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2021 年度 実績報告書

中枢神経疾患治療を目指した血液脳関門透過型人工ナノ粒子の創製

研究課題

研究課題/領域番号 20J20737
研究機関北海道大学

研究代表者

Abd Elwakil Mahmoud  北海道大学, 生命科学院, 特別研究員(DC1)

研究期間 (年度) 2020-04-24 – 2023-03-31
キーワードmRNA drugs / ionizable polyesters / Gene Therapy / Organocatalysis / Lipid Nanoparticles / Lung diseases / Combinatorial chemistry / Immunotherapy
研究実績の概要

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.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

Although we are at very hard times during COVID-19, my research projects were going very well and research output was really great because:
1. I have submitted two patents in one year.
2. Two manuscripts were prepared and are being submitted for publication in top tier scientific journals.

今後の研究の推進方策

In the coming year I plan to:
1. Apply my mRNA iPORT LNP technology for therapeutic application in lung diseases, cancer immunotherapy and infectious diseases vaccines such as COVID-19.
2. Extend my combinatorial chemistry for RNA delivery for other hard tissues such as bone and central nervous system.
3. Communicate my iPORT LNP technology with scientific community via attending international conferences and big pharmaceutical companies.

  • 研究成果

    (1件)

すべて 2021

すべて 雑誌論文 (1件)

  • [雑誌論文] Engineered ε-decalactone lipomers bypass the liver to selectively in vivo deliver mRNA to the lungs without targeting ligands2021

    • 著者名/発表者名
      Mahmoud M. Abd Elwakil, Tianle Gao, Takuya Isono, Yusuke Sato, Yaser H. A. Elewa, Toshifumi Satoh and Hideyoshi Harashima
    • 雑誌名

      Materials Horizons

      巻: 8 ページ: 2251-2259

    • DOI

      10.1039/D1MH00185J

URL: 

公開日: 2022-12-28  

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