# Verve Therapeutics: one base-editor dose cut ANGPTL3 protein by over 90% in primates for 3 years

- Published: 2026-11-07 21:06 UTC
- Section: Life & Health › Biotechnology
- Tags: ANGPTL3 base editing, CRISPR adenine base editor, GalNAc lipid nanoparticle, LDL-C lowering, triglyceride reduction, nonhuman primates, refractory hyperlipidemia, first-in-human trial, Verve Therapeutics, liver-selective gene inactivation
- URL: https://realtech.media/news/rt-62408b1509694aa1cc7d27bf_verve_therapeutics_one/

**Authors report that a CRISPR adenine base editor in a GalNAc–lipid nanoparticle inactivated liver ANGPTL3 in mice and primates; a first-in-human trial is ongoing.**

![Verve Therapeutics: one base-editor dose cut ANGPTL3 protein by over 90% in primates for 3 years](https://realtech.media/media/2026/11/7cdd919698216bf7.jpg)
*Syed Sajidul Islam, Wikimedia Commons, CC BY-SA 4.0*

Researchers at Verve Therapeutics, a wholly owned subsidiary of Eli Lilly and Company in Boston, together with colleagues from Mount Sinai and the University of Pennsylvania, describe in Nature a potential single-course approach to lowering blood lipids. An infusion of guide RNA and mRNA encoding a CRISPR adenine base editor, encapsulated in a GalNAc–lipid nanoparticle, leads to durable, liver-selective inactivation of the ANGPTL3 gene. In nonhuman primates, a single dose produced a mean reduction of more than 90% in circulating ANGPTL3 protein, with durability confirmed out to 3 years [1].

## Target and delivery

Circulating concentrations of low-density lipoprotein cholesterol (LDL-C) and triglyceride-rich lipoproteins are leading risk factors for atherosclerotic cardiovascular disease. The authors note that, despite several approved lipid-lowering medications, most patients fail to reach target lipid levels under the chronic care treatment model [1].

ANGPTL3 is a known driver of increased LDL-C and triglyceride concentrations. The base editor introduces a DNA base-pair change at the target ANGPTL3 locus, and the GalNAc–lipid nanoparticle is used to direct the editing to the liver [1].

## Safety and lipid results

Analyses in human liver cells in vitro confirmed the intended base-pair change at the target locus. According to the authors, there was no detectable off-target editing at any of approximately 3000 candidate sites and no treatment-related structural variants [1].

Targeted ANGPTL3 inactivation in nonhuman primates was well tolerated [1]. 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 [1].

## Stage of work

The results reported in the paper come from cell and animal studies. According to the authors, they provided the scientific foundation for starting an ongoing first-in-human clinical trial in patients with refractory hyperlipidemia syndromes [1].

## Sources

1. [Nature](https://doi.org/10.1038/s41586-026-11233-9)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-62408b1509694aa1cc7d27bf_verve_therapeutics_one/