CRISPR Gene-Editing Therapy Shows Promising Results in Lowering Cholesterol and Triglycerides

A Phase 1 clinical trial of CTX310, an investigational CRISPR-Cas9 gene-editing therapy, demonstrated significant reductions in LDL cholesterol and triglycerides with a favorable safety profile in patients with difficult-to-treat lipid disorders. The one-time infusion therapy targets angiopoietin-like protein 3 (ANGPTL3), a gene known to regulate blood lipid levels when naturally mutated. Researchers reported that cholesterol and triglyceride levels began dropping within two weeks after treatment and remained reduced for at least 60 days of follow-up, with the highest dose achieving up to 60% reductions in both parameters.

The trial involved 15 adult participants with elevated lipid levels despite maximum tolerated therapies, including patients with familial hypercholesterolemia and mixed dyslipidemia. CTX310 uses lipid nanoparticles to deliver the CRISPR editing mechanism to the liver, where it permanently turns off ANGPTL3 gene expression. This approach mimics the natural condition of people born with ANGPTL3 mutations who have lifelong low cholesterol and triglyceride levels without apparent harmful effects and reduced cardiovascular risk. The study was conducted at six sites in Australia, New Zealand and the United Kingdom between June 2024 and August 2025.

Safety monitoring revealed three participants experienced minor infusion-related reactions that resolved with medication, and one participant had a temporary rise in liver enzymes that returned to normal without treatment. No long-term or serious safety concerns were observed during the study period, though participants will be monitored for 15 years as recommended by the U.S. Food and Drug Administration for all CRISPR-based therapies. The full peer-reviewed manuscript was published simultaneously in The New England Journal of Medicine, and the preliminary results were presented at the American Heart Association's Scientific Sessions 2025.

The implications of these findings are substantial for cardiovascular disease prevention. High cholesterol affects approximately 86.4 million U.S. adults according to the American Heart Association's 2025 Heart Disease and Stroke Statistics, and poor adherence to daily cholesterol medications remains a significant challenge in clinical practice. Study co-author Steven E. Nissen emphasized that many patients stop taking their cholesterol medications within the first year, making a one-time treatment with lasting effects a potential major clinical advance. The American Heart Association recently launched the Lower Your LDL Cholesterol Now Initiative to address these challenges through improved testing and treatment adherence.

Future Phase 2 studies are planned to begin in late 2025 or early 2026, focusing on broader patient populations and long-term outcomes. Researchers caution that while these initial results are promising, larger studies with more diverse participants are needed to confirm the findings and evaluate the treatment's applicability across different demographic groups. The study's limitations include its small size, primarily male participant group, and concentration in specific geographic regions, which may affect generalizability to other populations.