Skip to main content
SpringerLink
Log in

Cell-SELEX: Aptamer Selection Against Whole Cells

  • Chapter
  • First Online:
Aptamers Selected by Cell-SELEX for Theranostics

Abstract

Changes at the molecular level always occur at different stages in diseased cells. The detection of these changes is critical for understanding the molecular mechanisms underlying pathogenesis, as well as accurately diagnosing disease states and monitoring therapeutic modalities. Cell-SELEX is a foundational tool used to select probes able to recognize molecular signatures on the surface of diseased cells. This technology has been increasingly used in biomarker discovery, as well as cancer diagnosis and therapy. In this chapter, the whole cell-SELEX process is described, including aptamer selection, identification, and validation. In addition, we will explore the challenges and prospects for cell-SELEX now and in the coming years. It is anticipated that this chapter will guide readers toward a better understanding of the working principles underlying the cell-SELEX technology and serve as a practical reference for bench scientists engaged in cell and molecular biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Tan W, Donovan MJ, Jiang J (2013) Aptamers from cell-based selection for bioanalytical applications. Chem Rev 113(4):2842–2862. doi:10.1021/cr300468w

    Article  CAS  Google Scholar 

  2. Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346(6287):818–822. doi:10.1038/346818a0

    Article  CAS  Google Scholar 

  3. Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249(4968):505–510

    Article  CAS  Google Scholar 

  4. Lee JF, Stovall GM, Ellington AD (2006) Aptamer therapeutics advance. Curr Opin Chem Biol 10(3):282–289. doi:10.1016/j.cbpa.2006.03.015

    Article  CAS  Google Scholar 

  5. Morris KN, Jensen KB, Julin CM, Weil M, Gold L (1998) High affinity ligands from in vitro selection: complex targets. Proc Natl Acad Sci USA 95(6):2902–2907. doi:10.1073/pnas.95.6.2902

    Article  CAS  Google Scholar 

  6. Blank M, Weinschenk T, Priemer M, Schluesener H (2001) Systematic evolution of a DNA aptamer binding to rat brain tumor microvessels. selective targeting of endothelial regulatory protein pigpen. J Biol Chem 276(19):16464–16468. doi:10.1074/jbc.M100347200

    Article  CAS  Google Scholar 

  7. Daniels DA, Chen H, Hicke BJ, Swiderek KM, Gold L (2003) A tenascin-C aptamer identified by tumor cell SELEX: systematic evolution of ligands by exponential enrichment. Proc Natl Acad Sci USA 100(26):15416–15421. doi:10.1073/pnas.2136683100

    Article  CAS  Google Scholar 

  8. Wang C, Zhang M, Yang G, Zhang D, Ding H, Wang H, Fan M, Shen B, Shao N (2003) Single-stranded DNA aptamers that bind differentiated but not parental cells: subtractive systematic evolution of ligands by exponential enrichment. J Biotechnol 102(1):15–22

    Article  CAS  Google Scholar 

  9. Shangguan D, Li Y, Tang Z, Cao ZC, Chen HW, Mallikaratchy P, Sefah K, Yang CJ, Tan W (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci USA 103(32):11838–11843. doi:10.1073/pnas.0602615103

    Article  CAS  Google Scholar 

  10. Jiang GH, Zhang M, Yue BH, Yang ML, Carter C, Al-Quran SZ, Li B, Li Y (2012) PTK7: a new biomarker for immunophenotypic characterization of maturing T cells and T cell acute lymphoblastic leukemia. Leuk Res 36(11):1347–1353. doi:10.1016/j.leukres.2012.07.004

    Article  CAS  Google Scholar 

  11. Shangguan D, Cao ZH, Meng L, Mallikaratchy P, Sefah K, Wang H, Li Y, Tan WH (2008) Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J Proteome Res 7(5):2133–2139. doi:10.1021/pr700894d

    Article  CAS  Google Scholar 

  12. Tang Z, Shangguan D, Wang K, Shi H, Sefah K, Mallikratchy P, Chen HW, Li Y, Tan W (2007) Selection of aptamers for molecular recognition and characterization of cancer cells. Anal Chem 79(13):4900–4907. doi:10.1021/ac070189y

