核糖核酸
微泡
清脆的
Cas9
小RNA
胞外囊泡
细胞毒性
DNA
寡核苷酸
基因组编辑
计算生物学
细胞生物学
核酸
化学
生物
基因
细胞内
生物化学
体外
作者
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,Bai-Liang He,Anskar Yu Hung Leung,Mian Yang,Ng Shyh‐Chang,William C. Cho,Jiahai Shi,Minh Vuong Le
标识
DOI:10.1038/s41467-018-04791-8
摘要
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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