Journal article
Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation
Scientific reports, Vol.8(1), pp.2980-10
02/14/2018
DOI: 10.1038/s41598-018-21233-z
PMCID: PMC5812997
PMID: 29445157
Abstract
Cochlear gene therapy holds promise for the treatment of genetic deafness. Assessing its impact in adult murine models of hearing loss, however, has been hampered by technical challenges that have made it difficult to establish a robust method to deliver transgenes to the mature murine inner ear. Here in we demonstrate the feasibility of a combined round window membrane injection and semi-circular canal fenestration technique in the adult cochlea. Injection of both AAV2/9 and AAV2/Anc80L65 via this approach in P15-16 and P56-60 mice permits robust eGFP transduction of virtually all inner hair cells throughout the cochlea with variable transduction of vestibular hair cells. Auditory thresholds are not compromised. Transduction rate and cell tropism is primarily influenced by viral titer and AAV serotype but not age at injection. This approach is safe, versatile and efficient. Its use will facilitate studies using cochlear gene therapy in murine models of hearing loss over a wide range of time points.
Details
- Title: Subtitle
- Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation
- Creators
- Hidekane Yoshimura - Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, JapanSeiji B Shibata - Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USAPaul T Ranum - Interdisciplinary Graduate Program in Molecular & Cellular Biology, The University of Iowa Graduate College, University of Iowa, Iowa City, IA, 52242, USARichard J H Smith - Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. richard-smith@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.8(1), pp.2980-10
- DOI
- 10.1038/s41598-018-21233-z
- PMID
- 29445157
- PMCID
- PMC5812997
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- England
- Grant note
- T32 DC000040 / NIDCD NIH HHS R01 DC003544 / NIDCD NIH HHS
- Language
- English
- Date published
- 02/14/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984006477502771
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