Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response.
BacMam is an insect-derived recombinant baculovirus that can deliver genes into mammalian cells. BacMam vectors carrying target genes are able to enter a variety of cell lines by endocytosis, but the level of expression of the transgene depends on the cell line and the state of the transduced cells. In this study, we demonstrated that the DNA damage response (DDR) could act as an alternative pathway to boost the transgene(s) expression by BacMam and be comparable to the inhibitors of histone deacetylase. Topoisomerase II (Top II) inhibitor-induced DDR can enhance the CMV-IE/enhancer mediated gene expression up to 12-fold in BacMam-transduced U-2OS cells. The combination of a Top II inhibitor, VM-26, can also augment the killing efficiency of a p53-expressing BacMam vector in U-2OS osteosarcoma cells. These results open a new avenue to facilitate the application of BacMam for gene delivery and therapy.
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan. lmk33@hotmail.com.
Ming-Kun
MK
Liu
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan. blackeye514@hotmail.com.
Jhe-Jhih
JJ
Lin
Department of Bioscience Technology, Chung Yuan Christian University, Chungli 320, Taiwan. cychen@cycu.edu.tw.
Chung-Yung
CY
Chen
Institute of Preventive Medicine, National Defense Medical Center, Taipei 237, Taiwan. szucheng@mail.ndmctsgh.edu.tw.
Szu-Cheng
SC
Kuo
Institute of Preventive Medicine, National Defense Medical Center, Taipei 237, Taiwan. yuming0724@gmail.com.
Yu-Ming
YM
Wang
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan. hlchan@life.nthu.edu.tw.
Hong-Lin
HL
Chan
Department of Bioscience Technology, Chung Yuan Christian University, Chungli 320, Taiwan. tywu@cycu.edu.tw.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan. tywu@cycu.edu.tw.
Tzong Yuan
TY
Wu
D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D061987:Sf9 Cells; D018411:Spodoptera; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology*; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D059005:Topoisomerase II Inhibitors; D016159:Tumor Suppressor Protein p53
BacMam; DNA damage response; baculovirus; p53; topoisomerase