脱氧核酶活性调控及其在生物医学领域中应用的研究进展

doi:10.13481/j.1671-587X.20250631

Abstract

Abstract:

RNA-cleaving deoxyribozymes （DNAzymes） are the DNA molecules with catalytic RNA cleavage activity， abd they can cleave the RNA substrates with high specificity with the advantages such as high specificity， no permanent impact on the genome， simple design and sequence- programmable， giving them great potential in biosensing and disease therapy. However， off-target activation of deoxyribozyme in vivo or complex biological environments limits their sensitivity and selectivity in various applications. Recent studies have focused on the chemical modification of deoxyribozymes， precise control for their catalytic activity its performed by introducing specific chemical groups； in addition， by combining deoxyribonucleases with aptamers， their precise recognition and efficient cleavage of target molecules can be realized； and the deoxyribozyme sequences can be used for logical operations and the development of molecular computers after suitable design. In this review， various approaches to the modification and design of DNAzymes were comprehensively discussed， with their unique advantages and superiority in biosensing and gene therapy， including examples of chemically and structurally modified RNA-cleaving depxurobozyme for therapeutic and sensing applications in the recent years.Ultimately， the review discussed the challenges and prospects of RNA-cleaving DNAzymeby for its applications in disease diagnostic and therapy， aiming to provide the reference farthe further application of deoxyribozyme in related fields.

Key words: Deoxyribozyme, Biosensor, Gene therapy, DNA nanostructures, Fluorescence probe

CLC Number:

Q554

Yuanyuan LI,Xin LIU,Tingshuang XU. Research progress in regulation of deoxyribozyme activity and its application in biomedical field[J].Journal of Jilin University(Medicine Edition), 2025, 51(6): 1736-1746.

