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Ex vivo pretreatment of human vessels with siRNA nanoparticles provides protein silencing in endothelial cells

Author

Listed:
  • Jiajia Cui

    (Yale University)

  • Lingfeng Qin

    (Yale University School of Medicine)

  • Junwei Zhang

    (Yale University)

  • Parwiz Abrahimi

    (Yale University School of Medicine)

  • Hong Li

    (Yale University)

  • Guangxin Li

    (Yale University School of Medicine)

  • Gregory T. Tietjen

    (Yale University)

  • George Tellides

    (Yale University School of Medicine)

  • Jordan S. Pober

    (Yale University School of Medicine)

  • W. Mark Saltzman

    (Yale University
    Yale University)

Abstract

Human endothelial cells are initiators and targets of the rejection response. Pre-operative modification of endothelial cells by small interfering RNA transfection could shape the nature of the host response post-transplantation. Ablation of endothelial cell class II major histocompatibility complex molecules by small interfering RNA targeting of class II transactivator can reduce the capacity of human endothelial cells to recruit and activate alloreactive T cells. Here, we report the development of small interfering RNA-releasing poly(amine-co-ester) nanoparticles, distinguished by their high content of a hydrophobic lactone. We show that a single transfection of small interfering RNA targeting class II transactivator attenuates major histocompatibility complex class II expression on endothelial cells for at least 4 to 6 weeks after transplantation into immunodeficient mouse hosts. Furthermore, silencing of major histocompatibility complex class II reduces allogeneic T-cell responses in vitro and in vivo. These data suggest that poly(amine-co-ester) nanoparticles, potentially administered during ex vivo normothermic machine perfusion of human organs, could be used to modify endothelial cells with a sustained effect after transplantation.

Suggested Citation

  • Jiajia Cui & Lingfeng Qin & Junwei Zhang & Parwiz Abrahimi & Hong Li & Guangxin Li & Gregory T. Tietjen & George Tellides & Jordan S. Pober & W. Mark Saltzman, 2017. "Ex vivo pretreatment of human vessels with siRNA nanoparticles provides protein silencing in endothelial cells," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00297-x
    DOI: 10.1038/s41467-017-00297-x
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    Cited by:

    1. C. Albert & L. Bracaglia & A. Koide & J. DiRito & T. Lysyy & L. Harkins & C. Edwards & O. Richfield & J. Grundler & K. Zhou & E. Denbaum & G. Ketavarapu & T. Hattori & S. Perincheri & J. Langford & A., 2022. "Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Alexandra S. Piotrowski-Daspit & Laura G. Bracaglia & David A. Eaton & Owen Richfield & Thomas C. Binns & Claire Albert & Jared Gould & Ryland D. Mortlock & Marie E. Egan & Jordan S. Pober & W. Mark S, 2024. "Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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