2 Search Results for "Kennedy, Tiernan"

Document
DOI: 10.4230/LIPIcs.DNA.31.11
Leakless Polymerase-Dependent Strand Displacement Systems

Authors: Zoë Evelyn Mōhalakealoha Derauf and Chris Thachuk

Published in: LIPIcs, Volume 347, 31st International Conference on DNA Computing and Molecular Programming (DNA 31) (2025)

Abstract
A grand challenge facing molecular programmers is the rational development of fast, robust, and isothermal architectures akin to "chemical central processing units" that can sense (bio-)chemical signals from their environment, perform complex computation, and orchestrate a physical response in situ. DNA strand displacement systems (DSDs) remain a compelling candidate, but are hampered by spurious reaction pathways that lead to incorrect output. DSDs that utilize the systematic leakless motif can be made arbitrarily robust at the cost of increasing redundancy and network size (scaling), and thus a degradation of kinetic performance. Another class of architectures utilize DNA hybridization, extension, and signal production of entirely sequestered outputs via strand-displacing polymerases (SDPs) that have resulted in impressive demonstrations; however, they face similar challenges of aberrant behavior such as mis-priming by incorrect signals. Our work introduces a unified polymerase-dependent toehold-mediated strand displacement (PD-TMSD) architecture that integrates the programmed specificity of DSDs with the unique advantages of SDPs. This unification enables systems that can be made arbitrarily robust, at any concentration range, without increasing network size. We propose a number of gate designs and composition rules to compute arbitrary Boolean functions, emulate arbitrary chemical reaction networks, and explore time-bounded probabilistic computation made possible by certain classes of SDPs. Our theoretical exploration is backed by preliminary experimental demonstrations. This contribution was inspired by the belief that molecular programming can meet or exceed the complexity exhibited in biology if we embrace its best understood molecular machinery and couple it with systematic design principles built upon a strong theoretical foundation.
Cite as

Zoë Evelyn Mōhalakealoha Derauf and Chris Thachuk. Leakless Polymerase-Dependent Strand Displacement Systems. In 31st International Conference on DNA Computing and Molecular Programming (DNA 31). Leibniz International Proceedings in Informatics (LIPIcs), Volume 347, pp. 11:1-11:19, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2025)

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@InProceedings{derauf_et_al:LIPIcs.DNA.31.11,
  author =	{Derauf, Zo\"{e} Evelyn M\={o}halakealoha and Thachuk, Chris},
  title =	{{Leakless Polymerase-Dependent Strand Displacement Systems}},
  booktitle =	{31st International Conference on DNA Computing and Molecular Programming (DNA 31)},
  pages =	{11:1--11:19},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-399-7},
  ISSN =	{1868-8969},
  year =	{2025},
  volume =	{347},
  editor =	{Schaeffer, Josie and Zhang, Fei},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.31.11},
  URN =		{urn:nbn:de:0030-drops-238608},
  doi =		{10.4230/LIPIcs.DNA.31.11},
  annote =	{Keywords: DNA strand displacement, strand-displacing polymerases, molecular computation, energy barriers, kinetics}
}
Document
DOI: 10.4230/LIPIcs.DNA.28.1
Fast and Robust Strand Displacement Cascades via Systematic Design Strategies

Authors: Tiernan Kennedy, Cadence Pearce, and Chris Thachuk

Published in: LIPIcs, Volume 238, 28th International Conference on DNA Computing and Molecular Programming (DNA 28) (2022)

Abstract
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.
Cite as

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)

Copy BibTex To Clipboard

@InProceedings{kennedy_et_al:LIPIcs.DNA.28.1,
  author =	{Kennedy, Tiernan and Pearce, Cadence and Thachuk, Chris},
  title =	{{Fast and Robust Strand Displacement Cascades via Systematic Design Strategies}},
  booktitle =	{28th International Conference on DNA Computing and Molecular Programming (DNA 28)},
  pages =	{1:1--1:17},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-253-2},
  ISSN =	{1868-8969},
  year =	{2022},
  volume =	{238},
  editor =	{Ouldridge, Thomas E. and Wickham, Shelley F. J.},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.DNA.28.1},
  URN =		{urn:nbn:de:0030-drops-167869},
  doi =		{10.4230/LIPIcs.DNA.28.1},
  annote =	{Keywords: DNA strand displacement, Energy barriers, Kinetics}
}
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