Single IV CRISPR Dose Produces ~50% LDL and Triglyceride Reductions at One Year in Early Trial

A single intravenous dose of the experimental CRISPR therapy CTX310 produced average reductions of about 50% in LDL cholesterol and triglycerides that were still present a year later in the highest-dose group of a small Phase 1a trial, an early sign that one-time gene editing could deliver lasting lipid lowering in people with difficult-to-treat disorders.

CTX310, developed by CRISPR Therapeutics, is an in-vivo CRISPR-Cas9 treatment, meaning the gene editing is done directly inside the body rather than on cells removed and returned later. The therapy is given as a one-time IV infusion of lipid nanoparticles carrying CRISPR components designed to inactivate the ANGPTL3 gene in liver cells. The one-year durability results were presented at the European Society of Cardiology Congress 2026 and published Aug. 28 in the New England Journal of Medicine as “Durability of CRISPR-Cas9 Gene Editing Targeting ANGPTL3 with CTX310.”

The data come from the Phase 1a portion of a first-in-human, open-label, ascending-dose trial. Fifteen participants were treated, and all had at least 12 months of follow-up at the data cutoff. In the highest-dose cohort, which received 0.8 mg/kg and included four patients, mean LDL cholesterol fell 52.5% at one year and mean triglycerides fell 47.8%. CRISPR Therapeutics also reported that ANGPTL3 protein levels in that group were down about 79% on average at one year.

The trial’s primary goals were safety and tolerability, with lipid changes measured as secondary endpoints. Through one year, investigators reported no treatment-related serious adverse events and no dose-limiting toxicities. Adverse events were generally mild to moderate. Earlier reports had included infusion-related reactions, one allergic reaction that resolved, and one transient aminotransferase elevation — a temporary rise in liver enzymes — that also resolved. No new treatment-related safety events were reported during the extended follow-up.

The study enrolled people with uncontrolled LDL cholesterol and/or triglycerides despite standard treatment. Most participants were already taking statins and/or ezetimibe, and 40% were on PCSK9 inhibitors, another class of cholesterol-lowering drugs. Participants were pretreated with corticosteroids and antihistamines before receiving the infusion.

ANGPTL3 is a liver-produced protein involved in lipid metabolism, and human genetic studies have linked naturally occurring loss-of-function variants in the gene with lower LDL and triglycerides as well as lower odds of coronary artery disease. That makes it a validated target for lipid-lowering therapy. The appeal of CTX310 is not just the size of the lipid reductions but the possibility that one infusion could replace years of daily pills or repeated injections if larger studies confirm the approach is safe and effective.

“What is compelling about this update is that the reductions in ANGPTL3, triglycerides, and LDL from a single infusion have persisted out to one-year, suggesting a sustained biological effect,” Steven E. Nissen, a senior author of the study, said in a statement released by the company.

Still, the findings come with important limits. This was a small, early-stage trial, and the roughly 50% reductions highlighted by the company come from just four patients in the highest-dose group. The study was not designed to show whether CTX310 lowers the risk of heart attacks, strokes or death. Because CRISPR editing is intended to be long-lasting, participants will continue long-term safety monitoring consistent with Food and Drug Administration guidance for genome-editing products, which can call for follow-up of up to 15 years.

The study was funded by CRISPR Therapeutics, and key investigators were affiliated with the Cleveland Clinic Coordinating Center for Clinical Research. CRISPR Therapeutics has said it is moving the program into Phase 1b, where larger studies will be needed to test whether the early durability signal holds up.