2023 Fiscal Year Final Research Report
Development of immunosuppressive dendritic cells and autoimmune disease treatment based on mRNA delivery technology
| Project/Area Number |
21K18035
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | Tohoku University (2023)
Chiba University (2021-2022) |
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Principal Investigator |
Tanaka Hiroki 東北大学, 薬学研究科, 准教授 (60801743)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | mRNAデリバリー / Lipid nanoparticles / ドラッグデリバリーシステム / 自己免疫疾患 |
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| Outline of Final Research Achievements |
In peripheral tissues during non-inflammation, antigen-presenting cells (APCs) such as dendritic cells and macrophages establish peripheral immune tolerance against constantly existing self-proteins. Cell therapy using tolerative dendritic cells (tol-DCs) has been proposed as a therapeutic principle utilizing this mechanism. In this study, we attempted to rewrite the phenotype of dendritic cells by introducing immunosuppressive factors by introducing in vitro transcribed mRNA into dendritic cells. We have developed a preparation that allows gene introduction into mouse bone marrow-derived dendritic cells for over 72 hours and allows anyone to easily obtain mRNA-LNP. We also discovered a transcription factor that can induce the production of IL-10.
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| Free Research Field |
mRNAデリバリー
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、誰でも簡単にｍＲＮＡ－ＬＮＰ製剤を作製可能な技術を開発し、それを用いて樹状細胞に遺伝子を導入することで、細胞の免疫学的な性質の改変を試みた。凍結乾燥を基盤とする新規の製剤を用いることで、だれでも５分程度でｍＲＮＡ－ＬＮＰを作製可能となった。本技術は遺伝子治療への参入障壁を大きく下げるものである。また、本技術を用いた３６種類のｍＲＮＡのスクリーニングにより、樹状細胞に免疫抑制性サイトカインであるＩＬ－１０の発現を誘導可能な候補を見出した。本知見は、遺伝子治療による自己免疫疾患治療の可能性を示唆するものと言える。
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