Portal de Periódicos da CAPES

Adenovirus-Mediated In Vivo Gene Transfer in Guinea Pig Middle Ear Mucosa

1998; Mary Ann Liebert, Inc.; Volume: 9; Issue: 8 Linguagem: Inglês

10.1089/hum.1998.9.8-1217

1557-7422

Michel Mondain, Sophie Restituito, Vincenzo Vincenti, Quentin Gardiner, Anna Paula Uziel, A. Delabre, Monique Mathieu, J Bousquet, P. Démoly,

Virus-based gene therapy research

This article describes a study designed to assess the feasibility of using recombinant adenovirus for delivering therapeutic peptides in vivo in the guinea pig middle ear cleft. A recombinant adenoviral vector AdCMVsp1 LacZ containing the Escherichia coli β-galactosidase was injected into the middle ear space. Qualitative assessment of cell middle ear transfection was performed on day 2 by light microscopy study, after injecting a multiplicity of infection (MOI) ranging from 0 to 1000. 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 more stained more than 90% of the cells. The duration of cell transfection 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 mucosal inflammation, consisting of a granulocytic infiltrate, was observed when an MOI above 50 was used. Even at a high MOI (500), no staining could be found in the cochlea, in the facial nerve, in the brain, or in visceral organs. These data suggest that recombinant adenovirus vectors can be used to transfer genes in the middle ear. This method appears to be safe, and may be envisaged as a short-duration treatment to transfer genes in vivo in the treatment of middle ear diseases. Otitis media is a common pathology in humans, and inflammatory cytokines or growth factors have been shown to play a role in its pathogenesis. Gene therapy is currently being tested in the treatment of many disorders. This method of delivery of therapeutic peptides into the ear should be considered with interest, but the potential use of gene therapy to deliver these substances in vivo to the middle ear mucosa has not been investigated so far. The purpose of this study was to assess the feasibility of using a recombinant adenovirus vector to target the middle ear of the Hartley guinea pig.