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学科主题: 临床医学
题名:
Protection against aminoglycoside-induced ototoxicity by regulated AAV vector-mediated GDNF gene transfer into the cochlea
作者: Liu, Yuhe2; Okada, Takashi1; Shimazaki, Kuniko; Sheykholeslami, Kianoush3; Nomoto, Tatsuya; Muramatsu, Shin-Ichi; Mizukami, Hiroaki; Kume, Akihiro; Xiao, Shuifang2; Ichimura, Keiichi; Ozawa, Keiya
刊名: MOLECULAR THERAPY
发表日期: 2008-03-01
DOI: 10.1038/sj.mt.6300379
卷: 16, 期:3, 页:474-480
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]: RECOMBINANT ADENOASSOCIATED VIRUS ; EXPRESSION IN-VIVO ; CELL-LINE ; NEUROTROPHIC FACTOR ; TRANSGENE EXPRESSION ; HEARING-LOSS ; HAIR-CELLS ; NONHUMAN-PRIMATES ; TIGHT CONTROL ; VIRAL VECTOR
英文摘要:

Since standard aminoglycoside treatment progressively causes hearing disturbance with hair cell degeneration, systemic use of the drugs is limited. Adeno-associated virus (AAV)-based vectors have been of great interest because they mediate stable transgene expression in a variety of postmitotic cells with minimal toxicity. In this study, we investigated the effects of regulated AAV1-mediated glial cell line-derived neurotrophic factor (GDNF) expression in the cochlea on aminoglycoside-induced damage. AAV1-based vectors encoding GDNF or vectors encoding GDNF with an rtTA2s- S2 Tet- on regulation system were directly microinjected into the rat cochleae through the round window at 5 x 10(10) genome copies/body. Seven days after the virus injection, a dose of 333 mg/kg of kanamycin was subcutaneously given twice daily for 12 consecutive days. GDNF expression in the cochlea was confirmed and successfully modulated by the Tet-on system. Monitoring of the auditory brain stem response revealed an improvement of cochlear function after GDNF transduction over the frequencies tested. Damaged spiral ganglion cells and hair cells were significantly reduced by GDNF expression. Our results suggest that AAV1-mediated expression of GDNF using a regulatedexpression system in the cochlea is a promising strategy to protect the cochlea from aminoglycoside-induced damage.

语种: 英语
WOS记录号: WOS:000253548100007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55147
Appears in Collections:北京大学第一临床医学院_耳鼻咽喉头颈外科_期刊论文

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作者单位: 1.Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mol Therapy, Tokyo 1878551, Japan
2.Peking Univ, Hosp 1, Dept Otolaryngol, Beijing 100871, Peoples R China
3.Northeastern Ohio Univ Coll Med & Pharm, Dept Neurobiol, Rootstown, OH 44272 USA

Recommended Citation:
Liu, Yuhe,Okada, Takashi,Shimazaki, Kuniko,et al. Protection against aminoglycoside-induced ototoxicity by regulated AAV vector-mediated GDNF gene transfer into the cochlea[J]. MOLECULAR THERAPY,2008,16(3):474-480.
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