PMID- 33850951 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210416 IS - 2329-0501 (Print) IS - 2329-0501 (Electronic) IS - 2329-0501 (Linking) VI - 21 DP - 2021 Jun 11 TI - Acerola exosome-like nanovesicles to systemically deliver nucleic acid medicine via oral administration. PG - 199-208 LID - 10.1016/j.omtm.2021.03.006 [doi] AB - Extracellular vesicles derived from mammalian cells could be useful carriers for drug delivery systems (DDSs); however, with regard to clinical application, there are several issues to be overcome. Acerola (Malpighia emarginata DC.) is a popular health food. In this study, the feasibility of orally administered nucleic acid drug delivery by acerola exosome-like nanoparticles (AELNs) was examined. AELNs were recovered from acerola juice using an affinity column instead of ultracentrifugation. MicroRNA (miRNA) was sufficiently encapsulated in AELNs by 30-min incubation on ice and was protected against RNase, strong acid, and base treatments. The administration of an AELN/miRNA mixture in cells achieved downregulation of the miRNA's target gene, and this mixture showed cytoplasmic localization. AELNs orally delivered small RNA to the digestive system in vivo. The target gene-suppressing effect in the small intestine and liver peaked 1 day after administration, indicating potential for use as an oral DDS for nucleic acid in the digestive system. CI - (c) 2021 The Author(s). FAU - Umezu, Tomohiro AU - Umezu T AD - Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan. FAU - Takanashi, Masakatsu AU - Takanashi M AD - Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan. FAU - Murakami, Yoshiki AU - Murakami Y AD - Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan. FAU - Ohno, Shin-Ichiro AU - Ohno SI AD - Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan. FAU - Kanekura, Kohsuke AU - Kanekura K AD - Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan. FAU - Sudo, Katsuko AU - Sudo K AD - Preclinical Research Center, Tokyo Medical University, Tokyo, Japan. FAU - Nagamine, Kenichi AU - Nagamine K AD - Research and Development, Global Innovation Center, Nichirei Biosciences inc, Tokyo, Japan. FAU - Takeuchi, Shin AU - Takeuchi S AD - Research and Development, Global Innovation Center, Nichirei Biosciences inc, Tokyo, Japan. FAU - Ochiya, Takahiro AU - Ochiya T AD - Department of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan. FAU - Kuroda, Masahiko AU - Kuroda M AD - Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20210310 PL - United States TA - Mol Ther Methods Clin Dev JT - Molecular therapy. Methods & clinical development JID - 101624857 PMC - PMC8010214 OTO - NOTNLM OT - acerola OT - nanovesicle OT - nucleic acid medicine OT - oral administration COIS- The authors declare no competing interests. EDAT- 2021/04/15 06:00 MHDA- 2021/04/15 06:01 PMCR- 2021/03/10 CRDT- 2021/04/14 06:35 PHST- 2020/09/23 00:00 [received] PHST- 2021/03/06 00:00 [accepted] PHST- 2021/04/14 06:35 [entrez] PHST- 2021/04/15 06:00 [pubmed] PHST- 2021/04/15 06:01 [medline] PHST- 2021/03/10 00:00 [pmc-release] AID - S2329-0501(21)00046-2 [pii] AID - 10.1016/j.omtm.2021.03.006 [doi] PST - epublish SO - Mol Ther Methods Clin Dev. 2021 Mar 10;21:199-208. doi: 10.1016/j.omtm.2021.03.006. eCollection 2021 Jun 11.