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DNA
Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-5 · IF 4.259

DNA Self-assembly Catalyzed by Artificial Agents

Shi Chao,Wang Yifan,Zhang Menghua,Ma Cuiping

Nucleic acids have been shown to be versatile molecules and engineered to produce various nanostructures. However, the poor rate of these uncatalyzed nucleic acid reactions has restricted the development and applications. Herein, we reported a novel finding that DNA self-assembly could be nonenzymatically catalyzed by artificial agents with an increasing dissociation rate constant K2. The catalytic role of several artificial agents in DNA self-assembly was verified by real-time fluorescent detection or agarose gel electrophoresis. We found that 20% PEG 200 could significantly catalyze DNA self-assembly and increase the reaction efficiency, such as linear hybridization chain reaction (HCR) and exponential hairpin assembly (EHA). Therefore, we foresee that a fast and efficient DNA self-assembly in structural DNA nanotechnology will be desirable.

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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2026 · IF 4.6

A label-free fluorescent biosensor leveraging cascaded DNA dual-cycle amplification and HCR for ultrasensitive detection of circulating tumor DNA

Ya Yun Lei,Xiao Yang,Yi Nuo Wang,Qi Tong Fu,Zhi Cheng Chen,Hong Qun Luo,Nian Bing Li

High-sensitivity circulating tumor DNA (ctDNA) detection technology is critical for early cancer diagnosis and treatment. However, the extremely low abundance of ctDNA in bodily fluids, coupled with various interfering factors, makes its effective detection particularly challenging. Herein, a label-free fluorescence sensor for ultrasensitive ctDNA detection was developed by integrating enzyme-assisted dual-DNA-loop amplification with a hybridization chain reaction (HCR). The target ctDNA binds to a hairpin probe, initiating a catalytic hairpin assembly cycle that forms a complex containing recognition sites for the endonuclease Nb. Bbv CI. Upon binding its recognition site, Nb.BbvCI cooperates with KF polymerase to induce strand displacement amplification (SDA), forming a dual-cycle amplification process that generates an HCR trigger probe to initiate HCR and produce abundant complementary DNA sequences with multiple C-myc repeats. In the presence of Mg 2+ , these sequences fold into G-quadruplex structures. Subsequent intercalation of thioflavin T results in a dramatic enhancement of the fluorescence signal, enabling quantitative detection of ctDNA. The sensor demonstrates a linear response to ctDNA concentrations ranging from 10 fM to 1 nM, with a detection limit as low as 2.48 aM. This highly sensitive detection strategy offers promising potential for advancing early cancer diagnosis and personalized treatment.

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ANALYTICAL CHEMISTRY · 2019 · IF 6.35

Ingenious Design of DNA Concatamers and G-Quadruplex Wires Assisted Assembly of Multibranched DNA Nanoarchitectures for Ultrasensitive Biosensing of miRNA

Jianguo Xu,Chao Yan,Xinxin Wang,Bangben Yao,Jianfeng Lu,Guodong Liu,Wei Chen

Facile and efficient assembly of intelligent DNA nano-objects with the ability to exert robust microRNA determination is essential for DNA nanobiotechnology and basic biomedical study. Herein, we present a novel target-triggered DNA assembly pathway for the construction of multibranched DNA nanoarchitectures by the combination of DNA concatamers with G-quadruplex wires. The DNA concatamers acting as the main body structures were assembled by hybridization chain reaction (HCR), while the G-quadruplex wires acting as the branch structures were generated by terminal deoxynucleotidyl transferase (TdT)-promoted polymerization and G-quadruplex units (GUs) based self-assembly. With a copious number of G-quadruplex replicates collected on the electrode surface, the obtained multibranched DNA nanoarchitectures were able to bind with lots of hemin, which further led to a significantly amplified electrochemical sensing signal for ultrasensitive and selective detection of miRNA-21. The detection limit was achieved as low as 0.2 fM with a wide dynamic response ranging from 10 fM to 100 nM, which is much more powerful or at least comparable to most of the reported studies. Furthermore, the electrochemical biosensor offered an excellent specificity, and even the single-base mutation against the perfectly matched target miRNA can be easily distinguished easily. Furthermore, the real biological samples were also desirably analyzed, indicating that the proposed strategy is an ideal platform for the fabrication of versatile DNA nanobiosensors.

