One-Time CRISPR Treatment Cut LDL Cholesterol by More Than 50% for a Year

Too much low-density lipoprotein, or LDL cholesterol, can contribute to plaque buildup in the arteries and increase the risk of heart attacks and strokes. Lifestyle changes and statin medications help many patients, but a substantial group either does not respond adequately or cannot tolerate existing therapies.

Researchers are now testing whether a single gene-editing treatment could permanently lower harmful blood fats. Using CRISPR technology, the experimental therapy CTX310 is designed to switch off a liver gene that controls production of a protein called ANGPTL3, which plays an important role in lipid metabolism.

How the CRISPR therapy works

Some people naturally carry loss-of-function variants in the ANGPTL3 gene and have very low levels of LDL cholesterol and triglycerides without obvious health problems. CTX310 aims to reproduce this protective genetic pattern by editing the same gene directly inside liver cells.

The treatment uses lipid nanoparticles delivered through an intravenous infusion to transport CRISPR instructions into hepatocytes, the main functional cells of the liver. Once there, the gene editor introduces a permanent change intended to sharply reduce production of ANGPTL3.

Promising phase 1 human data

A phase 1a dose-escalation trial enrolled 15 participants with serious lipid disorders that were not adequately controlled with standard medications. Each participant received a single infusion of CTX310 and was monitored for safety, side effects and changes in blood lipid levels over 12 months.

Among the four participants who received the highest dose, ANGPTL3 levels fell by an average of 78.6 percent after one year. LDL cholesterol declined by a mean of 52.5 percent, while triglycerides dropped by 47.8 percent, suggesting a sustained effect from the one-time intervention.

Across the entire group, researchers reported few adverse events during follow-up. One participant died 179 days after receiving treatment, but an independent review concluded that the death was unrelated to CTX310. No new serious safety concerns emerged beyond those observed earlier in the trial.

Benefits, risks and next steps

Scientists argue that a one-time gene-editing treatment could be easier for patients than taking daily or weekly medications, particularly for people at very high cardiovascular risk. The approach might also benefit those who struggle to adhere to long-term treatment or experience side effects from statins or PCSK9 inhibitors.

However, gene editing raises complex safety questions, including the possibility of off-target DNA changes and long-term immune reactions. Although CTX310 targets a gene in which naturally occurring loss-of-function variants are known to be harmless, the permanent nature of the genetic modification requires careful long-term monitoring.

The phase 1a study, published in The New England Journal of Medicine, was designed primarily to evaluate safety rather than prove clinical benefit. A phase 1b trial is now underway, using a fixed dose equivalent to the most effective level tested in the initial study and enrolling separate groups of patients with specific lipid disorders.

Larger and longer trials will be needed to determine whether durable reductions in LDL cholesterol ultimately translate into fewer heart attacks and strokes. Regulators will also examine manufacturing consistency, potential off-target effects and the balance between benefits and risks across different patient populations.

If future studies produce positive results, CTX310 could become one of the first in vivo CRISPR-based therapies aimed at common chronic diseases rather than rare genetic conditions. The research highlights a broader shift toward preventive gene-editing strategies for cardiovascular health.