Gene Editing with CTX310 Slashes Cholesterol and Triglycerides in Early trial, Offering Hope for Resistant Dyslipidemia
A groundbreaking phase I trial suggests a novel gene-editing therapy, CTX310, can significantly reduce levels of “bad” cholesterol and triglycerides with a single dose, perhaps transforming teh treatment landscape for patients with persistent high cholesterol. Published in The New England Journal of Medicine in 2025, the study evaluated CTX310, an mRNA-based therapy utilizing CRISPR-Cas9 technology to inactivate the ANGPTL3 gene in the liver.
The Promise of Targeting ANGPTL3
Angiopoietin-like 3 (ANGPTL3) is a protein produced by the liver that plays a crucial role in regulating lipid metabolism by inhibiting lipoprotein lipase and endothelial lipase. Genetic studies have shown that individuals with loss-of-function variants in ANGPTL3 tend to have lower levels of LDL cholesterol and triglycerides, and a reduced risk of atherosclerotic cardiovascular disease. This understanding has spurred the development of therapies aimed at blocking ANGPTL3’s activity, including monoclonal antibodies like evinacumab and now, gene editing approaches.
The trial enrolled 15 participants with persistent hypercholesterolemia, hypertriglyceridemia, or mixed dyslipidemia who had not responded adequately to maximal doses of existing lipid-lowering medications. Participants were divided into five groups receiving ascending doses of CTX310 (0.1,0.3, 0.6, 0.7, and 0.8 mg/kg) via intravenous infusion. The primary goal of the study was to assess safety.
favorable safety Profile and Significant Lipid Reduction
Researchers reported a favorable safety profile, with no dose-limiting toxicities directly attributed to CTX310. Mild infusion reactions and transient elevations in liver enzymes (transaminases) were observed, but no serious adverse events were recorded. Notably,one participant experienced a death and another a hospitalization for a herniated disc,but these were deemed unrelated to the study drug.
The most compelling results emerged from the pharmacodynamic data. At the highest doses tested (0.7-0.8 mg/kg), CTX310 achieved a remarkable 73-80% reduction in ANGPTL3 levels. This, in turn, translated to a 49% decrease in LDL-C and a 55% decrease in triglycerides at 60 days post-administration, with data available for up to 90 days.
“CTX310 achieves significant and durable reductions in ANGPTL3, LDL-C, and triglycerides with a single dose, representing a potentially transformative approach for patients with resistant dyslipidemia,” said Dr.Sekar Kathiresan, CEO of Verve Therapeutics, the company developing CTX310, in a press release.”These early results are highly encouraging and support further development of this therapy.”
Looking Ahead
While these findings are preliminary, they represent a significant step forward in the field of gene editing for cardiovascular disease. Further studies, including larger phase II and phase III trials, are needed to confirm these results, assess long-term safety and efficacy, and determine the optimal dose of CTX310.Though, the success of this phase I trial suggests that CRISPR-Cas9-based gene editing could become a relevant therapeutic tool in the coming years, offering a compelling preliminary advance toward a new approach to cardiovascular prevention.
References:
Laffin, L. J.,Nicholls,S. J.,Scott,R. S., Clifton, P.M.,Baker,J., Sarraju, A., singh, S., Wang, Q., Wolski, K., xu, H., Nielsen, J., patel, N., Duran, J. M., & Nissen, S. E. (2025). Phase 1 Trial of CRISPR-Cas9 Gene Editing targeting ANGPTL3. New England journal of Medicine, 393(22), 2119-2130.
Marston, N.