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.

Details

Title
Efficient RNA drug delivery using red blood cell extracellular vesicles
Author
Waqas Muhammad Usman 1 ; Pham, Tin Chanh 1 ; Yuk Yan Kwok 2 ; Luyen Tien Vu 1 ; Ma, Victor 2 ; Boya Peng 1 ; Yuen San Chan 1 ; Wei, Likun 1 ; Chin, Siew Mei 1 ; Azad, Ajijur 1 ; Alex Bai-Liang He 3 ; Leung, Anskar Y H 3 ; Yang, Mengsu 4 ; Shyh-Chang, Ng 5 ; Cho, William C 2 ; Shi, Jiahai 6 ; Le, Minh T N 6   VIAFID ORCID Logo 

1  Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong 
2  Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong 
3  Queen Mary Hospital and Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Island, Hong Kong 
4  Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong; Key Laboratory of Biochip Technology, Biotech and Health Centre, City University of Hong Kong Shenzhen Research Institute, Shenzhen, China 
5  Genome Institute of Singapore, Singapore, Singapore 
6  Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong; City University of Hong Kong Shenzhen Research Institute, Shenzhen, China 
Pages
1-15
Publication year
2018
Publication date
Jun 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-04791-8
ProQuest document ID
2055932036
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.