.

These are preclinical findings and do not establish efficacy or safety in people. Human trial results are not provided, and the animal lipid changes do not demonstrate reduced cardiovascular events or support a change in current clinical treatment.