Cochlear gene delivery through an intact round window membrane in mouse

被引:102
作者
Jero, J
Mhatre, AN
Tseng, CJ
Stern, RE
Coling, DE
Goldstein, JA
Hong, K
Zheng, WW
Hoque, ATMS
Lalwani, AK
机构
[1] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Lab Mol Otol, Epstein Labs, San Francisco, CA 94143 USA
[2] Univ Helsinki, Cent Hosp, Dept Otolaryngol, FIN-00290 Helsinki, Finland
[3] Calif Pacific Med Ctr, Res Inst, Liposome Res Lab, San Francisco, CA 94115 USA
[4] Natl Inst Dent & Cranofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1089/104303401300042465
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (RWM) or intracochlear infusion through a cochleostomy. However, the surgical trauma, inflammation, and hearing loss associated with these methods Lead us to investigate a less invasive delivery method. Herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, Gelfoam, for transgene delivery into the mouse cochlea through an intact RWM, The Gelfoam absorbed with liposomes and adenovirus, but not with adeno-associated virus (AAV), was successful in mediating transgene expression across an intact RWM in a variety of cochlear tissues. The Gelfoam technique proved to be an easy, atraumatic, and effective, but vector-dependent, method of delivering transgenes through an intact RWM, Compared with the more invasive gene delivery methods, this technique represents a safer and a more clinically viable route of cochlear gene delivery in humans.
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页码:539 / 548
页数:10
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