核酸适配体序列优化策略的研究进展
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摘要
核酸适配体作为新兴的识别分子,具有高亲和力、高特异性、易合成修饰、设计灵活等优点,已经被广泛应用于化学、生物学、医学相关的多个领域。然而,核酸适配体往往存在序列较长、构型设计复杂、标记成本较高等缺点,因此在核酸适配体的应用中常常需要对其序列进行改造。该综述简要介绍了核酸适配体的性质和筛选过程,并从序列截短、裂分和拼接等方面对核酸适配体序列的改造策略进行了阐述。此外,还对核酸适配体序列改造方法的发展方向进行了展望。
As emerging recognition molecules, nucleic acid aptamers have the advantages of high affinity, high specificity, easy synthesis, easy modification and flexible design, and have been widely used in the research fields of chemistry, biology and medicine. However, application of aptamers usually limited by long sequence, complex design and high cost of labeling, and so on. Therefore, it is urgently needed to optimize the original sequences of aptamers. This review briefly introduced the properties and screening process of aptamers, and the optimization strategies of aptamer sequences, such as sequence truncation, splitting and splicing. Furthermore, the future developments of the optimization methods of aptamer sequences were also discussed.
As emerging recognition molecules, nucleic acid aptamers have the advantages of high affinity, high specificity, easy synthesis, easy modification and flexible design, and have been widely used in the research fields of chemistry, biology and medicine. However, application of aptamers usually limited by long sequence, complex design and high cost of labeling, and so on. Therefore, it is urgently needed to optimize the original sequences of aptamers. This review briefly introduced the properties and screening process of aptamers, and the optimization strategies of aptamer sequences, such as sequence truncation, splitting and splicing. Furthermore, the future developments of the optimization methods of aptamer sequences were also discussed.
引文
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[2]Robertson D L,Joyce G F.Selection in vitro of an RNAenzyme that specifically cleaves single-stranded DNA[J].Nature,1990,344(6265):467-468.
[3]Ellington A D,Szostak J W.In vitro selection of RNAmolecules that bind specific ligands[J].Nature,1990,346(6287):818-822.
[4]Eissa S,Zourob M.Selection and characterization of DNAaptamers for electrochemical biosensing of carbendazim[J].Analytical Chemistry,2017,89(5):3138-3145.
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[6]Oliviero G,Stornaiuolo M,D'Atri V,et al.Screening platform toward new anti-HIV aptamers set on molecular docking and fluorescence quenching techniques[J].Analytical Chemistry,2016,88(4):2327-2334.
[7]Trausch J J,Shankretzlaff M,Verch T.Development and characterization of an HPV Type-16 specific modified DNA aptamer for the improvement of potency assays[J].Analytical Chemistry,2017,89(6):3554-3561.
[8]Li P,Yan Y,Wei S,et al.Isolation and characterization of a new class of DNA aptamers specific binding to Singapore grouper iridovirus(SGIV)with antiviral activities[J].Virus Research,2014,188:146-154.
[9]Wehbe M,Labib M,Muharemagic D,et al.Switchable aptamers for biosensing and bioseparation of viruses(SwAps-V)[J].Biosensors and Bioelectronics,2015,67:280-286.
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[12]Zhang N,Bing T,Shen L,et al.Intercellular connections related to cell-cell crosstalk specifically recognized by an aptamer[J].Angewandte Chemie International Edition,2016,128(12):3982-3986.
[13]Yuan B,Jiang X,Chen Y,et al.Metastatic cancer cell and tissue-specific fluorescence imaging using a new DNA aptamer developed by Cell-SELEX[J].Talanta,2017,170:56-62.
[14]Wu Q,Wu L,Wang Y,et al.Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging[J].Biosensors and Bioelectronics,2016,80:1-8.
[15]Wang H,Yang H,Ding X,et al.Abstract 3779:Evaluation of efficacy of an RNA aptamer toward non-small cell lung cancer[J].Cancer Research,2016,76(14 Supplement):3779-3779.
