Engineering synthetic RNA devices for cell control

The versatility of RNA in sensing and interacting with small molecules, proteins and other nucleic acids while encoding genetic instructions for protein translation makes it a powerful substrate for engineering biological systems. RNA devices integrate cellular information sensing, processing and actuation of specific signals into defined functions and have yielded programmable biological systems and novel therapeutics of increasing sophistication. However, challenges centred on expanding the range of analytes that can be sensed and adding new mechanisms of action have hindered the full realization of the field’s promise. Here, we describe recent advances that address these limitations and point to a significant maturation of synthetic RNA-based devices. Synthetic RNA devices integrate sensing, processing and actuation of signals into defined, programmable functions to control cell behaviour. This Review discusses the emerging applications of RNA devices in biomedical research and biomanufacturing, as well as progress in creating new ligand sensors and new mechanisms of action with engineered RNAs.