アデノウィルスを用いた内リンパ嚢経由ｇｅｎｅ ｔｒａｎｓｆｅｒの試み

Abstract

Gene transfer may be applied in a variety of organs, including the inner ear. For experimental purposes, adenoviral vectors have been inoculated into the scala tympani via cochleostomy or the round window membrane, which resulted in transgene expression restricted to the cochlear tissues in the perilymphatic spaces. In the current study, we injected an adenoviral vector expressing the bacterial lacZ reporter gene into the endolymphatic sac of guinea pigs, and observed the distribution of transgene expression. A large number of lacZ-positive cells were present in the endolymphatic duct and sac. LacZ was expressed in the saccule and utricle, as well as in the semicircular canals. In the cochlea, a greater amount of lacZ-positive cells was observed in basal turns compared to more apical turns; the lacZ-positive cells included Hensen cells and strial marginal cells. LacZ was not expressed in the hair cells in either the vestibule or the cochlea, suggesting that transgene expression to the sensory hair cells is difficult to achieve using an adenoviral vector. These findings indicate that inoculation of viral vectors into the endolymphatic sac can provide efficient gene transfer into a variety of cell types that are not accessible via scala tympani inoculation, and can expand the possibility of molecular research and therapy to more inner ear diseases.