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[19]Keefe A D,Pai S,Ellington A.Aptamers as therapeutics[J].Nature Reviews Drug Discovery,2010,9(7):537-550.
[20]Mercier M,Dontenwill M,Choulier L.Selection of nucleic acid aptamers targeting tumor cell-surface protein biomarkers[J].Cancers,2017,9(6):69.
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[26]Lao Y-H,Phua K K L,Leong K W.Aptamer nanomedicine for cancer therapeutics:barriers and potential for translation[J].ACS Nano,2015,9(3):2235-2254.
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[29]Shangguan D,Tang Z,Mallikaratchy P,et al.Optimization and modifications of aptamers selected from live cancer cell lines[J].Chembiochem:A European Journal of Chemical Biology,2007,8(6):603-606.
[30]Gu C,Xiang Y,Guo H,et al.Label-free fluorescence detection of melamine with a truncated aptamer[J].Analyst,2016,141(14):4511-4517.
[31]Alhadrami H A,Chinnappan R,Eissa S,et al.High affinity truncated DNA aptamers for the development of fluorescence based progesterone biosensors[J].Analytical Biochemistry,2017,525:78-84.
[32]Gao S,Hu B,Zheng X,et al.Gonyautoxin 1/4 aptamers with high-affinity and high-specificity:From efficient selection to aptasensor application[J].Biosensors and Bioelectronics,2016,79:938-944.
[33]Chen A,Yan M,Yang S.Split aptamers and their applications in sandwich aptasensors[J].Trends in Analytical Chemistry,2016,80:581-593.
[34]Stojanovic M N,de Prada P,Landry D W.Fluorescent sensors based on aptamer self-assembly[J].Journal of the American Chemical Society,2000,122(46):11547-11548.
[35]Freeman R,Sharon E,Tel-Vered R,et al.Supramolecular cocaine-aptamer complexes activate biocatalytic cascades[J].Journal of the American Chemical Society,2009,131(14):5028-5029.
[36]Zuo X,Xiao Y,Plaxco K W.High specificity,electrochemical sandwich assays based on single aptamer sequences and suitable for the direct detection of smallmolecule targets in blood and other complex matrices[J].Journal of the American Chemical Society,2009,131(20):6944-6945.
[37]Li Q,Wang Q,Yang X,et al.High sensitivity surface plasmon resonance biosensor for detection of microRNAand small molecule based on graphene oxide-gold nanoparticles composites[J].Talanta,2017,174:521-526.
[38]Wang Q,Yang X,Yang X,et al.An enzyme-free colorimetric assay using hybridization chain reaction amplification and split aptamers[J].Analyst,2015,140(22):7657-7662.
[39]Golub E,Pelossof G,Freeman R,et al.Electrochemical,photoelectrochemical,and surface plasmon resonance detection of cocaine using supramolecular aptamer complexes and metallic or semiconductor nanoparticles[J].Analytical Chemistry,2009,81(22):9291-9298.
[40]Chen J,Zhang J,Li J,et al.An ultrasensitive signal-on electrochemical aptasensor via target-induced conjunction of split aptamer fragments[J].Biosensors and Bioelectronics,2010,25(5):996-1000.
[41]Qu X,Zhang H,Hong C,et al.Convection-driven pulldown assays in nanoliter droplets using scaffolded aptamers[J].Analytical Chemistry,2017,89(6):3468-3473.
[42]Liu J,Bai W,Niu S,et al.Highly sensitive colorimetric detection of 17β-estradiol using split DNA aptamers immobilized on unmodified gold nanoparticles[J].Scientific Reports,2014,4:7571.
[43]Gosling J P.A decade of development in immunoassay methodology[J].Clinical Chemistry,1990,36(1):1408-1427.
