Nature communicationsSep 18, 2025

Improved gene editing restores hearing in a mouse model of inherited deafness

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

Updated Jun 27, 2026

Abstract

Essence

An optimized adenine base editor restored auditory function in a mouse model.

Evidence

This preclinical in vitro and mouse base-editing study screened editors for a Pou4f3 allele, achieved up to 48.5% in vitro editing, and used Anc80L65 AAV delivery in neonatal mice to recover hearing for at least four months.

Caveat

The result is limited to a neonatal mouse model with short follow-up and biosafety analyses, not clinical proof in humans.

Simplified

Genetic mutations cause hereditary deafness, in which mutations in the POU4 transcription factor 3 gene (POU4F3) lead to autosomal dominant non-syndromic deafness 15 (), 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 Pou4f3mutant mouse model mimicking DFNA15. We develop and screen adenine base editors (ABEs) targeting the Pou4f3allele 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 Pou4f3mice are treated via synthetic AAV (Anc80L65)-delivered SchABE8e-sgRNA3, resulting in near-complete hearing recovery, with the effect persisting for at least four months. Biosafety analyses further support the feasibility of base editing, providing a therapeutic strategy for DFNA15. WT/Q113 Q113 WT/Q113*

Key numbers

14.2 ± 2.5%

Editing Efficiency

-level editing efficiency in neonatal mouse cochleae.

60 dB SPL

Auditory Threshold

Average threshold in treated ears.

4 months

Duration of Hearing Recovery

Duration of stable hearing recovery post-treatment.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Funding

Competing interests

Competing interests: R.C., J.Q., M.W., Z.Z., F.T., X.W., L.Z., and X.C. have submitted a patent application to the China National Intellectual Property Administration pertaining to the application of SchABE8e inthe DFNA15 gene therapy aspect of this work (application number 202510477143.X; status: under review). The remaining authors declare no competing interests.

PubMed

Featured in

CRISPR Gene EditingIssue #4

CRISPR protein beats mRNA for cystic fibrosis repair, while gene editing restores hearing in deaf mice

↗

Improved gene editing restores hearing in a mouse model of inherited deafness

Abstract

Key numbers

Full Text

Funding

Competing interests

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

Abstract

Key numbers

Full Text

Funding

Competing interests

Related papers

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