Novel RNA Device – Designing Functional Nucleic Acids (No. Riboswitch)

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Living systems use short RNA sequences (RNA aptamers) known as riboswitches to detect the concentrations of small-molecule metabolites within cells and regulate the expression of genes that produce these metabolites. Like their naturally occurring counterparts, synthetic riboswitches can regulate the expression of any chosen gene in response to the presence of an endogenous/exogenous small molecule trigger. As such, they are powerful tools to control cell behavior for gene therapy and biotechnology applications. However, the development of new riboswitches is incredibly challenging, as most aptamers with high affinity to the trigger ligand in vitro are not functional within cells. An OIST research team led by Prof. Yohei Yokobayashi have developed an effective, iterative protocol to engineer highly efficient riboswitches that control gene expression in response to low concentrations of any given small molecule, with high signal-to-noise ratios.


Lead Researcher:
Yohei Yokobayashi

Faculty of Nucleic Acid Chemistry and Engineering Unit


  • Gene therapy
  • Cell therapy



  • Compact riboswitch
  • Chemical regulation of gene expression in bacteria and mammalian cells


Synthetic riboswitches control gene expression in response to low concentrations of a small molecule trigger.

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The technology is based on an iterative process: RNA aptamers with a high affinity to the desired small molecule ligand are selected through in-vitro screening, then tested to identify those with sufficient functionality within cells. Candidates are further fine-tuned through engineering, and the resulting aptamer variants are screened iteratively to maximise efficacy. Further optimization strategies include developing riboswitches with alternative mechanisms (e.g. splicing regulation) and explore combinations with aptazyme-based riboswitches to improve the ON/OFF ratio.


Media Coverage and Presentations



  Ryohei Yoshida
Technology Licensing Section