Tetracycline-inducible promoter-based conditionally replicative adenoviruses for the control of viral replication

H. Zhang, K. Takayama, L. Zhang, J. Uchino, A. Harada, T. Harada, J. Hisasue, N. Nakagaki, C. Zhou, Y. Nakanishi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The use of conditionally replicative adenoviruses (CRAds) as a promising strategy for cancer gene therapy has been developed to overcome inefficient transduction of solid tumor masses by replication-deficient adenoviruses. Many modifications have been made to CRAds to enlarge tropism, increase selectivity and lytic ability, and improve safety. However, safety is still a concern in the context of future clinical application of CRAds. Particularly, after injection into the body, viral replication cannot be controlled externally. Therefore, we constructed a novel CRAd using a tetracycline-inducible promoter system to realize external pharmacological control of its replication. The effect of this CRAd in vitro was measured at the levels of viral DNA replication, cell death and progeny production. We showed that CRAd replication was tightly controlled by the presence or absence of doxycycline (Dox). Moreover, this system showed a significant gene expression in vivo, in which the viral replication was controlled by the oral administration of Dox. This strategy may help improve the safety of cancer gene therapy.

Original languageEnglish
Pages (from-to)415-422
Number of pages8
JournalCancer Gene Therapy
Volume16
Issue number5
DOIs
Publication statusPublished - May 2009

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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