19 results on '"Wang, Fuan"'
Search Results
2. High-performance biosensing based on autonomous enzyme-free DNA circuits
- Author
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Wang, Hong, Wang, Huimin, Willner, Itamar, Wang, Fuan, Olivucci, Massimo, Editor-in-Chief, Wong, Wai-Yeung, Editor-in-Chief, Bayley, Hagan, Series Editor, Hughes, Greg, Series Editor, Hunter, Christopher A., Series Editor, Hwang, Seong-Ju, Series Editor, Ishihara, Kazuaki, Series Editor, Kirchner, Barbara, Series Editor, Krische, Michael J., Series Editor, Larsen, Delmar, Series Editor, Lehn, Jean-Marie, Series Editor, Luque, Rafael, Series Editor, Siegel, Jay S., Series Editor, Thiem, Joachim, Series Editor, Venturi, Margherita, Series Editor, Wong, Chi-Huey, Series Editor, Wong, Henry N.C., Series Editor, Yam, Vivian Wing-Wah, Series Editor, Yan, Chunhua, Series Editor, You, Shu-Li, Series Editor, Fan, Chunhai, editor, and Ke, Yonggang, editor
- Published
- 2020
- Full Text
- View/download PDF
3. A Label‐Free Deoxyribozyme Sensor for m6A Demethylase Activity Detection†.
- Author
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Wang, Xiuyuan, Yu, Shusheng, He, Yuqiu, Wang, Fuan, and Liu, Xiaoqing
- Subjects
DEMETHYLASE ,ADIPOSE tissues ,DEOXYRIBOZYMES ,NUCLEIC acids ,THIOFLAVINS ,DETECTORS ,BIOSENSORS - Abstract
Comprehensive Summary: A label‐free deoxyribozyme (DNAzyme) biosensor for m6A demethylase activity detection is developed. When demethylase FTO (Fat mass and obesity‐associated protein), an important m6A demethylase of ALKBH demethylase family is present, the m6A group is specifically demethylated, and the cleavage activity of DNAzyme is restored. This allows the cleavage product that contains G‐quadruplex sequence to bind to thioflavin T (ThT) and generate fluorescence signals. The biosensor shows high specificity and sensitivity, and fast reaction speed. Our study demonstrates a new design of allosteric DNAzyme for sensing. This method represents the first label‐free nucleic acid biosensor for FTO assay, providing a feasible route towards inhibitors screening. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. A Programmable DNAzyme for the Sensitive Detection of Nucleic Acids.
- Author
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Shi, Chenzhi, Yang, Donglei, Ma, Xiaowei, Pan, Li, Shao, Yuanchuan, Arya, Gaurav, Ke, Yonggang, Zhang, Chuan, Wang, Fuan, Zuo, Xiaolei, Li, Min, and Wang, Pengfei
- Subjects
DEOXYRIBOZYMES ,NUCLEIC acids ,PROSTATE cancer ,MOLECULAR diagnosis ,STOMACH cancer ,POINT-of-care testing - Abstract
Nucleic acids in biofluids are emerging biomarkers for the molecular diagnostics of diseases, but their clinical use has been hindered by the lack of sensitive detection assays. Herein, we report the development of a sensitive nucleic acid detection assay named SPOT (sensitive loop‐initiated DNAzyme biosensor for nucleic acid detection) by rationally designing a catalytic DNAzyme of endonuclease capability into a unified one‐stranded allosteric biosensor. SPOT is activated once a nucleic acid target of a specific sequence binds to its allosteric module to enable continuous cleavage of molecular reporters. SPOT provides a highly robust platform for sensitive, convenient and cost‐effective detection of low‐abundance nucleic acids. For clinical validation, we demonstrated that SPOT could detect serum miRNAs for the diagnostics of breast cancer, gastric cancer and prostate cancer. Furthermore, SPOT exhibits potent detection performance over SARS‐CoV‐2 RNA from clinical swabs with high sensitivity and specificity. Finally, SPOT is compatible with point‐of‐care testing modalities such as lateral flow assays. Hence, we envision that SPOT may serve as a robust assay for the sensitive detection of a variety of nucleic acid targets enabling molecular diagnostics in clinics. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Integration of Isothermal Enzyme‐Free Nucleic Acid Circuits for High‐Performance Biosensing Applications.
