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Efficient RNA drug delivery using red blood cell extracellular vesicles

Author

Listed:
  • Waqas Muhammad Usman

    (City University of Hong Kong)

  • Tin Chanh Pham

    (City University of Hong Kong)

  • Yuk Yan Kwok

    (Queen Elizabeth Hospital)

  • Luyen Tien Vu

    (City University of Hong Kong)

  • Victor Ma

    (Queen Elizabeth Hospital)

  • Boya Peng

    (City University of Hong Kong)

  • Yuen San Chan

    (City University of Hong Kong)

  • Likun Wei

    (City University of Hong Kong)

  • Siew Mei Chin

    (City University of Hong Kong)

  • Ajijur Azad

    (City University of Hong Kong)

  • Alex Bai-Liang He

    (The University of Hong Kong)

  • Anskar Y. H. Leung

    (The University of Hong Kong)

  • Mengsu Yang

    (City University of Hong Kong
    City University of Hong Kong Shenzhen Research Institute)

  • Ng Shyh-Chang

    (Genome Institute of Singapore)

  • William C. Cho

    (Queen Elizabeth Hospital)

  • Jiahai Shi

    (City University of Hong Kong
    City University of Hong Kong Shenzhen Research Institute)

  • Minh T. N. Le

    (City University of Hong Kong
    City University of Hong Kong Shenzhen Research Institute)

Abstract

Most of the current methods for programmable RNA drug therapies are unsuitable for the clinic due to low uptake efficiency and high cytotoxicity. Extracellular vesicles (EVs) could solve these problems because they represent a natural mode of intercellular communication. However, current cellular sources for EV production are limited in availability and safety in terms of horizontal gene transfer. One potentially ideal source could be human red blood cells (RBCs). Group O-RBCs can be used as universal donors for large-scale EV production since they are readily available in blood banks and they are devoid of DNA. Here, we describe and validate a new strategy to generate large-scale amounts of RBC-derived EVs for the delivery of RNA drugs, including antisense oligonucleotides, Cas9 mRNA, and guide RNAs. RNA drug delivery with RBCEVs shows highly robust microRNA inhibition and CRISPR–Cas9 genome editing in both human cells and xenograft mouse models, with no observable cytotoxicity.

Suggested Citation

  • Waqas Muhammad Usman & Tin Chanh Pham & Yuk Yan Kwok & Luyen Tien Vu & Victor Ma & Boya Peng & Yuen San Chan & Likun Wei & Siew Mei Chin & Ajijur Azad & Alex Bai-Liang He & Anskar Y. H. Leung & Mengsu, 2018. "Efficient RNA drug delivery using red blood cell extracellular vesicles," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04791-8
    DOI: 10.1038/s41467-018-04791-8
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