Aptamers Against Cell Surface Receptors: Selection, Modification and Application
Abstract
Aptamers are synthetic oligonucleotides selected from pools of random-sequence oligonucleotides which bind to a wide range of biomolecular targets with high affinity and specificity. Compared with antibodies, aptamers exhibit significant advantages including small size, easy synthesis and modification, as well as low immunogenicity. Many of the aptamers also show inhibition of their targets, making them potential therapeutic and targeting reagents in clinical applications. Compared with aptamers against intracellular proteins and molecules, however, the identification of aptamers against cell-surface receptors and receptor-related antigens is more difficult, due to the complex cellular environment in which receptors are located, and also the unique conformations and compositions of receptors to keep their activity. In this review, we will introduce the identification, modification and working mechanism of aptamers against cell-surface receptors. Based on the different characteristics of target receptors and selection strategies used, the identified aptamers show distinct binding affinity with recombinant targets or specific cell lines which express receptors on the surface in vitro. Some of the in vivo experiments also indicate that aptamers have the capability of inhibiting the overexpressing receptor-related tumor growth, working as potential anti-tumor therapeutic drugs. Despite of the difficulties during the selection of receptor aptamers and the study of their working mechanism during the present time, it is possible that in the future aptamers will increasingly exhibit therapeutic and diagnostic utility.
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High-affinity aptamers recognize more than 900 different targets.
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Yang, X., Zhu, J., Wang, Q., et al. (2012) · Analytical Methods · doi:10.1039/c2ay25428j · Cited by 14 · see citing works
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Slalmi, A., Rabbah, N., Battas, I., Debbarh, I., Medromi, H., & Abourriche, A. (2025) · Biomedicines · doi:10.3390/biomedicines13122877 · Cited by 9 · see citing works
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“Aptamers are highly structured single-stranded DNA or RNA molecules that bind to their cognate molecular targets with high affinity and selectivity, and aptamers can mediate themselves or conjugated nanoparticles to enter cells [48, 49].”
BackgroundShum, K., & Rossi, J. J. (2013) · RNA technologies · doi:10.1007/978-3-642-36853-0_16 · Cited by 3 · see citing works
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Shum, K., & Rossi, J. J. (2013) · Springer eBooks · doi:10.1007/978-3-662-45775-7_16 · Cited by 1 · see citing works
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Davydova, A., Vorobyeva, M., Zenkova, M. A., et al. (2013) · Molecular Biology · doi:10.1134/s0026893313060034
Авдонин, П. П., Trufanov, S. K., Tsitrina, A. A., Рыбакова, Е. Ю., Goncharov, N. V., & Avdonin, P. V. (2021) · Biochemistry (Moscow) · doi:10.31857/s0320972521020019
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Li, Y., Carter, C. M., Al‐Quran, S. Z., et al. (2015) · Biomarkers in disease · doi:10.1007/978-94-007-7681-4_7
Chen, S., Li, J., & Yang, H. (2024) · Wiley eBooks · doi:10.1002/9783527840816.ch13
- Authors
- Wang, J., & Li, G.
- Affiliations
- Nanjing University (CN)
- Corresponding author
- Li, G.
- Venue
- Current Medicinal Chemistry
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2011-09-01
- Volume
- 18
- Issue
- 27
- Pages
- 4107-4116
- ISSN
- 0929-8673 (ISSN-L)
- OpenAlex
- W1975749126
- Cited by
- 37
- References
- 0
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 8 · 2012: 2
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Fund for Distinguished Young Scholars
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- aptamers, cell surface receptors, SELEX, aptamer modification, receptor-targeted therapy, anticancer agents, receptor overexpression, tumor growth inhibition, diagnostic applications
- MeSH terms
- Animals, Humans, Receptors, Cell Surface, SELEX Aptamer Technique, Aptamers, Nucleotide
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