Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes

Yoko Nomura; Linlin Zhou; Anh Miu; Yohei Yokobayashi

doi:10.1021/sb400037a

Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes

Yoko Nomura, Linlin Zhou, Anh Miu, Yohei Yokobayashi

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

58 Scopus citations

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	https://doi.org/10.1021/sb400037a
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)

Access to Document

10.1021/sb400037a

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