Researchers have reported early human data suggesting that gene editing may significantly lower harmful cholesterol and triglyceride levels after a single treatment.
Findings published in The New England Journal of Medicine describe a Phase 1 clinical trial evaluating a CRISPR-based therapy designed to permanently reduce blood lipid levels. Experts from Cleveland Clinic also discussed the research in a recent medical podcast.
The trial tested an investigational gene-editing therapy aimed at reducing levels of low-density lipoprotein (LDL) cholesterol and triglycerides. Elevated LDL cholesterol is a known risk factor for atherosclerotic cardiovascular disease, which can lead to heart attacks and strokes. Current treatment strategies include daily oral medications such as statins and injectable lipid-lowering drugs. These therapies require long-term adherence.
The new approach uses CRISPR-Cas9 gene editing technology to permanently alter a gene involved in lipid regulation. Researchers targeted the ANGPTL3 gene in liver cells. Naturally occurring loss-of-function variants in this gene are associated with lower LDL cholesterol and triglyceride levels and reduced cardiovascular risk.
The Phase 1 study enrolled 15 adults with elevated LDL cholesterol and/or triglyceride levels despite receiving standard lipid-lowering therapy. Clinical sites in Australia, New Zealand, and the United Kingdom conducted the trial. Researchers administered a single intravenous infusion of the investigational therapy at escalating dose levels.
The primary objective was to assess safety and tolerability. Secondary endpoints included changes in lipid levels and ANGPTL3 protein concentrations.
Investigators reported reductions in lipid levels within two weeks of treatment. Participants who received higher doses experienced up to approximately 50% reductions in LDL cholesterol and around 55% reductions in triglycerides. These effects persisted through at least 60 days of follow-up at the time of publication.
Researchers observed transient infusion-related symptoms in some participants, including nausea and back pain. These symptoms resolved with supportive care. The study did not report serious long-term adverse events related to the therapy during the short follow-up period.
The therapy delivers CRISPR-Cas9 components into liver cells using lipid nanoparticles. Once inside the cell, the CRISPR system creates a targeted break in the ANGPTL3 gene, leading to reduced production of the protein. Lower ANGPTL3 activity results in decreased circulating LDL cholesterol and triglycerides.
Unlike conventional medications that require repeated dosing, this strategy aims to achieve a durable effect after a single treatment. However, because gene editing permanently modifies DNA, regulators typically require extended safety monitoring.
This study represents an early-phase trial with a small sample size. It was not designed to evaluate long-term cardiovascular outcomes such as heart attacks or stroke reduction. Researchers will need larger trials with longer follow-up to determine durability of lipid reduction, rare adverse effects, and overall clinical benefit.
Until such data become available, established therapies including statins and other lipid-lowering agents remain the standard of care.
Early human trial data suggest that gene editing targeting ANGPTL3 can substantially reduce LDL cholesterol and triglycerides after a single infusion. The findings provide proof of concept for long-term lipid control through genomic modification. Ongoing research will determine whether this approach can safely reduce cardiovascular events and become part of future treatment strategies.
1. Laffin, Luke J., Stephen J. Nicholls, Russell S. Scott, Peter M. Clifton, John Baker, Ashish Sarraju, Shweta Singh, et al. “CRISPR-Mediated Gene Editing for Therapeutic LDL Cholesterol Reduction.” The New England Journal of Medicine 395, no. 14 (October 3, 2025): 1245–1255. DOI: 10.1056/NEJMoa2511778
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