Fast and Robust Strand Displacement Cascades via Systematic Design Strategies

Authors Tiernan Kennedy, Cadence Pearce, Chris Thachuk

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Tiernan Kennedy
  • Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA, USA
Cadence Pearce
  • Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA, USA
Chris Thachuk
  • Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA, USA

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Tiernan Kennedy, Cadence Pearce, and Chris Thachuk. Fast and Robust Strand Displacement Cascades via Systematic Design Strategies. In 28th International Conference on DNA Computing and Molecular Programming (DNA 28). Leibniz International Proceedings in Informatics (LIPIcs), Volume 238, pp. 1:1-1:17, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2022)


A barrier to wider adoption of molecular computation is the difficulty of implementing arbitrary chemical reaction networks (CRNs) that are robust and replicate the kinetics of designed behavior. DNA Strand Displacement (DSD) cascades have been a favored technology for this purpose due to their potential to emulate arbitrary CRNs and known principles to tune their reaction rates. Progress on leakless cascades has demonstrated that DSDs can be arbitrarily robust to spurious "leak" reactions when incorporating systematic domain level redundancy. These improvements in robustness result in slower kinetics of designed reactions. Existing work has demonstrated the kinetic and thermodynamic effects of sequence mismatch introduction and elimination during displacement. We present a systematic, sequence modification strategy for optimizing the kinetics of leakless cascades without practical cost to their robustness. An in-depth case study explores the effects of this optimization when applied to a typical leakless translator cascade. Thermodynamic analysis of energy barriers and kinetic experimental data support that DSD cascades can be fast and robust.

Subject Classification

ACM Subject Classification
  • Applied computing → Chemistry
  • Computer systems organization → Molecular computing
  • DNA strand displacement
  • Energy barriers
  • Kinetics


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