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Selection of a novel DNA thioaptamer against HER2 structure

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Abstract

Purpose

Human epithelial growth factor receptor 2 (HER2) is over-expressed in several malignancies and represents an important therapeutic target. Aptamers are oligonucleotides that may potentially serve as tumor-homing ligand with excellent affinity and specificity for targeted cancer therapy. However, aptamers need to have nuclease resistance in order to function in vivo. The aim of this study was to generate a novel HER2 thioaptamer with enhanced nuclease resistance.

Methods

The HER2 thioaptamer is selected in an evolutionary process called systematic evolution of ligands by exponential enrichment.

Results

The thioaptamer could bind to the extracellular domain of HER2 with a K d of 172 nM and had minimal cross reactivity to trypsin or IgG. Moreover, the thioaptamer was found capable of binding with the HER2-positive breast cancer cells SK-BR-3 and MDA-MB-453, but not the HER2-negative cells MDA-MB-231. Notably, the thioaptamer HY6 largely maintained its structural integrity facing the nucleases in serum, while regular DNA aptamers were mostly digested. Additionally, the thioaptamer retained the capability of binding with the HER2-positive cells in the presence of serum, whereas non-thionated HER2 aptamer lost the binding function.

Conclusion

The results indicated that the selected thioaptamer was more resistant to nuclease than regular DNA aptamers and might potentially function as a HER2-targeting ligand in complicated environment.

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Acknowledgments

We acknowledge the funding support from the Chinese Ministry of Science and Technology (2011CB933504, 2011CB911003), and the 111 project from the Chinese Ministry of Education.

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China

    Y. Hu, J. Duan, B. Cao, L. Zhang & X.-D. Yang

  2. Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China

    X. Lu, F. Wang, F. Yao & Z. Zhu

  3. Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    W. Yuan

  4. National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100190, China

    C. Wang

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  1. Y. Hu
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  10. C. Wang
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  11. X.-D. Yang
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Corresponding authors

Correspondence to C. Wang or X.-D. Yang.

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Hu, Y., Duan, J., Cao, B. et al. Selection of a novel DNA thioaptamer against HER2 structure. Clin Transl Oncol 17, 647–656 (2015). https://doi.org/10.1007/s12094-015-1292-0

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  • DOI: https://doi.org/10.1007/s12094-015-1292-0

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