One CRISPR Infusion Cut Triglycerides 63% in People With Severe Hypertriglyceridemia
On November 9, 2026, CRISPR Therapeutics presented new Phase 1b results for CTX310, its one-time CRISPR therapy that switches off the ANGPTL3 gene in the liver. In 10 people with severe hypertriglyceridemia (sHTG), a single infusion cut triglycerides by 63% on average after 30 days. The data were shown in a late-breaking oral session at the American Heart Association (AHA) Scientific Sessions 2026 by Ashish Sarraju, M.D., a preventive cardiologist at the Cleveland Clinic.
This is the update we flagged in October, when one-year Phase 1a results showed a single dose kept LDL cholesterol and triglycerides down for a full year. The new study tests something different: one fixed dose, in patients with some of the highest triglyceride levels doctors see.
What is severe hypertriglyceridemia?
Triglycerides are the main form of fat carried in the blood. A healthy fasting level is below 150 mg/dL, and severe hypertriglyceridemia is generally defined as levels above 500 mg/dL. At very high levels, the risk of acute pancreatitis, a painful and potentially life-threatening inflammation of the pancreas, rises sharply.
The people in this trial were among the hardest to treat. All had fasting triglycerides above 500 mg/dL, and their median starting level was above 1,000 mg/dL. All of them had diabetes, 30% had a history of pancreatitis, and 20% had clinical atherosclerotic cardiovascular disease.
How CTX310 works
ANGPTL3 is a protein made by the liver. It blocks two enzymes, lipoprotein lipase and endothelial lipase, that break down fat-carrying particles in the blood. CTX310 is a lipid nanoparticle that delivers Cas9 messenger RNA and a guide RNA to liver cells. Cas9 cuts the ANGPTL3 gene, and the cell's repair process disables it. Because the change is written into the DNA, the effect is designed to be permanent.
The target comes from human genetics. People born with natural loss-of-function variants in ANGPTL3 have unusually low triglycerides and LDL cholesterol and a lower risk of coronary artery disease, with no known harm from lacking the protein. Protective mutations like this one, and how they become medicines, are the subject of my book The Cheat Codes of Our Genes.
What the trial showed
Each participant received one intravenous infusion at a flat dose: 40 mg for people under 85 kg, or 50 mg for people 85 kg and above. These doses were chosen to match the 0.8 mg/kg dose that worked best in Phase 1a. One Phase 1a participant who received 56.5 mg was also included.
Average changes at day 30:
ANGPTL3: down 65%
Triglycerides: down 63%
Non-HDL cholesterol: down 51%
ApoB: down 23%
LDL cholesterol: down 16%, from an already low average of 60 mg/dL
The reductions in ANGPTL3 and triglycerides held in the seven participants followed for at least 90 days.
Naimish Patel, M.D., CRISPR Therapeutics' chief medical officer, pointed to "substantial triglyceride lowering after a single-course treatment with CTX310."
Safety
No treatment-related serious adverse events were reported, and there were no clinically relevant rises in the liver enzymes AST and ALT, an important result for a therapy that edits liver cells. One participant had a Grade 2 infusion-related reaction that resolved. No cases of acute pancreatitis occurred during follow-up, even though three participants had a history of it.
Why it matters
Most treatments for high triglycerides must be taken for life, whether as daily pills or regular injections. CTX310 aims to replace that with a single treatment. The FDA recently granted CTX310 Regenerative Medicine Advanced Therapy (RMAT) designation for both sHTG and elevated LDL cholesterol. RMAT brings closer guidance from the FDA and can make a therapy eligible for priority review and accelerated approval.
The caveats
The study is small (10 people) and open-label, and the main results come from just 30 days of follow-up. Because the edit is permanent, long-term safety will take years to establish. The trial also has not yet shown that lowering triglycerides this way prevents pancreatitis or heart attacks.
What happens next
CRISPR Therapeutics says additional Phase 1b cohorts are ongoing in the U.S. and other countries. The company is also developing other one-time liver edits for cardiovascular disease, including CTX340, which targets AGT for refractory hypertension, and CTX321, which targets LPA for high lipoprotein(a).
The bottom line
A single CRISPR infusion cut triglycerides by nearly two-thirds in people whose levels started above 1,000 mg/dL, with no serious treatment-related side effects so far. The data are early, but they strengthen the case that one gene edit in the liver could replace a lifetime of lipid-lowering treatment.
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