A glucocorticoid reduces adverse effects of adenovirus vectors in the cochlea

Shin Ichi Ishimoto, Kohei Kawamoto, Timo Stöver, Sho Kanzaki, Tatsuya Yamasoba, Yehoash Raphael

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 μl 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.

Original languageEnglish
Pages (from-to)70-79
Number of pages10
JournalAudiology and Neuro-Otology
Volume8
Issue number2
DOIs
Publication statusPublished - 2003 Apr 2
Externally publishedYes

Keywords

  • Adenovirus
  • Dexamethasone
  • Gene therapy
  • Guinea pig
  • Immune response

ASJC Scopus subject areas

  • Physiology
  • Otorhinolaryngology
  • Sensory Systems
  • Speech and Hearing

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