Skip to main content

Advertisement

Log in

Application of a Novel Aptamer Beacon for Rapid Detection of IgG1 Antibody Drugs

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Antibody drugs have been widely used to treat many diseases and are the fastest-growing drug class. IgG1 is the most common type of antibody because of its good serum stability; however, effective methods for the rapid detection of IgG1-type antibodies are lacking. In this study, we designed two aptamer molecules derived from the reported aptamer probe that has been proven to bind to the Fc fragment of the IgG1 antibody. The results showed that Fc-1S could specifically bind to the human IgG1 Fc proteins. In addition, we modified the structure of Fc-1S and constructed three aptamer molecular beacons that could quantitatively detect IgG1-type antibodies within a short time. Furthermore, we unveiled that the Fc-1S37R beacon has the highest sensitivity for IgG1-type antibodies with a detection limit of 48.82813 ng/mL and can accurately detect serum antibody concentrations in vivo with consistent results to ELISA. Therefore, Fc-1S37R is an efficient method for the production monitoring and quality control of IgG1-type antibodies to enable the large-scale production and application of antibody drugs.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

All data generated and analyzed during this study are included in this article.

References

  1. Parr, M. K., Montacir, O., & Montacir, H. (2016). Physicochemical characterization of biopharmaceuticals. Journal of Pharmaceutical and Biomedical Analysis, 130, 366–389.

    Article  PubMed  CAS  Google Scholar 

  2. Strohl, W. R. (2018). Current progress in innovative engineered antibodies. Protein & Cell, 9(1), 86–120.

    Article  CAS  Google Scholar 

  3. Carter, P. J., & Lazar, G. A. (2018). Next generation antibody drugs: Pursuit of the “high-hanging fruit”. Nature Reviews. Drug Discovery, 17(3), 197–223.

    Article  PubMed  CAS  Google Scholar 

  4. Schumacher, D., et al. (2016). Current status: Site-specific antibody drug conjugates. Journal of Clinical Immunology, 36(Suppl 1), 100–107.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Kohler, G., & Milstein, C. (1975). Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 256(5517), 495–497.

    Article  PubMed  CAS  Google Scholar 

  6. McLaughlin, P., et al. (1998). Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: Half of patients respond to a four-dose treatment program. Journal of Clinical Oncology, 16(8), 2825–2833.

    Article  PubMed  CAS  Google Scholar 

  7. Yu, J., Song, Y., & Tian, W. (2020). How to select IgG subclasses in developing anti-tumor therapeutic antibodies. Journal of Hematology & Oncology, 13(1), 45.

  8. Yang, G., et al. (2020). Screening of aptamer for human IgG Fc fragment by capillary electrophoresis-systematic evolution of ligands by exponential enrichment. Chinese Journal of Analytical Chemistry, 48(5), 601–607.

    Article  CAS  Google Scholar 

  9. Andersen, C. B., et al. (2010). Aggregation of a multidomain protein: A coagulation mechanism governs aggregation of a model IgG1 antibody under weak thermal stress. Protein Science, 19(2), 279–290.

    Article  PubMed  CAS  Google Scholar 

  10. Robertson, J., et al. (2016). Essential medicines for cancer: WHO recommendations and national priorities. Bulletin of the World Health Organization, 94(10), 735–742.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Goydel, R. S., & Rader, C. (2021). Antibody-based cancer therapy. Oncogene, 40(21), 3655–3664.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Ellington, A. D., & Szostak, J. W. (1990). In vitro selection of RNA molecules that bind specific ligands. Nature, 346(6287), 818–822.

    Article  PubMed  CAS  Google Scholar 

  13. Acquah, C., et al. (2015). A review on immobilised aptamers for high throughput biomolecular detection and screening. Analytica Chimica Acta, 888, 10–18.

    Article  PubMed  CAS  Google Scholar 

  14. Sun, H., & Zu, Y. (2015). A highlight of recent advances in aptamer technology and its application. Molecules, 20(7), 11959–11980.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Hamula, C., et al. (2011). Selection and analytical applications of aptamers binding microbial pathogens. Trends Analyt Chem, 30(10), 1587–1597.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Yoshida, H., et al. (2020). Binding interaction analysis of RNA aptamer-Fc region of human immunoglobulin G using fragment molecular orbital calculation. Chemical Physics Letters, 738, 136854.

