Abstract
Hearing loss resulting from the death of hair cells in the organ of Corti or neurons in the spiral ganglion could be cured by the appropriate in vivo gene delivery into the cochlea. To date, less work has focused on gene delivery to the inner ear, and existing studies have primarily used adenovirus and adeno-associtated virus vectors. It has been shown that HVJ-liposome is a highly efficient vehicle for the introduction of oligonucleotides as well as for the transfer of genes <100kbp without damaging cells. The purpose of the present study was to assess the relative efficacy of gene delivery to the mouse cochlea, including cell specificity and toxicity, using HVJ-liposome. The HVJ-liposome (1000 HAU/5μl) bearing the E. Coli LacZ gene was directly injected into the scala tympani of the mouse cochlea in vivo, and the tissues were later assayed for the presence of the LacZ gene product, β-galactosidase (β-gal). The HVJ-liposome was found to infect and elicit transgene expression in many cell types of the mouse cochlea; neurons in the spiral ganglion, cells in the stria vascularis, cells in the organ of Corti, and cells in Reissner's membrane expressed β-gal. Transgene expression was persistent up to 7 days in these cells without any toxicity and inflammation.
The results suggest that HVJ-liposome might be useful as a gene transfer vehicle in the inner ear and in future might be used to develop gene therapy strategies for some forms of hearing loss.
