JOURNAL OF LIGHT INDUSTRY

CN 41-1437/TS  ISSN 2096-1553

Volume 41 Issue 4
August 2026
Article Contents
YE Hua, YAN Ziyi, WANG Mengyuan, et al. Research progress on aptamer post-SELEX technology[J]. Journal of Light Industry, 2026, 41(4): 1-12. doi: 10.12187/2026.04.001
Citation: YE Hua, YAN Ziyi, WANG Mengyuan, et al. Research progress on aptamer post-SELEX technology[J]. Journal of Light Industry, 2026, 41(4): 1-12. doi: 10.12187/2026.04.001 shu

Research progress on aptamer post-SELEX technology

  • Received Date: 2025-05-19
    Accepted Date: 2025-10-05
  • Aptamers are single-stranded DNA (ssDNA) or RNA molecules selected through Systematic Evolution of Ligands by Exponential Enrichment (SELEX). They are widely employed as molecular probes in areas such as food safety and biomedicine. However, aptamers derived from conventional SELEX often show limitations in affinity, specificity, and stability. To overcome these shortcomings, post-SELEX optimization technology developed in recent years enable multidimensional synergistic improvements, thereby enhancing aptamer performance in practical applications. This review classifies and summarizes post-SELEX technology into three main strategies: truncation, chemical modification, and artificial intelligence (AI)-assisted optimization. Studies indicate that truncation can markedly enhance binding affinity, chemical modification effectively improves stability, and AI-assisted approaches substantially increase the success rate of targeted aptamer engineering. However, each technology has inherent limitations. Truncation risks disrupting key binding domains, chemical modification may compromise affinity, and AI-assisted approaches are often challenged by data scarcity. Nevertheless, the application of these technologies has significantly improved the overall performance of aptamers, providing crucial technical support for broadening their industrial applications. Future research will focus on developing integrated strategies that combine truncation, chemical modification, and AI; elucidating the mechanisms underlying aptamer structure-activity relationships; and constructing dedicated aptamer databases, so as to promote the industrial translation of aptamers.
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    1. [1]

      TUERK C,GOLD L.Systematic evolution of ligands by exponential enrichment:RNA ligands to bacteriophage T4 DNA polymerase[J].Science,1990,249(4968):505-510.

    2. [2]

      ELLINGTON A D,SZOSTAK J W.In vitro selection of RNA molecules that bind specific ligands[J].Nature,1990,346(6287):818-822.

    3. [3]

      BAYAT P,NOSRATI R,ALIBOLANDI M,et al.SELEX methods on the road to protein targeting with nucleic acid aptamers[J].Biochimie,2018,154:132-155.

    4. [4]

      ZHANG S K,ZHANG Y M,NING Z Y,et al.Design and application of microfluidics in aptamer SELEX and aptasensors[J].Biotechnology Advances,2024,77:108461.

    5. [5]

      VU C Q,ROTKRUA P,TANTIRUNGROTECHAI Y,et al.Oligonucleotide hybridization combined with competitive antibody binding for the truncation of a high-affinity aptamer[J].ACS Combinatorial Science,2017,19(10):609-617.

    6. [6]

      TIAN Y,WANG Y,SHENG Z,et al.A colorimetric detection method of pesticide acetamiprid by fine-tuning aptamer length[J].Analytical Biochemistry,2016,513:87-92.

    7. [7]

      陈瑞鹏,孙云凤,霍冰洋,等.真菌毒素多重检测技术研究进展[J].食品科学,2021,42(17):267-274.
      CHEN R P,SUN Y F,HUO B Y,et al.Progress in multiple detection technologies for mycotoxins[J].Food Science,2021,42(17):267-274.

    8. [8]

      KWON Y S,AHMAD RASTON N H,GU M B.An ultra-sensitive colorimetric detection of tetracyclines using the shortest aptamer with highly enhanced affinity[J].Chemical Communications,2014,50(1):40-42.

    9. [9]

      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.

    10. [10]

      EATON B E,GOLD L,HICKE B J,et al.Post-SELEX combinatorial optimization of aptamers[J].Bioorganic & Medicinal Chemistry,1997,5(6):1087-1096.

