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Inner Ear Gene Therapy Program
Wade Chien, M.D., FACS, Otolaryngology Surgeon-Scientist
Our laboratory, which is part of the NIDCD Otolaryngology Surgeon-Scientist Program (OSSP), is focused on developing gene therapy as a treatment option for hearing loss and dizziness. Some patients with hereditary hearing loss and dizziness have mutations involving genes critical for inner ear development. Our laboratory is developing ways to delivery gene therapy to the mammalian inner ear in vivo. We are currently testing whether the delivery of normal copies of the mutated genes into animal models of hereditary hearing loss can restore hearing and balance.
Genome editing (zinc finger nucleases, TALENs, and CRISPR/Cas) allows modification of the genome at a single-nucleotide level. This can potentially be used to correct the mutation in the affected genes and restore normal function. We are currently studying whether genome editing can be used as a form of gene therapy to restore hearing and balance in animal models.
- Isgrig K, McDougald DS, Zhu J, Wang HJ, Bennett J, Chien, WW. AAV2.7m8 is a powerful viral vector for inner ear gene therapy. Nature Communications. 2019; volume 10, article number 427.
- Chien WW, Isgrig K, Roy S, Belyantseva IA, Drummond MC, May LA, Fitzgerald TS, Friedman TB, Cunningham LL. Gene therapy restores hair cell stereocilia morphology in inner ears of deaf whirler mice. Mol Ther. 2015 Aug 26.
- Zalewski CK*, Chien WW*, King KA, Muskett JA, Baron R, Butman JA, Griffith AJ, Brewer CC, Vestibular dysfunction in patients with enlarged vestibular aqueduct. Otolaryngol Head Neck Surg. 2015 Aug;153(2):257-62. *co-first authors
- Chien WW, McDougald DS, Roy S, Fitzgerald TS, Cunningham LL. Cochlear gene transfer mediated by adeno-associated virus: comparison of two surgical approaches. Laryngoscope. 2015 Apr 17. doi: 10.1002/lary.25317. [Epub ahead of print] (Triologic thesis with distinction)
- Chien WW, McDougald DS, Monzack EL, Cunningham LL. Gene therapy for sensorineural hearing loss. Ear Hear. 2015 Jan;36(1):1–7.
- Weinreich H, Francis HW, Niparko JK, Chien WW. Techniques in cochlear implantation. Operative Techniques in Otolaryngology-Head & Neck Surgery2014 25(4): 312–320.
- Sun DQ, Zhou L, Lin FR, Francis HW, Carey JP, Chien WW. Racial differences in cochlear pigmentation are associated with hearing loss. Otol Neurotol. 2014 Oct;35(9):1509–14.
- Chien WW, Leiding JW, Hsu AP, Zalewski C, King K, Holland SM, Brewer C. Auditory and vestibular phenotypes associated with GATA3 mutation. Otol Neurotol. 2014 Apr;35(4):577–81.
- Chien WW, Janky K, Minor LB, Carey JP. Superior canal dehiscence size: multivariate assessment of clinical impact. Otol Neurotol. 2012 Jul;33(5):810–5.
- Chien W, Lin FR. Prevalence of hearing aid use among older adults in the United States. Arch Intern Med. 2012 Feb 13;172(3):292–3.