並列タイトル等mRNA送達のための高い発現効率と安全性を有するアニオン性複合体
授与機関名Nagasaki University (長崎大学)
一般注記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.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1340号 学位授与年月日:令和3年3月22日
Author: Eri Hamada, Tomoaki Kurosaki, Junya Hashizume, Hitomi Harasawa, Hiroo Nakagawa, Tadahiro Nakamura, Yukinobu Kodama and Hitoshi Sasaki
Citation: Pharmaceutics, 13(1), 126; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-03-22)
http://hdl.handle.net/10069/00040609
DOIinfo:doi/10.3390/pharmaceutics13010126
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