Journal article
Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
Molecular therapy. Methods & clinical development, Vol.17, pp.1167-1177
06/12/2020
DOI: 10.1016/j.omtm.2020.05.007
PMCID: PMC7270144
PMID: 32518805
Abstract
Gene delivery is a key component for the treatment of genetic hearing loss. To date, a myriad of adeno-associated virus (AAV) serotypes and surgical approaches have been employed to deliver transgenes to cochlear hair cells, but the efficacy of dual transduction remains unclear. Herein, we investigated cellular tropism of single injections of AAV serotype 1 (AAV1), AAV2, AAV8, AAV9, and Anc80L65, and quantitated dual-vector co-transduction rates following co-injection of AAV2 and AAV9 vectors in adult murine cochlea. We used the combined round window membrane and canal fenestration (RWM+CF) injection technique for vector delivery. Single AAV2 injections were most robust and transduced 96.7% ± 1.1% of inner hair cells (IHCs) and 83.9% ± 2.0% of outer hair cells (OHCs) throughout the cochlea without causing hearing impairment or hair cell loss. Dual AAV2 injection co-transduced 96.9% ± 1.7% of IHCs and 65.6% ± 8.95% of OHCs. Together, RWM+CF-injected single or dual AAV2 provides the highest auditory hair cell transduction efficiency of the AAV serotypes we studied. These findings broaden the application of cochlear gene therapy targeting hair cells.
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Transduction efficiency of inner and outer hair cells in the mature murine cochlea is excellent with adeno-associated virus serotype 2 (AAV2) when a round window membrane and canal fenestration technique is used. Dual-vector co-transduction of AAV2:AVV2 is equally robust and efficient, making AAV2 an excellent choice for single and/or dual applications that require hair cell transduction.
Details
- Title: Subtitle
- Hair Cell Transduction Efficiency of Single- and Dual-AAV Serotypes in Adult Murine Cochleae
- Creators
- Ryotaro Omichi - Okayama UniversityHidekane Yoshimura - Shinshu UniversitySeiji B Shibata - Roy J. and Lucille A. Carver College of MedicineLuk H Vandenberghe - Broad InstituteRichard J.H Smith - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Molecular therapy. Methods & clinical development, Vol.17, pp.1167-1177
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.omtm.2020.05.007
- PMID
- 32518805
- PMCID
- PMC7270144
- ISSN
- 2329-0501
- eISSN
- 2329-0501
- Grant note
- name: NIH/NIDCD, award: T32 DC000040–17, R01 DC017955; name: AAO-HNSF
- Language
- English
- Date published
- 06/12/2020
- 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
- 9984256843802771
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