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; Minh T.N. Le

doi:10.1038/s41467-018-04791-8

Author(s)

Yuk Yan Kwok
Victor Ma
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
Minh T.N. Le

Related Research Unit(s)

Detail(s)

Original language	English
Article number	2359 (2018)
Journal / Publication	Nature Communications
Volume	9
Publication status	Published - 15 Jun 2018

Link(s)

DOI	DOI https://doi.org/10.1038/s41467-018-04791-8 Final Published version
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Attachment(s)	Documents 23928826.pdf Final Published version, 6.1 MB, PDF Publisher's Copyright Statement Usman, W. M., Pham, T. C., Kwok, Y. Y., Vu, L. T., Ma, V., Peng, B., ... Le, M. T. N. (2018). Efficient RNA drug delivery using red blood cell extracellular vesicles. Nature Communications, 9, [2359 (2018)]. DOI: 10.1038/s41467-018-04791-8. This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/
Link to Scopus	https://www.scopus.com/record/display.uri?eid=2-s2.0-85048721395&origin=recordpage
Permanent Link	https://scholars.cityu.edu.hk/en/publications/publication(5690d183-e436-4779-9cca-1bdb85b3e165).html

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.