In vivo CRISPR-Cas9 genome editing in mice identifies genetic modifiers of somatic CAG repeat instability in Huntington's disease.

ABSTRACT: Huntington's disease, one of more than 50 inherited repeat expansion disorders¹, is a dominantly inherited neurodegenerative disease caused by a CAG expansion in HTT². Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the disease is driven by the CAG length-dependent propensity of the repeat to further expand in the brain^3-9. Routes to slowing somatic CAG expansion, therefore, hold promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair pathway, modify somatic expansion in Huntington's disease mouse models¹⁰. To identify novel modifiers of somatic expansion, we used CRISPR-Cas9 editing in Huntington's disease knock-in mice to enable in viv

SUBMITTER: Mouro Pinto R 

PROVIDER: S-EPMC11821541 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature