MicroRNAs (miRNAs) are short noncoding regulatory RNAs that can repress gene expression post-transcriptionally and are therefore increasingly used as biomarkers of disease. Detecting miRNAs can be arduous and expensive as they require amplification, labelling and radioactive probes. In a recent report published on Science Advances, Arun Richard Chandrasekaran and co-workers at the RNA Institute and Department of Biological Sciences, at the University of Albany, State University of New York, reported on a single-step, non-enzyme microRNA detection assay using conformationally unresponsive DNA nanoswitches.