适体
信使核糖核酸
细胞生物学
化学
小RNA
分子生物学
生物
外体
微泡
基因
生物化学
作者
Siyan Zhang,Yan Dong,Yixiao Wang,Wenqi Sun,Mengying Wei,Lijun Yuan,Guodong Yang
出处
期刊:Nano Letters
[American Chemical Society]
日期:2021-10-14
卷期号:21 (20): 8563-8570
被引量:40
标识
DOI:10.1021/acs.nanolett.1c01817
摘要
Extracellular vesicles (EV)-based delivery of therapeutic mRNAs is challenged by the low loading efficiency. In this study, we designed a DNA aptamer consisting of two parts: the single strand part recognized the AUG region of target mRNA, preventing mRNA from translation and ribosome assembly; and the double strand part containing the elements recognized by the CD9-ZF (zinc finger) motifs, sorting DNA aptamer-mRNA complex into CD9-ZF engineered EVs. In vitro and in vivo studies revealed that the system could efficiently load functional mRNAs to the EVs. Furthermore, adipose specific delivery of loaded Pgc1α mRNA via the strategy could efficiently induce white adipocyte browning. Similarly, delivery of interleukin-10 (Il-10) mRNA via the strategy had potent anti-inflammatory effect in inflammatory bowel disease (IBD) mouse model. Together, our study has proposed an efficient strategy to load therapeutic mRNAs of interest into EVs, which could be used as a promising strategy for gene therapy.
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