2020 Fiscal Year Final Research Report
Development of self-degradable lipid like material based on intraparticle reaction
| Project/Area Number |
18K18377
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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 90120:Biomaterials-related
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| Research Institution | Chiba University |
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Principal Investigator |
Tanaka Hiroki 千葉大学, 大学院薬学研究院, 助教 (60801743)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | mRNA送達 / ドラッグデリバリー / 炎症性疾患 |
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| Outline of Final Research Achievements |
In this study, we developed a self-degradable lipid-like material which we refer as to ssPalmO-Phe for the delivery of mRNA. The ssPalmO-Phe can degrade itself under a reducing environment by intra-particle nucleophilic attacks to its phenyl ester moiety. The ssPalmO-Phe showed significant gene expression to the cells and moue liver. The toxicity of the ssPalmO-Phe was significantly lower than that of conventional lipid nanoparticle system. We then tried to cure the inflammatory diseases using fulminant hepatitis model and inflammatory bowel diseases. In the case of fulminant hepatitis, no therapeutic effect was observed. It's because the fulminant hepatitis model (D-Gal/LPS) was a lethal model and the supplementation of the protein by mRNA was not adequate modality. In the case of inflammatory bowel disease, we used DSS-colitis model. The introduction of IL-10, an immuno-suppressive cytokine, resulted in the amelioration of the disease.
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| Free Research Field |
薬物送達学
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| Academic Significance and Societal Importance of the Research Achievements |
インビトロ転写で合成されるIVT-mRNAを用いた遺伝子の導入は、SARS-CoV-2に対するRNAワクチンの登場で大きな注目を集めた。一方、IVT-mRNAは任意のタンパク質を導入可能であるものの、ワクチン以外の応用は実用化されていない。これは、IVT-mRNAの送達に用いられる技術それ自体が免疫刺激性であるためである。本研究では、生体内で自発的に自己分解する素材を開発し、生体への影響をできるだけ低減したベクターを開発した。本ベクターを用い、炎症を抑えることで、潰瘍性大腸炎に対する治療効果が得られた。このような刺激性の低い分子は、IVT-mRNAを用いた治療の実現に有用であると期待される。
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