Please use this identifier to cite or link to this item: https://doi.org/10.1093/nar/gkw447
Title: Engineering a robust DNA split proximity circuit with minimized circuit leakage
Authors: Ang, Yan Shan 
Tong, Rachel
Yung, Lin-Yue Lanry 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
HYBRIDIZATION CHAIN-REACTION
STRAND-DISPLACEMENT
PROTEIN INTERACTIONS
SIGNAL AMPLIFICATION
CELL-SURFACES
IN-SITU
ASSEMBLIES
CASCADES
DESIGN
ASSAYS
Issue Date: 19-Aug-2016
Publisher: OXFORD UNIV PRESS
Citation: Ang, Yan Shan, Tong, Rachel, Yung, Lin-Yue Lanry (2016-08-19). Engineering a robust DNA split proximity circuit with minimized circuit leakage. NUCLEIC ACIDS RESEARCH 44 (14). ScholarBank@NUS Repository. https://doi.org/10.1093/nar/gkw447
Abstract: © 2016 The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. DNA circuit is a versatile and highly-programmable toolbox which can potentially be used for the autonomous sensing of dynamic events, such as biomolecular interactions. However, the experimental implementation of in silico circuit designs has been hindered by the problem of circuit leakage. Here, we systematically analyzed the sources and characteristics of various types of leakage in a split proximity circuit which was engineered to spatially probe for target sites held within close proximity. Direct evidence that 3′-truncated oligonucleotides were the major impurity contributing to circuit leakage was presented. More importantly, a unique strategy of translocating a single nucleotide between domains, termed 'inter-domain bridging', was introduced to eliminate toehold-independent leakages while enhancing the strand displacement kinetics across a three-way junction. We also analyzed the dynamics of intermediate complexes involved in the circuit computation in order to define the working range of domain lengths for the reporter toehold and association region respectively. The final circuit design was successfully implemented on a model streptavidin-biotin system and demonstrated to be robust against both circuit leakage and biological interferences. We anticipate that this simple signal transduction strategy can be used to probe for diverse biomolecular interactions when used in conjunction with specific target recognition moieties.
Source Title: NUCLEIC ACIDS RESEARCH
URI: https://scholarbank.nus.edu.sg/handle/10635/168695
ISSN: 03051048
13624962
DOI: 10.1093/nar/gkw447
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