References 60

[1]	JAYANTHI V S P K S A， DAS A B， SAXENA U. Recent advances in biosensor development for the detection of cancer biomarkers［J］. Biosens Bioelectron， 2017， 91： 15-23.
[2]	WANG J， KOO K M， WANG Y L， et al. Engineering state-of-the-art plasmonic nanomaterials for SERS-based clinical liquid biopsy applications［J］. Adv Sci， 2019， 6（23）： 1900730.
[3]	HORBINSKI C， LIGON K L， BRASTIANOS P， et al. The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients［J］. Neuro Oncol， 2019， 21（12）： 1498-1508.
[4]	GAO X， LIU Y X， HUO W D， et al. RNA-cleaving DNAzymes for accurate biosensing and gene therapy［J］. Nanoscale， 2023， 15（27）： 11346-11365.
[5]	ZHAO Y， LI R M， SUN J L， et al. Multifunctional DNAzyme-anchored metal-organic framework for efficient suppression of tumor metastasis［J］. ACS Nano， 2022， 16（4）： 5404-5417.
[6]	HE L J， PAGNEUX Q， LARROULET I， et al. Label-free femtomolar cancer biomarker detection in human serum using graphene-coated surface plasmon resonance chips［J］. Biosens Bioelectron， 2017， 89： 606-611.
[7]	BREAKER R R， JOYCE G F. A DNA enzyme with Mg²⁺-dependent RNA phosphoesterase activity［J］. Chem Biol， 1995， 2（10）： 655-660.
[8]	CHANDRA M， SACHDEVA A， SILVERMAN S K. DNA-catalyzed sequence-specific hydrolysis of DNA［J］. Nat Chem Biol， 2009， 5（10）： 718-720.
[9]	FLYNN-CHARLEBOIS A， WANG Y M， PRIOR T K， et al. Deoxyribozymes with 2'-5'RNA ligase activity［J］. J Am Chem Soc， 2003， 125（9）： 2444-2454.
[10]	LI Y F， BREAKER R R. Phosphorylating DNA with DNA［J］. Proc Natl Acad Sci U S A， 1999， 96（6）： 2746-2751.
[11]	LI Y F， LIU Y， BREAKER R R. Capping DNA with DNA［J］. Biochemistry， 2000， 39（11）： 3106-3114.
[12]	LI Y F， SEN D. A catalytic DNA for porphyrin metallation［J］. Nat Struct Mol Biol， 1996， 3（9）： 743-747.
[13]	WALSH S M， SACHDEVA A， SILVERMAN S K. DNA catalysts with tyrosine kinase activity［J］. J Am Chem Soc， 2013， 135（40）： 14928-14931.
[14]	KUMAR S， JAIN S， DILBAGHI N， et al. Advanced selection methodologies for DNAzymes in sensing and healthcare applications［J］. Trends Biochem Sci， 2019， 44（3）： 190-213.
[15]	MCCONNELL E M， COZMA I， MOU Q B， et al. Biosensing with DNAzymes［J］. Chem Soc Rev， 2021， 50（16）： 8954-8994.
[16]	ZHANG R， WU J， AO H， et al. A rolling circle-amplified G-quadruplex/hemin DNAzyme for chemiluminescence immunoassay of the SARS-CoV-2 protein［J］. Anal Chem， 2021， 93（28）： 9933-9938.
[17]	WU Q， WANG H， GONG K K， et al. Construction of an autonomous nonlinear hybridization chain reaction for extracellular vesicles-associated microRNAs discrimination［J］. Anal Chem， 2019， 91（15）： 10172-10179.
[18]	YANG L， WU Q， CHEN Y Q， et al. Amplified microRNA detection and intracellular imaging based on an autonomous and catalytic assembly of DNAzyme［J］. ACS Sens， 2019， 4（1）： 110-117.
[19]	SAMARIDOU E， HEYES J， LUTWYCHE P. Lipid nanoparticles for nucleic acid delivery： Current perspectives［J］. Adv Drug Deliv Rev， 2020， 154/155： 37-63.
[20]	LEGIEWICZ M， LOZUPONE C， KNIGHT R， et al. Size， constant sequences， and optimal selection［J］. Rna， 2005， 11（11）： 1701-1709.
[21]	MUÑOZ-GONZÁLEZ M， SILVA-GALLEGUILLOS V， PARRA-MENESES V， et al. Catalytic mechanisms of the 8-17 and 10-23 DNAzymes： shared mechanistic strategies［J］. Org Biomol Chem， 2025， 23（19）： 4564-4577.
[22]	BROWN A K， LI J， PAVOT C M， et al. A lead-dependent DNAzyme with a two-step mechanism［J］. Biochemistry， 2003， 42（23）： 7152-7161.
[23]	CAIRNS M J. Optimisation of the 10-23 DNAzyme-substrate pairing interactions enhanced RNA cleavage activity at purine-cytosine target sites［J］. Nucleic Acids Res， 2003， 31（11）： 2883-2889.
[24]	LIU H H， YU X， CHEN Y Q， et al. Crystal structure of an RNA-cleaving DNAzyme［J］. Nat Commun， 2017， 8： 2006.
[25]	CIESLAK M， SZYMANSKI J， ADAMIAK R W， et al. Structural rearrangements of the 10–23 DNAzyme to β3 integrin subunit mRNA induced by cations and their relations to the catalytic activity［J］. J Biol Chem， 2003， 278（48）： 47987-47996.
[26]	YI J T， CHEN T T， HUO J， et al. Nanoscale zeolitic imidazolate framework-8 for ratiometric fluorescence imaging of microRNA in living cells［J］. Anal Chem， 2017， 89（22）： 12351-12359.
[27]	FAN H H， ZHAO Z L， YAN G B， et al. A smart DNAzyme-MnO₂ nanosystem for efficient gene silencing［J］. Angew Chem Int Ed， 2015， 54（16）： 4801-4805.
[28]	WANG H M， CHEN Y Q， WANG H， et al. DNAzyme-loaded metal-organic frameworks （MOFs） for self-sufficient gene therapy［J］. Angew Chem Int Ed， 2019， 58（22）： 7380-7384.
[29]	ZHANG C Y， LI Q T， XU T B， et al. New DNA-hydrolyzing DNAs isolated from an ssDNA library carrying a terminal hybridization stem［J］. Nucleic Acids Res， 2021， 49（11）： 6364-6374.
[30]	BORGGRÄFE J， VICTOR J， ROSENBACH H， et al. Time-resolved structural analysis of an RNA-cleaving DNA catalyst［J］. Nature， 2022， 601（7891）： 144-149.
[31]	SOUKUP G A， BREAKER R R. Nucleic acid molecular switches［J］. Trends Biotechnol， 1999， 17（12）： 469-476.
[32]	YANG Y J， HUANG J， YANG X H， et al. Aptazyme-gold nanoparticle sensor for amplified molecular probing in living cells［J］. Anal Chem， 2016， 88（11）： 5981-5987.
[33]	TANG W X， HU J H， LIU D R. Aptazyme-embedded guide RNAs enable ligand-responsive genome editing and transcriptional activation［J］. Nat Commun， 2017， 8： 15939.
[34]	ZHENG X D， YANG J， ZHOU C J， et al. Allosteric DNAzyme-based DNA logic circuit： operations and dynamic analysis［J］. Nucleic Acids Res， 2019， 47（3）： 1097-1109.
[35]	GAO Y S， ZHANG S B， WU C W， et al. Self-protected DNAzyme walker with a circular bulging DNA shield for amplified imaging of miRNAs in living cells and mice［J］. ACS Nano， 2021， 15（12）： 19211-19224.
[36]	STOJANOVIC M N， DE PRADA P， LANDRY D W. Catalytic molecular beacons［J］. ChemBioChem， 2001， 2（6）： 411-415.
[37]	WANG D Y， SEN D. A novel mode of regulation of an RNA-cleaving DNAzyme by effectors that bind to both enzyme and substrate［J］. J Mol Biol， 2001， 310（4）： 723-734.
[38]	WU Y N， HUANG J， YANG X H， et al. Gold nanoparticle loaded split-DNAzyme probe for amplified miRNA detection in living cells［J］. Anal Chem， 2017， 89（16）： 8377-8383.
[39]	ZHU D， WEI Y Q， SUN T， et al. Encoding DNA frameworks for amplified multiplexed imaging of intracellular microRNAs［J］. Anal Chem， 2021， 93（4）： 2226-2234.
[40]	WANG X Y， FENG M L， XIAO L， et al. Postsynthetic modification of DNA phosphodiester backbone for photocaged DNAzyme［J］. ACS Chem Biol， 2016， 11（2）： 444-451.
[41]	YOUNG D D， LIVELY M O， DEITERS A. Activation and deactivation of DNAzyme and antisense function with light for the photochemical regulation of gene expression in mammalian cells［J］. J Am Chem Soc， 2010， 132（17）： 6183-6193.
[42]	TORABI S F， WU P W， MCGHEE C E， et al. In vitro selection of a sodium-specific DNAzyme and its application in intracellular sensing［J］. Proc Natl Acad Sci U S A， 2015， 112（19）： 5903-5908.
[43]	YANG Z L， LOH K Y， CHU Y T， et al. Optical control of metal ion probes in cells and zebrafish using highly selective DNAzymes conjugated to upconversion nanoparticles［J］. J Am Chem Soc， 2018， 140（50）： 17656-17665.
[44]	KNUTSON S D， SANFORD A A， SWENSON C S， et al. Thermoreversible control of nucleic acid structure and function with glyoxal caging［J］. J Am Chem Soc， 2020， 142（41）： 17766-17781.
[45]	XIAO L， GU C M， XIANG Y. Orthogonal activation of RNA-cleaving DNAzymes in live cells by reactive oxygen species［J］. Angew Chem Int Ed， 2019， 58（40）： 14167-14172.
[46]	LIN Y， YANG Z L， LAKE R J， et al. Enzyme-mediated endogenous and bioorthogonal control of a DNAzyme fluorescent sensor for imaging metal ions in living cells［J］. Angew Chem Int Ed， 2019， 58（47）： 17061-17067.
[47]	WANG Z， YANG J， QIN G， et al. An intelligent nanomachine guided by DNAzyme logic system for precise chemodynamic therapy［J］. Angew Chem Int Ed， 2022， 61（38）： e202204291.
[48]	WANG R， HE W H， YI X， et al. Site-specific bioorthogonal activation of DNAzymes for on-demand gene therapy［J］. J Am Chem Soc， 2023， 145（32）： 17926-17935.
[49]	ILCHOVSKA D D， BARROW D M. An Overview of the NF-kB mechanism of pathophysiology in rheumatoid arthritis， investigation of the NF-kB ligand RANKL and related nutritional interventions［J］. Autoimmun Rev， 2021， 20（2）： 102741.
[50]	TIAN L， ZHANG J Y， ZHANG Y， et al. Bipedal DNAzyme walker triggered dual-amplification electrochemical platform for ultrasensitive ratiometric biosensing of microRNA-21［J］. Biosens Bioelectron， 2023， 220： 114879.
[51]	HOSSEINZADEH E， RAVAN H， MOHAMMADI A， et al. Target-triggered three-way junction in conjugation with catalytic concatemers-functionalized nanocomposites provides a highly sensitive colorimetric method for miR-21 detection［J］. Biosens Bioelectron， 2018， 117： 567-574.
[52]	YI D Y， ZHAO J， LI L L. An enzyme-activatable engineered DNAzyme sensor for cell-selective imaging of metal ions［J］. Angew Chem Int Ed， 2021， 60（12）： 6300-6304.
[53]	WANG X J， KIM G， CHU J L， et al. Noninvasive and spatiotemporal control of DNAzyme-based imaging of metal ions in vivo using high-intensity focused ultrasound［J］. J Am Chem Soc， 2022， 144（13）： 5812-5819.
[54]	HE X J， YAN Y L， DELAURIER A， et al. Observation of miRNA gene expression in zerbrafish embryos by in situ hybridization to microRNA primary transcripts［J］. Zerbrafish， 2011， 8（1）： 1-8.
[55]	MENG X D， ZHANG K， YANG F， et al. Biodegradable metal-organic frameworks power DNAzyme for in vivo temporal-spatial control fluorescence imaging of aberrant microRNA and hypoxic tumor［J］. Anal Chem， 2020， 92（12）： 8333-8339.
[56]	WEI J， WANG H M， WU Q， et al. A smart， autocatalytic， DNAzyme biocircuit for in Vivo， amplified， microRNA imaging［J］. Angew Chem Int Ed， 2020， 59（15）： 5965-5971.
[57]	LIU C Z， CHEN Y X， ZHAO J， et al. Self-assembly of copper-DNAzyme nanohybrids for dual-catalytic tumor therapy［J］. Angew Chem Int Ed， 2021， 60（26）： 14324-14328.
[58]	MOLDEN T A， NICCUM C T， KOLPASHCHIKOV D M. Cut and paste for cancer treatment： a DNA nanodevice that cuts out an RNA marker sequence to activate a therapeutic function［J］. Angew Chem Int Ed， 2020， 59（47）： 21190-21194.
[59]	ZHAO H X， ZHANG Z L， ZUO D， et al. A synergistic DNA-polydopamine-MnO₂ nano complex for near-infrared-light-powered DNAzyme-mediated gene therapy［J］. Nano Lett， 2021， 21（12）： 5377-5385.
[60]	WANG J， YU S S， WU Q， et al. A self-catabolic multifunctional DNAzyme nanosponge for programmable drug delivery and efficient gene silencing［J］. Angew Chem Int Ed， 2021， 60（19）： 10766-10774.

Research progress in regulation of deoxyribozyme activity and its application in biomedical field

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References 60

Related Articles 15

Metrics

Comments

Recommended 0

[1]	FANG Tengjiaozi, LIU Jie, GU Zhongyi, GONG Haihuan, BU Wenhuan, DONG Yue, SUN Hongchen. Osteogenesis differentiation of MC3T3-E1 cells induced by miRNA-2861 mimic transfection mediated by polyethylenimine [J]. Journal of Jilin University Medicine Edition, 2016, 42(05): 848-854.
[2]	RAO Feng, CUI Ganghua, WANG Yan, LIU Wei, CAO Weiwei, SHI Chenhui, WANG Weishan. Construction and identification of FRET-based MMP3 biosensor [J]. Journal of Jilin University Medicine Edition, 2016, 42(02): 210-214.
[3]	CUI Ganghua, RAO Feng, WANG Yan, CAO Weiwei, LIU Wei, WANG Weishan, SHI Chenhui. Construction and identification of urokinase-type plasminogen activator biosensor plasmid [J]. Journal of Jilin University Medicine Edition, 2015, 41(06): 1124-1129.
[4]	FANF Yang-giu,LIU Lei,TAN Yan,JIANG Yong-xing. Construction of specific expression vector of EGFP regulated by ODDD in cells under hypoxia and its significance [J]. J4, 2012, 38(5): 870-875.
[5]	CHEN Zhi-Yong, LIU Min, GONG Shou-Liang, DONG Li-Hua. Inhibitory effects of recombinant plasmid pshuttle-Egr1-shTRAIL transfection in combination with X-irradiation on growth of liver cancer cells SMMC7721 [J]. J4, 2011, 37(6): 981-984.
[6]	YANG Zhi-Guang, LIU Lin-Lin, SHAO Guo-Guang. Features of Bifidobacterium breve carrying ES and IFN&gamma\|and its anti-tumor effect \|in mice with \|lung cancer [J]. J4, 2011, 37(4): 596-602.
[7]	LIANG Zuo-Wen, ZHAO Li-Jing, JIA Hui-Jie, LI Xin, GAO Li-Fang, ZHANG Ling, ZHAO Xue-Jian. Construction of siRNA-Stat3 and GRIM-19 co-expression plasmid and study on its function [J]. J4, 2010, 36(5): 858-861.
[8]	YANG Yu, YANG Xin, SUN Xin, WU Hao, WANG Quan-Ying, YANG Guang-Xiao, WU Jiang. Neuroprotective effect of \|lentiviral vector secreting neuroprotective peptide \|on closed head injury in mice [J]. J4, 2010, 36(4): 616-619.
[9]	QI Xiao-yan,GAO Run-ping,ZHANG Rui-juan,LI Guo-feng,YANG Yong-guang. Effects of hammerhad ribozyme targeting connective tissue growth factor on collagen Ⅰ synthesis and cell cycle progression of human hepatic stellate cells [J]. J4, 2009, 35(1): 26-29.
[10]	XU Pei-ran,YANG Zhi-guang,YAO Xian-zhang,SHAO Guo-guang. Effect of anti-sense osteopontin on metastasis and infiltration of esophagus cancer [J]. J4, 2008, 34(2): 295-298.
[11]	WANG Jian-jun,LI Yan-ru,LI Xiao-min,ZHANG Hai-ying,WANG Lin. Hydrodynamic injection-mediated IL-12 gene therapyin mouse model of malignant ascites [J]. J4, 2008, 34(2): 179-182.
[12]	TIAN Yong，ZHANG Ling,JI Kun,GAO Li-fang,SUN Ying,LIU Yan-bo,XU De-qi,ZHAO Xue-jian. Therapeutic effect of attenuated salmonella typhimurium with siRNA-Stat3 plasmid on orthotopic transplantation tumor model of liver in mice [J]. J4, 2008, 34(1): 38-41.
[13]	CHE Guang-hua,GAO Hang,WANG Jian-wei,ZHANG Hai-ying，LU Ji-rong. Effects of adenovirus vector carrying murine IL-12 gene on expression of GATA-3 in lung tissue of mouse model with asthma [J]. J4, 2007, 33(6): 974-977.
[14]	WANG Yang,NIU Jun-qi,WANG Feng. Effect of RNAi on HBV replication and expression [J]. J4, 2007, 33(4): 616-620.
[15]	GAO Hang, WANG Jian-wei, CHE Guang-hua, ZHANG Hai-ying, CHEN Yuan-yao. Effects of recombinant murine interlukin-12 and GM-CSF gene adenovirus vectors on B16 melanoma [J]. J4, 2006, 32(6): 996-999.