In-human trial demonstrates CRISPR gene editing can safely reduce LDL cholesterol by nearly 50%
Single intravenous infusion shows lasting effects, potentially eliminating need for daily medications
Results published in New England Journal of Medicine and presented at American Heart Association Scientific Sessions 2025
In a development that researchers are calling "unprecedented," scientists have successfully used CRISPR gene editing technology to dramatically lower cholesterol levels in patients with difficult-to-treat lipid disorders. The groundbreaking Phase 1 clinical trial, published November 8, 2025, in the New England Journal of Medicine, represents a potential paradigm shift in how we approach cardiovascular disease prevention.
"Frankly, if you'd asked me 15 years ago if we would be able to do this, I would have thought you were crazy," said Dr. Steven E. Nissen, chief academic officer at the Cleveland Clinic's Heart, Vascular & Thoracic Institute and one of the study's principal investigators.
The timing of this breakthrough couldn't be more critical. According to the Centers for Disease Control and Prevention (CDC), high cholesterol affects millions of Americans:
11.3% of adults aged 20 and older have dangerously high total cholesterol levels (240 mg/dL or higher) as of August 2021-August 2023
Nearly 25 million adults in the United States have total cholesterol levels above 240 mg/dL
86 million US adults have total cholesterol levels above 200 mg/dL
Only 54.5% of adults who could benefit from cholesterol medication are currently taking it
High cholesterol prevalence peaks at 16.7% in adults aged 40-59
"High cholesterol has no symptoms, so many people don't know that their cholesterol is too high," warns the CDC.
The experimental therapy, called CTX310, represents an ingenious approach to treating high cholesterol. It targets a gene called ANGPTL3 (angiopoietin-like protein 3), which produces a protein that prevents the liver from breaking down cholesterol and triglycerides.
Scientists discovered that some people naturally have low-functioning versions of this gene, resulting in lifelong reductions in LDL cholesterol and triglyceride levels without any apparent adverse health effects. These individuals also enjoy a significantly lower lifetime risk of atherosclerotic cardiovascular disease.
CTX310 uses lipid nanoparticle (LNP) technology to deliver CRISPR-Cas9 gene editing components directly to liver cells, where they permanently switch off the ANGPTL3 gene. This allows the liver to break down more cholesterol and fats naturally.
"What's nice about this target of ANGPTL3 is that it not only lowers the LDL, the bad cholesterol, but it also has some effectiveness on people who have very high triglycerides," explained Dr. Elizabeth McNally, a human geneticist and cardiologist at Northwestern Feinberg School of Medicine.
The Phase 1 open-label, dose-escalation trial was conducted between June 2024 and August 2025 at six sites across Australia, New Zealand, and the United Kingdom. The study enrolled 15 adults aged 31 to 68 years who had:
Uncontrolled hypercholesterolemia, hypertriglyceridemia, or mixed dyslipidemia
Already receiving maximally tolerated lipid-lowering therapy
Median LDL cholesterol level of 155 mg/dL at baseline
Median triglyceride level of 192 mg/dL at baseline (well above the healthy threshold of 150 mg/dL)
Five different dose levels were tested, ranging from 0.1 to 0.8 mg per kilogram of body weight.
Minor adverse events included:
Infusion-related reactions in 3 participants (20%), including back pain and nausea, which were resolved with medication
One participant with pre-existing elevated liver enzymes experienced a transient elevation that peaked on day 4 and returned to baseline by day 14 without treatment
Two serious adverse events occurred but might be unrelated to the treatment: One participant experienced a spinal disk herniation and another participant died suddenly 179 days after receiving the lowest dose (0.1 mg/kg), but the death was not attributed to the treatment
Perhaps the most transformative aspect of CTX310 is its potential as a one-time treatment. Current cholesterol management typically requires:
Daily oral medications
Monthly or bi-weekly injections
Lifelong adherence to therapy
All participants will be monitored for one year following treatment, with additional long-term safety follow-up extending for 15 years as recommended by the U.S. Food and Drug Administration (FDA) for all gene-editing therapies.
While the results are promising, experts urge caution given the early stage of development.
"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 Dr. Luke J. Laffin, first author of the study and cardiologist at Cleveland Clinic. "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."
The CTX310 Phase 1 trial represents a significant step forward in the fight against cardiovascular disease. While larger trials are needed to confirm these initial findings, the prospect of a one-time gene-editing therapy that provides lasting cholesterol reduction offers hope to millions struggling with lipid disorders.
"If confirmed in larger trials, this one-and-done approach could transform care for people with lifelong lipid disorders and dramatically reduce cardiovascular risk," researchers concluded.
High total cholesterol is defined as 240 mg/dL or more. LDL cholesterol (often called "bad" cholesterol) should ideally be below 100 mg/dL for most people, or below 70 mg/dL for those with established cardiovascular disease. Triglycerides should be below 150 mg/dL.
Key Terms:
CRISPR-Cas9: A revolutionary gene-editing technology that allows precise modifications to DNA
ANGPTL3: A gene encoding a protein that regulates cholesterol and triglyceride levels
LDL cholesterol: Low-density lipoprotein, often called "bad" cholesterol because high levels of it increase heart disease risk.
HDL cholesterol: High-density lipoprotein, often called "good" cholesterol because it helps remove other forms of cholesterol from the bloodstream
Triglycerides: A type of fat found in the blood; high levels increase risk of heart disease
(Rh/VK)
