Efficient RNA drug delivery using red blood cell extracellular vesicles

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 Yang, Ng Shyh-Chang, William C. Cho, Jiahai Shi and Minh T. N. Le ()
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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
Ng Shyh-Chang: Genome Institute of Singapore
William C. Cho: Queen Elizabeth Hospital
Jiahai Shi: City University of Hong Kong
Minh T. N. Le: City University of Hong Kong

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04791-8

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