Conditional control of suicide gene expression in tumor cells with theophylline-responsive ribozyme

• Published in: Gene therapy Vol. 24; no. 2; pp. 84 - 91
• Main Authors: Zhang, Y, Wang, J, Cheng, H, Sun, Y, Liu, M, Wu, Z, Pei, R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2017; Nature Publishing Group
• Subjects: 14/63; 38/77; 38/89; 631/1647/1513/1967; 631/208/68; 631/61/201; 631/61/51/1844; 631/67; A549 Cells; Biomedical and Life Sciences; Biomedicine; Bronchodilator Agents - pharmacology; Cancer cells; Catalytic RNA; Cell Biology; Cytotoxicity; Gene Expression; Gene Expression Regulation, Enzymologic - drug effects; Gene regulation; Gene Therapy; Genes, Transgenic, Suicide - genetics; Genetic aspects; Genetic control; Genetic Engineering; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Health aspects; HeLa Cells; Human Genetics; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Mammalian cells; Nanotechnology; original-article; Ribonucleic acid; Ribozymes; RNA; RNA, Catalytic - genetics; Suicide; Suicide genes; Theophylline; Theophylline - pharmacology; Thymidine Kinase - genetics; Thymidine Kinase - metabolism; Tumor cells; Tumors
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2016.78

Numerous synthetic RNA-based controls for integrating sensing switches with function devices have been demonstrated in a variety of organisms for gene regulation. Although potential advantages of RNA-based genetic control strategies have been shown in clinical applications, successfully extending these engineered systems into medical applications has seldom been reported. Here, a synthetic RNA-based ribozyme system and its application in advancing rationally designed cellular therapy were described. The theophylline-responsive, ribozyme-based device provided a powerful platform for suicide gene expression regulation in tumor cells. Moreover, we demonstrate the ability of our synthetic controller to modulate effectively the viability of the cells in response to drug input. Our RNA-based regulatory system could dose-dependently fine-tune transgene expression in mammalian cells and address urgent limitations in existing genetic control strategies for gene- and cell-based therapies in the future.