Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer.
Cochlear gene transfer is a promising new approach for inner ear therapy. Previous studies have demonstrated hair cell protection with cochlear gene transfer not only in the inoculated, but also in the uninoculated ear. To characterize the kinetics of viral spread, we investigated the extent of transgene expression in the contralateral (uninoculated) cochlea after unilateral adenoviral cochlear gene transfer. We used a lacZ reporter gene vector, and demonstrated spread of the adenovirus into the cerebrospinal fluid (CSF) after cochlear inoculation of 25 microl viral vector. Direct virus application into the CSF resulted in transduction of both cochleae, whereas virus inoculation into the bloodstream did not. The cochlear aqueduct was identified as the most likely route of virus spread to the contralateral cochlea. These data enhance our understanding of the kinetics of virus-mediated transgene expression in the inner ear, and assist in the development of clinical applications for inner ear gene therapy. Our results showed a functional communication between the CSF and the perilymphatic space of the inner ear, that is not only of importance for otological gene transfer, but also for CNS gene transfer. Gene Therapy (2000) 7, 377-383.
Stöver
T
T
Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan Medical School, Ann Arbor, MI, USA.
Yagi
M
M
Raphael
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002555:Cerebrospinal Fluid / Q000502:physiology; D003051:Cochlea / Q000502:physiology*; D003052:Cochlear Aqueduct / Q000502:physiology; D004432:Ear, Middle / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D006168:Guinea Pigs; D007763:Lac Operon / Q000235:genetics; D014161:Transduction, Genetic / Q000235:genetics