- Author
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Wang, Siyuan, Shang, Jinhua, Zhao, Bingyue, Wang, Huimin, Yang, Changying, Liu, Xiaoqing, and Wang, Fuan
- Subjects
SMALL molecules ,HAIRPIN (Genetics) ,NUCLEIC acids ,BIOLOGICAL assay ,DRUG target ,DEOXYRIBOZYMES - Abstract
The isothermal enzyme‐free nucleic acid amplification method plays an indispensable role in biosensing by virtue of its simple, robust, and highly efficient properties without the assistance of temperature cycling or/and enzymatic biocatalysis. Up to now, enzyme‐free nucleic acid amplification has been extensively utilized for biological assays and has achieved the highly sensitive detection of various biological targets, including DNAs, RNAs, small molecules, proteins, and even cells. In this Review, the mechanisms of entropy‐driven reaction, hybridization chain reaction, catalytic hairpin assembly and DNAzyme are concisely described and their recent application as biosensors is comprehensively summarized. Furthermore, the current problems and the developments of these DNA circuits are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. DNA-Based Machines
- Author
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Wang, Fuan, Willner, Bilha, Willner, Itamar, Bayley, Hagan, Series editor, Houk, Kendall N., Series editor, Hughes, Greg, Series editor, Hunter, Christopher A., Series editor, Ishihara, Kazuaki, Series editor, Krische, Michael J, Series editor, Lehn, Jean-Marie, Series editor, Luque, Rafael, Series editor, Olivucci, Massimo, Series editor, Siegel, Jay S., Series editor, Thiem, Joachim, Series editor, Venturi, Margherita, Series editor, Wong, Chi-Huey, Series editor, Wong, Henry N.C., Series editor, Credi, Alberto, editor, and Silvi, Serena, editor
- Published
- 2014
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7. A Smart Deoxyribozyme‐Programmable Catalytic DNA Circuit for High‐Contrast MicroRNA Imaging.
- Author
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He, Yuqiu, Wang, Qing, Hong, Chen, Li, Ruomeng, Shang, Jinhua, Yu, Shanshan, Liu, Xiaoqing, and Wang, Fuan
- Subjects
DEOXYRIBOZYMES ,MICRORNA ,BIOLOGICAL systems ,ARTIFICIAL chromosomes ,CELL imaging - Abstract
Synthetic catalytic DNA circuits have been recognized as a promising signal amplification toolbox for sensitive intracellular imaging, yet their selectivity and efficiency are always constrained by uncontrolled off‐site signal leakage and inefficient on‐site circuitry activation. Thus, the endogenously controllable on‐site exposure/activation of DNA circuits is highly desirable for achieving the selective imaging of live cells. Herein, an endogenously activated DNAzyme strategy was facilely integrated with a catalytic DNA circuit for guiding the selective and efficient microRNA imaging in vivo. To prevent the off‐site activation, the circuitry constitute was initially caged without sensing functions, which could be selectively liberated by DNAzyme amplifier to guarantee the high‐contrast microRNA imaging in target cells. This intelligent on‐site modulation strategy can tremendously expand these molecularly engineered circuits in biological systems. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