CAS / MDL: 16009-13-5
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MICROCHIMICA ACTA · 2021 ·Vol. 188 ·期 6 ·1-8 · IF 5.833

l-Histidine-DNA interaction: a strategy for the improvement of the fluorescence signal of poly(adenine) DNA-templated gold nanoclusters

Wang Hai-Bo,Mao An-Li,Tao Bei-Bei,Zhang Hong-Ding,Xiao Zhong-Liang,Liu Yan-Ming

An interesting phenomenon is described that the fluorescence signal of poly(adenine) (A) DNA-templated gold nanoclusters (AuNCs) is greatly improved in the presence of l -histidine by means of l -histidine-DNA interaction. The modified nanoclusters display strong fluorescence emission with excitation/emission maxima at 290/475 nm. The fluorescence quantum yield (QY) is improved from 1.9 to 6.5%. Fluorescence enhancement is mainly ascribed to the l -histidine-DNA interaction leading to conformational changes of the poly(A) DNA template, which offer a better microenvironment to protect AuNCs. The assay enables l -histidine to be determined with good sensitivity and a linear response that covers the 1 to 50 nM  l -histidine concentration range with a 0.3 nM limit of detection. The proposed method has been applied to the determination of imidazole-containing drugs in pharmaceutical samples. Graphical abstract A turn-on fluorescent method has been designed for the sensitive detection of l -histidine as well as imidazole-containing drugs on the basis of the l -histidine-DNA interaction.

CAS / MDL: 16961-25-4 68-04-2
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ANALYTICA CHIMICA ACTA · 2020 · IF 5.977

A simple, one-pot and ultrasensitive DNA sensor via Exo III-Assisted target recycling and 3D DNA walker cascade amplification

Na Wu,Yi-Ting Wang,Xiao-Yan Wang,Xu- Wei Chen,Ting Yang,Jian-Hua Wang

Rapid, sensitive, and user-friendly nucleic acid detection is of growing importance in early clinical diagnosis. Here, we construct a simple, one-pot and ultrasensitive DNA sensor via exonuclease III (Exo III)-assisted target recycling amplification (ERA) combined with 3D DNA walker cascade amplification. In the presence of single-stranded DNA target, the ERA process is activated to generate numerous walker strands (WS). Thereafter, Exo III-powered WSs autonomously move along magnetic bead (MB)-based 3D track to release numerous AgNCs into the supernatant as an amplified signal output. This biosensor had a low detection limit of 18 fM and an analytical range of 40 fM to 1 pM. Furthermore, the practical application potential of this biosensor was also confirmed by the spiking experiments of p53 into human serum and urine samples.

CAS / MDL: 25952-53-8 6066-82-6
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SENSORS AND ACTUATORS B-CHEMICAL · 2015 · IF 4.097

A high-performance DNA biosensor based on the assembly of gold nanoparticles on the terminal of hairpin-structured probe DNA

Songling Li,Weiwei Qiu,Xuan Zhang,Jiancong Ni,Feng Gao,Qingxiang Wang

An ultrasensitive electrochemical DNA biosensor has been developed based on the assembly of highly conductive gold nanoparticles (AuNPs) on the free terminal of hairpin-structured probe DNA . The hairpin probe DNA was first immobilized on a gold electrode surface through Au S bond. Then the thioglycolic acid (TGA) was grafted on the 3′-end of hairpin DNA via the carboxylic-amino condensation reaction . Followed by, the AuNPs were further attached through reaction with the thiol-group of TGA. Thus, a highly conductive biointerface with ultralow charge-transfer resistance was obtained. Quantitative analysis exhibited that the target DNA could be detected over the range from 1.0   ×   10 −17 to 1.0   ×   10 −11   M. The detection limit was estimated to be 1.7   ×   10 −18   M. Also the biosensor showed good hybridization selectivity , stability and regeneration ability.

CAS / MDL: 68-11-1 77-86-1
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RSC Advances · 2017 ·Vol. 7 ·期 40 ·24628-24632 · IF 3.108

A novel, label-free fluorescence detection method for the formation of G-quadruplex DNA based on DNA-templated silver nanoclusters

