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

Man Wang, Ziyu Zhang, Xiaohan Wang, Liyan Zhang, Xiangyan Chen, Nianci Li, Qiuhan Sun, Yicheng Lu, Zuhong He, Hongbo Yang (), Fangzhi Tan (), Jieyu Qi () and Renjie Chai ()
Additional contact information
Man Wang: Southeast University
Ziyu Zhang: Southeast University
Xiaohan Wang: Southeast University
Liyan Zhang: Southeast University
Xiangyan Chen: Southeast University
Nianci Li: Southeast University
Qiuhan Sun: Southeast University
Yicheng Lu: Southeast University
Zuhong He: Southeast University
Hongbo Yang: Fudan University
Fangzhi Tan: Southeast University
Jieyu Qi: Beijing Institute of Technology
Renjie Chai: Southeast University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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 Pou4f3WT/Q113* mutant mouse model mimicking DFNA15. We develop and screen adenine base editors (ABEs) targeting the Pou4f3Q113* 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 Pou4f3WT/Q113* mice 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-63613-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63613-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-63613-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().