期刊
ACS SYNTHETIC BIOLOGY
卷 2, 期 12, 页码 684-689出版社
AMER CHEMICAL SOC
DOI: 10.1021/sb400037a
关键词
ribozyme; HDV ribozyme; riboswitch; aptazyme; logic gate
资金
- National Institutes of Health [GM099748]
We engineered small molecule responsive allosteric ribozymes based on the genomic hepatitis delta virus (HDV) ribozyme by replacing the P4-IA stem-loop with an RNA aptamer through a connector stem. When embedded in the 3' untranslated region of a reporter gene mRNA, these RNA devices enabled regulation of cis-gene expression by theophylline and guanine by up to 29.5-fold in mammalian cell culture. Furthermore, a NOR logic gate device was constructed by placing two engineered ribozymes in tandem, demonstrating the modularity of the RNA devices. The significant improvement in the regulatory dynamic range (ON/OFF ratio) of the RNA devices based on the HDV ribozyme should provide new opportunities for practical applications.
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