DNAzyme-based biosensors and nanodevices.

DNAzymes, screened through in vitro selection, have shown great promise as molecular tools in the design of biosensors and nanodevices. The catalytic activities of DNAzymes depend specifically on cofactors and show multiple enzymatic turnover properties, which make DNAzymes both versatile recognition elements and outstanding signal amplifiers. Combining nanomaterials with unique optical, magnetic and electronic properties, DNAzymes may yield novel fluorescent, colorimetric, surface-enhanced Raman scattering (SERS), electrochemical and chemiluminescent biosensors. Moreover, some DNAzymes have been utilized as functional components to perform arithmetic operations or as "walkers" to move along DNA tracks. DNAzymes can also function as promising therapeutics, when designed to complement target mRNAs or viral RNAs, and consequently lead to down-regulation of protein expression. This feature article focuses on the most significant achievements in using DNAzymes as recognition elements and signal amplifiers for biosensors, and highlights the applications of DNAzymes in logic gates, DNA walkers and nanotherapeutics.

[1]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[2]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[3]  R R Breaker,et al.  A DNA enzyme that cleaves RNA. , 1994, Chemistry & biology.

[4]  R R Breaker,et al.  Cleaving DNA with DNA. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Yingfu Li,et al.  DNA-enhanced peroxidase activity of a DNA-aptamer-hemin complex. , 1998, Chemistry & biology.

[6]  R R Breaker,et al.  Phosphorylating DNA with DNA. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Rossi,et al.  Inhibition of bcr-abl oncogene expression by novel deoxyribozymes (DNAzymes). , 1999, Human gene therapy.

[8]  G. F. Joyce,et al.  RNA cleavage by a DNA enzyme with extended chemical functionality. , 2000, Journal of the American Chemical Society.

[9]  Jing Li,et al.  A highly sensitive and selective catalytic DNA biosensor for lead ions [9] , 2000 .

[10]  P. Witting,et al.  The peroxidase activity of a hemin--DNA oligonucleotide complex: free radical damage to specific guanine bases of the DNA. , 2001, Journal of the American Chemical Society.

[11]  Levon M Khachigian.  DNAzymes: cutting a path to a new class of therapeutics. , 2002, Current opinion in molecular therapeutics.

[12]  S. Douthwaite,et al.  LNAzymes: incorporation of LNA-type monomers into DNAzymes markedly increases RNA cleavage. , 2002, Journal of the American Chemical Society.

[13]  Yingfu Li,et al.  Sequence diversity, metal specificity, and catalytic proficiency of metal-dependent phosphorylating DNA enzymes. , 2002, Chemistry & biology.

[14]  Yingfu Li,et al.  An efficient RNA-cleaving DNA enzyme that synchronizes catalysis with fluorescence signaling. , 2003, Journal of the American Chemical Society.

[15]  Yi Lu,et al.  Improving fluorescent DNAzyme biosensors by combining inter- and intramolecular quenchers. , 2003, Analytical chemistry.

[16]  Yi Lu,et al.  A colorimetric lead biosensor using DNAzyme-directed assembly of gold nanoparticles. , 2003, Journal of the American Chemical Society.

[17]  Levon M Khachigian,et al.  Transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumor growth , 2003, Nature Medicine.

[18]  Frank Baas,et al.  UvA-DARE ( Digital Academic Repository ) In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid ( LNA ) antisense oligonucleotides , 2017 .

[19]  Levon M Khachigian,et al.  Inhibition of human breast carcinoma proliferation, migration, chemoinvasion and solid tumour growth by DNAzymes targeting the zinc finger transcription factor EGR-1. , 2004, Nucleic acids research.

[20]  Juewen Liu,et al.  Accelerated color change of gold nanoparticles assembled by DNAzymes for simple and fast colorimetric Pb2+ detection. , 2004, Journal of the American Chemical Society.

[21]  Yi Lu,et al.  Adenosine-dependent assembly of aptazyme-functionalized gold nanoparticles and its application as a colorimetric biosensor. , 2004, Analytical chemistry.

