Researchers have hailed a “one-and-done” gene-editing therapy as “unprecedented” after it safely lowered both “bad” cholesterol and triglycerides in a first-in-human trial. The one-time infusion, called CTX310, simultaneously reduced LDL cholesterol by nearly 50 per cent and triglycerides by about 55 per cent.
The results of the 15-patient, Phase 1 trial were presented at the American Heart Association’s Scientific Sessions 2025. The study, which was simultaneously published in The New England Journal of Medicine, marks a major advance for patients with mixed lipid disorders, who have elevations in both blood fats.
“This is really unprecedented. A single treatment that simultaneously lowered LDL cholesterol and triglycerides,” said Luke J. Laffin, M.D., lead study author and a preventive cardiologist at the Cleveland Clinic. “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 editing genes in the liver. It uses CRISPR-Cas9 technology to durably turn off the ANGPTL3 gene, which is known to regulate LDL and triglyceride levels. Individuals born with natural mutations that turn off this gene have lifelong low cholesterol and a lower risk of heart disease.
Preventing heart disease
Reductions began within two weeks of treatment and were sustained for at least 60 days of follow-up. The treatment was found to be safe. Three participants had minor, resolvable infusion-related reactions, and one had a temporary rise in liver enzymes that returned to normal without treatment.
“Adherence to cholesterol-lowering therapy is one of the biggest challenges in preventing heart disease,” said Steven E. Nissen, M.D., FAHA, a co-author of the study and chief academic officer at the Cleveland Clinic Heart, Vascular and Thoracic Institute. “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.”
Participants in the trial will be monitored for 15 years, as recommended by the FDA for all CRISPR-based therapies. Researchers noted the trial was limited by its small, primarily male participant group. Larger, more diverse Phase 2 studies are planned to begin in late 2025 or early 2026.