[44]Yang C J,Jockusch S,Vicens M,et al.Light-switching excimer probes for rapid protein monitoring in complex biological fluids[J].Proceedings of the National Academy of Sciences of the United States of America,2005,102(48):17278-17283.
[45]Bai W,Zhu C,Liu J,et al.Split aptamer-based sandwich fluorescence resonance energy transfer assay for 19-nortestosterone[J].Microchimica Acta,2016,183(9):2533-2538.
[46]Yuan B,Zhou Y,Guo Q,et al.A signal-on split aptasensor for highly sensitive and specific detection of tumor cells based on FRET[J].Chemical Communications,2015,52(8):1590-1593.
[47]Tang J,Shi H,He X,et al.Tumor cell-specific split aptamers:target-driven and temperature-controlled selfassembly on the living cell surface[J].Chemical Communications,2016,52(7):1482-1485.
[48]Zimmermann G R,Jenison R D,Wick C L,et al.Interlocking structural motifs mediate molecular discrimination by a theophylline-binding RNA[J].Nature Structural Biology,1997,4(8):644-649.
[49]Anderson P C,Mecozzi S.Unusually short RNA sequences:design of a 13-mer RNA that selectively binds and recognizes theophylline[J].Journal of the American Chemical Society,2005,127(15):5290-5291.
[50]Patel D J.Structural analysis of nucleic acid aptamers[J].Current Opinion in Chemical Biology,1997,1(1):32-46.
[51]Kent A D,Spiropulos N G,Heemstra J M.General approach for engineering small-molecule-binding DNAsplit aptamers[J].Analytical Chemistry,2013,85(20):9916-9923.
[52]Li Q,Wang Y D,Shen G L,et al.Split aptamer mediated endonuclease amplification for small-molecule detection[J].Chemical Communications,2015,51(20):4196-4199.
[53]Mallikaratchy P R,Ruggiero A,Gardner J R,et al.Amultivalent DNA aptamer specific for the B-cell receptor on human lymphoma and leukemia[J].Nucleic Acids Research,2011,39(6):2458-2469.
[54]Yang L,Meng L,Zhang X,et al.Engineering polymeric aptamers for selective cytotoxicity[J].Journal of the American Chemical Society,2011,133(34):13380-13386.
[55]Kim Y,Cao Z,Tan W.Molecular assembly for highperformance bivalent nucleic acid inhibitor[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(15):5664-5669.
[56]Muller J,Freitag D,Mayer G,et al.Anticoagulant characteristics of HD1-22,a bivalent aptamer that specifically inhibits thrombin and prothrombinase[J].Journal of Thrombosis and Haemostasis,2008,6(12):2105-2112.
[57]Li W,Yang X,He L,et al.Self-assembled DNAnanocentipede as multivalent drug carrier for targeted delivery[J].ACS Appl Mater Interfaces,2016,8(39):25733-25740.
[58]Yu H,Canoura J,Guntupalli B,et al.A cooperativebinding split aptamer assay for rapid,specific and ultrasensitive fluorescence detection of cocaine in saliva[J].Chemical Science,2017,8(1):131-141.
[59]Kuai H,Zhao Z,Mo L,et al.Circular bivalent aptamers enable in vivo stability and recognition[J].Journal of the American Chemical Society,2017,139(27):9128-9131.
[60]Lei Y,Tang J,Shi H,et al.Nature-inspired smart DNAnanodoctor for activatable in vivo cancer imaging and insitu drug release based on recognition-triggered assembly of split aptamer[J].Analytical Chemistry,2016,88(23):11699-11706.
[2]Robertson D L,Joyce G F.Selection in vitro of an RNAenzyme that specifically cleaves single-stranded DNA[J].Nature,1990,344(6265):467-468.
[3]Ellington A D,Szostak J W.In vitro selection of RNAmolecules that bind specific ligands[J].Nature,1990,346(6287):818-822.
[4]Eissa S,Zourob M.Selection and characterization of DNAaptamers for electrochemical biosensing of carbendazim[J].Analytical Chemistry,2017,89(5):3138-3145.
