Synthetic switch-based baculovirus for transgene expression control and selective killing of hepatocellular carcinoma cells
| Autor: | Jih Ru Hwu, Min-Yuan Chou, Mei-Wei Lin, Yu-Chen Hu, Jaw Ching Wu, Chung-Ju Yeh, Yen Wen Tseng, Chin-Wei Chang, Mu-Nung Hsu, Chih-Che Shen |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Cell Survival Transgene Genetic Vectors RNA-binding protein Gene delivery Biology Spodoptera law.invention 03 medical and health sciences 0302 clinical medicine law In vivo Cell Line Tumor microRNA Gene expression Genetics Sf9 Cells Animals Humans Transgenes Gene Liver Neoplasms Reproducibility of Results Hep G2 Cells digestive system diseases Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology HEK293 Cells 030220 oncology & carcinogenesis Cancer research Recombinant DNA Methods Online Synthetic Biology Baculoviridae |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Baculovirus (BV) holds promise as a vector for anticancer gene delivery to combat the most common liver cancer–hepatocellular carcinoma (HCC). However, in vivo BV administration inevitably results in BV entry into non-HCC normal cells, leaky anticancer gene expression and possible toxicity. To improve the safety, we employed synthetic biology to engineer BV for transgene expression regulation. We first uncovered that miR-196a and miR-126 are exclusively expressed in HCC and normal cells, respectively, which allowed us to engineer a sensor based on distinct miRNA expression signature. We next assembled a synthetic switch by coupling the miRNA sensor and RNA binding protein L7Ae for translational repression, and incorporated the entire device into a single BV. The recombinant BV efficiently entered HCC and normal cells and enabled cis-acting transgene expression control, by turning OFF transgene expression in normal cells while switching ON transgene expression in HCC cells. Using pro-apoptotic hBax as the transgene, the switch-based BV selectively killed HCC cells in separate culture and mixed culture of HCC and normal cells. These data demonstrate the potential of synthetic switch-based BV to distinguish HCC and non-HCC normal cells for selective transgene expression control and killing of HCC cells. |
| Databáze: | OpenAIRE |
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