[22]  Itamar Willner,et al.  Lighting Up Biochemiluminescence by the Surface Self‐Assembly of DNA–Hemin Complexes , 2004, Chembiochem : a European journal of chemical biology.

[23]  Razvan Nutiu,et al.  Structure-switching allosteric deoxyribozymes , 2004 .

[24]  L. Khachigian,et al.  Effect of deoxyribozymes targeting c-Jun on solid tumor growth and angiogenesis in rodents. , 2004, Journal of the National Cancer Institute.

[25]  Itamar Willner,et al.  Catalytic beacons for the detection of DNA and telomerase activity. , 2004, Journal of the American Chemical Society.

[26]  Itamar Willner,et al.  DNAzyme-Functionalized Au Nanoparticles for the Amplified Detection of DNA or Telomerase Activity , 2004 .

[27]  Whitney E. Purtha,et al.  General deoxyribozyme-catalyzed synthesis of native 3'-5' RNA linkages. , 2005, Journal of the American Chemical Society.

[28]  R. Kane,et al.  Highly active and stable DNAzyme-carbon nanotube hybrids. , 2005, Journal of the American Chemical Society.

[29]  David G. Morris,et al.  Inhibition of urokinase receptor gene expression and cell invasion by anti‐uPAR DNAzymes in osteosarcoma cells , 2005, The FEBS journal.

[30]  P. Yin,et al.  A DNAzyme that walks processively and autonomously along a one-dimensional track. , 2005, Angewandte Chemie.

[31]  Yi Lu,et al.  Stimuli-responsive disassembly of nanoparticle aggregates for light-up colorimetric sensing. , 2005, Journal of the American Chemical Society.

[32]  L. Khachigian,et al.  Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression , 2006, Oncogene.

[33]  Kevin Robbie,et al.  Nanomaterials and nanoparticles: Sources and toxicity , 2007, Biointerphases.

[34]  F. Simmel,et al.  DNA-based nanodevices , 2007 .

[35]  Yi Lu,et al.  A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity , 2007, Proceedings of the National Academy of Sciences.

[36]  Kevin W Plaxco,et al.  Electrochemical detection of parts-per-billion lead via an electrode-bound DNAzyme assembly. , 2007, Journal of the American Chemical Society.

[37]  Yi Lu,et al.  Rational design of "turn-on" allosteric DNAzyme catalytic beacons for aqueous mercury ions with ultrahigh sensitivity and selectivity. , 2007, Angewandte Chemie.

[38]  Juewen Liu,et al.  Colorimetric Cu2+ detection with a ligation DNAzyme and nanoparticles. , 2007, Chemical communications.

[39]  I. Willner,et al.  Amplified analysis of low-molecular-weight substrates or proteins by the self-assembly of DNAzyme-aptamer conjugates. , 2007, Journal of the American Chemical Society.

[40]  Yi Lu,et al.  A DNAzyme catalytic beacon sensor for paramagnetic Cu2+ ions in aqueous solution with high sensitivity and selectivity. , 2007, Journal of the American Chemical Society.

[41]  E. Wang,et al.  G-quadruplex-based DNAzyme for facile colorimetric detection of thrombin. , 2008, Chemical communications.

[42]  Yi Lu,et al.  Highly sensitive and selective colorimetric sensors for uranyl (UO2(2+)): development and comparison of labeled and label-free DNAzyme-gold nanoparticle systems. , 2008, Journal of the American Chemical Society.

[43]  Zhiwei Zhu,et al.  Electrochemical DNAzyme sensor for lead based on amplification of DNA-Au bio-bar codes. , 2008, Analytical chemistry.

[44]  L. M. Khachigian,et al.  DNAzymes and cardiovascular disease , 2008, British journal of pharmacology.

[45]  Itamar Willner,et al.  Aptamer-DNAzyme hairpins for amplified biosensing. , 2009, Analytical chemistry.

