Adenovirus-mediated perilymphatic gene transfer

Abstract

Most of deafness is now incurable through conventional therapies. The application of gene transfer to cochlear gene therapy is attractive as a new medical intervention in deafness. In this study, LacZ (+)-adenoviral vectors were inoculated into the guinea pig cochlear perilymphatic space via cochleostomy. The expression of beta-galactosidase was estimated by both an enzymatic reaction with X-gal and immunohistochemical staining with an antibody to E. coli beta-galactosidase. The cells expressing beta-galactosidase were observed through all turns of cochlea. X-gal reaction demonstrated the predominant expression of beta-galactosidase in mesenchymal cells lining perilymphatic spaces and fibrocytes. The organ of Corti, stria vascularis and spiral ganglion cells were also reacted faintly with X-gal, which might indicate the beta-galactosidase expression, however, the immunohistochemical reaction resulted in the false positive X-gal reaction of these cells. The reporter gene inoculation into the perilymphatic space elucidated the ipsilateral cochlear gene expression with little damage to the tissue. No contamination could be detected in the contralateral cochlea or neighboring tissues. The perilymphatic gene transfer might develop into the cochlear gene therapy in future.