From gene identification to gene therapy

Sho Kanzaki, Kohei Kawamoto, Seung Ha Oh, Timo Stöver, Mitsuya Suzuki, Shinichi Ishimoto, Masao Yagi, Josef M. Miller, Margaret I. Lomax, Yehoash Raphael

研究成果: Article査読

21 被引用数 (Scopus)

抄録

Inner ear disease due to hair cell loss is common, and no restorative treatments for the balance and hearing impairment are currently available. To develop clinical means for enhancing protection and regeneration in the inner ear, it is necessary to understand the molecular basis for hereditary and acquired deafness and vestibular disorders. One approach is to identify and characterize genes that regulate protection or repair in other systems. For that purpose, we have used the differential display assay and compared gene expression between normal and acoustically traumatized inner ears of chicks. Several chick cDNAs that were identified are considered as candidates for roles in the reparative process that follows trauma in the basilar papilla. The mammalian vestibular epithelium has a limited regenerative capability. To identify genes that may participate in the regenerative response, we have used gene arrays profiling, comparing normal to drug-traumatized vestibular epithelia. We identified several genes that are differentially expressed in traumatized vestibular epithelium, including several insulin-like growth factor-I binding proteins. To use this molecular knowledge for enhancing protection and repair in the organ of Corti, it is necessary to overexpress the genes of choice in the inner ear. Using viral-mediated gene transfer, we overexpressed transgenic glial cell line-derived neurotrophic factor and demonstrated a robust protective effect against acoustic and ototoxic inner ear trauma. Future identification of the genes that are important for protection and regeneration, along with improved gene transfer technology, will allow the use of gene therapy for treating hereditary and environmental inner ear disease.

本文言語English
ページ(範囲)161-164
ページ数4
ジャーナルAudiology and Neuro-Otology
7
3
DOI
出版ステータスPublished - 2002
外部発表はい

ASJC Scopus subject areas

  • 生理学
  • 耳鼻咽喉科学
  • 感覚系
  • 言語聴覚療法

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