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Updated: Jul 14, 2026
In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
Published on: March 29, 2019
Cre/loxP system controlled by specific promoter for radiation-mediated gene therapy of hepatoma
Ya-Ju Hsieh1, Ren-Shyan Liu, Luen Hwu
1School of Medical Technology and Engineering, Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei City, Taiwan, ROC.
Background:
To specifically target malignant cells, cancer gene therapy needs to combine highly selective gene delivery with highly specific gene expression. In this study, hepatitis B virus (HBV) enhancer II was combined with alpha-fetoprotein (AFP) promoter which selectively controls the Cre/loxP system in hepatoma.
Materials And Methods:
pE4luc, pE4Tk, EIIAPA-Cre and E4CMV-STOP-Tk constructs and AFP promoter combined with HBV enhancer were constructed and transfected into HepG2, HeLa and NIH-3T3 cell lines.
Results:
The E4 enhancer showed the highest luciferase gene expression at a dose range of 5 approximately 7 Gy after 60 hours irradiation. The EIIAPA chimeric promoter which controls the Cre/loxP system provided high specificity only to the hepatoma cells. In addition, the E4 response to radiation encoded more Herpes simplex virus thymidine kinase (HSV1-Tk) protein and killed more tumor cells.
Conclusion:
The chimeric EIIAPA promoter can precisely control the Cre/loxP switch and the radiation effect on the EIIAPA-Cre and E4CMV-STOP-Tk system shows promising results in terms of cell survival of hepatocellular carcinoma (HCC).