[5]Sekhon S S,Lee S H,Lee K A,et al.Defining the copper binding aptamotif and aptamer integrated recovery platform(AIRP)[J].Nanoscale,2017,9(8):2883-2894.
[6]Oliviero G,Stornaiuolo M,D'Atri V,et al.Screening platform toward new anti-HIV aptamers set on molecular docking and fluorescence quenching techniques[J].Analytical Chemistry,2016,88(4):2327-2334.
[7]Trausch J J,Shankretzlaff M,Verch T.Development and characterization of an HPV Type-16 specific modified DNA aptamer for the improvement of potency assays[J].Analytical Chemistry,2017,89(6):3554-3561.
[8]Li P,Yan Y,Wei S,et al.Isolation and characterization of a new class of DNA aptamers specific binding to Singapore grouper iridovirus(SGIV)with antiviral activities[J].Virus Research,2014,188:146-154.
[9]Wehbe M,Labib M,Muharemagic D,et al.Switchable aptamers for biosensing and bioseparation of viruses(SwAps-V)[J].Biosensors and Bioelectronics,2015,67:280-286.
[10]Dua P,Ren S,Lee S W,et al.Cell-SELEX based identification of an RNA aptamer for escherichia coli and its use in various detection formats[J].Molecules&Cells,2016,39(11):807-813.
[11]Mozioglu E,Gokmen O,Tamerler C,et al.Selection of nucleic acid aptamers specific for mycobacterium tuberculosis[J].Applied Biochemistry&Biotechnology,2015,178(4):849-864.
[12]Zhang N,Bing T,Shen L,et al.Intercellular connections related to cell-cell crosstalk specifically recognized by an aptamer[J].Angewandte Chemie International Edition,2016,128(12):3982-3986.
[13]Yuan B,Jiang X,Chen Y,et al.Metastatic cancer cell and tissue-specific fluorescence imaging using a new DNA aptamer developed by Cell-SELEX[J].Talanta,2017,170:56-62.
[14]Wu Q,Wu L,Wang Y,et al.Evolution of DNA aptamers for malignant brain tumor gliosarcoma cell recognition and clinical tissue imaging[J].Biosensors and Bioelectronics,2016,80:1-8.
[15]Wang H,Yang H,Ding X,et al.Abstract 3779:Evaluation of efficacy of an RNA aptamer toward non-small cell lung cancer[J].Cancer Research,2016,76(14 Supplement):3779-3779.
[16]Wang H,Zhang Y,Chu C,et al.Abstract 2058:Identification of a specific RNA aptamer targeting non-small cell lung cancer by in vivo SELEX[J].Cancer Research,2016,76(14 Supplement):2058-2058.
[17]Wang H,Zhang Y,Yang H,et al.In vivo SELEX of an inhibitory NSCLC-specific RNA aptamer from PEGylated RNA library[J].Molecular Therapy Nucleic Acids,2018,10:187-198.
[18]Mayer G.The chemical biology of aptamers[J].Angewandte Chemie International Edition,2009,48(15):2672-2689.
[19]Keefe A D,Pai S,Ellington A.Aptamers as therapeutics[J].Nature Reviews Drug Discovery,2010,9(7):537-550.
[20]Mercier M,Dontenwill M,Choulier L.Selection of nucleic acid aptamers targeting tumor cell-surface protein biomarkers[J].Cancers,2017,9(6):69.
[21]Cho E J,Lee J W,Ellington A D.Applications of aptamers as sensors[J].Annual Review of Analytical Chemistry,2009,2(1):241-264.
[22]Stein C A,Castanotto D.FDA-approved oligonucleotide therapies in 2017[J].Molecular Therapy,2017,25(5):1069-1075.
[23]Zhou J,Rossi J.Aptamers as targeted therapeutics:current potential and challenges[J].Nature Reviews Drug Discovery,2017,16(3):181-202.
