scholarly journals A domain-level DNA strand displacement reaction enumerator allowing arbitrary non-pseudoknotted secondary structures

2020 ◽  
Vol 17 (167) ◽  
pp. 20190866 ◽  
Author(s):  
Stefan Badelt ◽  
Casey Grun ◽  
Karthik V. Sarma ◽  
Brian Wolfe ◽  
Seung Woo Shin ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Biophysical Model ◽  
Kinetic Properties ◽  
Strand Displacement ◽  
Natural Connection ◽  
Dna Strand Displacement ◽  
Wide Range ◽  
Dna Strand ◽  
High Level ◽  
Domain Level

Information technologies enable programmers and engineers to design and synthesize systems of startling complexity that nonetheless behave as intended. This mastery of complexity is made possible by a hierarchy of formal abstractions that span from high-level programming languages down to low-level implementation specifications, with rigorous connections between the levels. DNA nanotechnology presents us with a new molecular information technology whose potential has not yet been fully unlocked in this way. Developing an effective hierarchy of abstractions may be critical for increasing the complexity of programmable DNA systems. Here, we build on prior practice to provide a new formalization of ‘domain-level’ representations of DNA strand displacement systems that has a natural connection to nucleic acid biophysics while still being suitable for formal analysis. Enumeration of unimolecular and bimolecular reactions provides a semantics for programmable molecular interactions, with kinetics given by an approximate biophysical model. Reaction condensation provides a tractable simplification of the detailed reactions that respects overall kinetic properties. The applicability and accuracy of the model is evaluated across a wide range of engineered DNA strand displacement systems. Thus, our work can serve as an interface between lower-level DNA models that operate at the nucleotide sequence level, and high-level chemical reaction network models that operate at the level of interactions between abstract species.

scholarly journals Programming colloidal bonding using DNA strand-displacement circuitry

2020 ◽  
Vol 117 (11) ◽  
pp. 5617-5623 ◽  
Author(s):  
Xiang Zhou ◽  
Dongbao Yao ◽  
Wenqiang Hua ◽  
Ningdong Huang ◽  
Xiaowei Chen ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Thermal Annealing ◽  
Constant Temperature ◽  
Room Temperature ◽  
Dna Nanotechnology ◽  
Structural Transformations ◽  
Temperature Sensitive ◽  
Strand Displacement ◽  
Dna Strand Displacement ◽  
Dna Strand

As a strategy for regulating entropy, thermal annealing is a commonly adopted approach for controlling dynamic pathways in colloid assembly. By coupling DNA strand-displacement circuits with DNA-functionalized colloid assembly, we developed an enthalpy-mediated strategy for achieving the same goal while working at a constant temperature. Using this tractable approach allows colloidal bonding to be programmed for synchronization with colloid assembly, thereby realizing the optimal programmability of DNA-functionalized colloids. We applied this strategy to conditionally activate colloid assembly and dynamically switch colloid identities by reconfiguring DNA molecular architectures, thereby achieving orderly structural transformations; leveraging the advantage of room-temperature assembly, we used this method to prepare a lattice of temperature-sensitive proteins and gold nanoparticles. This approach bridges two subfields: dynamic DNA nanotechnology and DNA-functionalized colloid programming.

scholarly journals Cross-Inhibitor: a time-sensitive molecular circuit based on DNA strand displacement

2020 ◽  
Vol 48 (19) ◽  
pp. 10691-10701
Author(s):  
Chanjuan Liu ◽  
Yuan Liu ◽  
Enqiang Zhu ◽  
Qiang Zhang ◽  
Xiaopeng Wei ◽  
...  
Keyword(s):  
Input Signal ◽  
Dna Nanotechnology ◽  
Strand Displacement ◽  
Important Goal ◽  
Molecular Systems ◽  
Molecular Programming ◽  
Dna Strand Displacement ◽  
Input Signals ◽  
Biochemical Systems ◽  
Dna Strand

Abstract Designing biochemical systems that can be effectively used in diverse fields, including diagnostics, molecular computing and nanomachines, has long been recognized as an important goal of molecular programming and DNA nanotechnology. A key issue in the development of such practical devices on the nanoscale lies in the development of biochemical components with information-processing capacity. In this article, we propose a molecular device that utilizes DNA strand displacement networks and allows interactive inhibition between two input signals; thus, it is termed a cross-inhibitor. More specifically, the device supplies each input signal with a processor such that the processing of one input signal will interdict the signal of the other. Biochemical experiments are conducted to analyze the interdiction performance with regard to effectiveness, stability and controllability. To illustrate its feasibility, a biochemical framework grounded in this mechanism is presented to determine the winner of a tic-tac-toe game. Our results highlight the potential for DNA strand displacement cascades to act as signal controllers and event triggers to endow molecular systems with the capability of controlling and detecting events and signals.

