Cleveland Clinic First-In-Human Trial of CRISPR Gene-Editing Therapy Shown to Safely Lower Cholesterol and Triglycerides

Results from a Cleveland Clinic Phase 1, first-in-human clinical trial showed that a one-time infusion of a gene-editing therapy using CRISPR-Cas9 safely reduced LDL (“bad”) cholesterol and triglycerides in people with lipid disorders resistant to current medications.

The results were presented today during a late-breaking science presentation at the American Heart Association’s Scientific Sessions 2025 and were simultaneously published the New England Journal of Medicine.

In the trial, which included 15 patients, both LDL cholesterol and triglyceride levels were substantially reduced within two weeks after treatment and stayed at low levels for at least 60 days, with additional follow-up ongoing. The treatment did not result in any serious adverse events related to the treatment during short-term follow-up.

“This treatment is still very early in development but if future trials continue to demonstrate safety and efficacy, the therapy has the potential to change the way we treat lipid disorders,” said Cleveland Clinic cardiologist Luke Laffin, M.D., first author of the study. “Rather than a once-daily pill or monthly injection, this therapy would potentially offer a one-time infusion that is safe and durable for patients with high cholesterol.”

Too much LDL cholesterol (often referred to as the “bad” cholesterol) can lead to atherosclerotic disease – plaque buildup in the walls of arteries – that can increase the risk of a heart attack or stroke. Recent estimates show that as of 2018, 26.4% of U.S. adults have elevated LDL cholesterol.

High triglycerides can also lead to a higher risk of heart and vascular disease, including heart attack and stroke. About 25% of people in the U.S. have high triglycerides.

“Adherence to treatment is a significant issue for patients. In fact, half of the patients who are treated with cholesterol-lowering drugs stop taking them within a year,” said senior author Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic. “Although it is early in the study of gene-editing therapies, the efficacy demonstrated in the current trial is highly promising and represents a potential new frontier for drug development.”

CRISPR-Cas9 is a gene-editing technology that can be used to modify or correct specific regions of a person’s DNA to treat serious diseases.

This trial tested CTX310, an experimental CRISPR-Cas9 gene-editing treatment that is delivered as a one-time infusion. CTX310 carries the CRISPR editing mechanism into the liver, where it switches off a gene called ANGPTL3. Turning off this gene can lower LDL cholesterol and triglycerides, which are both linked to heart disease. People born with a loss-of-function genetic mutation in ANGPTL3 have lower lifetime risk of heart disease with no apparent adverse consequences.

The study was conducted between June 2024 and August 2025 at six sites in Australia, New Zealand and the United Kingdom. Study participants included 15 adults between the ages of 31 and 68. All participants had uncontrolled high triglycerides and high LDL cholesterol levels.

During the trial, CTX310 was administered as a one-time intravenous infusion at doses from 0.1 to 0.8 mg/kg during the single infusion, after pre-treatment with corticosteroids and antihistamines. Participants were monitored for safety of the treatment, and the effects of this gene therapy on ANGPTL3, LDL cholesterol, and triglyceride levels. CTX310 reduced both LDL cholesterol and triglycerides by approximately 50% on average at the highest dose.All patients had at least 60 days of safety follow-up.

Three participants experienced minor reactions such as back pain and nausea that were resolved with medication, and one participant with elevated liver enzymes before treatment had a temporary further rise in liver enzymes that lasted a few days and returned to normal without need for any treatment.

The study participants will be monitored for one year following the trial, with additional long-term safety follow-up for 15 years, as recommended by the FDA for all gene-editing therapies.

“Importantly, there were no serious safety events related to CTX310,” added Dr. Laffin. “However, this was a small and relatively short study, and we will need to continue to study the safety rigorously in future trials.”

Future Phase 2 studies are planned to begin in 2026, focusing on broader patient populations and longer-term outcomes.

The study was funded by CRISPR Therapeutics AG; Zug, Switzerland.

Dr. Nissen has served as a consultant for many pharmaceutical companies and has overseen recent clinical trials for Abbvie, Amgen, AstraZeneca, CRSPR Therapeutics, Kardigan, Eli Lilly, Novartis, New Amsterdam Pharma and Pfizer. However, he does not accept honoraria, consulting fees or other compensation from commercial entities.

Dr. Laffin serves or has served on steering or advisory committees for Recor, Medtronic, Eli Lilly, Novartis, Novo Nordisk, and Ripple Medical. His institution has received research funding from AstraZeneca, Arrowhead, Crispr Therapeutics, Kardigan, Mineralys, Retension. Dr. Laffin receives royalties from Belvoir Media Group and Elsevier.