8. A Self‐Catabolic Multifunctional DNAzyme Nanosponge for Programmable Drug Delivery and Efficient Gene Silencing.
- Author
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Wang, Jing, Yu, Shanshan, Wu, Qiong, Gong, Xue, He, Shizhen, Shang, Jinhua, Liu, Xiaoqing, and Wang, Fuan
- Subjects
GENE silencing ,GENE therapy ,APTAMERS ,CANCER cells ,DRUGS ,DNA primers - Abstract
DNAzyme‐based gene therapy holds immense prospects for effectively treating severe diseases, yet is constrained with inefficient delivery and unconditional activation. Herein, we designed a bioinspired self‐catabolic DNA nanocapsule for sustaining tumor‐specific cascade activation of therapeutic DNAzyme. The exquisite DNAzyme was temporarily masked by the self‐excising DNAzyme in the hierarchical rolling circle replication (RCR) nanostructures, thus stayed in an inactive state in physiological fluids. Through the multivalent tumor‐anchoring aptamer strands, the RCR nanocapsule was specifically accumulated in cancer cells and was sequentially activated for motivating the ultimate DNAzyme‐mediated gene silencing via the intelligent stimuli‐responsive cascade DNAzyme activation. By virtue of the programmable RCR assembly strategy, our compact DNAzyme nanoplatform shows great promise for developing versatile smart gene therapeutics and personalized nanomedicines. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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9. A Smart Theranostic Nanocapsule for Spatiotemporally Programmable Photo‐Gene Therapy.
- Author
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Gong, Xue, Li, Ruomeng, Wang, Jing, Wei, Jie, Ma, Kang, Liu, Xiaoqing, and Wang, Fuan
- Subjects
GENE silencing ,INDOCYANINE green ,MICRORNA ,PRODRUGS ,DNA primers ,DNA - Abstract
The therapeutic performance of DNAzyme‐involved gene silencing is significantly constrained by inefficient conditional activation and insufficient cofactor supply. Herein, a self‐sufficient therapeutic nanosystem was realized through the delicate design of DNAzyme prodrugs and MnO2 into a biocompatible nanocapsule with tumor‐specific recognition/activation features. The indocyanine green (ICG)‐modified DNA prodrugs are designed by splitting the DNAzyme and then reconstituted into the exquisite catalyzed hairpin assembly (CHA) amplification circuit. Based on the photothermal activation of ICG, the nanocapsule was disassembled to expose the MnO2 ingredient which was immediately decomposed into Mn2+ ions to supplement an indispensable DNAzyme cofactor on‐demand with a concomitant O2 generation for enhancing the auxiliary phototherapy. The endogenous microRNA catalyzes the amplified assembly of DNA prodrugs via an exquisite CHA principle, leading to the DNAzyme‐mediated simultaneous silencing of two key tumor‐involved mRNAs. This self‐activated theranostic nanocapsule could substantially expand the toolbox for accurate diagnosis and programmable therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
10. A Smart, Autocatalytic, DNAzyme Biocircuit for in Vivo, Amplified, MicroRNA Imaging.
- Author
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Wei, Jie, Wang, Huimin, Wu, Qiong, Gong, Xue, Ma, Kang, Liu, Xiaoqing, and Wang, Fuan
- Subjects
MICRORNA ,DNA probes ,MAGNETIC resonance imaging ,DEOXYRIBOZYMES - Abstract
DNAzymes have been recognized as promising transducing agents for visualizing endogenous biomarkers, but their inefficient intracellular delivery and limited amplification capacity (including insufficient cofactor supply) preclude their extensive biological application. Herein, an autocatalytic DNAzyme (ACD) biocircuit is constructed for amplified microRNA imaging in vivo based on a hybridization chain reaction (HCR) and DNAzyme biocatalysis, sustained by a honeycomb MnO2 nanosponge (hMNS). The hMNS not only delivers DNA probes, but also supplies Mn2+ as a DNAzyme cofactor and magnetic resonance imaging (MRI) agent. Through the subsequent cross‐activation of HCR and DNAzyme amplicons, the ACD amplifies the limited signal resulting from miRNA recognition. The hMNS/ACD system was used to image microRNA in vivo, thus demonstrating its great promise in cancer diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