scholarly journals Highly specific SNP detection using 2D graphene electronics and DNA strand displacement

2016 ◽  
Vol 113 (26) ◽  
pp. 7088-7093 ◽  
Author(s):  
Michael T. Hwang ◽  
Preston B. Landon ◽  
Joon Lee ◽  
Duyoung Choi ◽  
Alexander H. Mo ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
High Specificity ◽  
Practical Implementation ◽  
Strand Displacement ◽  
Snp Detection ◽  
Single Nucleotide ◽  
Specificity And Sensitivity ◽  
Dna Strand Displacement ◽  
Wide Range ◽  
Dna Strand

Single-nucleotide polymorphisms (SNPs) in a gene sequence are markers for a variety of human diseases. Detection of SNPs with high specificity and sensitivity is essential for effective practical implementation of personalized medicine. Current DNA sequencing, including SNP detection, primarily uses enzyme-based methods or fluorophore-labeled assays that are time-consuming, need laboratory-scale settings, and are expensive. Previously reported electrical charge-based SNP detectors have insufficient specificity and accuracy, limiting their effectiveness. Here, we demonstrate the use of a DNA strand displacement-based probe on a graphene field effect transistor (FET) for high-specificity, single-nucleotide mismatch detection. The single mismatch was detected by measuring strand displacement-induced resistance (and hence current) change and Dirac point shift in a graphene FET. SNP detection in large double-helix DNA strands (e.g., 47 nt) minimize false-positive results. Our electrical sensor-based SNP detection technology, without labeling and without apparent cross-hybridization artifacts, would allow fast, sensitive, and portable SNP detection with single-nucleotide resolution. The technology will have a wide range of applications in digital and implantable biosensors and high-throughput DNA genotyping, with transformative implications for personalized medicine.

scholarly journals Meta-DNA: synthetic biology via DNA nanostructures and hybridization reactions

2012 ◽  
Vol 9 (72) ◽  
pp. 1637-1653 ◽  
Author(s):  
Harish Chandran ◽  
Nikhil Gopalkrishnan ◽  
Bernard Yurke ◽  
John Reif
Keyword(s):  
Formal Model ◽  
Heat Denaturation ◽  
Dna Nanostructures ◽  
Strand Displacement ◽  
Dna Strand Displacement ◽  
Wide Range ◽  
Displacement Reactions ◽  
Repeated Applications ◽  
Polymerase Chain ◽  
Dna Strand

Can a wide range of complex biochemical behaviour arise from repeated applications of a highly reduced class of interactions? In particular, can the range of DNA manipulations achieved by protein enzymes be simulated via simple DNA hybridization chemistry? In this work, we develop a biochemical system which we call meta-DNA (abbreviated as mDNA), based on strands of DNA as the only component molecules. Various enzymatic manipulations of these mDNA molecules are simulated via toehold-mediated DNA strand displacement reactions. We provide a formal model to describe the required properties and operations of our mDNA, and show that our proposed DNA nanostructures and hybridization reactions provide these properties and functionality. Our meta-nucleotides are designed to form flexible linear assemblies (single-stranded mDNA ( ss mDNA)) analogous to single-stranded DNA. We describe various isothermal hybridization reactions that manipulate our mDNA in powerful ways analogous to DNA–DNA reactions and the action of various enzymes on DNA. These operations on mDNA include (i) hybridization of ss mDNA into a double-stranded mDNA ( ds mDNA) and heat denaturation of a ds mDNA into its component ss mDNA, (ii) strand displacement of one ss mDNA by another, (iii) restriction cuts on the backbones of ss mDNA and ds mDNA, (iv) polymerization reactions that extend ss mDNA on a template to form a complete ds mDNA, (v) synthesis of mDNA sequences via mDNA polymerase chain reaction, (vi) isothermal denaturation of a ds mDNA into its component ss mDNA, and (vii) an isothermal replicator reaction that exponentially amplifies ss mDNA strands and may be modified to allow for mutations.

scholarly journals Programming Cell-Free Biosensors with DNA Strand Displacement Circuits

2021 ◽  
Author(s):  
Jaeyoung K. Jung ◽  
Khalid K. Alam ◽  
Julius B. Lucks
Keyword(s):  
Response Times ◽  
Dna Nanotechnology ◽  
Fine Tuning ◽  
Digital Converter ◽  
Strand Displacement ◽  
Design Rules ◽  
Analog To Digital ◽  
Dna Strand Displacement ◽  
Dna Strand ◽  
Molecular Computations

