The data and the rate of gene expression in the canalostomy groups are summarized in Table 1. There was interanimal variability in the extent and location of transgene expression in the area remote to the inoculation site. The lining of the cochlear perilymphatic space, including Reissner's membrane, exhibited gene expression in 10 of 16 mice ( Fig. 2D) and, in 10 of 16 mice, in the perilymphatic space of the saccule ( Fig. In 11 of 16 mice, we found gene expression in the perilymphatic space of the utricle ( Fig. In 12 of 16 mice, we detected transgene expression in the posterior ampulla ( Fig. All animals showed gene expression in the cells lining the perilymphatic space in the PSCC ( Fig. All transduced cells were located in the perilymphatic space, except for one case in which gene expression was also detected in the sensory cells of the posterior crista ampullaris ( Fig. 1), the gene expression pattern was similar in the 0.5 μl and 1.0 μl Ad.CMV– lacZ inoculated groups. Our findings indicate that inoculation of adenovirus vectors into the mouse inner ear through the semicircular canal has the potential to efficiently introduce transgenes to the vestibular system and the cochlea without compromising hearing. Any vestibular function transiently lost after the canalostomy was recovered. Functional tests after the surgery showed that the canalostomy preserved hearing, whereas the cochleostomy did not. One canalostomy case showed gene expression in sensory cells of the crista ampullaris, whereas the cochleostomy group showed gene expression in the sensory cells in the organ of Corti and saccule. Both approaches caused lacZ to be expressed in cells lining the perilymphatic space. We administered the virus through the posterior semicircular canal (canalostomy) and into the cochlea (cochleostomy). We have developed a new approach for viral inoculation into the mature mouse inner ear, using a replication-deficient adenovirus expressing the bacterial gene lacZ. However, the small size of the mouse inner ear poses a particular challenge for surgical procedures. Mice present an ideal model for inner ear gene therapy because their genome is being rapidly sequenced, their generation time is relatively short, and they serve as a valuable model for human hereditary inner ear disease. Gene Editing: Technology & Applications.

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