[46]  Yi Lu,et al.  Abasic site-containing DNAzyme and aptamer for label-free fluorescent detection of Pb(2+) and adenosine with high sensitivity, selectivity, and tunable dynamic range. , 2009, Journal of the American Chemical Society.

[47]  E. Wang,et al.  G-Quadruplex-based DNAzyme as a sensing platform for ultrasensitive colorimetric potassium detection. , 2009, Chemical communications.

[48]  Juewen Liu,et al.  Functional nucleic acid sensors. , 2009, Chemical reviews.

[49]  M. Ali,et al.  Colorimetric sensing by using allosteric-DNAzyme-coupled rolling circle amplification and a peptide nucleic acid-organic dye probe. , 2009, Angewandte Chemie.

[50]  Juan Xu,et al.  A novel electrochemical DNAzyme sensor for the amplified detection of Pb2+ ions. , 2010, Chemical communications.

[51]  Tao Li,et al.  A lead(II)-driven DNA molecular device for turn-on fluorescence detection of lead(II) ion with high selectivity and sensitivity. , 2010, Journal of the American Chemical Society.

[52]  Chunhai Fan,et al.  A Graphene Nanoprobe for Rapid, Sensitive, and Multicolor Fluorescent DNA Analysis , 2010 .

[53]  Xiaoling Zhang,et al.  Single-walled carbon nanotube as an effective quencher , 2010, Analytical and bioanalytical chemistry.

[54]  Yi Lu,et al.  Catalytic and molecular beacons for amplified detection of metal ions and organic molecules with high sensitivity. , 2010, Analytical chemistry.

[55]  J. Niewiarowska,et al.  DNAzyme as an efficient tool to modulate invasiveness of human carcinoma cells. , 2010, Acta biochimica Polonica.

[56]  Yi Lu,et al.  A highly selective lead sensor based on a classic lead DNAzyme. , 2010, Chemical communications.

[57]  Zhongxin Lu,et al.  A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene , 2010, Molecules.

[58]  P. Choong,et al.  A nanoparticulate system that enhances the efficacy of the tumoricide Dz13 when administered proximal to the lesion site. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[59]  Bang-Ce Ye,et al.  DNAzyme self-assembled gold nanoparticles for determination of metal ions using fluorescence anisotropy assay. , 2010, Analytical biochemistry.

[60]  Itamar Willner,et al.  CdSe/ZnS quantum dots-G-quadruplex/hemin hybrids as optical DNA sensors and aptasensors. , 2010, Analytical chemistry.

[61]  Sai Bi,et al.  Triggered polycatenated DNA scaffolds for DNA sensors and aptasensors by a combination of rolling circle amplification and DNAzyme amplification. , 2010, Analytical chemistry.

[62]  Itamar Willner,et al.  Amplified biosensing using the horseradish peroxidase-mimicking DNAzyme as an electrocatalyst. , 2010, Analytical chemistry.

[63]  I. Willner,et al.  Optical, electrical and surface plasmon resonance methods for detecting telomerase activity. , 2010, Analytical chemistry.

[64]  Guo-Li Shen,et al.  Graphene-DNAzyme based biosensor for amplified fluorescence "turn-on" detection of Pb2+ with a high selectivity. , 2011, Analytical chemistry.

[65]  Jie Wu,et al.  Ultrasensitive immunoassay of protein biomarker based on electrochemiluminescent quenching of quantum dots by hemin bio-bar-coded nanoparticle tags. , 2011, Analytical chemistry.

[66]  Jian-hui Jiang,et al.  Homogeneous label-free genotyping of single nucleotide polymorphism using ligation-mediated strand displacement amplification with DNAzyme-based chemiluminescence detection. , 2011, Analytical chemistry.

[67]  Chaoyong James Yang,et al.  DNAzyme crosslinked hydrogel: a new platform for visual detection of metal ions. , 2011, Chemical communications.

