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

在过去的一年里，我开发了一种新的平台，用于mRNA递送，超越肝细胞，称为电离聚酯/聚醚RNA转运蛋白（iPORT LNP）。过去一年的主要发现是：1。开发可电离的脂质聚醚RNA转运蛋白（iPORT），其通过使用甾体引发剂的甘氨酰胺单体的有机催化开环聚合产生。有趣的是，iPORT的立构规整度对体外和体内RNA递送效率和向性具有显著影响，并且这种影响依赖于单体结构。表现最好的雌三醇-GA 05 -30 iPORT LNP在治疗性、预防性模型中引发强抗肿瘤活性，并且在小鼠中耐受良好。这项技术正在通过北海道大学申请专利。此外，还向JACS提交了一份手稿，Mandarin pt ID：ja-2022-017103）。可电离聚酯RNA转运蛋白LNP的开发，可在全身给药后选择性转染脾细胞和肺。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，以提交出版物。

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.