Biocomputing Based on DNA Strand Displacement Reactions

Abstract

The 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.

Controlling Dynamic DNA Reactions at the Surface of Single-Walled Carbon Nanotube Electrodes to Design Hybridization Platforms with a Specific Amperometric Readout

“…Toehold-mediated strand displacement is likely the most simple and versatile programmable process to carry out molecular operations enabling applications in sensing, information processing, and synthetic biology. 40 − 43 …”

DNA Input Classification by a Riboregulator-Based Cell-Free Perceptron

“…The versatile and highly programmable nature of DNA and RNA has proven to be exceptionally useful when performing biomolecular computations. ,− This widespread usage stems from the ability to rationally design novel DNA and RNA strands, which hybridize predictably with complementary constructs. A majority of the previously published classification networks utilize single-stranded DNA templates and rely upon binding competition and DNA strand displacement reactions. ,, However, designs based solely on DNA strand displacement reactions, where DNA strands are prepared synthetically and subsequently combined, lack the information storage capabilities and the broader ability to integrate the circuits into larger, more complex biological systems due to a lack of transcriptional and translational control.…”

DNA Strand Displacement Driven by Host–Guest Interactions

“…The design of dynamic molecular- and nanomachines and their higher-order interaction networks is a cross-disciplinary research area that has seen tremendous recent growth. − In terms of achieving practical applications, such machines need to be coupled to the outside world, and in particular, need to function effectively in aqueous/biological media. In this regard, dynamic DNA chemistry/nanotechnology has led the way generating controlled dynamic systems with potential therapeutic, diagnostic, and computational applications. − In particular, the invention of base-pair-driven toehold-mediated strand displacement (BP-TMSD) , has served as a founding principle to generate functional DNA-based machines − including tweezers, , autonomous walkers, , molecular diagnostic agents, ,− and higher-order networksthat show neural mimicry, , control intra/intercell interactions, − and perform computational tasks. − In BP-TMSD, an invading fuel sequence uses Watson–Crick–Franklin-based toehold/toe interactions to achieve isothermal displacement of an output sequence from a stable duplex substrate (Figure A). This system couples an input to the release of a specific output and can be integrated into functional machines and layered reactions.…”

“…In this regard, dynamic DNA chemistry/nanotechnology has led the way generating controlled dynamic systems with potential therapeutic, diagnostic, and computational applications. 5−10 In particular, the invention of base-pair-driven toehold-mediated strand displacement (BP-TMSD) 11,12 has served as a founding principle to generate functional DNA-based machines 13−17 � including tweezers, 18,19 autonomous walkers, 20,21 molecular diagnostic agents, 17,22−25 and higher-order networks�that show neural mimicry, 26,27 control intra/intercell interactions, 28−30 and perform computational tasks. 31−35 In BP-TMSD, an invading fuel sequence uses Watson−Crick− Franklin-based toehold/toe interactions to achieve isothermal displacement of an output sequence from a stable duplex substrate (Figure 1A).…”