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© 2021 Wiley–VCH GmbHThe high sequence specificity and precise base complementary pairing principle of DNA provides a rich orthogonal molecular library for molecular programming, making it one of the most promising materials for developing bio–compatible intelligence. In recent years, DNA has been extensively studied and applied in the field of biological computing. Among them, the toehold–mediated strand displacement reaction (SDR) with properties including enzyme free, flexible design and precise control, have been extensively used to construct biological computing circuits. This review provides a systemic overview of SDR design principles and the applications. Strategies for designing DNA–only, enzymes–assisted, other molecules–involved and external stimuli–controlled SDRs are described. The recently realized computing functions and the application of DNA computing in other fields are introduced. Finally, the advantages and challenges of SDR–based computing are discussed.
