Selective Encapsulation of Therapeutic mRNA in Engineered Extracellular Vesicles by DNA Aptamer


Posted: 2021-10-14 19:00:00
. 2021 Oct 14. doi: 10.1021/acs.nanolett.1c01817. Online ahead of print. Affiliations Expand Affiliations 1 Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, People's Republic of China. 2 Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China. 3 The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University Xi'an, 710032, People's Republic of China. Item in Clipboard Siyan Zhang et al. Nano Lett. 2021. Show details Display options Display options Format . 2021 Oct 14. doi: 10.1021/acs.nanolett.1c01817. Online ahead of print. Affiliations 1 Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, People's Republic of China. 2 Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China. 3 The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University Xi'an, 710032, People's Republic of China. Item in Clipboard Full text links CiteDisplay options Display options Format Abstract 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. Keywords: DNA aptamer; Extracellular vesicles; browning of white adipocytes; encapsulation; engineering; inflammatory bowel disease; therapeutic mRNA. LinkOut - more resources Full Text Sources

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バイオクイックニュース日本語版
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