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Int. J. Mol. Sci. 2016, 17(6), 931;

Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan
Department of Bioscience Technology, Chung Yuan Christian University, Chungli 320, Taiwan
Institute of Preventive Medicine, National Defense Medical Center, Taipei 237, Taiwan
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan
Author to whom correspondence should be addressed.
Academic Editor: Guillermo T. Sáez
Received: 14 March 2016 / Revised: 21 May 2016 / Accepted: 7 June 2016 / Published: 14 June 2016
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases)
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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. View Full-Text
Keywords: baculovirus; BacMam; DNA damage response; topoisomerase; p53 baculovirus; BacMam; DNA damage response; topoisomerase; p53

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Liu, M.-K.; Lin, J.-J.; Chen, C.-Y.; Kuo, S.-C.; Wang, Y.-M.; Chan, H.-L.; Wu, T.Y. Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response. Int. J. Mol. Sci. 2016, 17, 931.

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