CRISPR Gene-Editing Therapy Shows Promise in Reducing Cholesterol and Triglycerides in First Human Trial

In a Phase 1 clinical trial involving 15 participants, a one-time infusion of an investigational CRISPR-Cas9 therapy targeting angiopoietin-like protein 3 (ANGPTL3) demonstrated significant reductions in LDL cholesterol and triglycerides with an acceptable safety profile. The therapy, called CTX310, reduced LDL cholesterol by nearly 50% and triglycerides by about 55% on average at the highest dose, with effects appearing within two weeks and sustained for at least 60 days of follow-up.

The treatment represents a potential breakthrough for patients with difficult-to-treat lipid disorders who struggle with medication adherence. According to the American Heart Association's cholesterol information, high cholesterol affects approximately 86.4 million U.S. adults and is a major risk factor for heart disease and stroke, the leading causes of death worldwide. The Association recently launched the Lower Your LDL Cholesterol Now Initiative, a three-year national effort to improve cholesterol management.

Study author Dr. Luke J. Laffin, a preventive cardiologist at the Cleveland Clinic, described the results as unprecedented. "A single treatment that simultaneously lowered LDL cholesterol and triglycerides," he said. "If confirmed in larger trials, this one-and-done approach could transform care for people with lifelong lipid disorders and dramatically reduce cardiovascular risk." The therapy works by using tiny fat-based particles to deliver the CRISPR editing mechanism into the liver, where it switches off the ANGPTL3 gene, mimicking natural mutations that provide lifelong protection against high cholesterol.

The trial included participants with various lipid disorders, including familial hypercholesterolemia and mixed dyslipidemia, who had elevated lipid levels despite maximum tolerated therapies. Conducted between June 2024 and August 2025 at six sites in Australia, New Zealand and the United Kingdom, the study followed participants for safety, how the gene therapy was processed in the body, and cholesterol and triglyceride levels. All patients had at least 60 days of safety follow-up for inclusion in the analysis.

Safety monitoring revealed three participants experienced minor infusion-related reactions, such as back pain and nausea that resolved with medication, and one participant with elevated liver enzymes at screening had a temporary further rise that returned to normal without treatment. No long-term or serious safety concerns were observed, though participants will be monitored for one year within the trial and for 15 years as recommended by the FDA for all CRISPR-based therapies.

Dr. Steven E. Nissen, study co-author and chief academic officer at the Cleveland Clinic Heart, Vascular and Thoracic Institute, emphasized the importance of addressing medication adherence challenges. "Adherence to cholesterol-lowering therapy is one of the biggest challenges in preventing heart disease," he said. "Many patients stop taking their cholesterol medications within the first year. The possibility of a one-time treatment with lasting effects could be a major clinical advance."

The study's limitations include its small size, primarily male participant group, and focus on patients in specific countries, meaning results may not be applicable to broader populations. Future Phase 2 studies are planned to begin in late 2025 or early 2026, focusing on more diverse patient populations and long-term outcomes. The full study was simultaneously published as a peer-reviewed manuscript in The New England Journal of Medicine.