[24]Dunn M R,Jimenez R M,Chaput J C.Analysis of aptamer discovery and technology[J].Nature Reviews Chemistry,2017,1(10):s41570-017-0076.
[25]Zhou J H,Rossi J.Aptamers as targeted therapeutics:current potential and challenges[J].Nature Reviews Drug Discovery,2017,16(3):181-202.
[26]Lao Y-H,Phua K K L,Leong K W.Aptamer nanomedicine for cancer therapeutics:barriers and potential for translation[J].ACS Nano,2015,9(3):2235-2254.
[27]Gao S,Zheng X,Jiao B,et al.Post-SELEX optimization of aptamers[J].Analytical and Bioanalytical Chemistry,2016,408(17):4567-4573.
[28]Cowperthwaite M C,Ellington A D.Bioinformatic analysis of the contribution of primer sequences to aptamer structures[J].Journal of Molecular Evolution,2008,67(1):95-102.
[29]Shangguan D,Tang Z,Mallikaratchy P,et al.Optimization and modifications of aptamers selected from live cancer cell lines[J].Chembiochem:A European Journal of Chemical Biology,2007,8(6):603-606.
[30]Gu C,Xiang Y,Guo H,et al.Label-free fluorescence detection of melamine with a truncated aptamer[J].Analyst,2016,141(14):4511-4517.
[31]Alhadrami H A,Chinnappan R,Eissa S,et al.High affinity truncated DNA aptamers for the development of fluorescence based progesterone biosensors[J].Analytical Biochemistry,2017,525:78-84.
[32]Gao S,Hu B,Zheng X,et al.Gonyautoxin 1/4 aptamers with high-affinity and high-specificity:From efficient selection to aptasensor application[J].Biosensors and Bioelectronics,2016,79:938-944.
[33]Chen A,Yan M,Yang S.Split aptamers and their applications in sandwich aptasensors[J].Trends in Analytical Chemistry,2016,80:581-593.
[34]Stojanovic M N,de Prada P,Landry D W.Fluorescent sensors based on aptamer self-assembly[J].Journal of the American Chemical Society,2000,122(46):11547-11548.
[35]Freeman R,Sharon E,Tel-Vered R,et al.Supramolecular cocaine-aptamer complexes activate biocatalytic cascades[J].Journal of the American Chemical Society,2009,131(14):5028-5029.
[36]Zuo X,Xiao Y,Plaxco K W.High specificity,electrochemical sandwich assays based on single aptamer sequences and suitable for the direct detection of smallmolecule targets in blood and other complex matrices[J].Journal of the American Chemical Society,2009,131(20):6944-6945.
[37]Li Q,Wang Q,Yang X,et al.High sensitivity surface plasmon resonance biosensor for detection of microRNAand small molecule based on graphene oxide-gold nanoparticles composites[J].Talanta,2017,174:521-526.
[38]Wang Q,Yang X,Yang X,et al.An enzyme-free colorimetric assay using hybridization chain reaction amplification and split aptamers[J].Analyst,2015,140(22):7657-7662.
[39]Golub E,Pelossof G,Freeman R,et al.Electrochemical,photoelectrochemical,and surface plasmon resonance detection of cocaine using supramolecular aptamer complexes and metallic or semiconductor nanoparticles[J].Analytical Chemistry,2009,81(22):9291-9298.
[40]Chen J,Zhang J,Li J,et al.An ultrasensitive signal-on electrochemical aptasensor via target-induced conjunction of split aptamer fragments[J].Biosensors and Bioelectronics,2010,25(5):996-1000.
[41]Qu X,Zhang H,Hong C,et al.Convection-driven pulldown assays in nanoliter droplets using scaffolded aptamers[J].Analytical Chemistry,2017,89(6):3468-3473.
