Leak-Resistant Design of DNA Strand Displacement Systems

Although a number of dynamically-controlled nanostructures and programmable DNA Strand Displacement (DSD) systems have been designed using DNA strand displacement, predictability and scalability of these DNA-based systems remain limited due to leakages introduced by spuriously triggered displacement events. We present a systematic design method for implementing leak-resistant DNA strand displacement systems in which each legitimate displacement event requires signal species to bind cooperatively at the two designated toehold binding sites in the protected fuel complexes, and thus inhibits spurious displacement events. To demonstrate the potential of the leak-resistant design approach for the construction of arbitrary complex digital circuits and systems with analog behaviors, we present domain-level designs and displacement pathways of the basic building blocks of the DNA strand displacement cascades, e.g. OR, AND gates, and an elementary bimolecular reaction.