    Article  CAS  Google Scholar 

  13. Chen HW, Medley CD, Sefah K, Shangguan D, Tang Z, Meng L, Smith JE, Tan W (2008) Molecular recognition of small-cell lung cancer cells using aptamers. ChemMedChem 3(6):991–1001. doi:10.1002/cmdc.200800030

    Article  CAS  Google Scholar 

  14. Shangguan D, Meng L, Cao ZC, Xiao Z, Fang X, Li Y, Cardona D, Witek RP, Liu C, Tan W (2008) Identification of liver cancer-specific aptamers using whole live cells. Anal Chem 80(3):721–728. doi:10.1021/ac701962v

    Article  CAS  Google Scholar 

  15. Li WM, Bing T, Wei JY, Chen ZZ, Shangguan DH, Fang J (2014) Cell-SELEX-based selection of aptamers that recognize distinct targets on metastatic colorectal cancer cells. Biomaterials 35(25):6998–7007. doi:10.1016/j.biomaterials.2014.04.112

    Article  CAS  Google Scholar 

  16. Wang Y, Luo Y, Bing T, Chen Z, Lu M, Zhang N, Shangguan D, Gao X (2014) DNA aptamer evolved by cell-SELEX for recognition of prostate cancer. PLoS ONE 9(6):e100243. doi:10.1371/journal.pone.0100243

    Article  Google Scholar 

  17. Sefah K, Bae KM, Phillips JA, Siemann DW, Su Z, McClellan S, Vieweg J, Tan W (2013) Cell-based selection provides novel molecular probes for cancer stem cells. Int J Cancer 132(11):2578–2588. doi:10.1002/ijc.27936

    Article  CAS  Google Scholar 

  18. Sefah K, Tang ZW, Shangguan DH, Chen H, Lopez-Colon D, Li Y, Parekh P, Martin J, Meng L, Phillips JA, Kim YM, Tan WH (2009) Molecular recognition of acute myeloid leukemia using aptamers. Leukemia 23(2):235–244. doi:10.1038/leu.2008.335

    Article  CAS  Google Scholar 

  19. Tang Z, Parekh P, Turner P, Moyer RW, Tan W (2009) Generating aptamers for recognition of virus-infected cells. Clin Chem 55(4):813–822. doi:10.1373/clinchem.2008.113514

    Article  CAS  Google Scholar 

  20. Zhao Z, Xu L, Shi X, Tan W, Fang X, Shangguan D (2009) Recognition of subtype non-small cell lung cancer by DNA aptamers selected from living cells. Analyst 134(9):1808–1814. doi:10.1039/b904476k

    Article  CAS  Google Scholar 

  21. Parekh P, Tang Z, Turner PC, Moyer RW, Tan W (2010) Aptamers recognizing glycosylated hemagglutinin expressed on the surface of vaccinia virus-infected cells. Anal Chem 82(20):8642–8649. doi:10.1021/ac101801j

    Article  CAS  Google Scholar 

  22. Sefah K, Meng L, Lopez-Colon D, Jimenez E, Liu C, Tan W (2010) DNA aptamers as molecular probes for colorectal cancer study. PLoS ONE 5(12):e14269. doi:10.1371/journal.pone.0014269

    Article  Google Scholar 

  23. Stoltenburg R, Reinemann C, Strehlitz B (2007) SELEX-A (r)evolutionary method to generate high-affinity nucleic acid ligands. Biomol Eng 24(4):381–403. doi:10.1016/j.bioeng.2007.06.001

    Article  CAS  Google Scholar 

  24. Sefah K, Shangguan D, Xiong X, O’Donoghue MB, Tan W (2010) Development of DNA aptamers using cell-SELEX. Nat Protoc 5(6):1169–1185. doi:10.1038/nprot.2010.66

    Article  CAS  Google Scholar 

  25. Hicke BJ, Marion C, Chang YF, Gould T, Lynott CK, Parma D, Schmidt PG, Warren S (2001) Tenascin-C aptamers are generated using tumor cells and purified protein. J Biol Chem 276(52):48644–48654. doi:10.1074/jbc.M104651200

    Article  CAS  Google Scholar 

  26. Liu J, Liu H, Sefah K, Liu B, Pu Y, Van Simaeys D, Tan W (2012) Selection of aptamers specific for adipose tissue. PLoS ONE 7(5):e37789. doi:10.1371/journal.pone.0037789

