Use of Single-Site-Functionalized PEG Dendrons To Prepare Gene Vectors that Penetrate Human Mucus Barriers

Authors

  • Dr. Anthony J. Kim,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
    2. Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore (USA)
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    • These authors contributed equally to this work.

  • Dr. Nicholas J. Boylan,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
    2. Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore (USA)
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    • These authors contributed equally to this work.

  • Dr. Jung Soo Suk,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
    2. Department of Biomedical Engineering, Johns Hopkins University, Baltimore (USA)
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  • Minyoung Hwangbo,

    1. Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore (USA)
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  • Tao Yu,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
    2. Department of Biomedical Engineering, Johns Hopkins University, Baltimore (USA)
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  • Benjamin S. Schuster,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
    2. Department of Biomedical Engineering, Johns Hopkins University, Baltimore (USA)
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  • Dr. Liudimila Cebotaru,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
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  • Dr. Wojciech G. Lesniak,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
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  • Joon Seok Oh,

    1. Department of Biomedical Engineering, Johns Hopkins University, Baltimore (USA)
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  • Pichet Adstamongkonkul,

    1. Department of Biomedical Engineering, Johns Hopkins University, Baltimore (USA)
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  • Ashley Y. Choi,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
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  • Prof. Dr. Rangaramanujam M. Kannan,

    1. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
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  • Prof. Dr. Justin Hanes

    Corresponding author
    1. Departments of Ophthalmology, Biomedical Engineering, Chemical & Biomolecular Engineering and Oncology, Center for Cancer Nanotechnology Excellence and Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231 (USA)
    2. The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University, Baltimore (USA)
    3. Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore (USA)
    4. Department of Biomedical Engineering, Johns Hopkins University, Baltimore (USA)
    • Departments of Ophthalmology, Biomedical Engineering, Chemical & Biomolecular Engineering and Oncology, Center for Cancer Nanotechnology Excellence and Center for Nanomedicine, Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231 (USA)
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  • This project was supported by the National Heart, Lung, and Blood Institute (grant numbers P01L51811 and F32L103137 to A.J.K.) and the National Institute of Biomedical Imaging and Bioengineering (grant number R01EB003558). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute, the National Institute of Biomedical Imaging and Bioengineering, or the National Institutes of Health. We thank Dr. Michael Boyle and Meghan Ramsay at the Johns Hopkins Adult Cystic Fibrosis Center for CF sputum collection. We also thank Dr. Himat Patel and Dr. Qingguo Xu for helpful comments.

Abstract

original image

Mucus-penetrating DNA nanoparticles: A novel synthetic strategy was used to achieve a dense PEG coating on the surface of cationic polymer-based DNA nanoparticles. The dense PEG coating (blue in scheme) endows the nanoparticles with a muco-inert surface, which enables their rapid mucus penetration (trajectory indicated by gray line) and provides efficient gene transfer in various cell types.

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