DNAzyme amplifiers have been extensively explored as a useful sensing platform,but single DNAzyme amplifier is limited in biosensing applications by its low sensitivity.Herein,a cascade DNAzyme amplifier was designed ...DNAzyme amplifiers have been extensively explored as a useful sensing platform,but single DNAzyme amplifier is limited in biosensing applications by its low sensitivity.Herein,a cascade DNAzyme amplifier was designed by exploiting concurrent amplification cycle principles of toehold-mediated strand displacement reaction(TSDR)and Zn^(2+)-assisted DNAzyme cycle with lower cost and simpler procedures.Compared with single DNAzyme amplifier,the proposed TSDR-propelled cascade DNAzyme amplifier exhibited higher sensitivity by releasing more DNAzyme through TSDR to cleave substrate strand during the DNAzyme cycle.Base on this,let-7a could be sensitively detected in the range of 5-50 nmol/L with a detection limit of 64 pmol/L.Furthermore,the dual signal amplification strategy of the cascade DNAzyme amplifier exhibited excellent selectivity to distinguish single-base mismatched DNA strands,which has been successfully applied to the determination of let-7a in blood serum,showing high promise in early cancer diagnosis.展开更多
Background： The DNA strand displacement reaction, which uses flexible and programmable DNA molecules as reaction components, is the basis of dynamic DNA nanotechnology, and has been widely used in the design of compl...Background： The DNA strand displacement reaction, which uses flexible and programmable DNA molecules as reaction components, is the basis of dynamic DNA nanotechnology, and has been widely used in the design of complex autonomous behaviors. Results： In this review, we first briefly introduce the concept of toehold-mediated strand displacement reaction and its kinetics regulation in pure solution. Thereafter, we review the recent progresses in DNA complex circuit, the assembly of AuNPs driven by DNA molecular machines, and the detection of single nucleotide polymorphism （SNP） using DNA toehold exchange probes in pure solution and in interface state. Lastly, the applications of toehold-mediated strand displacement in the genetic regulation and silencing through combining gene circuit with RNA interference systems are reviewed. Conclusions： The toehold-mediated strand displacement reaction makes DNA an excellent material for the fabrication of molecular machines and complex circuit, and may potentially be used in the disease diagnosis and the regulation of gene silencing in the near future.展开更多
Strand displacement reaction enables the construction of enzyme-free DNA reaction networks,thus has been widely applied to DNA circuit and nanotechnology.It has the characteristics of high efficiency,universality and ...Strand displacement reaction enables the construction of enzyme-free DNA reaction networks,thus has been widely applied to DNA circuit and nanotechnology.It has the characteristics of high efficiency,universality and regulatability.However,the existing regulation tools cannot enable effective control of the reaction sequence,which undoubtedly limits the construction of complex nucleic acid circuits.Herein,we developed a regulation tool,toehold lock,and achieved strict control of reaction sequence without loss of the main reaction signal output.Furthermore,we applied the tool to scenarios such as seesaw circuits,AND/OR logic gates,and entropy-driven circuits,and respectively demonstrated its significant superiority compared to the original method.We believe that the proposed toehold lock has greatly optimized the efficiency of DNA strand displacement-based networks,and we anticipate that the tool will be widely used in multiple fields.展开更多
Early detection of cancer biomarkers applied in real-time disease diagnosis and therapies can increase the survival rate of patients.Circulating tumor DNA(ct DNA)as a typical cancer biomarker plays a great role in the...Early detection of cancer biomarkers applied in real-time disease diagnosis and therapies can increase the survival rate of patients.Circulating tumor DNA(ct DNA)as a typical cancer biomarker plays a great role in the process of tumor disease monitoring,especially in early diagnosis.Unfortunately,most ct DNA detection systems have not been widely used due to their low sensitivity,poor specificity,and high cost.Herein,we developed an alternative ct DNA detection system to present the levels of ct DNA by recording the fluorescence signals of the system containing upconversion nanoparticles(UCNPs),Fe_(3)O_(4),and entropy-driven strand displacement reaction.The method has a practical sensitivity with a wide linear range from 100 amol L^(-1)to 1 nmol L^(-1)and a low detection limit of 1.6 amol L^(-1).Furthermore,the system demonstrates a practical application in mouse blood serum samples and meets the requirements for rapid,sensitive,specific,and economical diagnosis of cancers.Thus,this ct DNA detection system may have great potential for ct DNAdetection and clinical diagnosis.展开更多
基金financially supported by the National Natural Science Foundation of China(NSFC,Nos.22074124 and 22134005)the fund of Fundamental Research Funds for the Central Universities(No.XDJK2020TY001)+1 种基金Chongqing Talents Program for Outstanding Scientists(No.cstc2021ycjh-bgzxm0178)the Chongqing Graduate Student Scientific Research Innovation Project(No.CYB21119)。
文摘DNAzyme amplifiers have been extensively explored as a useful sensing platform,but single DNAzyme amplifier is limited in biosensing applications by its low sensitivity.Herein,a cascade DNAzyme amplifier was designed by exploiting concurrent amplification cycle principles of toehold-mediated strand displacement reaction(TSDR)and Zn^(2+)-assisted DNAzyme cycle with lower cost and simpler procedures.Compared with single DNAzyme amplifier,the proposed TSDR-propelled cascade DNAzyme amplifier exhibited higher sensitivity by releasing more DNAzyme through TSDR to cleave substrate strand during the DNAzyme cycle.Base on this,let-7a could be sensitively detected in the range of 5-50 nmol/L with a detection limit of 64 pmol/L.Furthermore,the dual signal amplification strategy of the cascade DNAzyme amplifier exhibited excellent selectivity to distinguish single-base mismatched DNA strands,which has been successfully applied to the determination of let-7a in blood serum,showing high promise in early cancer diagnosis.
