Enhancement of Transduction Efficiency and Antitumor Effects of IL-12N220L-expressing Adenovirus by Co-delivery of DOTAP
Immune Network
; : 179-185, 2007.
Article
Dans En
| WPRIM
| ID: wpr-198233
Responsable en Bibliothèque :
WPRO
ABSTRACT
BACKGROUND:
Adenovirus (Ad) vectors have been widely used for many gene therapy applications because of their high transduction ability and broad tropism. However, their utility for cancer gene therapy is limited by their poor transduction into cancer cells lacking the primary receptor, coxsackievirus and adenovirus receptor (CAR).METHODS:
To achieve CAR-independent gene transfer via Ad, we pretreated Ad with 1,2-dioleoyl-3- trimethylammonium propane (DOTAP) and analyzed their transduction efficiency into cancer cells in vitro and in vivo comparing with the virus alone.RESULTS:
Treatment of DOTAP significantly increased adenoviral gene transfer in tumor cells in vitro. Moreover, DOTAP at an optimum dose (10 microngram/ml) enhanced IL-12 transgene expression by fivefold in tumor, and twofold in serum after intratumoral injection of adenovirus expressing IL-12N220L (Ad/IL-12N220L). In addition, cotreatment of DOTAP decreased tumor growth rate in the Ad/IL-12N220L-transduced tumor model, finally leading to enhanced survival rate.CONCLUSION:
Our results strongly suggest that DOTAP could be of great utility for improving adenovirus-mediated cancer gene therapy.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Propane
/
Thérapie génétique
/
Adenoviridae
/
Taux de survie
/
Tropisme
/
Interleukine-12
/
Transgènes
/
Gènes tumoraux
/
Liposomes
Type d'étude:
Prognostic_studies
langue:
En
Texte intégral:
Immune Network
Année:
2007
Type:
Article