It is important to develop a method that controls gene expression and cell fate depending on the intracellular state. For example, if we could develop sophisticated “cell-classifier circuits”, we may be able to induce apoptosis in target cancer cells but not in non-target cells. Here we show “synthetic RNA switches” that control translation depending on intracellular protein or RNA expression. We use two components to construct a RNA switch: the RNA aptamer module that binds to the trigger factor (i.e., protein or RNA), and the designed mRNA as a gene expression controller: The aptamer module was successfully incorporated into the synthetic mRNA to generate functional RNA-ON/OFF switches. The designed switches detect the expression of the trigger factor and repress or activate the expression of a desired protein (e.g.; apoptosis regulator) in the target cells such as differentiated cells derived from human pluripotent stem cells (hiPSCs).

Additionally, we have developed synthetic RNA-protein nanostructures with modular functions. Interestingly, single-RNA-Protein (RNP) interaction was directly visualized in real-time by using high-speed atomic force microscopy. The RNP structural images collected in solution showed that a single RNP interaction induces a conformational change in the RNA scaffold, which supports the nanostructure formation designed. We also developed and visualized functional RNP nanostructures (e.g., to detect human cancer cells) by attaching a protein or RNA module to the same RNA scaffold at an optimal size. The synthetic RNA switches and nanostructures can be used to detect and control functions of target mammalian cells.