Gene editing in a Myo6 semi-dominant mouse model rescues auditory function.

ABSTRACT: Myosin VI（MYO6） is an unconventional myosin that is vital for auditory and vestibular function. Pathogenic variants in the human MYO6 gene cause autosomal-dominant or -recessive forms of hearing loss. Effective treatments for Myo6 mutation causing hearing loss are limited. We studied whether adeno-associated virus (AAV)-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9 (SaCas9-KKH)-single-guide RNA (sgRNA) complexes could ameliorate hearing loss in a Myo6^WT/C442Y mouse model that recapitulated the phenotypes of human patients. The in vivo editing efficiency of the AAV-SaCas9-KKH-Myo6-g2 system on Myo6^C442Y is 4.05% on average in Myo6^WT/C442Y mice, which was ∼17-fold greater than editing efficiency of Myo6^WT alleles. Rescue of

SUBMITTER: Xue Y 

PROVIDER: S-EPMC8753286 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature