Gene transduction for experimental brain tumors using recombinant adenovirus vector

Tomotsugu Ichikawa, Takashi Tamiya, Yoshiaki Adachi, Yasuhiro Ono, Kengo Matsumoto, Tomohisa Furuta, Takashi Ohmoto, Yoko Yoshida, Hirofumi Hamada

Research output: Contribution to journalArticle

Abstract

Recent advances in molecular biology have permitted significant progress toward the treatment of malignant brain tumors using gene transduction methods. Adenovirus vectors have recently been shown to transduce genes successfully into brain tumor cells both in vitro and in vivo. We have investigated the feasibility of gene transduction for brain tumors using adenovirus vectors. To evaluate in vitro transduction rate by adenovirus vectors, rat 9L gliosarcoma cells or human glioblastoma cells were infected with recombinant replication-deficient adenovirus vectors containing the E. coli β-galactosidase gene (AdexCALacZ) and stained with X-Gal. We observed a multiplicity of infection (MOI)-dependent and time dependent increase in transduction rate. Approximately 100% transgene expression was achieved at a MOI of 5 after seven days of incubation. To evaluate transgene expression in a rat brain tumor model, AdexCALacZ was stereotactically injected into established rat 9L brain tumors. Intratumoral injection of AdexCALacZ resulted in high transgene expression in tumor cells. Although injection of AdexCALacZ in the normal basal ganglia resulted in broad and diffuse transduction into endogenous neural cells, direct intratumoral injection resulted in transduction that was relatively restricted to the tumor cells as well as some neighboring normal cells. Transduction rates were relatively elevated at the margin of the tumor. Our results suggest that adenovirus vectors might be a feasible method to transfer therapeutic genes into malignant brain tumors.

Original languageEnglish
Pages (from-to)731-738
Number of pages8
JournalBrain and Nerve
Volume50
Issue number8
Publication statusPublished - Aug 1 1998

Keywords

  • Adenovirus
  • Brain tumors
  • Gene therapy
  • β-galactosidase

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Ichikawa, T., Tamiya, T., Adachi, Y., Ono, Y., Matsumoto, K., Furuta, T., Ohmoto, T., Yoshida, Y., & Hamada, H. (1998). Gene transduction for experimental brain tumors using recombinant adenovirus vector. Brain and Nerve, 50(8), 731-738.