[42]Liu J,Bai W,Niu S,et al.Highly sensitive colorimetric detection of 17β-estradiol using split DNA aptamers immobilized on unmodified gold nanoparticles[J].Scientific Reports,2014,4:7571.
[43]Gosling J P.A decade of development in immunoassay methodology[J].Clinical Chemistry,1990,36(1):1408-1427.
[44]Yang C J,Jockusch S,Vicens M,et al.Light-switching excimer probes for rapid protein monitoring in complex biological fluids[J].Proceedings of the National Academy of Sciences of the United States of America,2005,102(48):17278-17283.
[45]Bai W,Zhu C,Liu J,et al.Split aptamer-based sandwich fluorescence resonance energy transfer assay for 19-nortestosterone[J].Microchimica Acta,2016,183(9):2533-2538.
[46]Yuan B,Zhou Y,Guo Q,et al.A signal-on split aptasensor for highly sensitive and specific detection of tumor cells based on FRET[J].Chemical Communications,2015,52(8):1590-1593.
[47]Tang J,Shi H,He X,et al.Tumor cell-specific split aptamers:target-driven and temperature-controlled selfassembly on the living cell surface[J].Chemical Communications,2016,52(7):1482-1485.
[48]Zimmermann G R,Jenison R D,Wick C L,et al.Interlocking structural motifs mediate molecular discrimination by a theophylline-binding RNA[J].Nature Structural Biology,1997,4(8):644-649.
[49]Anderson P C,Mecozzi S.Unusually short RNA sequences:design of a 13-mer RNA that selectively binds and recognizes theophylline[J].Journal of the American Chemical Society,2005,127(15):5290-5291.
[50]Patel D J.Structural analysis of nucleic acid aptamers[J].Current Opinion in Chemical Biology,1997,1(1):32-46.
[51]Kent A D,Spiropulos N G,Heemstra J M.General approach for engineering small-molecule-binding DNAsplit aptamers[J].Analytical Chemistry,2013,85(20):9916-9923.
[52]Li Q,Wang Y D,Shen G L,et al.Split aptamer mediated endonuclease amplification for small-molecule detection[J].Chemical Communications,2015,51(20):4196-4199.
[53]Mallikaratchy P R,Ruggiero A,Gardner J R,et al.Amultivalent DNA aptamer specific for the B-cell receptor on human lymphoma and leukemia[J].Nucleic Acids Research,2011,39(6):2458-2469.
[54]Yang L,Meng L,Zhang X,et al.Engineering polymeric aptamers for selective cytotoxicity[J].Journal of the American Chemical Society,2011,133(34):13380-13386.
[55]Kim Y,Cao Z,Tan W.Molecular assembly for highperformance bivalent nucleic acid inhibitor[J].Proceedings of the National Academy of Sciences of the United States of America,2008,105(15):5664-5669.
[56]Muller J,Freitag D,Mayer G,et al.Anticoagulant characteristics of HD1-22,a bivalent aptamer that specifically inhibits thrombin and prothrombinase[J].Journal of Thrombosis and Haemostasis,2008,6(12):2105-2112.
[57]Li W,Yang X,He L,et al.Self-assembled DNAnanocentipede as multivalent drug carrier for targeted delivery[J].ACS Appl Mater Interfaces,2016,8(39):25733-25740.
[58]Yu H,Canoura J,Guntupalli B,et al.A cooperativebinding split aptamer assay for rapid,specific and ultrasensitive fluorescence detection of cocaine in saliva[J].Chemical Science,2017,8(1):131-141.
[59]Kuai H,Zhao Z,Mo L,et al.Circular bivalent aptamers enable in vivo stability and recognition[J].Journal of the American Chemical Society,2017,139(27):9128-9131.
[60]Lei Y,Tang J,Shi H,et al.Nature-inspired smart DNAnanodoctor for activatable in vivo cancer imaging and insitu drug release based on recognition-triggered assembly of split aptamer[J].Analytical Chemistry,2016,88(23):11699-11706.