11. DNAzyme‐Loaded Metal–Organic Frameworks (MOFs) for Self‐Sufficient Gene Therapy.
- Author
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Wang, Huimin, Chen, Yuqi, Wang, Hong, Liu, Xiaoqing, Zhou, Xiang, and Wang, Fuan
- Subjects
DEOXYRIBOZYMES ,METAL-organic frameworks ,GENE therapy ,PHOTODYNAMIC therapy ,NANOPARTICLES ,CANCER cells - Abstract
DNAzymes have been recognized as potent therapeutic agents for gene therapy, while their inefficient intracellular delivery and insufficient cofactor supply precludes their practical biological applications. Metal–organic frameworks (MOFs) have emerged as promising drug carriers without in‐depth consideration of their disassembled ingredients. Herein, we report a self‐sufficient MOF‐based chlorin e6‐modified DNAzyme (Ce6‐DNAzyme) therapeutic nanosystem for combined gene therapy and photodynamic therapy (PDT). The ZIF‐8 nanoparticles (NPs) could efficiently deliver the therapeutic DNAzyme without degradation into cancer cells. The pH‐responsive ZIF‐8 NPs disassemble with the concomitant release of the guest DNAzyme payloads and the host Zn2+ ions that serve, respectively, as messenger RNA‐targeting agent and required DNAzyme cofactors for activating gene therapy. The auxiliary photosensitizer Ce6 could produce reactive oxygen species (ROS) and provide a fluorescence signal for the imaging‐guided gene therapy/PDT. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
12. Single-Molecule Visualization of the Activity of a Zn2+-Dependent DNAzyme.
- Author
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Endo, Masayuki, Takeuchi, Yosuke, Suzuki, Yuki, Emura, Tomoko, Hidaka, Kumi, Wang, Fuan, Willner, Itamar, and Sugiyama, Hiroshi
- Subjects
SINGLE molecules ,DEOXYRIBOZYMES ,CATALYSIS ,NANOSTRUCTURED materials ,DNA analysis ,BIOCHEMICAL substrates - Abstract
We demonstrate the single-molecule imaging of the catalytic reaction of a Zn
2+ -dependent DNAzyme in a DNA origami nanostructure. The single-molecule catalytic activity of the DNAzyme was examined in the designed nanostructure, a DNA frame. The DNAzyme and a substrate strand attached to two supported dsDNA molecules were assembled in the DNA frame in two different configurations. The reaction was monitored by observing the configurational changes of the incorporated DNA strands in the DNA frame. This configurational changes were clearly observed in accordance with the progress of the reaction. The separation processes of the dsDNA molecules, as induced by the cleavage by the DNAzyme, were directly visualized by high-speed atomic force microscopy (AFM). This nanostructure-based AFM imaging technique is suitable for the monitoring of various chemical and biochemical catalytic reactions at the single-molecule level. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
13. DNA-Schalter: Grundlagen und Anwendungen.
- Author
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Wang, Fuan, Liu, Xiaoqing, and Willner, Itamar
- Abstract
Die Basensequenz der Nukleinsäuren verschlüsselt strukturelle und funktionelle Eigenschaften in einem Biopolymer. Strukturelle Informationen beinhalten die Bildung von Duplexen, G ‐ Quadruplexen, i ‐ Motiven und kooperativ stabilisierten Anordnungen. Funktionelle Informationen betreffen z. B. den Prozess der Strangverdrängung, Erkennungseigenschaften von Aptameren und die katalytische Funktion von DNAzymen. Dieser Aufsatz befasst sich mit der Implementierung der in Nukleinsäuren kodierten Informationen zur Entwicklung von DNA ‐ Schaltern. Ein DNA ‐ Schalter ist eine supramolekulare Nukleinsäureanordnung, die in Gegenwart geeigneter Auslöser und Gegenauslöser wie pH, Metallionen/Liganden, photonischen und elektrischen Stimuli zyklische, schaltbare Übergänge zwischen zwei Zuständen eingeht. Anwendungen von schaltbaren DNA ‐ Systemen umfassen maßgeschneiderte DNA ‐ Hydrogele für die kontrollierte Wirkstofffreisetzung und die Aktivierung schaltbarer Enzymkaskaden. Intelligente DNA: Die reizgesteuerte, reversible Rekonfiguration von i ‐ Motiven, G ‐ Quadruplexen und Duplex ‐ DNA ‐ Strukturen oder von DNA ‐ Bausteinen wie Pinzetten, Nanofedern und Walkern ist die Grundlage für die Entwicklung schaltbarer DNA ‐ Nanostrukturen mit Auslösern wie pH ‐ Wert, Metallionen oder elektrochemischen Signalen. Potenzielle Anwendungen von DNA ‐ Schaltern umfassen die kontrollierte Wirkstoff ‐ Freisetzung, das Öffnen/Schließen von Poren und schaltbare Katalyse. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
