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Cited by 300Hearing, Cochlea, Tinnitus, GeneticsVirus-based gene therapy researchRNA Interference and Gene Delivery

Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model

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Akil, Omar, Dyka, Frank, Calvet, Charlotte, Emptoz, Alice, Lahlou, Ghizlene, Nouaille, Sylvie, Boutet de Monvel, Jacques, Hardelin, Jean-Pierre +5 more·2019·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1817537116PMC PMC6410774
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Abstract

Significance: In humans, inner ear development is completed in utero, with hearing onset at ∼20 weeks of gestation. However, genetic forms of congenital deafness are typically diagnosed during the neonatal period. Gene therapy approaches in animal models should therefore be tested after the period of hearing onset, to determine whether they can reverse an existing deafness phenotype. Here, we used a mouse model of DFNB9, a human deafness form accounting for 2–8% of all cases of congenital genetic deafness. We show that local gene therapy in the mutant mice not only prevents deafness when administered to immature hearing organs, but also durably restores hearing when administered at a mature stage, raising hopes for future gene therapy trials in DFNB9 patients.

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Crossref · 10.1073/pnas.1817537116

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  • Al-Moyed and colleagues employed AAV2-OTOF hybrid vectors for cochlear delivery, demonstrating sustained correction of deafness in Otof -/-mice.

    “For example, Al-Moyed and colleagues have employed AAV2-OTOF hybrid vectors for cochlear delivery, demonstrating sustained correction of deafness in Otof -/-mice [108].”

    From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [108]

    The Materials and Methods describe cochlear delivery of an AAV2-Otof vector pair to Otof−/− mice, and the Results and Discussion report restored hearing thresholds that persisted for 20 weeks. The cited paper is by Akil and colleagues, however, not Al-Moyed and colleagues, so it does not support the claim’s attribution of the experiment to them. (LLM, conf=0.88)

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  • When this therapy was administered before hearing onset in mice, it was found to prevent deafness altogether.

    “Interestingly, when this therapy was administered before hearing onset in mice, it was found to prevent deafness altogether.”

    From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [108]

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Research works printed but not linked: 37

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Authors
Akil, O., Dyka, F., Calvet, C., Emptoz, A., Lahlou, G., Nouaille, S., Boutet de Monvel, J., Hardelin, J.-P., Hauswirth, W. W., Avan, P., Petit, C., Safieddine, S., & Lustig, L. R.
Affiliations
  • University of California, San Francisco (US)
  • University of Florida (US)
  • Inserm (FR)
  • Genetics and Physiology of Hearing Laboratory, Institut Pasteur, 75015 Paris, France;
  • Université Clermont Auvergne (FR)
  • NewYork–Presbyterian Hospital (US)
Corresponding author
Petit, Christine
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2019-02-19
Volume
116
Issue
10
Pages
4496-4501
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.1817537116
PMC
PMC6410774
OpenAlex
W2916730093
Cited by
300
References
5
Citations by year
2026: 36 · 2025: 45 · 2024: 61 · 2023: 43 · 2022: 27 · 2021: 39 · 2020: 40 · 2019: 9
FWCI
17.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, cc-by-nc-nd)
Funders
Agence Nationale de la Recherche (ANR-17-CE18-0027, ANR-11-IDEX-0004, ANR-10-LABX-0065)
Topics
  • Life Sciences › Neuroscience › Sensory Systems › Hearing, Cochlea, Tinnitus, Genetics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
DFNB9, congenital hearing loss, gene therapy, adeno-associated virus vectors, hearing restoration, inner ear development, mouse model, GJB2, connexin 26, hereditary hearing loss
MeSH terms
Dependovirus, Animals, Deafness, Disease Models, Animal, Genetic Vectors, Humans, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Genetic Therapy, Mice

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