Viral-mediated gene transfer in the cochlea.
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.
Weiss
M A
MA
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical School, Ann Arbor 48109-0648, USA.
Frisancho
J C
JC
Roessler
B J
BJ
Raphael
Y
Y
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003051:Cochlea / Q000166:cytology / Q000502:physiology*; D003638:Deafness / Q000139:chemically induced / Q000235:genetics / Q000523:psychology; D015870:Gene Expression / Q000235:genetics; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006168:Guinea Pigs; D006801:Humans; D007763:Lac Operon; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology