Cleveland Clinic

Type: Lab / Clinical Research Institution (Cardiovascular Gene Therapy)

Cleveland Clinic conducted the first-in-human clinical trial of CRISPR gene editing for cholesterol reduction. The Phase 1 trial of CTX310, led by Luke Laffin and Steven Nissen, targeted the ANGPTL3 gene in liver cells using lipid nanoparticle delivery. Results published in November 2025 showed dramatic reductions: LDL cholesterol down approximately 50% and triglycerides down approximately 55% within two weeks of a single infusion, with effects sustained for over 60 days and no serious adverse events.

Steven Nissen is one of the most prominent cardiologists in the world, known for rigorous trial design and his role in exposing the cardiovascular risks of Vioxx. His involvement lends significant credibility to the ANGPTL3 trial results. Luke Laffin, the trial's lead investigator, is a specialist in preventive cardiology and clinical hypertension.

The trial is significant beyond its clinical results because it demonstrates the one-time treatment paradigm for cardiovascular disease — the world's leading cause of death. Current standard of care (statins, PCSK9 inhibitors) requires lifelong daily medication, and adherence data shows roughly half of patients discontinue statins within a year. A single gene editing infusion that permanently reduces cholesterol-related risk would transform cardiovascular prevention.

Key Contributions

• First-in-human CRISPR cholesterol trial (Phase 1, CTX310) (Cleveland Clinic Trial)
• LDL -50%, triglycerides -55%, sustained 60+ days, 15 patients (Cleveland Clinic Trial)
• No serious adverse events (Cleveland Clinic Trial)
• Lipid nanoparticle delivery to liver demonstrated in humans (Cleveland Clinic Trial)

Mentioned In

• CRISPR Clinical Translation — Leading clinical trial site
• Gene Therapy Delivery — LNP delivery demonstrated in trial

Related Entities

• Broad Institute — Foundational CRISPR research enabling the trial