Nature publishes study on in vivo CRISPR base editing of ANGPTL3 for durable lipid lowering
A Nature study reports that a single infusion of a CRISPR adenine base editor led to durable ANGPTL3 inactivation and lipid reductions in nonhuman primates, supporting an ongoing first-in-human clinical trial.
In brief
- A Nature study reports durable ANGPTL3 inactivation from a single infusion of a CRISPR adenine base editor in nonhuman primates.
- The treatment led to a > 90% mean reduction in circulating ANGPTL3 protein, durable out to 3 years after a single dose.
- In hyperlipidemia models, LDL-C fell approximately 40 to 50% and triglycerides fell 50 to 70%.
- The findings support an ongoing first-in-human clinical trial in patients with refractory hyperlipidemia syndromes.
Study findings
A study published in Nature on 06 November 2026 describes a potential single-course treatment in which an infusion of guide RNA and mRNA encoding a CRISPR adenine base editor—encapsulated within a GalNAc–lipid nanoparticle—leads to durable, liver-selective inactivation of angiopoietin-like 3 (ANGPTL3), a known driver of increased LDL-C and triglyceride concentrations.
Analyses in human liver cells in vitro confirmed that the base editor introduces a DNA base-pair change at the target ANGPTL3 locus with no detectable off-target editing at any of approximately 3000 candidate sites or treatment-related structural variants.
Targeted ANGPTL3 inactivation in nonhuman primates was well-tolerated and led to a > 90% mean reduction in circulating ANGPTL3 protein, with durability confirmed out to 3 years following a single dose. In mouse and nonhuman primate models of hyperlipidemia, gene inactivation was associated with reductions of approximately 40 to 50% in LDL-C and 50 to 70% in triglycerides.
Clinical trial and authors
These results provided the scientific foundation for initiation of an ongoing first-in-human clinical trial in patients with refractory hyperlipidemia syndromes.
The corresponding author is Amit V. Khera. Authors are affiliated with Verve Therapeutics, Inc. (a wholly owned subsidiary of Eli Lilly and Company), Boston, MA, USA; Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA; GV Management Company, LLC, Boston, MA, USA; and Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Why it matters
Circulating concentrations of low-density lipoprotein cholesterol (LDL-C) and triglyceride-rich lipoproteins are leading risk factors for atherosclerotic cardiovascular disease. Despite several approved lipid-lowering medications, most patients fail to achieve target lipid levels under the chronic care treatment model.
Sources
This article was drafted with AI assistance and checked against the sources above. Company claims are reported as claims. Cover image is AI-generated.
Questions readers ask
- What did the Nature study published on 06 November 2026 find regarding ANGPTL3 inactivation?
- The study describes a potential single-course treatment using a GalNAc–lipid nanoparticle infusion that leads to durable, liver-selective inactivation of angiopoietin-like 3 (ANGPTL3).
- How effective was the treatment in reducing lipid levels in animal models?
- In mouse and nonhuman primate models of hyperlipidemia, gene inactivation was associated with reductions of approximately 40 to 50% in LDL-C and 50 to 70% in triglycerides.
- How long did the effects of the treatment last in nonhuman primates?
- Durability was confirmed out to 3 years following a single dose, which also led to a > 90% mean reduction in circulating ANGPTL3 protein.
- Who is the corresponding author of the study and what company are they affiliated with?
- The corresponding author is Amit V. Khera, who is affiliated with Verve Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company.
- Why is this research significant for patients with hyperlipidemia?
- It provides the scientific foundation for an ongoing first-in-human clinical trial in patients with refractory hyperlipidemia syndromes, addressing the issue that most patients fail to achieve target lipid levels under the chronic care treatment model.
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