Efficient RNA drug delivery using red blood cell extracellular vesicles

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Original languageEnglish
Article number2359 (2018)
Journal / PublicationNature Communications
Volume9
Publication statusPublished - 15 Jun 2018

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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.

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Citation Format(s)

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

In: Nature Communications, Vol. 9, 2359 (2018), 15.06.2018.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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