Creation of blood-brain barrier transparent artificial nanoparticles for the treatment of central nervous system diseases

血脑屏障透明人工纳米粒子的研制用于治疗中枢神经系统疾病

• 批准号: 20J20737
• 负责人: Abd Elwakil Mahmoud
• 金额: $ 2.18万
• 依托单位: Hokkaido University
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20J20737/
• 关键词: mRNA drugs; ionizable polyesters; Gene Therapy; Organocatalysis; Lipid Nanoparticles; Lung diseases; Combinatorial chemistry; Immunotherapy; Biomaterials

During the past year I have developed a novel platform for mRNA delivery beyond the hepatocytes referred as to ionizable polyester/polyether RNA-Transporters (iPORT LNP). The key findings for the past year are:1. Development of ionizable lipo-polyether RNA transporters (iPORTs) that are produced via the organocatalytic ring-opening polymerization of glycidylamine monomers using steroidal initiators. Interestingly, the tacticity of the iPORTs had a significant impact on in vitro and in vivo RNA delivery efficiency and tropism and this impact was dependent of monomeric structure. The top performing Estriol-GA05-30 iPORT LNPs elicited strong antitumor activity in a therapeutic, prophylactic model and were well-tolerated in mice. This technology is being filed as a patent through Hokkaido University. Additionally a manuscript has been submitted to JACS, Manuscript ID: ja-2022-017103).2. Development of ionizable polyester RNA-Transporters LNP that selectively transfect splenocytes and lungs after systemic administration. The results of this project is being filed as a patent through Hokkaido University as well. Furthermore, a manuscript is being prepared for submission to publications.

在过去的一年里，我开发了一种新的肝细胞外mRNA递送平台，称为可电离聚酯/聚醚rna转运体（iPORT LNP）。过去一年的主要发现是：1。利用甾体引发剂有机催化开环聚合制备可电离脂聚醚RNA转运体（iPORTs）的研究进展。有趣的是，iPORTs的策略性对体外和体内RNA传递效率和趋向性有显著影响，这种影响依赖于单体结构。表现最好的Estriol-GA05-30 iPORT LNPs在治疗性、预防性模型中具有很强的抗肿瘤活性，并且在小鼠中具有良好的耐受性。这项技术正在通过北海道大学申请专利。论文已投稿至JACS，投稿号：ja-2022-017103。在全身给药后选择性转染脾细胞和肺的可电离聚酯rna转运蛋白LNP的研制。该项目的成果也正在通过北海道大学申请专利。此外，正在编写一份手稿，准备提交出版物。

项目成果

Engineered polyesters for mRNA delivery to the lungs

用于将 mRNA 输送至肺部的工程聚酯

• 发表时间: 2020