[68]  G. Shen,et al.  A nanoscale DNA-Au dendrimer as a signal amplifier for the universal design of functional DNA-based SERS biosensors. , 2011, Chemical communications.

[69]  Weihong Tan,et al.  A ligation-triggered DNAzyme cascade for amplified fluorescence detection of biological small molecules with zero-background signal. , 2011, Journal of the American Chemical Society.

[70]  S. Aguirre,et al.  Fluorogenic DNAzyme probes as bacterial indicators. , 2011, Angewandte Chemie.

[71]  X. Shuai,et al.  Ultrasensitive detection of lead(II) with DNAzyme and gold nanoparticles probes by using a dynamic light scattering technique. , 2011, Chemical communications.

[72]  Yan Jin,et al.  Gold nanorods-based FRET assay for sensitive detection of Pb2+ using 8-17DNAzyme. , 2011, The Analyst.

[73]  Tao Li,et al.  Bifunctional colorimetric oligonucleotide probe based on a G-quadruplex DNAzyme molecular beacon. , 2011, Analytical chemistry.

[74]  Jingnan Shen,et al.  Ezrin mRNA target site selection for DNAzymes using secondary structure and hybridization thermodynamics , 2011, Tumor Biology.

[75]  Chunhai Fan,et al.  Metal ion-modulated graphene-DNAzyme interactions: design of a nanoprobe for fluorescent detection of lead(II) ions with high sensitivity, selectivity and tunable dynamic range. , 2011, Chemical communications.

[76]  M. Thompson,et al.  DNA-nanoparticle micelles as supramolecular fluorogenic substrates enabling catalytic signal amplification and detection by DNAzyme probes. , 2011, Chemical communications.

[77]  Itamar Willner,et al.  Chemiluminescent and chemiluminescence resonance energy transfer (CRET) detection of DNA, metal ions, and aptamer-substrate complexes using hemin/G-quadruplexes and CdSe/ZnS quantum dots. , 2011, Journal of the American Chemical Society.

[78]  Wenwan Zhong,et al.  Combing DNAzyme with single-walled carbon nanotubes for detection of Pb(II) in water. , 2011, The Analyst.

[79]  Itamar Willner,et al.  Amplified analysis of DNA by the autonomous assembly of polymers consisting of DNAzyme wires. , 2011, Journal of the American Chemical Society.

[80]  E. Wang,et al.  Label-free DNAzyme-based fluorescing molecular switch for sensitive and selective detection of lead ions. , 2011, Chemical communications.

[81]  Itamar Willner,et al.  Amplified detection of DNA through an autocatalytic and catabolic DNAzyme-mediated process. , 2011, Angewandte Chemie.

[82]  Joseph Irudayaraj,et al.  A SERS DNAzyme biosensor for lead ion detection. , 2011, Chemical communications.

[83]  Bong Hyun Chung,et al.  Improving Pb2+ detection using DNAzyme-based fluorescence sensors by pairing fluorescence donors with gold nanoparticles. , 2011, Biosensors & bioelectronics.

[84]  Ming Zhou,et al.  G-Quadruplex-based DNAzyme for colorimetric detection of cocaine: using magnetic nanoparticles as the separation and amplification element. , 2011, The Analyst.

[85]  Itamar Willner,et al.  Following Glucose Oxidase Activity by Chemiluminescence and Chemiluminescence Resonance Energy Transfer (CRET) Processes Involving Enzyme-DNAzyme Conjugates , 2011, Sensors.

[86]  Jilin Yan,et al.  DNAzyme-based turn-on chemiluminescence assays in homogenous media. , 2012, Biosensors & bioelectronics.

[87]  Zhiliang Jiang,et al.  Colorimetric sensing of trace UO2(2+) by using nanogold-seeded nucleation amplification and label-free DNAzyme cleavage reaction. , 2012, The Analyst.

[88]  Itamar Willner,et al.  Fluorescence detection of DNA, adenosine-5'-triphosphate (ATP), and telomerase activity by zinc(II)-protoporphyrin IX/G-quadruplex labels. , 2012, Analytical chemistry.