14. A Label‐Free Deoxyribozyme Sensor for m6A Demethylase Activity Detection†.
- Author
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Wang, Xiuyuan, Yu, Shusheng, He, Yuqiu, Wang, Fuan, and Liu, Xiaoqing
- Subjects
- *
DEMETHYLASE , *ADIPOSE tissues , *DEOXYRIBOZYMES , *NUCLEIC acids , *THIOFLAVINS , *DETECTORS , *BIOSENSORS - Abstract
Comprehensive Summary: A label‐free deoxyribozyme (DNAzyme) biosensor for m6A demethylase activity detection is developed. When demethylase FTO (Fat mass and obesity‐associated protein), an important m6A demethylase of ALKBH demethylase family is present, the m6A group is specifically demethylated, and the cleavage activity of DNAzyme is restored. This allows the cleavage product that contains G‐quadruplex sequence to bind to thioflavin T (ThT) and generate fluorescence signals. The biosensor shows high specificity and sensitivity, and fast reaction speed. Our study demonstrates a new design of allosteric DNAzyme for sensing. This method represents the first label‐free nucleic acid biosensor for FTO assay, providing a feasible route towards inhibitors screening. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
15. Stimuli‐Responsive RNA‐Cleaving DNAzyme for Biomedical Application.
- Author
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Wang, Siyuan, Liu, Yaqi, Shang, Jinhua, Wang, Huimin, Yang, Changying, Liu, Xiaoqing, and Wang, Fuan
- Abstract
DNAzymes are synthetic deoxynucleotide oligomers with catalytic properties selected through in vitro systematic evolution of ligands by exponential enrichment (SELEX) technique. RNA‐cleaving DNAzymes have attracted increasing attentions in bioanalysis and biomedical applications due to their simple synthesis and modification, stable structure, and high catalytic activity. Especially, their different modes of activity regulation enable their extensive theranostic development. This review introduces the in vitro selection of DNAzymes and some typical ones, followed by the description of various stimuli‐responsive regulation strategies on DNAzyme activity, including metal ion cofactors, small molecules, protease, light, and heat. Then the recent advances of DNAzyme‐based biosensors, therapeutic applications, cell‐cell interaction regulation, and logic operation are summarized. At last, the current challenges and possible development of DNAzyme‐based biosensors are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
