Document Detail

Tetracycline-inducible promoter-based conditionally replicative adenoviruses for the control of viral replication.
MedLine Citation:
PMID:  19148207     Owner:  NLM     Status:  MEDLINE    
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.
H Zhang; K Takayama; L Zhang; J Uchino; A Harada; T Harada; J Hisasue; N Nakagaki; C Zhou; Y Nakanishi
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Publication Detail:
Type:  Journal Article     Date:  2009-01-16
Journal Detail:
Title:  Cancer gene therapy     Volume:  16     ISSN:  1476-5500     ISO Abbreviation:  Cancer Gene Ther.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-16     Completed Date:  2009-09-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9432230     Medline TA:  Cancer Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  415-22     Citation Subset:  IM    
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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MeSH Terms
Adenoviridae / drug effects*,  genetics,  growth & development,  metabolism
Cell Line
Cell Line, Tumor
Gene Expression Regulation, Viral / drug effects*
Gene Therapy / methods*
Genetic Vectors / genetics
Hela Cells
Neoplasms / therapy*
Promoter Regions, Genetic*
Protein Synthesis Inhibitors / pharmacology*
Tetracycline / pharmacology
Virus Replication / drug effects,  genetics,  physiology*
Reg. No./Substance:
0/Protein Synthesis Inhibitors; 60-54-8/Tetracycline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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