Mediated Cochlear Gene Transfer
Gene Therapy (2000) 7, 377–383 2000 Macmillan Publishers Ltd All rights reserved 0969-7128/00 $15.00 www.nature.com/gt VIRAL TRANSFER TECHNOLOGY RESEARCH ARTICLE Transduction of the contralateral ear after adenovirus- mediated cochlear gene transfer T Sto¨ver1,2, M Yagi1,3 and Y Raphael1 1Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan Medical School, Ann Arbor, MI, USA; 2Department of Otolaryngology, Medizinische Hochschule Hannover, Hannover, Germany; and 3Department of Otolaryngology, Kansai Medical University, Osaka, Japan Cochlear gene transfer is a promising new approach for cochleae, whereas virus inoculation into the bloodstream did inner ear therapy. Previous studies have demonstrated hair not. The cochlear aqueduct was identified as the most likely cell protection with cochlear gene transfer not only in the route of virus spread to the contralateral cochlea. These data inoculated, but also in the uninoculated ear. To characterize enhance our understanding of the kinetics of virus-mediated the kinetics of viral spread, we investigated the extent of transgene expression in the inner ear, and assist in the transgene expression in the contralateral (uninoculated) development of clinical applications for inner ear gene ther- cochlea after unilateral adenoviral cochlear gene transfer. apy. Our results showed a functional communication We used a lacZ reporter gene vector, and demonstrated between the CSF and the perilymphatic space of the inner spread of the adenovirus into the cerebrospinal fluid (CSF) ear, that is not only of importance for otological gene trans- after cochlear inoculation of 25 l viral vector. Direct virus fer, but also for CNS gene transfer.
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