16. Construction of a simple dual-mode ATP-sensing system for reliable fish freshness evaluation.
- Author
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Si, Qingyang, Li, Yumeng, Huang, Ziling, Liu, Chuanyi, Chen, Xiaomei, Wei, Jie, and Wang, Fuan
- Subjects
- *
FISH spoilage , *NUCLEIC acid probes , *ADENOSINE triphosphate , *DEOXYRIBOZYMES , *QUADRUPLEX nucleic acids , *FOOD quality , *FOOD safety , *PROTEIN content of food - Abstract
Adenosine triphosphate (ATP), the main carrier of chemical energy, plays a key role in various biochemical reactions such as cellular metabolism. Currently, ATP levels are considered important indicators of microbial content in food safety, and food freshness can be determined by detecting ATP content. Some ATP sensing strategies have been applied to evaluate food freshness. However, cumbersome nanomaterial preparation, low sensitivity, and low reliability hamper their widespread application. Herein, a simple, high-performance, and reliable dual-mode sensing system based on hemin-G-quadruplex (G4) DNAzyme was established to detect ATP and assess fish freshness. Two nucleic acid probes, including subunits of the hemin-G4 DNAzyme in inactive structures and anti-ATP aptamer, self-assemble upon the input of ATP into the active hemin-G4 DNAzyme unit. The generated DNAzyme acts as a biocatalyst for colorimetric or fluorescent readout of the sensing process. The colorimetric and fluorescent dual-mode sensing system enables highly sensitive and reliable analysis of target ATP with detection limits of 71 nM and 73 nM, respectively. Moreover, the biosensor exhibited good selectivity for differentiating ATP from other interfering analytes. The proposed system was used to detect ATP in perch samples, and a linear correlation between ATP level and microbial content was confirmed. The established ATP-sensing system reliably evaluated fish freshness. Notably, in comparison with microbiological counts, the proposed DNAzyme-based dual-mode strategy for freshness evaluation is facile, highly efficient, and cost-effective, thus providing a promising method for food safety and quality monitoring. [Display omitted] • A reliable dual-mode ATP-sensing system based on hemin/G-quadruplex was devised. • The proposed system allows the highly sensitive and selective detection of ATP. • The dual-mode system could enable the reliable evaluation of fish freshness. • The strategy for freshness evaluation is facile, high-efficiency and cost-effective. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
17. Chemical and structural modification of RNA-cleaving DNAzymes for efficient biosensing and biomedical applications.
- Author
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Wang, Qing, Wang, Zeyue, He, Yuqiu, Xiong, Bin, Li, Yingfu, and Wang, Fuan
- Subjects
- *
SINGLE-stranded DNA , *SMALL molecules , *MOLECULAR weights , *DEOXYRIBOZYMES , *METAL ions , *MEDICAL research , *NUCLEIC acids - Abstract
Deoxyribozyme (DNAzyme) is single-stranded catalytic DNA that possesses various physical and chemical features, including small molecular weight, higher stability, excellent programmability, and cost-effectiveness. Considerable efforts are spent on the incorporation of RNA-cleaving DNAzyme (RCD) into biosensor and biomedical researches. However, their in vivo application is constrained by off-target activation (always turn-on) in complex biological environment. Therefore, there is a pursuit to develop spatiotemporally controlled DNAzyme in desired locations and time-points. Herein, we provide a timely and comprehensive overview of various chemical modification and structural reconfiguration methods to realize the specific stimulation/regulation of RCD activities, including metal ions, small molecules, nucleic acids, proteins, and external photo/thermal stimuli. The specific examples of using chemically and/or structurally caged RCD for stimuli-responsive biosensing and biomedical research have also been reviewed within the past five years. Lastly, the challenges and perspectives of stimuli-responsive RCD are suggested to further advance the RCD toolbox in clinical application. • Stimuli-responsive RNA-cleaving DNAzyme (RCD) represents a powerful toolbox for biological research. • The off-site signal leakage of RCD can be eliminated by chemical or/and structural modifications. • The spatiotemporally controlled RCD is summarized for bioimaging and biomedical applications. • The ongoing challenge and future development of stimuli-responsive RCD are properly summarized. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
