Precise detection of CRISPR-Cas9 editing in hair cells in the treatment of autosomal dominant hearing loss.

ABSTRACT: Gene therapy would benefit from the effective editing of targeted cells with CRISPR-Cas9 tools. However, it is difficult to precisely assess the editing performance in vivo because the tissues contain many non-targeted cells, which is one of the major barriers to clinical translation. Here, in the Atoh1-GFP;Kcnq4 ^+/G229D mice, recapitulating a novel mutation we identified in a hereditary hearing loss pedigree, the high-efficiency editing of CRISPR-Cas9 in hair cells (34.10% on average) was precisely detected by sorting out labeled cells compared with only 1.45% efficiency in the whole cochlear tissue. After injection of the developed AAV_SaCas9-KKH_sgRNA agents, the Kcnq4 ^+/G229D mice showed significantly lower auditory brains

SUBMITTER: Cui C 

PROVIDER: S-EPMC9386031 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature