Viral‐mediated gene transfer in the cochlea

International Journal of Developmental Neuroscience - Tập 15 - Trang 577-583 - 1997
Melissa A Weiss1, Juan C Frisancho1, Blake J Roessler2, Yehoash Raphael1
1Kresge Hearing Research Institute, Department of Otolaryngology, The University of Michigan Medical School, MSRB Ill Room 9303, USA
2Department of Internal Medicine, The University of Michigan Medical School, MSRB I Room 5520C, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0648, U.S.A.

Tóm tắt

Abstract

Gene transfer is an exciting new tool in medical therapy and scientific investigation, but only very recently has it begun to be developed in the auditory system. This paper describes in vivo and ex vivo experiments using an adenoviral vector (Ad. RSVntlacZ), which is a replication‐deficient virus based on a human adenoviral (serotype 5) genomic backbone. The in vivo experiments demonstrate successful gene transfer into multiple types of cochlear cells. We observed a relatively efficient transduction, several weeks of sustained transgene expression and an absence of major lethal cytotoxicity in spiral ganglion and epithelial cells of the cochlea in adult animals. The ex vivo experiments were performed using fibroblasts transduced in vitro with Ad. RSVntlacZ. Two weeks after inoculation of the fibroblasts into the perilymph, we observed transplanted fibroblasts, which were adherent to the lining of the perilymphatic spaces, and were expressing the lacZ transgene. We speculate that, as the genetic basis of degenerative cochlear diseases is characterized on a mutational level, transgene expression will allow us to test hypotheses regarding the effects of specific genes on cochlear cell biology. Gene transfer will not only increase our understanding of the pathophysiology of hearing loss, but also may provide gene therapy for disease.


Tài liệu tham khảo

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International Journal of Developmental Neuroscience

Tập 15

577-583

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