Transduction of the contralateral ear after adenovirus-mediated cochlear gene transfer

Cochlear gene transfer is a promising new approach for inner ear therapy. P revious studies have demonstrated hair cell protection with cochlear gene t ransfer not only in the inoculated, but also in the uninoculated ear. To ch aracterize the kinetics of viral spread, we investigated the extent of tran sgene expression in the contralateral (uninoculated) cochlea after unilater al adenoviral cochlear gene transfer We used a lacZ reporter gene vector, a nd demonstrated spread of the adenovirus into the cerebrospinal fluid (CSF) after cochlear inoculation of 25 mu l viral vector. Direct virus applicati on into the CSF resulted in transduction of both cochleae, whereas virus in oculation into the bloodstream did not. The cochlear aqueduct was identifie d as the most likely route of virus spread to the contralateral cochlea. Th ese data enhance our understanding of the kinetics of virus-mediated transg ene expression in the inner ear, and assist in the development of clinical applications for inner ear gene therapy. Our results showed a functional co mmunication between the CSF and the perilymphatic space of the inner ear, t hat is not only of importance for otological gene transfer, but also for CN S gene transfer.