Tetracycline-inducible promoter-based conditionally replicative adenoviruses for the control of viral replication.
Cancer Gene Ther
; 16(5): 415-22, 2009 May.
Article
in En
| MEDLINE
| ID: mdl-19148207
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Replication
/
Protein Synthesis Inhibitors
/
Genetic Therapy
/
Gene Expression Regulation, Viral
/
Adenoviridae
/
Promoter Regions, Genetic
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Cancer Gene Ther
Journal subject:
GENETICA MEDICA
/
NEOPLASIAS
/
TERAPEUTICA
Year:
2009
Document type:
Article
Affiliation country:
Japan