Inner ear transgene expression after adenoviral vector inoculation in the endolymphatic sac

Gene transfer has been performed in a variety of organs. In the mammalian i nner ear, viral vectors have been used to introduce exogenous reporter gene s via the scala tympani into the cochlea, While scala tympani inoculation i s clinically feasible, it is not without risks. Moreover, transgene express ion has so far been restricted to the cochlear tissues in the perilymphatic spaces that are contiguous with the scala tympani, To achieve gene transfe r of vestibular organs and cells surrounding the endolymphatic space, and t o extend the clinical utility of inner ear gene therapy, we developed a new surgical approach for vector inoculation. A replication-deficient adenovir al vector, Ad,RSVntlacZ, was injected into the guinea pig endolymphatic sac , A large number of blue (LacZ-positive) cells was observed in the endolymp hatic sac and duct, the vestibule, and the ampulla, Blue cells were also de tected in the cochlea, mainly in cells bordering the endolymphatic space: m arginal cells in the stria vascularis and supporting cells in the organ of Corti, These findings indicate that inoculation of viral vectors into the e ndolymphatic sac can provide efficient gene transfer into a variety of cell types that are not accessible via scala tympani inoculation.