Nature biomedical engineeringJul 29, 2026

Using gene editing inside the body to treat Huntington's disease

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

Updated Aug 3, 2026

Abstract

CRISPR base editors reduced HTT fragment formation by disrupting the splice acceptor of HTT exon 13.

Huntington's disease is linked to a mutant protein from an expanded CAG repeat in the huntingtin gene.
Proteolytic cleavage of this mutant protein generates toxic fragments associated with neuronal dysfunction.
Disruption of the splice acceptor in exon 13 of the huntingtin gene may prevent the production of these toxic fragments.
In a rodent model of Huntington's disease, the application of CRISPR base editors led to decreased aggregation of HTT fragments.
The treatment also improved functional deficits and reduced brain atrophy in the model.

Simplified

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat within exon 1 of the huntingtin (HTT) gene, resulting in a mutant protein that drives neuronal dysfunction and loss. A key event in the pathogenesis of HD is proteolytic cleavage of mutant HTT, which generates aggregation-prone N-terminal fragments that contribute to toxicity. Strategies that prevent this process thus hold therapeutic potential. Here we develop CRISPR base editors that generate proteolysis-resistant HTT isoforms by disrupting the splice acceptor of HTT exon 13, an exon that encodes critical proteolytic cleavage sites implicated in N-terminal fragment production. When delivered to the striatum of an HD rodent model, these editors reduced HTT fragment formation, decreased aggregation, improved functional deficits and attenuated brain atrophy. Collectively, these results demonstrate the potential of base editing and splice-site modulation to mitigate mutant HTT toxicity in HD.

Full Text

Full text is available at the source.

View Full Text ↗

Featured in

CRISPR Gene EditingIssue #48

CRISPR base editors delivered to rat brains reduced Huntington's protein fragments and improved movement

↗

Using gene editing inside the body to treat Huntington's disease

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