    Article  CAS  Google Scholar 

  27. Cao XX, Li SH, Chen LC, Ding HM, Xu H, Huang YP, Li J, Liu NL, Cao WH, Zhu YJ, Shen BF, Shao NS (2009) Combining use of a panel of ssDNA aptamers in the detection of Staphylococcus aureus. Nucleic Acids Res 37:4621–4628. doi:10.1093/nar/gkp489

  28. Turek D, Van Simaeys D, Johnson J, Ocsoy I, Tan W (2013) Molecular recognition of live methicillin-resistant staphylococcus aureus cells using DNA aptamers. World J Transl Med 2(3):67–74. doi:10.5528/wjtm.v2.i3.67

    Article  Google Scholar 

  29. Bayrac AT, Sefah K, Parekh P, Bayrac C, Gulbakan B, Oktem HA, Tan W (2011) In vitro selection of DNA aptamers to glioblastoma multiforme. ACS Chem Neurosci 2(3):175–181. doi:10.1021/cn100114k

    Article  CAS  Google Scholar 

  30. Jimenez E, Sefah K, Lopez-Colon D, Van Simaeys D, Chen HW, Tockman MS, Tan W (2012) Generation of lung adenocarcinoma DNA aptamers for cancer studies. PLoS ONE 7(10):e46222. doi:10.1371/journal.pone.0046222

    Article  CAS  Google Scholar 

  31. Bing T, Yang XJ, Mei HC, Cao ZH, Shangguan DH (2010) Conservative secondary structure motif of streptavidin-binding aptamers generated by different laboratories. Bioorg Med Chem 18(5):1798–1805. doi:10.1016/j.bmc.2010.01.054

    Article  CAS  Google Scholar 

  32. Shangguan D, Tang ZW, Mallikaratchy P, Xiao ZY, Tan WH (2007) Optimization and modifications of aptamers selected from live cancer cell lines. ChemBioChem 8(6):603–606. doi:10.1002/cbic.200600532

    Article  CAS  Google Scholar 

  33. Legiewicz M, Yarus M (2005) A more complex isoleucine aptamer with a cognate triplet. J Biol Chem 280(20):19815–19822. doi:10.1074/jbc.M502329200

    Article  CAS  Google Scholar 

  34. Manimala JC, Wiskur SL, Ellington AD, Anslyn EV (2004) Tuning the specificity of a synthetic receptor using a selected nucleic acid receptor. J Am Chem Soc 126(50):16515–16519. doi:10.1021/ja0478476

    Article  CAS  Google Scholar 

  35. Sayer NM, Cubin M, Rhie A, Bullock M, Tahiri-Alaoui A, James W (2004) Structural determinants of conformationally selective, prion-binding aptamers. J Biol Chem 279(13):13102–13109. doi:10.1074/jbc.M310928200

    Article  CAS  Google Scholar 

  36. Green LS, Jellinek D, Jenison R, Ostman A, Heldin CH, Janjic N (1996) Inhibitory DNA ligands to platelet-derived growth factor B-chain. Biochemistry 35(45):14413–14424. doi:10.1021/bi961544+

    Article  CAS  Google Scholar 

  37. Zuker M (2003) Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31(13):3406–3415

    Article  CAS  Google Scholar 

  38. Mei HC, Bing T, Yang XJ, Qi C, Chang TJ, Liu XJ, Cao ZH, Shangguan DH (2012) Functional-group specific aptamers indirectly recognizing compounds with alkyl amino group. Anal Chem 84(17):7323–7329. doi:10.1021/ac300281u

    Article  CAS  Google Scholar 

  39. Qi C, Bing T, Mei HC, Yang XJ, Liu XJ, Shangguan DH (2013) G-quadruplex DNA aptamers for zeatin recognizing. Biosens Bioelectron 41:157–162. doi:10.1016/j.bios.2012.08.004

    Article  CAS  Google Scholar 

  40. Yang XJ, Bing T, Mei HC, Fang CL, Cao ZH, Shangguan DH (2011) Characterization and application of a DNA aptamer binding to L-tryptophan. Analyst 136(3):577–585. doi:10.1039/c0an00550a

    Article  CAS  Google Scholar 

  41. Bing T, Chang TJ, Yang XJ, Mei HC, Liu XJ, Shangguan DH (2011) G-quadruplex DNA aptamers generated for systemin. Bioorg Med Chem 19(14):4211–4219. doi:10.1016/j.bmc.2011.05.061

