Robust heterochiral strand displacement using leakless translators

Molecular computing offers a powerful framework for in situ biosensing and signal processing at the nanoscale. However, for in vivo applications, the use of conventional DNA components can lead to false positive signals being generated due to degradation of circuit components by nuclease enzymes. Here, we use hybrid chiral molecules, consisting of both L- and D-nucleic acid domains, to implement leakless signal translators that enable D-nucleic acid signals to be detected by hybridization and then translated into a robust L-DNA signal for further analysis. We show that our system is robust to false positive signals even if the D-DNA components are degraded by nucleases, thanks to circuit-level robustness. This work thus broadens the scope and applicability of DNA-based molecular computers for practical, in vivo applications.

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ACS Synthetic Biology 9(7), 1907–1910