Jiaona Xu,Chunying Wei

A novel, label-free fluorescence detection method was proposed for the formation of the G-quadruplex DNAs based on placing two DNA-Ag NCs together to light-up fluorescence. Herein, we designed two tailored DNA sequences noted as target DNA (abbreviated as T-DNA) and complementary DNA (abbreviated as C-DNA), respectively. T-DNA contains two cytosine-rich sequences at the 3′- and 5′-end responsible for Ag NCs synthesis, together with the guanine-rich (G-rich) DNA sequence in the middle segment. C-DNA was designed completely complementary to the G-rich segment of the T-DNA. Provided that the middle G-rich oligonucleotide of T-DNA folds into G-quadruplex in the presence of monovalent cations, the located at 3′ and 5′ terminuses two darkish DNA-Ag NCs approximate, leading to the enhanced fluorescence signal readout. Upon addition of the C-DNA, the G-quadruplex structure is unfolded and the two DNA-Ag NCs are separated, then the fluorescence signal is quenched. On the contrary, when the G-rich oligonucleotide with mutational bases failed to form the G-quadruplex, the fluorescence signal decreased clearly. This design allowed specific and general detection of the formation of diverse G-quadruplexes with easy operation and low cost. We believed that the proposed approach laid a foundation for the researchers in bioimaging, pharmacology, diagnostics, and other fields.

CAS / MDL: 16940-66-2 7761-88-8
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JOURNAL OF CONTROLLED RELEASE · 2021 · IF 9.776

Maintaining manganese in tumor to activate cGAS-STING pathway evokes a robust abscopal anti-tumor effect

Chao Wang,Zhaoyi Sun,Chenxuan Zhao,Zhewei Zhang,Haoran Wang,Yang Liu,Yunfei Guo,Bingtao Zhang,Lihong Gu,Yue Yu,Yiqiao Hu,Jinhui Wu

Radiotherapy (RT)-induced DNA damage leaked into cytosol can elicit host antitumor immune response. However, such response rate is unpromising due to limited cyclic GMP-AMP synthase (cGAS) recognition of cytosolic DNA, which could be digested inherently by host DNases . Here we show that synchronizing Mn 2+ delivery with accumulated cytosolic DNA after RT can promote the activation of cGAS-STING pathway, thereby enhancing RT-induced antitumor immunity. Intratumoral Mn 2+ injection immediately after RT cannot enhance RT, while intratumoral Mn 2+ injection 24 h after RT can. Direct-injected Mn 2+ can be metabolized out from tumor in minutes while RT-induced DNA damage need cells mitotic progression for up to 24 h to accumulate into cytosol. Alginate can maintain Mn 2+ in tumor for up to 24 h due to it can chelate divalent cations . When the release profile of Mn 2+ is controlled by alginate (Alg) and synchronized with the accumulation of RT-induced DNA damage, over 90% inhibition rate can be obtained even in the unirradiated tumor, and survival time is significantly extended. This synchronizing strategy provides a simple and novel approach to effectively activate cGAS-STING pathway in tumor and promote RT-induced immunity.

研究领域: 肿瘤学 · 免疫学 · 放射生物学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2021 · IF 4.098

Protective effect of baicalein on DNA oxidative damage and its binding mechanism with DNA: An in vitro and molecular docking study

Rui Wang,Jian Li,De-Bao Niu,Fei-Yue Xu,Xin-An Zeng

In this work, the protective effect of baicalein on DNA oxidative damage and its possible protection mechanisms were investigated. 2-thiobarbituric acid (TBA) colorimetry and agarose gel electrophoresis study found that baicalein protected the deoxyribose residue and double-stranded backbone of DNA from the damage of hydroxyl radicals. Antioxidant analysis results showed that baicalein has excellent radicals scavenging effects and Fe 2+ chelating ability, which might be the mechanism of baicalein protecting DNA. DNA binding studies indicated that baicalein bound to the minor groove of DNA with moderate binding affinity ( K  = (7.35 ± 0.91) × 10 3 M −1 ). Hydrogen bonding and van der Waals forces played a major role in driving the binding process. Molecular docking further confirmed the experimental results. This binding could stabilize DNA double helix structure, thereby protecting DNA from oxidative damage. This study may provide theoretical basis for designing new functional foods of baicalein for DNA damage protection.