基金We would like to thank the National Natural Science Foundation of China （Nos. 91427304, 21434007, 21574122, 51573175, and 21404098）, the National Basic Research Program of China （No. 2012CB821500）, and the Fundamental Research Funds for the Central Universities （WK3450000002 and WK2060200017） for their financial support.
文摘Background： The DNA strand displacement reaction, which uses flexible and programmable DNA molecules as reaction components, is the basis of dynamic DNA nanotechnology, and has been widely used in the design of complex autonomous behaviors. Results： In this review, we first briefly introduce the concept of toehold-mediated strand displacement reaction and its kinetics regulation in pure solution. Thereafter, we review the recent progresses in DNA complex circuit, the assembly of AuNPs driven by DNA molecular machines, and the detection of single nucleotide polymorphism （SNP） using DNA toehold exchange probes in pure solution and in interface state. Lastly, the applications of toehold-mediated strand displacement in the genetic regulation and silencing through combining gene circuit with RNA interference systems are reviewed. Conclusions： The toehold-mediated strand displacement reaction makes DNA an excellent material for the fabrication of molecular machines and complex circuit, and may potentially be used in the disease diagnosis and the regulation of gene silencing in the near future.
基金the financial support from the National Key Research and Development Program of China(No.2021YFC2701402)the Open Research Fund of State Key Laboratory of Bioelectronics,Southeast University(No.Sklb2021-k06)+2 种基金the Open Foundation of NHC Key Laboratory of Birth Defect for Research and Prevention(Hunan Provincial Maternal and Child Health Care Hospital)(No.KF2020007)Hunan Province Assisted Reproduction and Regenerative Medicine Clinical Demonstration Center Funded Project(No.2020SK4019)the Open Foundation of Translational Medicine National Science and Technology Infrastructure(Shanghai)(No.TMSK-2021-141)。
文摘Strand displacement reaction enables the construction of enzyme-free DNA reaction networks,thus has been widely applied to DNA circuit and nanotechnology.It has the characteristics of high efficiency,universality and regulatability.However,the existing regulation tools cannot enable effective control of the reaction sequence,which undoubtedly limits the construction of complex nucleic acid circuits.Herein,we developed a regulation tool,toehold lock,and achieved strict control of reaction sequence without loss of the main reaction signal output.Furthermore,we applied the tool to scenarios such as seesaw circuits,AND/OR logic gates,and entropy-driven circuits,and respectively demonstrated its significant superiority compared to the original method.We believe that the proposed toehold lock has greatly optimized the efficiency of DNA strand displacement-based networks,and we anticipate that the tool will be widely used in multiple fields.
基金supported by the Science and Technology Cooperation Project between Chinese and Australian Governments (2017YFE0132300)the National Natural Science Foundation of China (NSFC 51929201, 51672268, 51720105015, 51972138, 51872263, and 51828202)+1 种基金the Science and Technology Development Planning Project of Jilin Province (20190201232JC)the CASCroucher Funding Scheme for Joint Laboratories (CAS18204)
文摘Early detection of cancer biomarkers applied in real-time disease diagnosis and therapies can increase the survival rate of patients.Circulating tumor DNA(ct DNA)as a typical cancer biomarker plays a great role in the process of tumor disease monitoring,especially in early diagnosis.Unfortunately,most ct DNA detection systems have not been widely used due to their low sensitivity,poor specificity,and high cost.Herein,we developed an alternative ct DNA detection system to present the levels of ct DNA by recording the fluorescence signals of the system containing upconversion nanoparticles(UCNPs),Fe_(3)O_(4),and entropy-driven strand displacement reaction.The method has a practical sensitivity with a wide linear range from 100 amol L^(-1)to 1 nmol L^(-1)and a low detection limit of 1.6 amol L^(-1).Furthermore,the system demonstrates a practical application in mouse blood serum samples and meets the requirements for rapid,sensitive,specific,and economical diagnosis of cancers.Thus,this ct DNA detection system may have great potential for ct DNAdetection and clinical diagnosis.
