Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes

Yoko Nomura, Linlin Zhou, Anh Miu, Yohei Yokobayashi

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)684-689
Number of pages6
JournalACS Synthetic Biology
Volume2
Issue number12
DOIs
StatePublished - Dec 20 2013

Fingerprint

Hepatitis Delta Virus
Catalytic RNA
RNA
Viruses
Gene expression
Gene Expression
Equipment and Supplies
Nucleotide Aptamers
Logic gates
Guanine
Gene Expression Regulation
3' Untranslated Regions
Theophylline
Reporter Genes
Cell culture
Cell Culture Techniques
Genes
Messenger RNA
Molecules

Keywords

  • aptazyme
  • HDV ribozyme
  • logic gate
  • riboswitch
  • ribozyme

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Biomedical Engineering
  • Medicine(all)

Cite this

Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes. / Nomura, Yoko; Zhou, Linlin; Miu, Anh; Yokobayashi, Yohei.

In: ACS Synthetic Biology, Vol. 2, No. 12, 20.12.2013, p. 684-689.

Research output: Contribution to journalArticle

Nomura, Yoko ; Zhou, Linlin ; Miu, Anh ; Yokobayashi, Yohei. / Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes. In: ACS Synthetic Biology. 2013 ; Vol. 2, No. 12. pp. 684-689.
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