PMID- 34647460 OWN - NLM STAT- MEDLINE DCOM- 20211110 LR - 20211110 IS - 1530-6992 (Electronic) IS - 1530-6984 (Linking) VI - 21 IP - 20 DP - 2021 Oct 27 TI - Selective Encapsulation of Therapeutic mRNA in Engineered Extracellular Vesicles by DNA Aptamer. PG - 8563-8570 LID - 10.1021/acs.nanolett.1c01817 [doi] AB - 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 Pgc1alpha 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. FAU - Zhang, Siyan AU - Zhang S AUID- ORCID: 0000-0002-9446-0053 AD - Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, People's Republic of China. FAU - Dong, Yan AU - Dong Y AD - Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, People's Republic of China. FAU - Wang, Yixiao AU - Wang Y AD - Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, People's Republic of China. FAU - Sun, Wenqi AU - Sun W AD - Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, People's Republic of China. FAU - Wei, Mengying AU - Wei M AUID- ORCID: 0000-0002-0445-9586 AD - The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University Xi'an, 710032, People's Republic of China. FAU - Yuan, Lijun AU - Yuan L AUID- ORCID: 0000-0001-5651-2564 AD - Department of Ultrasound Diagnostics, Tangdu Hospital, Fourth Military Medical University, 710038 Xi'an, People's Republic of China. FAU - Yang, Guodong AU - Yang G AUID- ORCID: 0000-0002-6307-2963 AD - The State Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University Xi'an, 710032, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211014 PL - United States TA - Nano Lett JT - Nano letters JID - 101088070 RN - 0 (Aptamers, Nucleotide) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - *Aptamers, Nucleotide MH - Cell Movement MH - Disease Models, Animal MH - *Extracellular Vesicles MH - Mice MH - RNA, Messenger/genetics OTO - NOTNLM OT - DNA aptamer OT - Extracellular vesicles OT - browning of white adipocytes OT - encapsulation OT - engineering OT - inflammatory bowel disease OT - therapeutic mRNA EDAT- 2021/10/15 06:00 MHDA- 2021/11/11 06:00 CRDT- 2021/10/14 08:36 PHST- 2021/10/15 06:00 [pubmed] PHST- 2021/11/11 06:00 [medline] PHST- 2021/10/14 08:36 [entrez] AID - 10.1021/acs.nanolett.1c01817 [doi] PST - ppublish SO - Nano Lett. 2021 Oct 27;21(20):8563-8570. doi: 10.1021/acs.nanolett.1c01817. Epub 2021 Oct 14.