A glucocorticoid reduces adverse effects of adenovirus vectors in the cochlea.
Gene transfer using a recombinant adenovirus is a powerful tool for research and clinical applications, but its cytotoxicity and immune response limit its use, especially when repeated application of the vector is necessary. This study investigated the effects of dexamethasone (DEX)-induced immunosuppression on the outcome of adenovirus gene transfer in guinea pig inner ears. Animals received DEX for 29 days. Their inner ear was inoculated with 5 micro l of adenovirus vector twice, on days 5 and 26. Auditory brainstem response was measured on days 1, 8 and 29. The animals were sacrificed on day 29, and reporter gene expression was evaluated. In control animals that received no DEX, postinoculation threshold shifts and lesions in the organ of Corti were observed and reporter gene expression was absent. In contrast, DEX-treated ears were largely protected, and transduction of inner ear cells was readily apparent. These data demonstrate that immunosuppressive treatment can reduce the negative consequences of repeated adenovirus-mediated gene therapy.
Ishimoto
Shin-ichi
S
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Mich. 48109-0506, USA. yoash@umich.edu
Kawamoto
Kohei
K
Stöver
Timo
T
Kanzaki
Sho
S
Yamasoba
Tatsuya
T
Raphael
Yehoash
Y
D000257:Adenoviridae Infections / Q000235:genetics / Q000628:therapy* / Q000821:virology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015834:Cochlear Diseases / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D046508:Culture Techniques; D003907:Dexamethasone / Q000627:therapeutic use*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000473:pathology / Q000821:virology; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D009925:Organ of Corti / Q000473:pathology / Q000821:virology
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone