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Covalent stabilization of DNA nanostructures on cell membranes for efficient surface receptor-mediated labeling and function regulations

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Abstract

One major challenge of using DNA nanostructures for cellular and in vivo applications is their insufficiently structural integrity that stems from the non-covalent base pairing and stacking in complex cellular and physiological environment. The establishment of covalent bonds in DNA nanostructures can link individual strands more stably and therefore should improve the performance of DNA nanostructures in different scenarios where structural integrity is required. Here, we developed a convenient and effective method for constructing covalently stabilized DNA nanostructures by chemically inserting photo-cross-linker (CNVK) in DNA sequences. These covalently linked DNA nanostructures were found to be more resistant to external interference, such as low cation concentrations and unspecific displacement on cell membranes. We also demonstrated that our strategy could improve the efficiency of cell surface receptor-mediated labeling and function regulations in living cells, which sheds light on broadening the biomedical applications of DNA nanostructures.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2021YFA0909400), the National Natural Science Foundation of China (21974087, 81974315), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20181709), Shanghai Rising-Star Program (20QA1405800), and the General Projects of China Postdoctoral Fund (2021M692104). Innovative Research Team of High-Level Local Universities in Shanghai, faculty start-up funding support from the Institute of Molecular Medicine of Shanghai Jiao Tong University, and Recruitment Program of Global Youth Experts of China.

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China

    Dandan Chao, Xuemei Xu, Yanyan Miao, Linlin Yang, Qianqian Gao, Rui Xu, Yuan Tian, Yumeng Zhao & Da Han

  2. Department of Laboratory Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200127, China

    Yuzhen Du

Authors
  1. Dandan Chao
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  2. Xuemei Xu
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  3. Yanyan Miao
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  4. Linlin Yang
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  5. Qianqian Gao
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  6. Rui Xu
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  7. Yuan Tian
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  8. Yumeng Zhao
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  9. Yuzhen Du
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  10. Da Han
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Corresponding authors

Correspondence to Yuzhen Du or Da Han.

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Supporting information The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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11426_2022_1413_MOESM1_ESM.docx

Covalent stabilization of DNA nanostructures on cell membranes for efficient surface receptor-mediated labeling and function regulations

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Chao, D., Xu, X., Miao, Y. et al. Covalent stabilization of DNA nanostructures on cell membranes for efficient surface receptor-mediated labeling and function regulations. Sci. China Chem. 65, 2327–2334 (2022). https://doi.org/10.1007/s11426-022-1413-5

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  • DOI: https://doi.org/10.1007/s11426-022-1413-5

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