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Anionic Complex with Efficient Expression and Good Safety Profile for mRNA Delivery
http://hdl.handle.net/10069/00040515
http://hdl.handle.net/10069/00040515e212d594-0add-4c11-bed0-015855d1b20e
名前 / ファイル | ライセンス | アクション |
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Pharmaceutics13_126.pdf (1.0 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-02-19 | |||||
タイトル | ||||||
タイトル | Anionic Complex with Efficient Expression and Good Safety Profile for mRNA Delivery | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | MRNA | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Nanoparticles | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Polyethyleneimine | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | γ-polyglutamic acid | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Hamada, Eri
× Hamada, Eri× Kurosaki, Tomoaki× Hashizume, Junya× Harasawa, Hitomi× Nakagawa, Hiroo× Nakamura, Tadahiro× Kodama, Yukinobu× Sasaki, Hitoshi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | We previously found that a complex comprising plasmid DNA (pDNA), polyethylenimine (PEI), and γ-polyglutamic acid (γ-PGA) had high transgene efficiency without cytotoxicity in vitro and in vivo. However, messenger RNA (mRNA) remains an attractive alternative to pDNA. In this study, we developed a safe and effective delivery system for mRNA to prevent its degradation and efficiently deliver it into target cells. Various cationic and anionic complexes were produced containing PEI, γ-PGA, and an mRNA encoding firefly luciferase. Their physicochemical properties and cytotoxicities were analyzed and the in vitro and in vivo protein expression were determined. The cationic mRNA/PEI complex showed high in vitro protein expression with strong cytotoxicity. The anionic complex was constructed as mRNA/PEI8/γ-PGA12 complex with a theoretical charge ratio of 1:8:12 based on the phosphate groups of the mRNA, nitrogen groups of PEI, and carboxylate groups of γ-PGA. It was stable and showed high in vitro protein expression without cytotoxicity. After intravenous administration of mRNA/PEI8/γ-PGA12 complex to mice, high protein expression was observed in the spleen and liver and slight expression was observed in the lung over 24 h. Thus, the newly constructed mRNA/PEI8/γ-PGA12 complex provides a safe and effective strategy for the delivery of mRNA. | |||||
書誌情報 |
Pharmaceutics 巻 13, 号 1, p. 126, 発行日 2021-01-19 |
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出版者 | ||||||
出版者 | MDPI | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1999-4923 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/pharmaceutics13010126 | |||||
権利 | ||||||
権利情報 | ©2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Pharmaceutics, 13(1), art.no.126; 2021 |