ABSTRACTCell-free biosensors are emerging as powerful platforms for monitoring human and environmental health. Here, we expand the capabilities of biosensors by interfacing their outputs with toehold-mediated strand displacement circuits, a dynamic DNA nanotechnology that enables molecular computation through programmable interactions between nucleic acid strands. We develop design rules for interfacing biosensors with strand displacement circuits, show that these circuits allow fine-tuning of reaction kinetics and faster response times, and demonstrate a circuit that acts like an analog-to-digital converter to create a series of binary outputs that encode the concentration range of the target molecule being detected. We believe this work establishes a pathway to create “smart” diagnostics that use molecular computations to enhance the speed, robustness and utility of biosensors.

scholarly journals Abstractions for DNA circuit design

2011 ◽  
Vol 9 (68) ◽  
pp. 470-486 ◽  
Author(s):  
Matthew R. Lakin ◽  
Simon Youssef ◽  
Luca Cardelli ◽  
Andrew Phillips
Keyword(s):  
Reaction Kinetics ◽  
Computational Cost ◽  
Logic Gates ◽  
Strand Displacement ◽  
Levels Of Detail ◽  
Molecular Detail ◽  
Dna Strand Displacement ◽  
Displacement System ◽  
Dna Strand ◽  
High Level

DNA strand displacement techniques have been used to implement a broad range of information processing devices, from logic gates, to chemical reaction networks, to architectures for universal computation. Strand displacement techniques enable computational devices to be implemented in DNA without the need for additional components, allowing computation to be programmed solely in terms of nucleotide sequences. A major challenge in the design of strand displacement devices has been to enable rapid analysis of high-level designs while also supporting detailed simulations that include known forms of interference. Another challenge has been to design devices capable of sustaining precise reaction kinetics over long periods, without relying on complex experimental equipment to continually replenish depleted species over time. In this paper, we present a programming language for designing DNA strand displacement devices, which supports progressively increasing levels of molecular detail. The language allows device designs to be programmed using a common syntax and then analysed at varying levels of detail, with or without interference, without needing to modify the program. This allows a trade-off to be made between the level of molecular detail and the computational cost of analysis. We use the language to design a buffered architecture for DNA devices, capable of maintaining precise reaction kinetics for a potentially unbounded period. We test the effectiveness of buffered gates to support long-running computation by designing a DNA strand displacement system capable of sustained oscillations.

scholarly journals DNA breathing initiated strand displacement circuits for mimicking ant foraging with nanopore readout

2021 ◽  
Author(s):  
Jinbo Zhu ◽  
Jinglin Kong ◽  
Ulrich Keyser ◽  
Erkang Wang
Keyword(s):  
Single Molecule ◽  
Dna Nanotechnology ◽  
Path Selection ◽  
Strand Displacement ◽  
Initiation Mechanism ◽  
Single Molecule Level ◽  
Sensing Platform ◽  
Dna Strand Displacement ◽  
Dna Strand Exchange ◽  
Dna Strand

Abstract DNA strand displacement reaction is essential for the development of molecular computing based on DNA nanotechnology. Additional DNA strand exchange strategies with high selectivity for input will enable novel complex systems including biosensing applications. Most approaches use bulk readout methods based on fluorescent probes that complicate the monitoring of parallel computations. Herein we propose an autocatalytic strand displacement (ACSD) circuit, which is initiated by DNA breathing and accelerated by seesaw catalytic reaction. The special initiation mechanism of the ACSD circuit enables detection of single base mutations at multiple sites in the input strand with much higher sensitivity than classic toehold-mediated strand displacement. A swarm intelligence model is constructed using the ACSD circuit to mimic foraging behaviour of ants. We introduce a multiplexed nanopore sensing platform to report the output results of a parallel path selection system on the single-molecule level. The ACSD strategy and nanopore multiplexed readout method enhance the toolbox for the future development of DNA computing.

scholarly journals Kinetics of DNA Strand Displacement Systems with Locked Nucleic Acids

2017 ◽  
Vol 121 (12) ◽  
pp. 2594-2602 ◽  
Author(s):  
Xiaoping Olson ◽  
Shohei Kotani ◽  
Bernard Yurke ◽  
Elton Graugnard ◽  
William L. Hughes
Keyword(s):  
Nucleic Acids ◽  
Strand Displacement ◽  
Dna Strand Displacement ◽  
Locked Nucleic Acids ◽  
Dna Strand ◽  
Kinetics Of
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