An experimental CRISPR-Cas9 therapy reduced LDL cholesterol and triglycerides by approximately half for one year in patients with difficult-to-treat lipid disorders, according to results from a phase I trial.
The treatment, CTX310, targets the ANGPTL3 gene in liver cells to reduce circulating blood lipids. Among four patients receiving the highest dose, LDL cholesterol fell by an average of 52.5 percent and triglycerides by 47.8 percent at 12 months.
ANGPTL3 regulates lipid metabolism, and naturally occurring variants that disable the gene are associated with a lower risk of atherosclerotic cardiovascular disease. CTX310, developed by CRISPR Therapeutics, uses lipid nanoparticles to deliver CRISPR-Cas9 messenger RNA and guide RNA to liver cells, where they disrupt the gene.
The open-label, multicenter trial enrolled 15 adults with uncontrolled hypercholesterolemia, moderate or severe hypertriglyceridemia, or mixed dyslipidemia. Participants received a single infusion of CTX310 at one of five dose levels ranging from 0.1 to 0.8 mg/kg.
At the highest dose, ANGPTL3 levels fell by an average of 78.6 percent after one year. Non-HDL cholesterol and apolipoprotein B, two additional markers associated with cardiovascular risk, declined by 52.0 percent and 37.2 percent, respectively.
The results extend earlier findings reported after two months, indicating that the lipid-lowering effects persisted without further treatment during the follow-up period.
No dose-limiting toxicity was reported. Two serious adverse events were considered unrelated to CTX310, and no new serious adverse events occurred during the extended follow-up. One participant experienced a transient elevation in liver enzymes shortly after treatment, with no further elevations reported.
"Building upon the initial data presented in November 2025, the durability of the lipid-lowering effect was impressive," said Luke Laffin, a Cleveland Clinic cardiologist and first author of the study, in a statement.
The trial was limited to 15 patients, including four at the highest dose, and did not establish whether the lipid reductions translate into fewer cardiovascular events. Longer-term monitoring will also be needed to assess the safety of permanent gene editing.
A phase Ib trial is now evaluating CTX310 in patients with refractory lipid disorders, with separate cohorts assessing responses across different conditions.
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