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

Liu, Ming-Kun; Lin, Jhe-Jhih; Chen, Chung-Yung; Kuo, Szu-Cheng; Wang, Yu-Ming; Chan, Hong-Lin; Wu, Tzong Yuan

doi:10.3390/ijms17060931

Open AccessArticle

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

by

Ming-Kun Liu

¹,

Jhe-Jhih Lin

¹,

Chung-Yung Chen

²,

Szu-Cheng Kuo

³,

Yu-Ming Wang

³,

Hong-Lin Chan

¹ and

Tzong Yuan Wu

^2,4,*

¹

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan

²

Department of Bioscience Technology, Chung Yuan Christian University, Chungli 320, Taiwan

³

Institute of Preventive Medicine, National Defense Medical Center, Taipei 237, Taiwan

⁴

Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2016, 17(6), 931; https://doi.org/10.3390/ijms17060931

Submission 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)

Download

Browse Figures

Versions Notes

Abstract

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.

Keywords: baculovirus; BacMam; DNA damage response; topoisomerase; p53

Graphical Abstract

Share and Cite

MDPI and ACS Style

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. https://doi.org/10.3390/ijms17060931

AMA Style

Liu M-K, Lin J-J, Chen C-Y, Kuo S-C, Wang Y-M, Chan H-L, Wu TY. Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response. International Journal of Molecular Sciences. 2016; 17(6):931. https://doi.org/10.3390/ijms17060931

Chicago/Turabian Style

Liu, Ming-Kun, Jhe-Jhih Lin, Chung-Yung Chen, Szu-Cheng Kuo, Yu-Ming Wang, Hong-Lin Chan, and Tzong Yuan Wu. 2016. "Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response" International Journal of Molecular Sciences 17, no. 6: 931. https://doi.org/10.3390/ijms17060931

APA Style

Liu, M.-K., Lin, J.-J., Chen, C.-Y., Kuo, S.-C., Wang, Y.-M., Chan, H.-L., & Wu, T. Y. (2016). Topoisomerase II Inhibitors Can Enhance Baculovirus-Mediated Gene Expression in Mammalian Cells through the DNA Damage Response. International Journal of Molecular Sciences, 17(6), 931. https://doi.org/10.3390/ijms17060931

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

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

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI