Aptamers in early disease diagnosis: modern approaches to proteomic biomarker detection

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Early detection of diseases is a key factor for successful treatment, reducing the negative impact of the disease on both the patient and society as a whole. One of the main strategies for early diagnosis is to search for molecules whose concentration changes in biological samples indicate the development of a pathological process. Such disease indicators are called biomarkers. Considerable interest of researchers is focused on dynamic changes in the proteome, which accurately reflects the state of the organism, including against the background of disease or therapy. Among the methods of studying the proteome in general and individual protein biomarkers, diagnostic systems based on the use of antibodies are of great clinical and scientific importance.

Aptamers or chemical antibodies are definitely structured oligonucleotides or peptides capable of binding with high specificity to the target. To date, many studies have demonstrated the great potential for the use of aptamers in the development of both diagnostic platforms and means of drug delivery or therapeutic action. This allows aptamers to be considered as an alternative to antibodies in all areas of their application, including for early disease diagnosis.

This review systematizes information about the biochemical fundamentals and methods of aptamer production by systematic evolution of ligands by exponential enrichment (SELEX) and its modifications, comparative advantages over antibodies (synthetic nature, thermostability, low immunogenicity, cost-effectiveness), integration into diagnostic platforms (electrochemical, optical and mass-sensitive biosensors), as well as aptamer-based multiplexed technologies (SomaScan). Examples of successful application of aptasensors for early detection of oncological (lung, bladder, breast cancer, leukemia), infectious (SARS-CoV-2, hepatitis viruses), neurodegenerative (Alzheimer's, Parkinson's disease) and cardiovascular pathologies are analyzed. Current limitations of the technology (sensitivity to nucleases, rapid clearance, lack of standardization, regulatory barriers) and promising directions of development are discussed, including integration with artificial intelligence, microfluidics, portable point-of-care devices and personalized diagnostic solutions, which opens the way for creating more accurate, accessible and effective systems for early disease detection.

全文:

受限制的访问

作者简介

I. Dobrokhotov

Federal State Budgetary Scientific Institution "Russian Research Center of Surgery named after Academician B.V. Petrovsky"

Email: e-yakushenko@mail.ru
ORCID iD: 0000-0001-8831-4781
SPIN 代码: 3465-7904

Ph.D. (Med.), Senior Researcher, Aging Biomarkers Group, Longevity Mechanisms Laboratory, Institute of Biology of Aging and Healthy Longevity Medicine with the Preventive Medicine Clinic

俄罗斯联邦, Tsyurupy St., Building 3, Moscow, 117418

E. Yakushenko

Federal State Budgetary Scientific Institution "Russian Research Center of Surgery named after Academician B.V. Petrovsky"

编辑信件的主要联系方式.
Email: e-yakushenko@mail.ru
ORCID iD: 0000-0002-5048-9188
SPIN 代码: 2098-6017

Dr.Sc. (Med.), Leading Researcher, Aging Biomarkers Group, Longevity Mechanisms Laboratory, Institute of Biology of Aging and Healthy Longevity Medicine with the Preventive Medicine Clinic

俄罗斯联邦, Tsyurupy St., Building 3, Moscow, 117418

A. Moskalev

Federal State Budgetary Scientific Institution "Russian Research Center of Surgery named after Academician B.V. Petrovsky"

Email: amoskalev@med.ru
ORCID iD: 0000-0002-3248-1633
SPIN 代码: 7012-7456

Dr.Sc. (Biol.), Professor, Corresponding Member of the Russian Academy of Sciences, Director, Institute of Biology of Aging and Healthy Longevity Medicine with the Preventive Medicine Clinic

俄罗斯联邦, Tsyurupy St., Building 3, Moscow, 117418

参考

  1. Kliuchnikova A.A., Ilgisonis E.V., Archakov A.I. et al. Systematic Review. Int J Mol Sci. 2024; 25(23). doi: 10.3390/ijms252312634.
  2. Santos R., Ursu O., Gaulton A., Bento A.P. et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov. 2017;16(1):19–34. doi: 10.1038/nrd.2016.230.
  3. Соловаров И.С., Хаснатинов М.А., Ляпунова Н.А. и др. Разработка подходов к селекции ДНК-аптамеров на основе мембранной ультрафильтрации комплекса аптамер – мишень. Acta Biomedica Scientifica. 2022; 7(6): 119–127. doi: 10.29413/ABS.2022-7.6.12. [Solovarov I.S., Khasnatinov M.A., Liapunova N.A. et al. Development of DNA aptamer selection approach based on membrane ultrafiltration of aptamer/target complex. Acta Biomedica Scientifica. 2022; 7(6): 119–127. (In Russ.)].
  4. Субач М.Ф., Хренова М.Г., Зверева М.Э. Современные методы химической модификации аптамеров и принципы выбора библиотек аптамеров. Вестн. Моск. ун-та. Сер. 2. Химия. 2024; 65(2): 78–86. doi: 10.55959/MSU0579-9384-2-2024-65-2-78-86. [Subach M.F., Khrenova M.G., Zvereva M.I. Modern methods of aptamer chemical modification And principles of aptamer library selection. Vestn. Mosk. un-ta. Ser. 2. Chemistry. 2024; 65(2): 78–86. (In Russ.)].
  5. Fallah A., Imani Fooladi A.A., Havaei S.A. et al. Recent advances in aptamer discovery, modification and improving performance. Biochem Biophys Rep. 2024; 40: 101852. doi: 10.1016/j.bbrep.2024.101852.
  6. Chung Y.D., Tsai Y.C., Wang C.H., Lee G.B. Aptamer selection via versatile microfluidic platforms and their diverse applications. Lab Chip. 2025; 25(5): 1047–80. doi: 10.1039/d4lc00859f.
  7. Wu Z., Yao W., Chen J. et al. Droplet digital PCR-based single aptamer selection. Talanta. 2025; 292: 127924. doi: 10.1016/j.talanta.2025.127924.
  8. Buglak A.A., Samokhvalov A.V., Zherdev A.V. et al. Methods and Applications of In Silico Aptamer Design and Modeling. Int J Mol Sci. 2020; 21(22). doi: 10.3390/ijms21228420.
  9. Chen Z., Hu L., Zhang B.T. Lu A. et al. Artificial Intelligence in Aptamer-Target Binding Prediction. Int J Mol Sci. 2021; 22(7). doi: 10.3390/ijms22073605.
  10. Traber G.M., Yu A.M. RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies. J Pharmacol Exp Ther. 2023; 384(1): 133–54. doi: 10.1124/jpet.122.001234.
  11. Alsaidan O.A. Recent advancements in aptamers as promising nanotool for therapeutic and diagnostic applications. Anal Biochem. 2025; 702: 115844. doi: 10.1016/j.ab.2025.115844.
  12. Hu Y.Y., Yang G., Qu F. Research advances in non-immobilized aptamer screening techniques for small-molecule targets. Se Pu. 2025; 43(4): 297–308. doi: 10.3724/SP.J.1123.2024.04012.
  13. Domsicova M., Korcekova J., Poturnayova A. et al. New Insights into Aptamers: An Alternative to Antibodies in the Detection of Molecular Biomarkers. Int J Mol Sci. 2024; 25(13). doi: 10.3390/ijms25136833.
  14. Yang L.F., Ling M., Kacherovsky N. et al. Aptamers 101: aptamer discovery and in vitro applications in biosensors and separations. Chem Sci. 2023; 14(19): 4961–78. doi: 10.1039/d3sc00439b.
  15. Liu R., Li J, Salena B.J., Li Y. Aptamer and DNAzyme Based Colorimetric Biosensors for Pathogen Detection. Angew Chem Int Ed Engl. 2025; 64(4): e202418725. doi: 10.1002/anie.202418725.
  16. Sakib S., Bajaj K., Sen P. et al. Comparative Analysis of Machine Learning Algorithms Used for Translating Aptamer-Antigen Binding Kinetic Profiles to Diagnostic Decisions. ACS Sens. 2025; 10(2): 907–20. doi: 10.1021/acssensors.4c02682.
  17. Liu Y., Pandey R., McCarthy M.J. et al. Electrochemical Aptamer-Based Biosensors for Cocaine Detection in Human Saliva: Exploring Matrix Interference. Anal Chem. 2025; 97(2): 1097–106. doi: 10.1021/acs.analchem.4c03423.
  18. Patil S., Suleman S., Anzar N. et al. Origami-Inspired Biosensors: Exploring Diverse Applications and Techniques for Shape-Changing Sensor Platforms. Chemosensors. 2024; 12(12): 276. doi: 10.3390/chemosensors12120276.
  19. Erkocyigit B., Man E., Efecan E. et al. Non-Invasive Point-of-Care Detection of Methamphetamine and Cocaine via Aptamer-Based Lateral Flow Test. Biosensors (Basel). 2025; 15(1). doi: 10.3390/bios15010031.
  20. Rohloff J.C., Gelinas A.D., Jarvis T.C. et al. Nucleic Acid Ligands With Protein-like Side Chains: Modified Aptamers and Their Use as Diagnostic and Therapeutic Agents. Mol Ther Nucleic Acids. 2014; 3(10): e201. doi: 10.1038/mtna.2014.49.
  21. Kraemer S., Schneider D.J., Paterson C. et al. Crossing the Halfway Point: Aptamer-Based, Highly Multiplexed Assay for the Assessment of the Proteome. J Proteome Res. 2024; 23(11): 4771–88. doi: 10.1021/acs.jproteome.4c00411.
  22. Wik L., Nordberg N., Broberg J. et al. Proximity Extension Assay in Combination with Next-Generation Sequencing for High-throughput Proteome-wide Analysis. Mol Cell Proteomics. 2021; 20: 100168. doi: 10.1016/j.mcpro.2021.100168.
  23. Puerta R., Cano A., Garcia-Gonzalez P. et al. Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort. Int J Mol Sci. 2024; 26(1). doi: 10.3390/ijms26010286.
  24. Sun H., Li J., Li L. et al. Construction of test strips for lung cancer detection based on aptamers. J Pharm Biomed Anal. 2024; 242: 115976. doi: 10.1016/j.jpba.2024.115976.
  25. Shin Y., Perera A.P., Park M.K. Label-free DNA sensor for detection of bladder cancer biomarkers in urine. Sensors and Actuators B: Chemical. 2013; 178: 200–206. doi: 10.1016/j.snb.2012.12.057.
  26. Xue X., Zheng F., Luo Y. et al. A multifunctional Pt/DMSN nanozyme-based colorimetric-fluorescence sensing platform for breast cancer detection. Mikrochim Acta. 2025; 192(4): 228. doi: 10.1007/s00604-025-07082-4.
  27. Grechkin Y.A., Grechkina S.L., Zaripov E.A. et al. Aptamer-Conjugated Tb(III)-Doped Silica Nanoparticles for Luminescent Detection of Leukemia Cells. Biomedicines. 2020; 8(1). doi: 10.3390/biomedicines8010014.
  28. Mohsin D.H., Mashkour M.S., Fatemi F. Design of aptamer-based sensing platform using gold nanoparticles functionalized reduced graphene oxide for ultrasensitive detection of Hepatitis B virus. Chemical Papers. 2021; 75(1): 279–295. doi: 10.1007/s11696-020-01292-1.
  29. Torres-Vazquez B., de Lucas A.M., Garcia-Crespo C. et al. In vitro Selection of High Affinity DNA and RNA Aptamers that Detect Hepatitis C Virus Core Protein of Genotypes 1 to 4 and Inhibit Virus Production in Cell Culture. J Mol Biol. 2022; 434(7): 167501. doi: 10.1016/j.jmb.2022.167501.
  30. Chinchilla-Cardenas D.J., Cruz-Mendez J.S., Petano-Duque J.M. et al. Current developments of SELEX technologies and prospects in the aptamer selection with clinical applications. J Genet Eng Biotechnol. 2024; 22(3): 100400. doi: 10.1016/j.jgeb.2024.100400.
  31. Hu C., Yang S., Li S. et al. Viral aptamer screening and aptamer-based biosensors for virus detection: A review. Int J Biol Macromol. 2024; 276(Pt 2): 133935. doi: 10.1016/j.ijbiomac.2024.133935.
  32. Андрианова М.С., Панова О.С., Титов А.А. и др. Электрохимические биосенсоры для определения sars-cov-2. Вестник Московского университета. Серия 2. Химия. 2023; 64(5): 407–440. [Andrianova M.S., Panova O.S., Titov A.A. et al. Electrochemical Biosensors for SARS-CоV-2 Detection Vestn. Mosk. un-ta. Ser. 2. Chemistry. 2023; 64(5): 407–440. (In Russ.)].
  33. Ospina-Villa J.D., Lopez-Camarillo C., Castanon-Sanchez C.A. et al. Advances on Aptamers against Protozoan Parasites. Genes (Basel). 2018; 9(12). doi: 10.3390/genes9120584.
  34. Wilson D.M., Cookson M.R., Van Den Bosch L. et al. Hallmarks of neurodegenerative diseases. Cell. 2023; 186(4): 693–714. doi: 10.1016/j.cell.2022.12.032.
  35. Tu Y., Wu J., Chai K. et al. A turn-on unlabeled colorimetric biosensor based on aptamer-AuNPs conjugates for amyloid-beta oligomer detection. Talanta. 2023; 260: 124649. doi: 10.1016/j.talanta.2023.124649.
  36. Lu X., Hou X., Tang H. et al. Quality CdSe/CdS/ZnS Quantum-Dot-Based FRET Aptasensor for the Simultaneous Detection of Two Different Alzheimer's Disease Core Biomarkers. Nanomaterials (Basel). 2022; 12(22). doi: 10.3390/nano12224031.
  37. Deng C., Liu H., Si S. et al. An electrochemical aptasensor for amyloid-beta oligomer based on double-stranded DNA as "conductive spring". Mikrochim Acta. 2020; 187(4): 239. doi: 10.1007/s00604-020-4217-8.
  38. Cheng T., Afshan N., Jiao J. et al. Current progress in aptamer-based sensors for the detection of protein biomarkers in neurodegenerative diseases. Biosensors and Bioelectronics: X. 2024; 20: 100528. doi: 10.1016/j.biosx.2024.100528.
  39. Sun K., Xia N., Zhao L. et al. Aptasensors for the selective detection of alpha-synuclein oligomer by colorimetry, surface plasmon resonance and electrochemical impedance spectroscopy. Sensors and Actuators B: Chemical. 2017; 245: 87–94. doi: 10.1016/j.snb.2017.01.171.
  40. Meehan C., Lecocq S., Penner G. A reproducible approach for the use of aptamer libraries for the identification of Aptamarkers for brain amyloid deposition based on plasma analysis. PLoS One. 2024;19(8):e0307678. doi: 10.1371/journal.pone.0307678.
  41. Di Mauro V., Lauta F.C., Modica J. et al. Diagnostic and Therapeutic Aptamers: A Promising Pathway to Improved Cardiovascular Disease Management. JACC Basic Transl Sci. 2024; 9(2): 260–77. doi: 10.1016/j.jacbts.2023.06.013.
  42. Yu H., Yu J., Yao G. Recent Advances in Aptamers-Based Nanosystems for Diagnosis and Therapy of Cardiovascular Diseases: An Updated Review. Int J Nanomedicine. 2025; 20: 2427–43. doi: 10.2147/IJN.S507715.
  43. Qin S.N., Nong Y.C., Cao C.L. et al. A nanoporous electrochemical aptamer-based sensors for rapid detection of cardiac troponin I in blood. Talanta. 2025; 284: 127250. doi: 10.1016/j.talanta.2024.127250.
  44. Cen Y., Wang Z., Ke P. et al. Development of a novel ssDNA aptamer targeting cardiac troponin I and its clinical applications. Anal Bioanal Chem. 2021; 413(28): 7043–7053. doi: 10.1007/s00216-021-03667-z.
  45. Timsina J., Gomez-Fonseca D., Wang L. et al. Comparative Analysis of Alzheimer's Disease Cerebrospinal Fluid Biomarkers Measurement by Multiplex SOMAscan Platform and Immunoassay-Based Approach. J Alzheimers Dis. 2022; 89(1): 193–207. doi: 10.3233/JAD-220399.
  46. Bege M., Borbas A. The Medicinal Chemistry of Artificial Nucleic Acids and Therapeutic Oligonucleotides. Pharmaceuticals (Basel). 2022; 15(8). doi: 10.3390/ph15080909.
  47. Molina Ramirez S.R., Samiseresht N., Martinez-Roque M.A. et al. A Truncated Multi-Thiol Aptamer-Based SARS-CoV-2 Electrochemical Biosensor: Towards Variant-Specific Point-of-Care Detection with Optimized Fabrication. Biosensors (Basel). 2025; 15(1). doi: 10.3390/bios15010024.

补充文件

附件文件
动作
1. JATS XML
下载
2. Fig. 1. Stages of development of a diagnostic platform based on aptamers

下载 (106KB)
索引源数据
3. Fig. 2. Schematic illustration of the SELEX protocol

下载 (124KB)
索引源数据

版权所有 © Russkiy Vrach Publishing House, 2025