ADENOVIRUS-MEDIATED IN-VIVO GENE-TRANSFER IN GUINEA-PIG MIDDLE-EAR MUCOSA

This article describes a study designed to assess the feasibility of u sing recombinant adenovirus for delivering therapeutic peptides in viv o in the guinea pig middle ear cleft. A recombinant adenoviral vector AdCMVsp1 LacZ containing the Escherichia coli beta-galactosidase was i njected into the middle ear space. Qualitative assessment of cell midd le ear transfection was performed on day 2 by light microscopy study, after injecting a multiplicity of infection (MOI) ranging from 0 to 10 00, At an MOI of 30, 30% of the promontory area epithelial cells were stained. An MOI of 50 stained 60% of the cells and an MOI of 100 or mo re stained more than 90% of the cells. The duration of cell transfecti on was studied after injecting an MOI of 50, The percentage of stained cells was 60% on day 2, 10% on day 7, and 0% on day 14, Middle ear mu cosal inflammation, consisting of a granulocytic infiltrate, was obser ved when an MOI above 50 was used. Even at a high MOI (500), no staini ng could be found in the cochlea, in the facial nerve, in the brain, o r in visceral organs. These data suggest that recombinant adenovirus v ectors can be used to transfer genes in the middle ear. This method ap pears to be safe, and may be envisaged as a short-duration treatment t o transfer genes in vivo in the treatment of middle ear diseases.