| Project/Area Number |
17K19473
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmaceutical Sciences and related fields
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| Research Institution | Chiba University |
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Principal Investigator |
Akita Hidetaka 千葉大学, 大学院薬学研究院, 教授 (80344472)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | リガンド / 脂質様材料 / DDS / 脂質 / ナノバイオ / ナノマシン |
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| Outline of Final Research Achievements |
In this project, we have established a method for the rapid identification of targeting ligand by using a phage display library. Also, we developed a lipid-like materials that can deliver the nucleic acids via intravenous administration. As to the first project, the extracellular domain of membrane-translocating protein was fixed onto the beads, and its binding antibody was identified from the phage library that encoded a randomized domain antibody. In the second project, the lipid-like materials that mounts ternary amine and disulfide bonging as a pH-triggered protonation unit and reductive environment-triggered cleavable unit, respectively was developed as a nucleic acid delivery system. We clarified that an oleic acid is useful for the application via intravenous administration. As one example, the application to the siRNA delivery system was also demonstrated.
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| Academic Significance and Societal Importance of the Research Achievements |
本方法は、これまで困難であった膜蛋白質の細胞外ドメインに結合する抗体を簡便かつ迅速に同定する方法として、広く応用できる。また、本研究で開発した脂質用材料は中性な核酸搭載ナノ粒子の調製を可能とし、細胞内に取り込まれた後には効率的にエンドソーム脱出をし、さらに自己崩壊することで搭載分子を細胞内に導入できることから、リガンドを搭載することで、様々な受容体を標的とするナノ粒子製剤として発展させることできる。本材料に関しては国際的な供給も開始しており、様々な創剤技術として発展が期待される。
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