Development of Novel mRNA Delivery Systems based on Flexible Biodegradable Block Copolymers

基于柔性可生物降解嵌段共聚物的新型 mRNA 递送系统的开发

• 批准号: 20J13458
• 负责人: 楊 文セイ
• 金额: $ 1.34万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-24 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20J13458/
• 关键词: Nanomedicine; Polymeric micelles; messenger RNA

Here, we focused on the development of nanocarriers for safe and stable systemic delivery of mRNA. Thus, we have developed a library of polymers, and chemically modified with amino acids which could stable mRNA by hydrophobic interaction and π-π interaction. We confirmed that these polymers were biodegradable in physiological conditions. Polymeric micelles prepared by polymers with π-π interaction were found to be safe in vitro after incubation with 50% Fetal Bovine Serum, could achieve a highest mRNA expression in vitro. We found that micelles with π-π interaction with mRNA showed higher protein expression in the lung of mouse after 24 h intratracheal administration. Moreover, these micelles maintained over 10% of loaded mRNA in mice blood after 10 mins of intravenous administration.

在这里，我们专注于开发用于安全和稳定的mRNA全身递送的纳米载体。因此，我们开发了一个聚合物库，并用氨基酸进行化学修饰，这些氨基酸可以通过疏水相互作用和π-π相互作用稳定mRNA。我们证实了这些聚合物在生理条件下是可生物降解的。由π-π相互作用的聚合物制备的聚合物胶束在体外与50%胎牛血清孵育后发现是安全的，可以在体外获得最高的mRNA表达。结果表明，与mRNA有π-π相互作用的胶束，在小鼠肺内给药24 h后，蛋白质表达量明显增加。此外，这些胶束在静脉内给药10分钟后在小鼠血液中保持超过10%的负载mRNA。

项目成果

Influence of PEG-Polycation Chain Flexibility on the Assembly of siRNA into Polyion Complexes

PEG-聚阳离子链柔韧性对 siRNA 组装成聚离子复合物的影响

• 发表时间: 2021
• 作者: Wenqian Yang;Takuya Miyazaki;Pengwen Chen;Taehun Hong and Horacio Cabral
• 通讯作者: Taehun Hong and Horacio Cabral

Bioinspired design of stable siRNA-loaded polyion complex micelles from strong Tryptophan/Tyrosine-RNA interactions for siRNA delivery

基于色氨酸/酪氨酸-RNA 强相互作用的稳定 siRNA 负载聚离子复合胶束的仿生设计，用于 siRNA 递送

• 发表时间: 2020
• 作者: Wenqian Yang;Takuya Miyazaki;Yasuhiro Nakagawa;Satoshi Uchida;Kazunori Kataoka;Horacio Cabral
• 通讯作者: Horacio Cabral

Enhanced mRNA Delivery by Polyion Complex Micelles from Flexible Block Ionomers

柔性嵌段离聚物聚离子复合胶束增强 mRNA 递送

• 发表时间: 2021
• 作者: Horacio Cabral;Takuya Miyazaki;Wenqian Yang;Satoshi Uchida
• 通讯作者: Satoshi Uchida

Effect of PEG-Polycation Chain Flexibility on siRNA loaded Polyion Complex Micelles Assembly

PEG-聚阳离子链柔韧性对 siRNA 负载的聚离子复合胶束组装的影响

• 发表时间: 2020
• 作者: Wenqian Yang;Takuya Miyazaki;Yasuhiro Nakagawa;Pengwen Chen;Taehun Hong;Horacio Cabral
• 通讯作者: Horacio Cabral