NatureFeb 18, 2026

Using gene editing on Chd3 to improve behavior problems in living mice

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

Brain-wide base editing of a pathogenic Chd3 variant improved behavioral abnormalities in a mouse model of Snijders Blok-Campeau syndrome.

Evidence

This preclinical gene-editing study used dual-AAV delivery of an adenine base editor in a humanized Chd3 mouse model and showed efficient on-target correction across cortical and hippocampal regions, restored CHD3 protein levels, and improved social, cognitive, and motor phenotypes; intrathecal delivery in nonhuman primates showed widespread neuronal transduction.

Caveat

The therapeutic effect was demonstrated in animal models, not in patients, so the translational relevance and long-term safety of postnatal brain base editing remain uncertain.

Simplified

Neurodevelopmental disorders that arise from de novo mutations in chromatin-remodelling genes lack targeted treatments. Snijders Blok-Campeau syndrome (SNIBCPS), which is caused by pathogenic variants in CHD3, manifests with intellectual disability, autistic-like behaviours and motor deficits. Whether somatic gene correction can reverse such phenotypes in vivo remains unknown. Here we show that modelling the recurrent CHD3 variant p.R1025W in a humanized mouse model (Chd3) recapitulates key features of SNIBCPS, including reduced CHD3 protein levels and abnormalities in social communication, cognition and motor coordination. We engineered a TadA-embedded adenine base editor (TeABE) and delivered it brain-wide using a dual adeno-associated virus (AAV) system and achieved efficient on-target A•T-to-G•C correction across multiple cortical and hippocampal regions with minimal bystander activity. This intervention restored CHD3 levels and ameliorated behavioural abnormalities in vivo. Furthermore, intrathecal dual AAV delivery in nonhuman primates resulted in widespread neuronal transduction and efficient TeABE reconstitution, a result that supports its translational feasibility. These findings establish in vivo base editing as a viable therapeutic approach for CHD3-related neurodevelopmental disease. More broadly, they demonstrate that precise single-base correction in the postnatal brain can restore protein dosage and function, thereby offering a framework for the treatment of monogenic neurodevelopmental disorders. 1 2hR1025W/+

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

CRISPR Gene EditingIssue #25

Gene editing in mouse brains fixes autism-like behaviors caused by genetic mutations

↗

Using gene editing on Chd3 to improve behavior problems in living mice

Abstract

Full Text

Featured in

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the crispr gene editing brief