    Article  CAS  Google Scholar 

  42. Xiao Z, Shangguan D, Cao Z, Fang X, Tan W (2008) Cell-specific internalization study of an aptamer from whole cell selection. Chem (Easton) 14(6):1769–1775. doi:10.1002/chem.200701330

    CAS  Google Scholar 

  43. Fang X, Tan W (2010) Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach. Acc Chem Res 43(1):48–57. doi:10.1021/ar900101s

    Article  CAS  Google Scholar 

  44. Pu Y, Zhu Z, Liu H, Zhang J, Liu J, Tan W (2010) Using aptamers to visualize and capture cancer cells. Anal Bioanal Chem 397(8):3225–3233. doi:10.1007/s00216-010-3715-7

    Article  CAS  Google Scholar 

  45. Ye M, Hu J, Peng M, Liu J, Liu J, Liu H, Zhao X, Tan W (2012) Generating aptamers by cell-SELEX for applications in molecular medicine. Int J Mol Sci 13(3):3341–3353. doi:10.3390/ijms13033341

    Article  CAS  Google Scholar 

  46. Meyer C, Hahn U, Rentmeister A (2011) Cell-specific aptamers as emerging therapeutics. J Nucleic Acids 2011:904750. doi:10.4061/2011/904750

    Article  Google Scholar 

  47. Van Simaeys D, Turek D, Champanhac C, Vaizer J, Sefah K, Zhen J, Sutphen R, Tan WH (2014) Identification of cell membrane protein stress-induced phosphoprotein 1 as a potential ovarian cancer biomarker using aptamers selected by cell systematic evolution of ligands by exponential enrichment. Anal Chem 86(9):4521–4527. doi:10.1021/ac500466x

    Article  Google Scholar 

  48. Mallikaratchy P, Tang ZW, Kwame S, Meng L, Shangguan DH, Tan WH (2007) Aptamer directly evolved from live cells recognizes membrane bound immunoglobin heavy mu chain in Burkitt’s lymphoma cells. Mol Cell Proteomics 6(12):2230–2238. doi:10.1074/mcp.M700026-MCP200

    Article  CAS  Google Scholar 

  49. Yang ML, Jiang GH, Li WJ, Qiu K, Zhang M, Carter CM, Al-Quran SZ, Li Y (2014) Developing aptamer probes for acute myelogenous leukemia detection and surface protein biomarker discovery. J Hematol Oncol 7:14. doi:10.1186/1756-8722-7-5

    Article  Google Scholar 

  50. Raddatz MS, Dolf A, Endl E, Knolle P, Famulok M, Mayer G (2008) Enrichment of cell-targeting and population-specific aptamers by fluorescence-activated cell sorting. Angew Chem Int Ed Engl 47(28):5190–5193. doi:10.1002/anie.200800216

    Article  CAS  Google Scholar 

  51. Mayer G, Ahmed MS, Dolf A, Endl E, Knolle PA, Famulok M (2010) Fluorescence-activated cell sorting for aptamer SELEX with cell mixtures. Nat Protoc 5(12):1993–2004. doi:10.1038/nprot.2010.163

    Article  CAS  Google Scholar 

  52. Hung LY, Wang CH, Hsu KF, Chou CY, Lee GB (2014) An on-chip Cell-SELEX process for automatic selection of high-affinity aptamers specific to different histologically classified ovarian cancer cells. Lab Chip. doi:10.1039/c4lc00587b

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, People’s Republic of China

    Dihua Shangguan, Tao Bing & Nan Zhang

Authors
  1. Dihua Shangguan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao Bing
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dihua Shangguan .

Editor information

Editors and Affiliations

  1. Department of Chemistry, Hunan University, Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical Engineering, Changsha, China & University of Florida, Gainesville, Florida, USA

    Weihong Tan

  2. Institute of Chemistry, Chinese Academy of Sciences, Beijing, China

    Xiaohong Fang

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Shangguan, D., Bing, T., Zhang, N. (2015). Cell-SELEX: Aptamer Selection Against Whole Cells. In: Tan, W., Fang, X. (eds) Aptamers Selected by Cell-SELEX for Theranostics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46226-3_2

Download citation

Publish with us

Policies and ethics

Search

Navigation