Ultrasound Assisted Exosomal Delivery of Tissue Responsive mRNA for Enhanced Efficacy and Minimized Off-Target Effects
Ultrasound Assisted Exosomal Delivery of Tissue Responsive mRNA for Enhanced Efficacy and Minimized Off-Target Effects
复制标题
超声辅助外泌体递送组织响应性 mRNA，以增强功效并最大限度地减少脱靶效应
DOI：
10.1016/j.omtn.2020.03.016
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发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
Yuan Lijun
中科院分区：
文献类型：
--
作者：
Sun Wenqi;Xing Changyang;Zhao Lianbi;Zhao Ping;Yang Guodong;Yuan Lijun
Exosome-mediated nucleic acids delivery has been emerging as a promising strategy for gene therapy. However, the intrinsic off-target effects due to non-specific uptake of exosomes by other tissues remain the big hurdle for clinical application. In this study, we aimed to enhance the efficacy and minimize the off-target effects by simultaneously encapsulating engineered mRNA translationally activated by tissue-specific microRNA (miRNA) and increasing targeted delivery efficiency via ultrasound-targeted microbubble destruction (UTMD). Briefly, the upstream of interest transcript was engineered to harbor an internal ribosome entry site (IRES) modified with two miRNA recognition sites.In vitroreporter experiments revealed that the engineered mRNA could be encapsulated into exosomes and can be translationally activated by corresponding miRNAs in the recipient cells. By a proof-of-principlein vivoexperiment, we encapsulated miR-148a (an adipose relatively specific miRNA)-responsive PGC1α mRNA into exosomes and delivered the exosomes into the adipose tissue with the aid of UTMD. Efficient PGC1α translation was activated in the adipose tissue, together with obvious browning induction. Moreover, there was much lower off-target translation of PGC1 α in lungs and other tissues. Taken together, our study establishes a novel adipose-specific exosome delivery strategy to enhance efficacy and minimize off-target effects simultaneously.
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影响因子：
6.2
作者：
Webb, T. E.;Hughes, A.;Smalley, D. S.;Spriggs, K. A.
通讯作者：
Spriggs, K. A.
影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
超声靶向微泡破坏辅助外泌体在难治性组织中的有效递送
影响因子：
6
作者：
Sun, Wenqi;Li, Zhelong;Yuan, Lijun
通讯作者：
Yuan, Lijun
影响因子：
16.6
作者：
Isgrig, Kevin;McDougald, Devin S.;Chien, Wade W.
通讯作者：
Chien, Wade W.
影响因子：
--
作者：
C. Zheng;B. Baum
通讯作者：
C. Zheng;B. Baum