18. Triggered amplification of gene theranostics with high accuracy and efficacy using metallo-nanoassemblies.
- Author
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Hu, Jialing, Zou, Zhiqiao, Mo, Fengye, Lin, Xue, Zhao, Yun, Shi, Tianhui, Wang, Fuan, and Liu, Xiaoqing
- Subjects
- *
GENE amplification , *DEOXYRIBOZYMES , *NANOMEDICINE , *GENE silencing , *GENETIC regulation , *COMPANION diagnostics - Abstract
An on-site activatable gene theranostic platform is constructed with DNA prodrug-laden metallo-nanoassemblies. Under microenvironment stimuli, the inactive DNAs are sensitively transformed into active DNAzymes via chain reaction, and the metallo-nanoassembly allows self-sufficient enzymatic cofactors and accelerated RNA-cleavage activity of the DNAzymes. Such amplified orthogonal activation of gene theranostics may offer new way for precision nanomedicine. [Display omitted] • A programmable and responsive nanoplatform for tumor-specific gene theranostics. • High-performance metallo-nanoassemblies as effective oligonucleotide drug vehicles. • Multiple biomarkers-triggered signal amplification and dual-mode imaging. • On-site DNAzyme activation and self-boosted gene silencing for precise and robust cancer therapy. • Such amplified orthogonal activation of gene regulation approach benefits precision nanomedicine. RNA-cleaving DNAzymes hold great promise for gene regulation, yet the low in vivo catalytic efficacy and the unavoidable nonspecific response in normal tissues hinder their practical applications. Herein, we develop a DNA prodrug-laden metallo-nanoassembly for sensitive orthogonal activation of DNAzymes to regulate disease gene with high precision and efficacy. With rich positive charges, metallo-nanoassemblies efficiently load DNA prodrugs (functional DNAzyme subunits), and thus improve drug stability and cellular uptake efficacy. Under tumor microenvironment, the cancer-specific biomarker triggers the amplified assembly of DNA prodrugs into active DNAzymes to efficiently cleave tumor-involved mRNA. Meanwhile, these glutathione-responsive metallo-nanoassemblies decompose and release metal ions as self-sufficient DNAzyme cofactors, which are accommodated into the afore-assembled DNAzymes to enhance the gene cleavage activity. Moreover, upon laser stimulus, these photothermal metallo-nanoassemblies can also remarkably promote the catalytic reaction of DNAzymes via the elevated local temperature. Such a smart delivery approach allows disease diagnosis via sensitive fluorescence and photothermal imaging, and achieves the precise and robust gene regulation with photothermal ablation as an auxiliary therapy. These results provide a new route to design programmable and activatable prodrugs for precision nanomedicine. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
19. Acid-improved DNAzyme-based chemiluminescence miRNA assay coupled with enzyme-free concatenated DNA circuit.
- Author
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Yang, Huiran, Weng, Benrui, Liu, Sijia, Kang, Nana, Ran, Jiabing, Deng, Zhangshuang, Wang, Huimin, Yang, Changying, and Wang, Fuan
- Subjects
- *
CHEMILUMINESCENCE assay , *DNA , *DEOXYRIBOZYMES , *SIGNAL-to-noise ratio , *CATALYTIC activity - Abstract
DNAzyme-based chemiluminescence assay exhibits excellent performance in bioanalysis but their operation in acid conditions remains challengeable. Herein, we constructed an acid-improved DNAzyme-based isothermal enzyme-free concatenated DNA circuit with significantly reduced background and simultaneously improved signal-to-noise ratio for miRNA detection. The chemiluminescence miRNA assay is composed of catalyzed hairpin assembly (CHA), hybridization chain reaction (HCR), and hemin/G-quadruplex DNAzyme units. The analyte initiates the self-assembly of CHA hairpins into numerous dsDNA, which triggers the subsequent autonomous cross-opening of HCR hairpins to generate long nanowires consisting of the hemin/G-quadruplex DNAzyme. The DNAzyme catalyzes the oxidation of luminol by hydrogen peroxide for the cascaded amplified chemiluminescence signal. The acid-improved property was demonstrated to be closely associated with the low catalytic activity of aggregated hemin under acidic conditions and the remained multiple amplified signal through concatenated DNA circuit. The general DNA circuit exhibited high sensitivity for miRNA-21 detection and chemiluminescence imaging under acidic conditions with a recognition hairpin. The acid-improved DNAzyme-based concatenated DNA circuit is promising to expand the application of chemiluminescence assay and provide a valuable strategy for early diagnosis and prognosis of cancer. An acid-improved concatenated chemiluminescence DNA circuit was successfully constructed for sensitive and selective detection and imaging of miRNA with significantly reduced background and simultaneously improved signal-to-noise ratio. [Display omitted] • The acid-improved hemin/G-quadruplex DNAzyme-based concatenated DNA circuit was constructed with high signal-to-noise ratio. • The acid-improved property is demonstrated to be closely associated with the low catalytic activity of aggregated hemin. • The concatenated chemiluminescence DNA biosensor exhibits high sensitivity and selectivity for miRNA detection and imaging. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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