| Project/Area Number |
22K19541
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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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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Cabral Horacio 東京大学, 大学院工学系研究科(工学部), 准教授 (10533911)
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| Co-Investigator(Kenkyū-buntansha) |
持田 祐希 公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 副主幹研究員 (60739134)
松元 亮 東京医科歯科大学, 生体材料工学研究所, 教授 (70436541)
宮崎 拓也 地方独立行政法人神奈川県立産業技術総合研究所, 貼るだけ人工膵臓グループ (松元G), 非常勤研究員 (80844779)
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| Project Period (FY) |
2022-06-30 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2023: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | mRNA / polymeric micelles / in situ Treg / Immunosuppression / Treg / Foxp3 / in vivo CAR T / nanomedicine / immunotherapy / autoimmune disease |
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| Outline of Research at the Start |
Herein, we will prepare mRNA-loaded micelles for generating CAR-Tregs in vivo. In the first year, we will prepare the micelles and check the ability to generate the CAR-Tregs in vitro and in vivo. In the second year, we will test the therapeutic effect of the CAR-Tregs in a mouse model of diabetes.
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| Outline of Final Research Achievements |
Herein, we used polymeric micelles installed with anti-CD3 F(ab')2 antibodies to effectively deliver mRNA to T cells, aiming to induce the production of regulatory T cells (Tregs). The mRNA was derived from in vitro transcription of a plasmid encoding Foxp3 protein. Foxp3 can facilitate the generation of Tregs, known for their immune regulatory role. The micelles loaded the mRNA by self-assembly in aqueous conditions. Moreover, the surface of the micelles was modified with anti-CD3 F(ab')2 by click chemistry. The resulting micelles were around 100 nm in diamter. These micelles selectively targeted CD3+ T cells, both in vitro and in vivo, resulting in the production of Tregs. Remarkably, the modified T cells displayed an anti-inflammatory profile, characterized by the secretion of cytokines such as IL-10, IL-4, and Tgf-beta. These findings support the potential of this approach for generating immunomodulating T cells in various disease contexts.
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| Academic Significance and Societal Importance of the Research Achievements |
By using micelles to deliver mRNA encoding Foxp3 protein, we can induce Tregs that mediate immunosuppression, which has potential for treating autoimmune diseases, allergies and inflammatory disorders. The approach could reduce costs and burden of cellular therapies by in situ generation of Tregs.
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