[89]  Itamar Willner,et al.  Optical aptasensors for the analysis of the vascular endothelial growth factor (VEGF). , 2012, Analytical chemistry.

[90]  Dan Zhu,et al.  A novel optical thrombin aptasensor based on magnetic nanoparticles and split DNAzyme. , 2012, Analytica chimica acta.

[91]  Cuichen Wu,et al.  A logical molecular circuit for programmable and autonomous regulation of protein activity using DNA aptamer-protein interactions. , 2012, Journal of the American Chemical Society.

[92]  Yongxi Zhao,et al.  Amplified fluorescence detection of mercury(II) ions (Hg2+) using target-induced DNAzyme cascade with catalytic and molecular beacons. , 2012, The Analyst.

[93]  Lifang Yang,et al.  Use of DNAzymes for cancer research and therapy , 2012 .

[94]  Françoise Remacle,et al.  Logic reversibility and thermodynamic irreversibility demonstrated by DNAzyme-based Toffoli and Fredkin logic gates , 2012, Proceedings of the National Academy of Sciences.

[95]  Itamar Willner,et al.  Zn(2+)-ligation DNAzyme-driven enzymatic and nonenzymatic cascades for the amplified detection of DNA. , 2012, Journal of the American Chemical Society.

[96]  Weihong Tan,et al.  An autonomous and controllable light-driven DNA walking device. , 2012, Angewandte Chemie.

[97]  Itamar Willner,et al.  Amplified surface plasmon resonance and electrochemical detection of Pb2+ ions using the Pb2+-dependent DNAzyme and hemin/G-quadruplex as a label. , 2012, Analytical chemistry.

[98]  X. Shuai,et al.  Detection of Pb²⁺ at attomole levels by using dynamic light scattering and unmodified gold nanoparticles. , 2012, Analytical biochemistry.

[99]  Chunhai Fan,et al.  DNAzyme-based rolling-circle amplification DNA machine for ultrasensitive analysis of microRNA in Drosophila larva. , 2012, Analytical chemistry.

[100]  Kevin Yehl,et al.  Catalytic deoxyribozyme-modified nanoparticles for RNAi-independent gene regulation. , 2012, ACS nano.

[101]  Guonan Chen,et al.  A G-quadruplex based label-free fluorescent biosensor for lead ion. , 2012, Biosensors & bioelectronics.

[102]  Weian Zhao,et al.  Colorimetric and ultrasensitive bioassay based on a dual-amplification system using aptamer and DNAzyme. , 2012, Analytical chemistry.

[103]  Juan Tang,et al.  Nanogold-functionalized DNAzyme concatamers with redox-active intercalators for quadruple signal amplification of electrochemical immunoassay. , 2013, ACS applied materials & interfaces.

[104]  Itamar Willner,et al.  Smart mesoporous SiO2 nanoparticles for the DNAzyme-induced multiplexed release of substrates. , 2013, Journal of the American Chemical Society.

[105]  Weihong Tan,et al.  Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics , 2013, Proceedings of the National Academy of Sciences.

[106]  Meng Zhang,et al.  Three-dimensional paper-based electrochemiluminescence device for simultaneous detection of Pb2+ and Hg2+ based on potential-control technique. , 2013, Biosensors & bioelectronics.

[107]  Yunlei Zhou,et al.  Electrochemical determination of microRNA-21 based on bio bar code and hemin/G-quadruplet DNAenzyme. , 2013, The Analyst.

[108]  Itamar Willner,et al.  Switchable catalytic acrylamide hydrogels cross-linked by hemin/G-quadruplexes. , 2013, Nano letters.

[109]  Highly sensitive fluorescent immunoassay of human immunoglobulin G based on PbS nanoparticles and DNAzyme. , 2013, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[110]  Bing Zhang,et al.  Cleavage of metal-ion-induced DNAzymes released from nanolabels for highly sensitive and specific immunoassay. , 2013, Bioconjugate chemistry.

