Expression of adeno-associated virus integrated transgene within the mammalian vestibular organs.

摘要

HYPOTHESIS: Adeno-associated virus (AAV) is a suitable viral vector for transgene expression within the mammalian vestibular organs. BACKGROUND: In vivo introduction and expression of a foreign gene within the cochlear tissues have been established using a variety of viral vectors and guinea pig as the animal model. However, the vestibular neuroepithelia of the mammalian inner ear as a potential target for transgene expression remain to be investigated. METHODS: Transgene expression was assessed within the vestibular neuroepithelia of guinea pigs after intracochlear infusion of the recombinant AAV vector with the aid of an osmotic minipump. Evaluation of the transgene within the vestibular apparatus focused on its duration of expression from 2-24 weeks after intracochlear AAV infusion using immunohistochemistry. RESULTS: In the AAV-beta-galactosidase (beta-gal)-infused animals, the sensory hair cells as well as the supporting epithelial cells of cristae and maculae were positive for the transgene expression. The relative level of beta-gal expression was noted to decrease progressively over time. Transduction of the vestibular neuroepithelia also was observed in the contralateral ear, a finding that has been documented previously in AAV-integrated transgene expression in the cochlea. CONCLUSION: This study reports the first demonstration of introduction and long-term transgene expression within the vestibular neuroepithelia. The ability to express a foreign gene with the vestibular system allows the possibility of experimental and therapeutic application of gene therapy technology to address vestibular function and dysfunction.