title: Conditional control of suicide gene expression in tumor cells with theophylline-responsive ribozyme.
abstract: 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.
authors.affiliation: Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.|University of Science and Technology of China, Hefei, China.|Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China.
authors.forename: R
authors.initials: R
authors.lastname: Pei
mesh_terms: D000072283:A549 Cells; D001993:Bronchodilator Agents / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D005818:Genetic Engineering; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016337:RNA, Catalytic / Q000235:genetics*; D013806:Theophylline / Q000494:pharmacology*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D001993:Bronchodilator Agents; D016337:RNA, Catalytic; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D013806:Theophylline; D013937:Thymidine Kinase