    11. [11]

      MUSAFIA B,OREN-BANAROYA R,NOIMAN S.Designing anti-influenza aptamers:novel quantitative structure activity relationship approach gives insights into aptamer-virus interaction[J].PLoS One,2014,9(5):e97696.

    12. [12]

      GU H J,DUAN N,WU S J,et al.Graphene oxide-assisted non-immobilized SELEX of okdaic acid aptamer and the analytical application of aptasensor[J].Scientific Reports,2016,6:21665.

    13. [13]

      YANG X J,BING T,MEI H C,et al.Characterization and application of a DNA aptamer binding to L-tryptophan[J].Analyst,2011,136(3):577-585.

    14. [14]

      YU H,ZHU J X,SHEN G Q,et al.Improving aptamer performance:key factors and strategies[J].Microchimica Acta,2023,190(7):255.

    15. [15]

      CHEN K R,ZHU L J,LI J,et al.High-content tailoring strategy to improve the multifunctionality of functional nucleic acids[J].Biosensors and Bioelectronics,2024,261:116494.

    16. [16]

      KILGOUR M,LIU T,WALKER B D,et al.E2EDNA:simulation protocol for DNA aptamers with ligands[J].Journal of Chemical Information and Modeling,2021,61(9):4139-4144.

    17. [17]

      CUI W,LI S P,ZENG J H,et al.A double-stranded aptamer for highly sensitive fluorescent detection of glutathione S-transferases[J].Biosensors,2024,14(10):476.

    18. [18]

      CHEN Y Q,WANG Z M,LIU S Y,et al.A highly sensitive and group-targeting aptasensor for total phthalate determination in the environment[J].Journal of Hazardous Materials,2021,412:125174.

    19. [19]

      YE H,DUAN N,GU H J,et al.Fluorometric determination of lipopolysaccharides via changes of the graphene oxide-enhanced fluorescence polarization caused by truncated aptamers[J].Microchimica Acta,2019,186(3):173.

    20. [20]

      LEE E H,LIM H J,LEE S D,et al.Highly sensitive detection of bisphenol A by nanoaptamer assay with truncated aptamer[J].ACS Applied Materials & Interfaces,2017,9(17):14889-14898.

    21. [21]

      YANG C Y,DU C Y,SU R F,et al.A signal-on fluorescent aptasensor by sensitized Tb3+ luminescence for detection of melamine in milk[J].Talanta,2022,236:122842.

    22. [22]

      KIMOTO M,NAKAMURA M,HIRAO I.Post-ExSELEX stabilization of an unnatural-base DNA aptamer targeting VEGF165 toward pharmaceutical applications[J].Nucleic Acids Research,2016,44(15):7487-7494.

    23. [23]

      ZHAO L H,QI X Y,YAN X C,et al.Engineering aptamer with enhanced affinity by triple helix-based terminal fixation[J].Journal of the American Chemical Society,2019,141(44):17493-17497.

    24. [24]

      BAI Y L,LI Y P,ZHANG D P,et al.Enhancing the affinity of anti-human α-thrombin 15-mer DNA aptamer and anti-immunoglobulin E aptamer by PolyT extension[J].Analytical Chemistry,2017,89(17):9467-9473.

    25. [25]

      QIAO L,WANG H,HE J L,et al.Truncated affinity-improved aptamers for 17β-estradiol determination by AuNPs-based colorimetric aptasensor[J].Food Chemistry,2021,340:128181.

    26. [26]

      GAO L,ZHANG Y,CHEN L,et al.Study of dual binding specificity of aptamer to ochratoxin A and norfloxacin and the development of fluorescent aptasensor in milk detection[J].Talanta,2024,273:125935.

    27. [27]

      QIN Y D,QIN Y N,BUBIAJIAER H,et al.Engineering constructed of high selectivity dexamethasone aptamer based on truncation and mutation technology[J].Frontiers in Bioengineering and Biotechnology,2022,10:994711.

    28. [28]

      CANOURA J,YU H X,ALKHAMIS O,et al.Accelerating post-SELEX aptamer engineering using exonuclease digestion[J].Journal of the American Chemical Society,2021,143(2):805-816.

    29. [29]

      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.

    30. [30]

      SUN Y Q,YUAN B Y,DENG M T,et al.A light-up fluorescence assay for tumor cell detection based on bifunctional split aptamers[J].Analyst,2018,143(15):3579-3585.

    31. [31]

      SANTA C,PARK S,GEJT A,et al.Real-time monitoring of vancomycin using a split-aptamer surface plasmon resonance biosensor[J].Analyst,2025,150(1):131-141.

    32. [32]

      CHANG C C,YEH C Y.Using simple-structured split aptamer for gold nanoparticle-based colorimetric detection of estradiol[J].Analytical Sciences,2021,37(3):479-483.

    33. [33]

      WANG W J,ZHAI F,XU F P,et al.Enzyme-free amplified and one-step rapid detection of bisphenol A using dual-terminal labeled split aptamer probes[J].Microchemical Journal,2022,183:107977.

    34. [34]

      ZHU P,ASUMADU P,ZHOU S Y,et al.Recognition mechanism of split T-2 toxin aptamer coupled with reliable dual-mode detection in peanut and beer[J].Food Bioscience,2024,60:104268.

    35. [35]

      KENT A D,SPIROPULOS N G,HEEMSTRA J M.General approach for engineering small-molecule-binding DNA split aptamers[J].Analytical Chemistry,2013,85(20):9916-9923.

    36. [36]

      郑业坤,杜聪聪,李泓霖,等.AFM1劈裂适配体的识别能力研究[J].食品工业科技,2024,45(19):296-306.
      ZHEN Y K,DU C C,LI H L,et al.Investigation on the recognition of split aflatoxin M1 aptamer[J].Science and Technology of Food Industry,2024,45(19):296-306.

    37. [37]

      CHEN A L,YAN M M,YANG S M.Split aptamers and their applications in sandwich aptasensors[J].TrAC Trends in Analytical Chemistry,2016,80:581-593.

    38. [38]

      BRISTOW P,SCHANTZ K,MOOSBRUGGER Z,et al.Aptamer-targeted dendrimersomes assembled from azido-modified Janus dendrimers "clicked" to DNA[J].Biomacromolecules,2024,25(3):1541-1549.

    39. [39]

      ZIPERMAN E D,FITZPATRICK K B,NAIR M A,et al.A system for in vitro selection of fully 2'-modified RNA aptamers[J].Organic & Biomolecular Chemistry,2025,23(10):2375-2379.

    40. [40]

      VARIZHUK I V,TSVETKOV V B,TOROPYGIN I Y,et al.The regioselective conjugation of the 15-nt thrombin aptamer with an optimized tripeptide sequence greatly increases the anticoagulant activity of the aptamer[J].Pharmaceutics,2023,15(2):604.

    41. [41]

      CAI T J,CHEN M L,YANG J,et al.An AuNPs-based electrochemical aptasensor for the detection of 25-hydroxy vitamin D3[J].Analytical Sciences,2024,40(4):599-607.

    42. [42]

      GE G,WANG T L,LIU Z H,et al.A self-assembled DNA double-crossover-based fluorescent aptasensor for highly sensitivity and selectivity in the simultaneous detection of aflatoxin M1 and aflatoxin B1[J].Talanta,2023,265:124908.

    43. [43]

      DA PIEVE C,BLACKSHAW E,MISSAILIDIS S,et al.PEGylation and biodistribution of an anti-MUC1 aptamer in MCF-7 tumor-bearing mice[J].Bioconjugate Chemistry,2012,23(7):1377-1381.

    44. [44]

      DOLOT R,LAM C H,SIERANT M,et al.Crystal structures of thrombin in complex with chemically modified thrombin DNA aptamers reveal the origins of enhanced affinity[J].Nucleic Acids Research,2018,46(9):4819-4830.

    45. [45]

      SMIRNOV I,KOLGANOVA N,TROISI R,et al.Expanding the recognition interface of the thrombin-binding aptamer HD1 through modification of residues T3 and T12[J].Molecular Therapy Nucleic Acids,2021,23:863-871.

    46. [46]

      QI S,DUAN N,KHAN I M,et al.Strategies to manipulate the performance of aptamers in SELEX,post-SELEX and microenvironment[J].Biotechnology Advances,2022,55:107902.

    47. [47]

      ZHOU Y J,KAJINO R,ISHII S,et al.Synthesis and evaluation of (S)-5'-C-aminopropyl and (S)-5'-C-aminopropyl-2'-arabinofluoro modified DNA oligomers for novel RNase H-dependent antisense oligonucleotides[J].RSC Advances,2020,10(68):41901-41914.

    48. [48]

      NICOLAI M,STEINBERG J,OBERMANN H L,et al.Identification of an optimal TLR8 ligand by alternating the position of 2'-O-ribose methylation[J].International Journal of Molecular Sciences,2022,23(19):11139.

    49. [49]

      DAI L J,ZHANG J N,WANG X N,et al.Protein DEK and DTA aptamers:insight into the interaction mechanisms and the computational aptamer design[J].Frontiers in Molecular Biosciences,2022,9:946480.

    50. [50]

      MAIO G E,ENWERONYE O,ZUMRUT H E,et al.Systematic optimization and modification of a DNA aptamer with 2'-O-methyl RNA analogues[J].ChemistrySelect,2017,2(7):2335-2340.

    51. [51]

      YING G Q,LU X R,MEI J F,et al.A structure-activity relationship of a thrombin-binding aptamer containing LNA in novel sites[J].Bioorganic & Medicinal Chemistry,2019,27(14):3201-3207.

    52. [52]

      FÖRSTER C,ZYDEK M,ROTHKEGEL M,et al.Properties of an 'LNA'-modified ricin RNA aptamer[J].Biochemical and Biophysical Research Communications,2012,419(1):60-65.

    53. [53]

      李亚洲.基于固相合成的化学修饰核酸适体的构建及其应用研究[D].长沙:湖南大学,2022. LI Y Z.Construction and application research of chemically modified nucleic acid aptamers based on solid-phase synthesis[D].Changsha:Hunan University,2022.

    54. [54]

      WATANABE D,TERAUCHI H,OSAWA H,et al.Phosphorothioate-modified DNA aptamer-based PROTACs for targeted degradation of estrogen receptor α[J].Bioconjugate Chemistry,2025,36(10):2172-2180.

    55. [55]

      CAI R F,CHEN X,ZHANG Y T,et al.Systematic bio-fabrication of aptamers and their applications in engineering biology[J].Systems Microbiology and Biomanufacturing,2023,3(2):223-245.

    56. [56]

      WU J,WANG S H,LI X,et al.Selective anti-melanoma effect of phosphothioated aptamer encapsulated by neutral cytidinyl/cationic lipids[J].Frontiers in Cell and Developmental Biology,2021,9:660233.

    57. [57]

      FLIERL U,NERO T L,LIM B,et al.Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators[J].The Journal of Experimental Medicine,2015,212(2):129-137.

    58. [58]

      ZHOU J H,ROSSI J.Aptamers as targeted therapeutics:current potential and challenges[J].Nature Reviews Drug Discovery,2017,16(3):181-202.

    59. [59]

      KAKIUCHI-KIYOTA S,WHITELEY L O,RYAN A M,et al.Development of a method for profiling protein interactions with LNA-modified antisense oligonucleotides using protein microarrays[J].Nucleic Acid Therapeutics,2016,26(2):93-101.

    60. [60]

      STANZIONE F,GIANGRECO I,COLE J C.Chapter four-use of molecular docking computational tools in drug discovery[M]//WITTY D R,COX B.Progress in Medicinal Chemistry.Amsterdam:Elsevier,2021:273-343.

    61. [61]

      刘佳,杨志芳,王闯,等.基于分子对接和步进序列群的蓖麻毒素核酸适配体序列优化[J].生物化学与生物物理进展,2023,50(9):2243-2254.
      LIU J,YANG Z F,WANG C,et al.Molecular docking and stepping sequence cluster design prompted sequence optimization of ricin nucleic acid aptamers[J].Progress in Biochemistry and Biophysics,2023,50(9):2243-2254.

    62. [62]

      LUO Y,JIN Z Y,WANG J E,et al.The isolation of a DNA aptamer to develop a fluorescent aptasensor for the thiamethoxam pesticide[J].Analyst,2021,146(6):1986-1995.

    63. [63]

      WEI H,CAI R F,YUE H,et al.Screening and application of a truncated aptamer for high-sensitive fluorescent detection of metronidazole[J].Analytica Chimica Acta,2020,1128:203-210.

