CRISPR-mediated strand displacement logic circuits with toehold-free DNA

DNA nanotechnology, and DNA computing in particular, has grown extensively over the past decade to end with a variety of functional stable structures and dynamic circuits. However, the use as designer elements of regular DNA pieces, perfectly complementary double strands, has remained elusive. Here, we report the exploitation of CRISPR-Cas systems to engineer logic circuits based on isothermal strand displacement that perform with toehold-free double-stranded DNA. We designed and implemented molecular converters for signal detection and amplification, showing good interoperability between enzymatic and nonenzymatic processes. Overall, these results contribute to enlarge the repertoire of substrates and reactions (hardware) for DNA computing.The work was supported by the Spanish Ministry of Economy and Competitiveness grants BFU2015-66894-P (to GR) and BIO2017-83184-R (to JAD) and by the Spanish Ministry of Science, Innovation, and Universities grant PGC2018-101410-B-I00 (to GR); grants cofinanced by the European Regional Development Fund.Peer reviewe