Key result
Gene and epigenetic therapies favorably reduce ANGPTL3, PCSK9, LDL-C, and triglycerides in early clinical trials.
Why the study?
Many therapies for dyslipidemia are limited by suboptimal long-term adherence, prompting exploration of gene editing and epigenetic therapies.
Do gene editing therapies reduce lipid and lipoprotein risk factors in patients with dyslipidemia?
Key Points
- To summarize the therapeutic potential and clinical progress of gene, base, and epigenomic editing for targeting causal lipid and lipoprotein risk factors in atherosclerotic cardiovascular disease.
- Narrative review synthesizing recent advances in genomic engineering platforms, including CRISPR gene editing, base editing, and epigenomic editing.
- Evaluation of early-phase human clinical trials targeting dyslipidemia-associated genes, primarily ANGPTL3 and PCSK9.
- Targeted editing achieves notable reductions in ANGPTL3 and PCSK9 expression, resulting in downstream decreases in circulating low-density lipoprotein cholesterol and triglycerides.
- Therapies demonstrate favorable short-term safety and tolerability in early clinical evaluation, with adverse events largely restricted to mild-to-moderate infusion reactions.
Structured PICO
Do gene editing therapies reduce lipid and lipoprotein risk factors in patients with dyslipidemia?
P
Population
Patients with dyslipidemia and atherosclerotic cardiovascular disease risk factors
I
Intervention
Gene editing, base editing, and epigenomic editing therapies (including CRISPR) targeting ANGPTL3 and PCSK9
O
Outcome
Reductions in ANGPTL3, PCSK9, low-density lipoprotein cholesterol (LDL-C), and triglyceridessurrogate
Gene editing therapies targeting ANGPTL3 and PCSK9 show early promise for robust and durable reductions in atherogenic lipids, though further clinical trials are needed.
Limitations
- Requires further evaluation in clinical trials to determine how these agents will enter clinical practice
Ask about this paper
Answers are grounded in this paper and cite their sources.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“ongoing surveillance will be essential to assess the persistence of safety and lipid-lowering efficacy of CTX310.”
“Seeing a single-course treatment safely lower both LDL cholesterol and triglycerides is truly unprecedented.”
“I really would expect the effects of the gene editing to be durable for the long term. Many years, decades — quite possibly a lifetime.”
Implication
Should not yet change dyslipidemia practice; leaves open gene editing's role pending larger trials.
Abstract
PURPOSE OF REVIEW: Several lipid and lipoprotein risk factors play an important role in the causality of atherosclerotic cardiovascular disease. Many therapies are limited by suboptimal long-term adherence. This narrative review summarizes the potential for gene editing and epigenetic therapy for the management of dyslipidemia. RECENT FINDINGS: Recent advances in genomic engineering permit the ability to develop gene editing, base editing and epigenomic editing of specific regions of DNA in humans. These therapies have advanced to early phase clinical evaluation with initial reports demonstrating favorable reductions in ANGPTL3 and proprotein convertase subtilisin kexin type 9, with consequent decreases in levels of low-density lipoprotein cholesterol and triglycerides. Apart from mild-moderate infusion reactions, the early experience with these therapies appears to be well tolerated. SUMMARY: Advances in genomic engineering have developed a number of agents with the potential for robust and durable changes to atherosclerotic lipid and lipoprotein risk factors. How these agents will enter clinical practice will require further evaluation in clinical trials.
Discussion
No takes yet. Share an insight, caveat, or question.
Cite This Study
Stephen J. Nicholls (2026) conducted a review in dyslipidemia. Gene editing and epigenetic therapy was evaluated. Gene editing and epigenetic therapies for dyslipidemia demonstrate favorable reductions in ANGPTL3, PCSK9, LDL cholesterol, and triglycerides in early phase clinical evaluation.