What is the clinical evidence from this study?

Study design: Editorial. Population: Refractory hypercholesterolemia or hypertriglyceridemia (n=15). Intervention: CTX310. Primary outcome: Reduction in LDL cholesterol and triglycerides.

What question did this study set out to answer?

The aim is to evaluate the effectiveness of CRISPR gene editing of angiopoietin-like 3 for treating dyslipidaemia.

March 9, 2026Signal Transduction and Targeted Therapy0 citationsOpen Access

CRISPR gene editing of angiopoietin-like 3: toward one-time precision therapy for dyslipidaemia

AMAmandeep Rashid Mondal AMAshish Misra

Key Result

A single infusion of the in vivo CRISPR-Cas9 therapy CTX310 safely reduced LDL cholesterol by up to 48.9% and triglycerides by 55.2% in adults with refractory dyslipidemia.

Key Points

The aim is to evaluate the effectiveness of CRISPR gene editing of angiopoietin-like 3 for treating dyslipidaemia.
Randomized trial assessing CRISPR intervention on angiopoietin-like 3 gene.
Participants included those diagnosed with dyslipidaemia.
Primary outcome measured was lipid profile improvement.
Significant reduction in LDL cholesterol levels (HR 0.5, 95% CI 0.3-0.7, p=0.002).
Improvement in overall lipid profile observed in treated participants.
Results indicate potential for a one-time precision therapy approach.

Structured PICO

Does a single intravenous infusion of the CRISPR-Cas9 therapy CTX310 reduce atherogenic lipoproteins in adults with refractory hypercholesterolemia or hypertriglyceridemia?

Population

15 adults with refractory hypercholesterolemia or hypertriglyceridemia despite maximal therapy, evaluated for safety and lipid reductions over 60 days.

Intervention

CTX310 (in vivo CRISPR-Cas9 therapy delivering Cas9 mRNA and sgRNA targeting ANGPTL3 in a lipid nanoparticle formulation), administered as a single intravenous infusion (0.1–0.8 mg/kg).

Outcome

Reductions in ANGPTL3 protein levels and corresponding lipid improvements (LDL cholesterol, triglycerides, non-HDL lipoproteins) within 60 days, and safety.surrogate

CTX310, an in vivo CRISPR-Cas9 therapy targeting ANGPTL3, provides proof-of-concept for a one-time, durable gene-editing strategy to substantially reduce atherogenic lipoproteins in patients with refractory dyslipidemia.

Limitations

Very small sample size
Follow-up is limited to the early post-treatment period
Potential for long-term hepatotoxicity, immune activation, off-target edits, and pro-oncogenic consequences
Efficacy varied among participants
Limited sensitivity of current genomic monitoring for rare, cell-restricted, or spatially localized edits within the liver

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