[111]  Itamar Willner,et al.  Switching photonic and electrochemical functions of a DNAzyme by DNA machines. , 2013, Nano letters.

[112]  D. Tang,et al.  A difunctional DNA-AuNP dendrimer coupling DNAzyme with intercalators for femtomolar detection of nucleic acids. , 2013, Chemical communications.

[113]  H. Cui,et al.  A homogeneous hemin/G-quadruplex DNAzyme based turn-on chemiluminescence aptasensor for interferon-gamma detection via in-situ assembly of luminol functionalized gold nanoparticles, deoxyribonucleic acid, interferon-gamma and hemin. , 2013, Analytica chimica acta.

[114]  I. Willner,et al.  Nucleic acid/quantum dots (QDs) hybrid systems for optical and photoelectrochemical sensing. , 2013, ACS applied materials & interfaces.

[115]  Chun-yang Zhang,et al.  Sensitive detection of DNA methyltransferase using hairpin probe-based primer generation rolling circle amplification-induced chemiluminescence. , 2013, Analytical chemistry.

[116]  Weihong Tan,et al.  Versatile DNAzyme-based amplified biosensing platforms for nucleic acid, protein, and enzyme activity detection. , 2013, Analytical chemistry.

[117]  C. Huang,et al.  A graphene oxide enhanced fluorescence anisotropy strategy for DNAzyme-based assay of metal ions. , 2013, Chemical communications.

[118]  Shusheng Zhang,et al.  A sensitive SERS assay of L-histidine via a DNAzyme-activated target recycling cascade amplification strategy. , 2013, Chemical communications.

[119]  Guonan Chen,et al.  DNAzyme-based magneto-controlled electronic switch for picomolar detection of lead (II) coupling with DNA-based hybridization chain reaction. , 2013, Biosensors & bioelectronics.

[120]  Yi Lu,et al.  An invasive DNA approach toward a general method for portable quantification of metal ions using a personal glucose meter. , 2013, Chemical communications.

[121]  Byong-Seok Choi,et al.  Deoxyribozyme-loaded nano-graphene oxide for simultaneous sensing and silencing of the hepatitis C virus gene in liver cells. , 2013, Chemical communications.

[122]  Weihong Tan,et al.  Noncanonical self-assembly of multifunctional DNA nanoflowers for biomedical applications. , 2013, Journal of the American Chemical Society.

[123]  Ke-Jing Huang,et al.  A highly sensitive and selective biosensing strategy for the detection of Pb2+ ions based on GR-5 DNAzyme functionalized AuNPs , 2013 .

[124]  Yi Lu,et al.  A DNAzyme-gold nanoparticle probe for uranyl ion in living cells. , 2013, Journal of the American Chemical Society.

[125]  R. Corn,et al.  DNAzyme footprinting: detecting protein-aptamer complexation on surfaces by blocking DNAzyme cleavage activity. , 2013, Journal of the American Chemical Society.

[126]  Shaojun Dong,et al.  A visible multi-digit DNA keypad lock based on split G-quadruplex DNAzyme and silver microspheres. , 2013, Chemical communications.

[127]  Lingwen Zeng,et al.  An enzyme-free and label-free assay for copper(II) ion detection based on self-assembled DNA concatamers and Sybr Green I. , 2013, The Analyst.

[128]  Hongyuan Chen,et al.  Efficient quenching of electrochemiluminescence from K-doped graphene-CdS:Eu NCs by G-quadruplex-hemin and target recycling-assisted amplification for ultrasensitive DNA biosensing. , 2013, Chemical communications.

[129]  Weihong Tan,et al.  DNA nanoflowers for multiplexed cellular imaging and traceable targeted drug delivery. , 2014, Angewandte Chemie.

[130]  Yifan Lv,et al.  DNA Dendrimer: An Efficient Nanocarrier of Functional Nucleic Acids for Intracellular Molecular Sensing , 2014, ACS nano.