Exosome-mediated mRNA Delivery in vivo is safe and can be used to induce SARS-CoV-2 immunity


Posted: 2021-10-03 19:00:00
J Biol Chem . 2021 Sep 30;101266. doi: 10.1016/j.jbc.2021.101266. Online ahead of print. Affiliations Expand Affiliations 1 Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205. 2 Capricor Therapeutics, Inc. 8840 Wilshire Blvd. 2nd Floor, Beverly Hills, CA 90211. 3 Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205. Electronic address: sgould@jhmi.edu. Item in Clipboard Shang Jui Tsai et al. J Biol Chem. 2021. Show details Display options Display options Format J Biol Chem . 2021 Sep 30;101266. doi: 10.1016/j.jbc.2021.101266. Online ahead of print. Affiliations 1 Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205. 2 Capricor Therapeutics, Inc. 8840 Wilshire Blvd. 2nd Floor, Beverly Hills, CA 90211. 3 Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205. Electronic address: sgould@jhmi.edu. Item in Clipboard CiteDisplay options Display options Format Abstract Functional delivery of mRNA has high clinical potential. Previous studies established that mRNAs can be delivered to cells in vitro and in vivo via RNA-loaded lipid nanoparticles (LNPs). Here we describe an alternative approach using exosomes, the only biologically normal nanovesicle. In contrast to LNPs, which elicited pronounced cellular toxicity, exosomes had no adverse effects in vitro or in vivo at any dose tested. Moreover, mRNA-loaded exosomes were characterized by efficient mRNA encapsulation (∼90%), high mRNA content, consistent size, and a polydispersity index under 0.2. Using an mRNA encoding the red light-emitting luciferase Antares2, we observed that mRNA-loaded exosomes were superior to mRNA-loaded LNPs at delivering functional mRNA into human cells in vitro. Injection of Antares2 mRNA-loaded exosomes also led to strong light emission following injection into the vitreous fluid of the eye or into the tissue of skeletal muscle in mice. Furthermore, we show that repeated injection of Antares2 mRNA-loaded exosomes drove sustained luciferase expression across six injections spanning at least 10 weeks, without evidence of signal attenuation or adverse injection site responses. Consistent with these findings, we observed that exosomes loaded with mRNAs encoding immunogenic forms of the SARS-CoV-2 Spike and Nucleocapsid proteins induced long-lasting cellular and humoral responses to both. Taken together, these results demonstrate that exosomes can be used to deliver functional mRNA to and into cells in vivo. Keywords: COVID19; T-cell; antibody; cationic lipid; exosome; extracellular vesicles; lipofection; mRNA; nucleocapsid; spike. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. Conflict of interest statement Disclosures: S.J.G is a paid consultant for Capricor, holds equity in Capricor, and is co-inventor of intellectual property licensed by Capricor. S.J.T. is co-inventor of intellectual property licensed by Capricor. C.G. is co-inventor of intellectual property licensed by Capricor. N.A., J.N., M.C., A.Sa., A.S., S.K., S.S., and C.L. contributed to this work as employees of Capricor. [x] Cite Copy Format: Send To [x]

参考サイト PubMed: exsome



バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
10月 19, 2018 バイオアソシエイツ

エクソソームがパーキンソン病の脳の特定領域にドーパミンを直接送達することがマウスでの研究で実証された

2018年9月5日にParkinson's Disease Todayに掲載された研究コラムニストのAlice Melao氏の記事によれば、血液中を自然循環するエクソソームは脳を含む中枢神経系に効果的に薬を運搬することができ、マウスでの初期の研究ではパーキンソン病の影響を受けた脳の特定の領域にドーパミンを直接的に送達することができたことを示唆しているという。…

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