Evidence map›Paper›PMID 41090360›Full record

ArticleThe Journal of clinical investigation2025

Single-dose genome editing therapy rescues auditory and vestibular functions in adult mice with DFNA41 deafness.

Wei Wei, Wenliang Zhu, Stewart Silver, Ariel M Armstrong, Fletcher S Robbins, Arun Prabhu Rameshbabu, Katherina Walz, Yizhou Quan, Wan Du, Yehree Kim and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Wei WeiDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Wenliang ZhuDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Stewart SilverDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Ariel M ArmstrongDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Fletcher S RobbinsDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Arun Prabhu RameshbabuDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Katherina WalzDr. John T. Macdonald Foundation Department of Human Genetics and.
Yizhou QuanDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Wan DuDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Yehree KimDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Artur A IndzhykulianDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Yilai ShuENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science.
Xue-Zhong LiuDr. John T. Macdonald Foundation Department of Human Genetics and.
Zheng-Yi ChenDepartment of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.

Funding

AAV-mediated editing to treat human autosomal dominant hearing loss DFNA41 and DFNA2U01TR005352 · NCATS · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Zheng-Yi Chen · 2024 to 2026
$11.2M
Molecular Basis of Hair Cell Stereocilia Bundle MorphologyR01DC017166 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI INDZHYKULIAN, ARTUR · 2018 to 2022
$3.5M
Development of Gene Therapy for Hereditary Deafness using Rational Protein EngineeringR01DC020190 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI DAVID P COREY, Artur Indzhykulian · 2022 to 2026
$3.3M
Development of Genome Editing as Treatment for Genetic Hearing LossR01DC016875 · NIDCD · MASSACHUSETTS EYE AND EAR INFIRMARY · PI CHEN, ZHENG-YI · 2019 to 2023
$3.0M
Development of CRISPR/Cas9-based exon-skipping strategies for the treatment of USH-associated deafnessR01DC019404 · NIDCD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI SUSAN HALLORAN BLANTON, Zheng-Yi Chen · 2022 to 2026
$2.8M
Calcium Regulation in Cochlear CellsR01DC021795 · NIDCD · CASE WESTERN RESERVE UNIVERSITY · PI Artur Indzhykulian, Ruben Stepanyan · 2025 to 2026
$1.3M
NCATS NIH HHS U01 TR005352NIDCD NIH HHS R01 DC016875NIDCD NIH HHS R01 DC017166NIDCD NIH HHS R01 DC019404NIDCD NIH HHS R01 DC020190NIDCD NIH HHS R01 DC021795
6 · The paper itself

Abstract

Genome editing has the potential to treat genetic hearing loss. However, current editing therapies for genetic hearing loss have shown efficacy only in hearing rescue. In this study, we evaluated a rescue strategy using adeno-associated virus (AAV) type 2-mediated delivery of Staphylococcus aureus Cas9-sgRNA in the mature inner ear of the P2rx2V61L/+ mouse model of autosomal dominant deafness-41 (DFNA41), a dominant, delayed-onset, and progressive hearing loss in humans. We demonstrate that local injection in adult mice results in efficient and specific editing that abolishes the mutation without notable off-target effects or AAV genome integration. Editing effectively restores long-term auditory and vestibular function. Editing further protects P2rx2V61L/+ mice from hypersensitivity to noise-induced hearing loss, a phenotype also observed in patients with DFNA41. Intervention in mice at a juvenile stage broadens the frequency range rescued, highlighting the importance of early intervention. An effective and specific gRNA for the human P2RX2 V60L mutation has been identified. Our study establishes the feasibility of editing to treat DFNA41 caused by P2RX2 V60L mutation in humans and opens an avenue for using editing to rescue hearing and vestibular function while mitigating noise-induced hearing loss.

Indexed as

DeafnessGene EditingGenetic TherapyVestibule, LabyrinthAnimalsCRISPR-Cas SystemsDependovirusDisease Models, AnimalHumansMiceMutation, MissenseGene therapyGenetic diseasesMouse modelsOtologyTherapeutics

Identifiers

PMID41090360
PMCPMC12520686

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.