    Article  CAS  Google Scholar 

  17. Cai, R., et al. (2019). Functional chimera aptamer and molecular beacon based fluorescent detection of Staphylococcus aureus with strand displacement-target recycling amplification. Analytica Chimica Acta, 1075, 128–136.

    Article  PubMed  CAS  Google Scholar 

  18. Feng, X., et al. (2019). Quantitative detection and real-time monitoring of endogenous mRNA at the single live cell level using a ratiometric molecular beacon. ACS Applied Materials & Interfaces, 11(32), 28752–28761.

    Article  CAS  Google Scholar 

  19. Sherrill-Mix, S., et al. (2021). Detection of SARS-CoV-2 RNA using RT-LAMP and molecular beacons. Genome Biology, 22(1), 169.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Hong, P., Li, W., & Li, J. (2012). Applications of aptasensors in clinical diagnostics. Sensors (Basel), 12(2), 1181–1193.

    Article  PubMed  CAS  Google Scholar 

  21. Sharma, A., et al. (2016). Development of structure switching aptamer assay for detection of aflatoxin M1 in milk sample. Talanta, 158, 35–41.

    Article  PubMed  CAS  Google Scholar 

  22. Yang, C. J., et al. (2005). Light-switching excimer probes for rapid protein monitoring in complex biological fluids. Proc Natl Acad Sci U S A, 102(48), 17278–17283.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Shi, H., et al. (2011). Activatable aptamer probe for contrast-enhanced in vivo cancer imaging based on cell membrane protein-triggered conformation alteration. Proc Natl Acad Sci U S A, 108(10), 3900–3905.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Zhao, B., et al. (2015). Designing activatable aptamer probes for simultaneous detection of multiple tumor-related proteins in living cancer cells. Biosensors & Bioelectronics, 68, 763–770.

    Article  CAS  Google Scholar 

  25. Walsh, G. (2018). Biopharmaceutical benchmarks 2018. Nature Biotechnology, 36(12), 1136–1145.

    Article  PubMed  CAS  Google Scholar 

  26. Chen, K., et al. (2020). Aptamers as versatile molecular tools for antibody production monitoring and quality control. Journal of the American Chemical Society, 142(28), 12079–12086.

    Article  PubMed  CAS  Google Scholar 

  27. Bellassai, N., D’Agata, R., & Spoto, G. (2021). Novel nucleic acid origami structures and conventional molecular beacon-based platforms: A comparison in biosensing applications. Analytical and Bioanalytical Chemistry, 413(24), 6063–6077.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Li, B., et al. (2022). The source structure design of the rotating magnetic beacon based on phase-shift direction finding system. Sensors (Basel), 22(21), 8304.

    Article  PubMed  Google Scholar 

  29. Moutsiopoulou, A., et al. (2019). Molecular aptamer beacons and their applications in sensing, imaging, and diagnostics. Small (Weinheim an der Bergstrasse, Germany), 15(35), 1902248.

    Article  Google Scholar 

  30. Brylev, V. A., et al. (2021). Molecular beacon DNA probes with fluorescein bifluorophore. Russian Journal of Bioorganic Chemistry, 47(3), 734–740.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Saisuk, W., et al. (2022). A molecular beacon biosensor for viral RNA detection based on HyCaSD strategy. Analytica Chimica Acta, 1221, 340134.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Puze Long for excellent technical support. This work was supported by the Guangxi Natural Science Foundation Program (Grant numbers [2019GXNSFDA245031; 2021GXNSFAA220097]).

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Cai-Wen Duan, Kai-Ming Chen, Ke-Yang, Wei-Wei Zheng, and Xiu-Song Huang. The first draft of the manuscript was written by Cai-Wen Duan and Ke-Yang. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Kai-Ming Chen or Cai-Wen Duan.

Ethics declarations

Ethical Approval

Permission from the Institutional Animal Ethical Committee was received before making these experiments.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file 1

(PNG 643 kb)

High resolution image (TIF 10151 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yang, K., Zheng, WW., Huang, XS. et al. Application of a Novel Aptamer Beacon for Rapid Detection of IgG1 Antibody Drugs. Appl Biochem Biotechnol 195, 7075–7085 (2023). https://doi.org/10.1007/s12010-023-04471-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-023-04471-4

Keywords

Navigation