Controlling mammalian gene expression by allosteric hepatitis delta virus ribozymes

Yoko Nomura, Linlin Zhou, Anh Miu, Yohei Yokobayashi

Research output: Contribution to journalArticle

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