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End modification of the toehold domain or near to it using fluorophore dyes or quenchers can significantly modulate the kinetics of the toehold-mediated strand displacement reaction (TMSDR) by almost two orders of magnitude. The labels at the end of the signal strand impede the TMSDR, while those at the end of the toehold domain of the substrate strand accelerate the TMSDR kinetics.
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http://dx.doi.org/10.1039/d2cc01072k | DOI Listing |
Nano Lett
September 2025
School of Mathematics and Physics, Faculty of Engineering and Physical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom.
Dynamic DNA nanotechnology creates programmable reaction networks and nanodevices by using DNA strands. The key reaction in dynamic DNA nanotechnology is the exchange of DNA strands between different molecular species, achieved through three- and four-way strand exchange reactions. While both reactions have been widely used, the four-way exchange reaction has traditionally been slower and less efficient than the three-way reaction.
View Article and Find Full Text PDFAnal Chem
September 2025
Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan 430074, P. R. China.
Finely tunable detection of microRNAs (miRNAs) is crucial for personalized medicine and cancer diagnosis, and it is a challenge to construct a tunable sensor for miRNA detection due to the diversity and complexity of cancer patient samples. This study introduces a three-dimensional (3D) DNA walker mediated by a remote toehold strand displacement reaction, which addresses the challenge of achieving tunable detection limits and sensitivities for microRNA-21 (miR-21) at a kinetic level, enabling specific recognition of cancer cells. By engineering a spacer domain within the DNA walker, the kinetics of the strand displacement reaction can be precisely modulated, thereby controlling the walking efficiency and achieving tunable detection with a detection limit range from 32 aM to 290 pM and a broad dynamic range from ∼1100-fold to ∼283,000-fold.
View Article and Find Full Text PDFAnal Chem
July 2025
Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016, P.R. China.
The inherent programmability of DNA, dictated by Watson-Crick base-pairing and sequence diversity, renders it a versatile biomolecule for nanoscale engineering. Toehold-mediated strand displacement (TMSD) enhances DNA strand exchange by over 4 orders of magnitude, underpinning applications in molecular circuits, biosensing, and nanodevices. However, its efficiency is constrained by the instability of the toehold duplexes and the reversibility of the initial binding step.
View Article and Find Full Text PDFChemistry
April 2025
State Key Laboratory of Advanced Optical Communication Systems and Networks, Key Laboratory for Laser Plasmas (Ministry of Education), School of Physics and Astronomy, Shanghai Jiao Tong University, Shanghai, 200240, China.
Toehold-mediated strand displacement (TMSD) reaction is a widely used programming language in DNA nanotechnology, but its performance is significantly limited by slow kinetics, especially for low-concentration reactants. Herein, we report on polyquaternium-2 (PQ2) as an effective and efficient accelerator of TMSD reaction. We show that PQ2 could drastically increase the reaction constant of 1-nt TMSD by 10-fold.
View Article and Find Full Text PDFMicromachines (Basel)
November 2024
Department of Intelligent and Control Systems, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka 820-8502, Fukuoka, Japan.
DNA chemical reaction networks can perform complex information processing through careful design of reaction kinetics, which involves the reaction network structure, rate constants, and initial concentrations. The toehold-mediated strand displacement reaction (TMSDR) is a key mechanism in creating DNA circuits, offering a rational design approach by integrating individually designed TMSDRs. Tools such as VisualDSD and NUPACK facilitate the efficient design of these systems by allowing precise tuning of reaction parameters.
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