研究领域: 药理学 · 分子生物学 · 生物化学
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Materials Today Bio · 2026 · IF 11

Rational design of a V-shaped DNA-targeted photosensitizer enables endogenous DNA damage-driven cGAS-STING activation and systemic antitumor immunity

Yi Cai,Cai-Yun Wang,Min Dong,Zhang Lin,Cai-Qiang Liao,Ze-Jun Li,Tian-Yi Qin,Zhao-Hui Wang,Ya-Long Wang,Ming-Qiang Zhu

The cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway is a central driver of antitumor immunity, yet its safe and efficient activation in solid tumors remains challenging. Here we report a V-shaped photosensitizer, 2C6, that functions as an in situ DNA-fragmentation agent by directly targeting double-stranded DNA (dsDNA). Owing to its A–π–D–π–A molecular framework, 2C6 exhibits efficient reactive oxygen species (ROS) generation under low-power white-light irradiation. Photoactivation of 2C6 induces concurrent mitochondrial and nuclear DNA damage, leading to the accumulation of oxidized dsDNA fragments in the cytosol, which is closely associated with activation of the cGAS–STING signaling pathway. In parallel, 2C6-PDT induces pyroptosis and immunogenic cell death (ICD), as evidenced by elevated levels of pyroptosis-associated markers (including NLRP3, cleaved caspase-1, and GSDMD), along with features of ICD such as CRT exposure, ATP secretion, and HMGB1 release. In a murine 4T1 triple-negative breast cancer (TNBC) postsurgical residual model, a single intraoperative 2C6-PDT prevented local tumor recurrence, established immune memory within the observation period, and suppressed distant tumor growth and lung metastasis without immunoadjuvants. Collectively, 2C6 couples photoinduced DNA damage to cytosolic dsDNA sensing, type I interferon signaling, and adaptive immune activation through a defined cascade encompassing DNA damage, dsDNA accumulation, cGAS-STING engagement, inflammatory signaling, and immune-cell infiltration. Together, these findings demonstrate that rationally engineered DNA-targeted photosensitizers can convert localized photodynamic tumor ablation into a systemic photoimmunotherapeutic response, providing a strategy to transform immunologically “cold” tumors into immune-responsive states.

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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

Three-way DNA junction structure combined with enzyme-powered cascade amplification for ultrasensitive electrochemiluminescence detection of microRNA via smart DNA walker

Qian Kuang,Chunli Li,Zhiwei Qiu,Guifen Jie,Shuyan Niu,Tingyu Huang

In this work, a target-triggered three-way junction (3-WJ) structure was combined with enzyme-powered cascade amplification strategy for ultrasensitive electrochemiluminescence (ECL) detection of microRNA via free-running DNA walker. In the presence of target microRNA-21 (miRNA-21), a three-way junction structure was formed to trigger enzyme-aided multiple DNA amplification, and thus exponentially amplified triggers were generated. Then, the trigger DNA could hybridize with the blocking DNA on the electrode to release walker DNA, which specifically combined with the quantum dots (QDs)-DNA probe, and formed a recognition site for Nt.BbvCI. The movement of DNA walker is powered by the nicking endonuclease that cleaves specific QDs-DNA probes on the track. Thus one walker DNA can automatically cleave multiple QDs probes on the electrode during the movement, resulting in significantly amplified changes of ECL signal, which could be used for the highly sensitive detection of target miRNA-21. Under the optimal conditions, the ECL signal change is linear with the concentration of miRNA-21 in the range from 10 −14 M to 10 -7 M with a detection limit of 1.5 fM. This newly established strategy could achieve rapid, isothermal, and homogeneous signal amplification for specific nucleic acids in complicated biomatrix, which hold great potential for application in early clinical diagnosis.

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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Construction of a sensitive ratiometric electrochemical sensing platform for DNA methylation detection based on the design of multistep DNA amplification circuits

Hui Zhou,Hui Shen,Baoting Dou,Qiumei Feng,Xiguang Han,Po Wang

Methylated DNA is a promising epigenetic biomarker for diseases diagnosis, therapy monitoring, and prognosis. Here, we developed a sensitive ratiometric electrochemical biosensor for the detection of methylated DNA based on the design of multistep DNA amplification circuits. The methylated target DNA firstly initiates the DNAzyme-assisted amplification circuit and produces a number of single-stranded triggers that catalyze the subsequent double-step catalytic hairpin assembly circuits to release numerous four-way DNA junctions. The four-way DNA junctions displace the methylene blue (MB)-modified signal probes for intercalating doxorubicin (DOX) molecules on the sensing interface, resulting in a significantly increased value of i DOX / i MB to achieve sensitive monitoring of methylated DNA. Taking advantage of the significant signal amplification of multistep DNA amplification circuits, the proposed method exhibited high sensitivity for target analysis with a detection limit of 4 aM and a dynamic linear range of 10 aM to 20 pM. Moreover, the proof-of-concept application of the sensing platform was investigated, suggesting that the system is promising for potential applications in early cancer diagnosis and the fundamental research of epigenetics.

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