    64. [64]

      YU Y X,CHEN K R,DU Z H,et al.Magnetic aptamer copper nanoclusters fluorescent biosensor for the visual detection of Zearalenone based on docking-aided rational tailoring[J].Food Chemistry,2024,448:139127.

    65. [65]

      NIE J J,YUAN L Y,JIN K,et al.Electrochemical detection of tobramycin based on enzymes-assisted dual signal amplification by using a novel truncated aptamer with high affinity[J].Biosensors & Bioelectronics,2018,122:254-262.

    66. [66]

      SALO-AHEN O M H,ALANKO I,BHADANE R,et al.Molecular dynamics simulations in drug discovery and pharmaceutical development[J].Processes,2021,9(1):71.

    67. [67]

      FILIPE H A L,LOURA L M S.Molecular dynamics simulations:advances and applications[J].Molecules,2022,27(7):2105.

    68. [68]

      MUKUT K M,ROY S,GOUDELI E.Molecular arrangement and fringe identification and analysis from molecular dynamics (MAFIA-MD):a tool for analyzing the molecular structures formed during reactive molecular dynamics simulation of hydrocarbons[J].Computer Physics Communications,2022,276:108325.

    69. [69]

      XIE Y C,ERIKSSON L A,ZHANG R B.Molecular dynamics study of the recognition of ATP by nucleic acid aptamers[J].Nucleic Acids Research,2020,48(12):6471-6480.

    70. [70]

      PENG K M,LIU X N,YUAN H E,et al.A novel fluorescent biosensor based on affinity-enhanced aptamer-peptide conjugate for sensitive detection of lead(Ⅱ)in aquatic products[J].Analytical and Bioanalytical Chemistry,2023,415(17):3463-3474.

    71. [71]

      CUI X L,SONG M H,LIU Y,et al.Identifying conformational changes of aptamer binding to theophylline:a combined biolayer interferometry,surface-enhanced Raman spectroscopy,and molecular dynamics study[J].Talanta,2020,217:121073.

    72. [72]

      MORENA F,ARGENTATI C,TORTORELLA I,et al.De novo ssRNA aptamers against the SARS-CoV-2 main protease:in silico design and molecular dynamics simulation[J].International Journal of Molecular Sciences,2021,22(13):6874.

    73. [73]

      BASHIR A,YANG Q,WANG J P,et al.Machine learning guided aptamer refinement and discovery[J].Nature Communications,2021,12:2366.

    74. [74]

      郭兴,孙莹,刘树萍,等.深度学习在食品质量与安全检测中的应用进展[J].食品工业科技,2025,46(6):20-29.
      GUO X,SUN Y,LIU S P,et al.Advance in application of deep learning in food quality and safety detection[J].Science and Technology of Food Industry,2025,46(6):20-29.

    75. [75]

      丁浩晗,王龙,侯浩钶,等.深度学习在食品安全检测与风险预警中的应用[J].食品科学,2025,46(6):295-308.
      DING H H,WANG L,HOU H K,et al.Application of deep learning in food safety detection and risk early warning[J].Food Science,2025,46(6):295-308.

    76. [76]

      CHEN Z H,HU L,ZHANG B T,et al.Artificial intelligence in aptamer-target binding prediction[J].International Journal of Molecular Sciences,2021,22(7):3605.

    77. [77]

      YANG X,CHAN C H,YAO S S,et al.DeepAptamer:advancing high-affinity aptamer discovery with a hybrid deep learning model[J].Molecular Therapy Nucleic Acids,2025,36(1):102436.

    78. [78]

      SHIN I,KANG K,KIM J,et al.AptaTrans:A deep neural network for predicting aptamer-protein interaction using pretrained encoders[J].BMC Bioinformatics,2023,24(1):447.

    79. [79]

      EMAMI N,FERDOUSI R.AptaNet as a deep learning approach for aptamer-protein interaction prediction[J].Scientific Reports,2021,11:6074.

    80. [80]

      YU X,WANG Y,YANG H,et al.Prediction of the binding affinity of aptamers against the influenza virus[J].SAR and QSAR in Environmental Research,2019,30(1):51-62.

    81. [81]

      ADACHI T,NAKAMURA S,MICHISHITA A,et al.RaptGen-assisted generation of an RNA/DNA hybrid aptamer against SARS-CoV-2 spike protein[J].Biochemistry,2024,63(7):906-912.

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