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Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer

Author

Listed:
  • Shiyan Dong

    (Jilin University
    The University of Texas MD Anderson Cancer Center)

  • Xuan Liu

    (The University of Texas MD Anderson Cancer Center
    Louisiana Tech University)

  • Ye Bi

    (Changchun University of Chinese Medicine)

  • Yifan Wang

    (The University of Texas MD Anderson Cancer Center)

  • Abin Antony

    (The University of Texas MD Anderson Cancer Center)

  • DaeYong Lee

    (The University of Texas MD Anderson Cancer Center)

  • Kristin Huntoon

    (The University of Texas MD Anderson Cancer Center)

  • Seongdong Jeong

    (The University of Texas MD Anderson Cancer Center)

  • Yifan Ma

    (The Ohio State University)

  • Xuefeng Li

    (The University of Texas MD Anderson Cancer Center)

  • Weiye Deng

    (The University of Texas MD Anderson Cancer Center)

  • Benjamin R. Schrank

    (The University of Texas MD Anderson Cancer Center)

  • Adam J. Grippin

    (The University of Texas MD Anderson Cancer Center)

  • JongHoon Ha

    (The University of Texas MD Anderson Cancer Center)

  • Minjeong Kang

    (The University of Texas MD Anderson Cancer Center)

  • Mengyu Chang

    (The University of Texas MD Anderson Cancer Center)

  • Yarong Zhao

    (Jilin University)

  • Rongze Sun

    (Jilin University)

  • Xiangshi Sun

    (Jilin University)

  • Jie Yang

    (Jilin University)

  • Jiayi Chen

    (Jilin University)

  • Sarah K. Tang

    (The University of Texas MD Anderson Cancer Center)

  • L. James Lee

    (The Ohio State University
    Spot Biosystems Ltd.)

  • Andrew S. Lee

    (Shenzhen Bay Laboratory
    Peking University Shenzhen Graduate School)

  • Lirong Teng

    (Jilin University)

  • Shengnian Wang

    (Louisiana Tech University)

  • Lesheng Teng

    (Jilin University)

  • Betty Y. S. Kim

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Zhaogang Yang

    (Jilin University
    The University of Texas MD Anderson Cancer Center)

  • Wen Jiang

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

Abstract

The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.

Suggested Citation

  • Shiyan Dong & Xuan Liu & Ye Bi & Yifan Wang & Abin Antony & DaeYong Lee & Kristin Huntoon & Seongdong Jeong & Yifan Ma & Xuefeng Li & Weiye Deng & Benjamin R. Schrank & Adam J. Grippin & JongHoon Ha &, 2023. "Adaptive design of mRNA-loaded extracellular vesicles for targeted immunotherapy of cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42365-5
    DOI: 10.1038/s41467-023-42365-5
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