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Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy
Open accessAbstract
Summary Mice lacking the vesicular glutamate transporter-3 (VGLUT3) are congenitally deaf due to loss of glutamate release at the inner hair cell afferent synapse. Cochlear delivery of VGLUT3 using adeno-associated virus-1 (AAV1) leads to transgene expression in only inner hair cells (IHC), despite broader viral uptake. Within two weeks of AAV1-VGLUT3 delivery, acoustic brainstem response (ABR) thresholds normalize, along with partial rescue of the startle response. Lastly, we demonstrate partial reversal of the morphologic changes seen within the afferent IHC ribbon synapse. These findings represent the first successful restoration of hearing by gene replacement in mice, which is an important step towards gene therapy of human deafness.
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Cited by
Vainchtein, I. D., Chin, G., Cho, F. S., Kelley, K. W., Miller, J. G., Chien, E. C., Liddelow, S. A., Nguyen, P. T., Nakao-Inoue, H., Dorman, L. C., et al. (2018) · Science · doi:10.1126/science.aal3589 · Cited by 657
Self-citationTherapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality
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AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial
Lv, J., Wang, H., Cheng, X., Chen, Y., Wang, D., Zhang, L., Cao, Q., Tang, H., Hu, S., Gao, K., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(23)02874-x · Cited by 361
Delivery of therapeutics to the inner ear: The challenge of the blood-labyrinth barrier
Nyberg, S., Abbott, N. J., Shi, X., Steyger, P. S., & Dabdoub, A. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aao0935 · Cited by 336
A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear
Landegger, L. D., Pan, B., Askew, C., Wassmer, S. J., Gluck, S. D., Galvin, A., Taylor, R., Forge, A., Stankovic, K. M., Holt, J. R., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3781 · Cited by 325
Metadata
- Authors
- Akil, O., Seal, R. P., Burke, K., Wang, C., Alemi, A., During, M., Edwards, R. H., & Lustig, L. R.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 75
- Issue
- 2
- Pages
- 283-293
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2034060287
- Cited by
- 404
- References
- 0
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Akil, O., Seal, R. P., Burke, K., Wang, C., Alemi, A., During, M., Edwards, R. H., & Lustig, L. R. (2012). Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy. Neuron. https://doi.org/10.1016/j.neuron.2012.05.019
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