Optimized in vivo base editing restores auditory function in a DFNA15 mouse model.

ABSTRACT: Genetic mutations cause hereditary deafness, in which mutations in the POU4 transcription factor 3 gene (POU4F3) lead to autosomal dominant non-syndromic deafness 15 (DFNA15), for which no effective clinical treatment currently exists. Gene editing holds promise for precisely repairing mutated nucleotides, thus offering a potential cure for hereditary hearing loss. Here, we establish a Pou4f3^WT/Q113* mutant mouse model mimicking DFNA15. We develop and screen adenine base editors (ABEs) targeting the Pou4f3^Q113* allele by fusing diverse adenine deaminases to Cas9 we discovered before. SchABE8e accomplishes highly precise and efficient editing (up to 48.5%) at sgRNA3 in vitro. Neonatal Pou4f3^WT/Q113* mice are treated via synthetic AAV (Anc80L65)-delivered Sch

SUBMITTER: Wang M 

PROVIDER: S-EPMC12446455 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature