Evidence map›Paper›PMID 40121530›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Combined AAV-mediated specific Gjb2 expression restores hearing in DFNB1 mouse models.

Qiuhan Sun, Fangzhi Tan, Liyan Zhang, Yicheng Lu, Hao Wei, Nianci Li, Lulu Jiang, Yinyi Zhou, Tian Chen, Ling Lu and 4 more

Abstract read
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In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing 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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

19 citing papers in PubMed.

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  16. Treating Hearing Loss: From Cochlear Implantation to Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  17. IsMedComm · 2025
    Article
  18. Novel AAV-based GJB2 gene therapy restores hearing function.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  19. Review
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.

Qiuhan SunState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Fangzhi TanState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China. Electronic address: 101013491@seu.edu.cn.
Liyan ZhangState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Yicheng LuState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Hao WeiDepartment of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Jiangsu Provincial Key Medical Discipline (Laboratory), Nanjing, China; Research Institute of Otolaryngology, Nanjing, China.
Nianci LiState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
Lulu JiangOtovia Therapeutics Inc., Suzhou 215101, China.
Yinyi ZhouDepartment of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
Tian ChenState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China.
Ling LuDepartment of Otolaryngology-Head and Neck Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing 210096, China. Electronic address: entluling60@126.com.
Geng-Lin LiDepartment of Otorhinolaryngology, ENT Institute, and NHC Key Laboratory of Hearing Medicine, Eye & ENT Hospital, Fudan University, Shanghai 200031, China; Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China. Electronic address: genglin.li@fdeent.org.
Jieyu QiDepartment of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; State Key Laboratory of Hearing and Balance Science, Beijing Institute of Technology, Beijing 100081, China; School of Medical Engineering, Affiliated Zhuhai People's Hospital, Beijing Institute of Technology, Zhuhai 519088, China; Advanced Technology Research Institute, Beijing Institute of Technology, Jinan 250300, China. Electronic address: qijieyu@bit.edu.cn.
Shiming YangState Key Laboratory of Hearing and Balance Science, Beijing Institute of Technology, Beijing 100081, China; Senior Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China; National Clinical Research Center for Otolaryngologic Diseases, Beijing 100853, China; Key Laboratory of Hearing Science, Ministry of Education, Beijing 100853, China; Beijing Key Laboratory of Hearing Impairment Prevention and Treatment, Beijing 100853, China. Electronic address: yangshiming@301hospital.com.cn.
Renjie ChaiState Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, School of Medicine, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing 210096, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China; Department of Neurology, Aerospace Center Hospital, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China; Southeast University Shenzhen Research Institute, Shenzhen 518063, China. Electronic address: renjiec@seu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pathogenic mutations in the Gjb2 gene, encoding connexin 26, are the leading cause of autosomal recessive hereditary deafness. Gene therapy holds significant promise for treating this. Adeno-associated virus (AAV)-mediated therapeutic gene delivery has been shown to be safe and effective in restoring hearing in both animal models and human patients. However, Gjb2 gene therapy has been hindered by the limited specificity and efficiency of the available AAV vectors. In this study, we screened AAV serotypes and found that co-administration of AAV1 and AAV-ie could effectively target Gjb2-expressing cells. However, the ectopic Gjb2 expression in hair cells induced by these AAVs could cause ototoxicity, which was addressed by employing the specific promoter SCpro. Co-injection of AAV1 and AAV-ie carrying exogenous Gjb2 driven by SCpro effectively restored hearing function in Gjb2-deficient mice. Moreover, the combined AAV system can transduce the cochleae of Bama miniature pigs and AAV administration into the inner ear of cynomolgus monkeys did not impair hearing and showed negligible systemic toxicity, indicating the efficiency and safety of this gene therapy in large animals. Thus, this study provides a strategy for Gjb2 gene therapy and lays a foundation for future clinical applications.

Indexed as

ConnexinsDependovirusGenetic TherapyGenetic VectorsHearingAnimalsConnexin 26Disease Models, AnimalGene ExpressionGene Transfer TechniquesHumansMacaca fascicularisMiceSwineSwine, MiniatureTransduction, GeneticConnexin 26ConnexinsGJB2 protein, humanGjb2 protein, mousecombined AAVsgene therapyGjb2hearing restorationspecific promoter

Identifiers

PMID40121530
PMCPMC12266026

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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.