Abstract
We engineered small molecule responsive allosteric ribozymes based on the genomic hepatitis delta virus (HDV) ribozyme by replacing the P4-L4 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 684-689 |
| Number of pages | 6 |
| Journal | ACS Synthetic Biology |
| Volume | 2 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 20 2013 |
Keywords
- aptazyme
- HDV ribozyme
- logic gate
- riboswitch
- ribozyme
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Biomedical Engineering
- Medicine(all)
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Cite this
Nomura, Y., Zhou, L., Miu, A., & Yokobayashi, Y. (2013). Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes. ACS Synthetic Biology, 2(12), 684-689. https://doi.org/10.1021/sb400037a