Liu Ming-Kun, Lin Jhe-Jhih, Chen Chung-Yung, Kuo Szu-Cheng, Wang Yu-Ming, Chan Hong-Lin, Wu Tzong Yuan
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan.
Department of Bioscience Technology, Chung Yuan Christian University, Chungli 320, Taiwan.
Int J Mol Sci. 2016 Jun 14;17(6):931. doi: 10.3390/ijms17060931.
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.
杆状病毒表达载体系统（BacMam）是一种源自昆虫的重组杆状病毒，能够将基因导入哺乳动物细胞。携带靶基因的BacMam载体能够通过内吞作用进入多种细胞系，但转基因的表达水平取决于细胞系和转导细胞的状态。在本研究中，我们证明DNA损伤反应（DDR）可作为一种替代途径来提高BacMam介导的转基因表达，并且与组蛋白脱乙酰酶抑制剂相当。拓扑异构酶II（Top II）抑制剂诱导的DDR可使BacMam转导的U-2OS细胞中巨细胞病毒立即早期启动子/增强子（CMV-IE/enhancer）介导的基因表达提高至12倍。Top II抑制剂VM-26的联合使用还可增强表达p53的BacMam载体在U-2OS骨肉瘤细胞中的杀伤效率。这些结果为促进BacMam在基因递送和治疗中的应用开辟了一条新途径。
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