Simulation‐Assisted Localized DNA Logical Circuits for Cancer Biomarkers Detection and Imaging

Kou, Qiaoni; Wang, Lei; Zhang, Linghao; Ma, Liang; Fu, Shengnan; Su, Xin

doi:10.1002/smll.202205191

Cited by 28 publications

(16 citation statements)

References 52 publications

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“…To the best of our knowledge, this sensitivity is comparable and even superior to most of previously reported fluorescent sensors or methods (Table S2, Supporting Information). [33][34][35][36][37][38][39][40] The selectivity of APE1 detection was also investigated by testing the signal response resulted from several protein and enzymes. As shown in Figure 5D, compared with APE1 that resulted in strong fluorescence signal, the other analytes such as flap endonuclease 1 (FEN1), T4 ligase, exonuclease III (Exo III), Exo I, glucose oxidase (GOx), alkaline phosphatase (ALP), bovine serum albumin (BSA), and trypsin only caused weak detectable signal which were close to the blank background.…”

Section: Sensitivity and Selectivity Of Ape1 Detectionmentioning

confidence: 99%

Closed Cyclic DNA Machine for Sensitive Logic Operation and APE1 Detection

Chai

Chen

Zeng

et al. 2023

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systems usually require abundant inputs to guarantee equivalent output signals that can be detected or distinguished, the strategies that are able to convert weak inputs to strong outputs are highly desired for high order logic operations and highly sensitive sensing. In recent years, researchers have made, and continue to make efforts to develop advanced synthetic DNA circuit systems for biological engineering. Dynamic DNA assembly which is concerned primarily with the construction of DNA circuits or nanostructures based on DNA hybridization attracted increasing research interests. [7][8][9] Especially, the dynamic and isothermal cyclic reactions such as hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) have been extensively utilized as robust strategies of enzymefree signal amplification in molecular recognition and sensing. [10,11] HCR is an established technique to obtain duplex DNA nanowires via the initiator-triggered cross-opening of hairpin reactants, which usually contributed to significant signal amplification and ease of operation in bio/chemosensing. [12][13][14] CHA is realized through initiator-catalyzed hybridizations of different DNA hairpins and thus result in the accumulation of short duplex DNA products. [15,16] Despite the advantages and achievements in signal amplification, these unitary DNA assembly strategies usually suffer from the signal leakage and limited amplification depth, which greatly hindered their applications in precisely sensing and profiling biomarkers with trace amounts.The advanced HCR and CHA, as well as the cascade integration of them are anticipated to theoretically offer improved amplification depth and stronger anti-interference capacity to break through the primary obstacles of their widely applications in sensing. For instance, compared to typical linear HCR, the nonlinear HCR and hyperbranched HCR were developed to program assembly systems with higher-order growth kinetics and amplification depth. [17][18][19] Apart from short linear DNA product, branched DNA products such as Y-shaped, X-shaped structures were obtained through CHA pathway, which could effectively reduce the signal leakage in some degree. [20][21][22] What's more, rational combination of HCR and CHA could achieve cascade amplification and enabled ultrasensitive homogeneous detection of target. [23][24][25][26][27] It is worthy noting that most of these assembly pathways were programmed to amplify DNA self-assembly has been developed as a kind of robust signal amplification strategy, but most of reported assembly pathways are programmed to amplify signal in one direction. Herein, based on mutual-activated cascade cycle of hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA), a closed cycle circuit (CCC) based DNA machine is developed for sensitive logic operation and molecular recognition. Benefiting from the synergistically accelerated signal amplification, the closed cyclic DNA machine enabled the logic computing with strong and significant output signals even...

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Section: Sensitivity and Selectivity Of Ape1 Detectionmentioning

confidence: 99%

Closed Cyclic DNA Machine for Sensitive Logic Operation and APE1 Detection

Chai

Chen

Zeng

et al. 2023

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“…Furthermore, APE1 is frequently found to be overexpressed in various cancer cells, making it a potential cancer biomarker. 18,19 Considering the recognition of multiple cancer biomarkers that are overexpressed in tumor cells is crucial for precise cancer diagnosis, we believe it is significant to utilize APE1 in conjunction with other biomarkers, such as miRNA, to create a dual-trigger “AND” logic gate for in vitro detection and in vivo biological imaging. 16,20 This innovative approach of incorporating APE1 in constructing biosensors has the potential to simultaneously establish sensitive and logic-controllable dual-trigger detection systems for precise tumor diagnosis.…”

Section: Introductionmentioning

confidence: 99%

A cascade signal-amplified fluorescent biosensor combining APE1 enzyme cleavage-assisted target cycling with rolling circle amplification

Liu,

Yang,

Zhang

et al. 2024

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“…Research has shown that localized DNA functional modules increase the local concentration, promoting interactions between DNA strands. − However, irrational localization strategies offer limited improvement in the hybridization efficiency between DNA strands compared to nonlocalized approaches. Coarse-grained models have been widely employed to simulate and analyze the DNA structural properties, providing insights into the mechanical characteristics of DNA behaviors. − The simplicity of interactions between DNA strands and the predictability of mechanical properties makes it possible to use coarse-grained models to rationalize numerous synthetic structures …”

Section: Introductionmentioning

confidence: 99%

Enhanced DNA Entropy-Driven Circuit by Locked Nucleic Acids and Simulation-Guided Localization

Kou,

Yang,

Wang

et al. 2023

ACS Appl. Mater. Interfaces

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Signal amplification methods based on DNA molecular interactions are promising tools for detecting various biomarkers in low abundance. The entropy-driven circuit (EDC), as an enzyme-free signal amplification method, has been used in detecting and imaging a variety of biomarkers. The localization strategy can effectively increase the local concentration of the DNA reaction modules to improve the signal amplification effect. However, the localization strategy may also amplify the leak reaction of the EDC, and effective signal amplification can be limited by the unclear structure−function relationship. Herein, we utilized locked nucleic acid (LNA) modification to enhance the stability of the localized entropy-driven circuit (LEDC), which suppressed a 94.6% leak signal. The coarse-grained model molecular simulation was used to guide the structure design of the LEDC, and the influence of critical factors such as the localized distance and spacer length was analyzed at the molecular level to obtain the best reaction performance. The sensitivities of miR-21 and miR-141 detected by a simulation-guided optimal LEDC probe were 17.45 and 65 pM, 1345 and 521 times higher than free-EDC, respectively. The LEDC was further employed for the fluorescence imaging of miRNA in cancer cells, showing excellent specificity and sensitivity. This work utilizes LNA and molecular simulations to comprehensively improve the performance of a localized DNA signal amplification circuit, providing an advanced DNA probe design strategy for biosensing and imaging as well as valuable information for the designers of DNA-based probes.

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Simulation‐Assisted Localized DNA Logical Circuits for Cancer Biomarkers Detection and Imaging

Cited by 28 publications

References 52 publications

Closed Cyclic DNA Machine for Sensitive Logic Operation and APE1 Detection

Closed Cyclic DNA Machine for Sensitive Logic Operation and APE1 Detection

A cascade signal-amplified fluorescent biosensor combining APE1 enzyme cleavage-assisted target cycling with rolling circle amplification

Enhanced DNA Entropy-Driven Circuit by Locked Nucleic Acids and Simulation-Guided Localization

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