| Project/Area Number |
17K08379
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | Shujitsu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
新井 祐志 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50347449)
長塚 仁 岡山大学, 医歯薬学総合研究科, 教授 (70237535)
山崎 勤 就実大学, 薬学部, 助教 (80596148)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 関節リウマチ / CD81 / テトラスパニン / 遺伝子治療 / キメラ抗体 / 遺伝子クローニング / 間接リウマチ |
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| Outline of Final Research Achievements |
We have established mouse hybridoma clones which produce anti-CD81 monoclonal antibodies effective for treatment of rheumatoid arthritis. The genes encoding this anti-CD81 antibody (H+L) chains were cloned from mouse hybridoma cells and the chimeric genes containing mouse V region derived from this cloned gene and rat C region were constructed. The chimeric gene was introduced into CHO cells and chimeric antibodies were produced in the medium of cultured CHO cells. These chimeric antibodies also bound to CD81 protein. Then these chimeric genes were cloned into vectors for gene therapy. At first, control vector containing one GFP gene was introduced into the joints of CIA rats. Control vectors were effectively introduced into synovial tissue of the joints. Then chimeric genes have been introduced into the joints of CIA rats for treatment of rheumatoid arthritis.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究は関節リウマチの治療を遺伝子治療で行う初めての試みである。我々は既に、siRNAや抗体治療実験によって、CD81分子が関節リウマチの治療標的になりうることを示しているが、今回、この治療用抗体遺伝子をクローニングして遺伝子治療用ベクターに搭載し、関節内にこのベクターを導入し、持続的に抗体を関節で生産させることで、従来の抗体投与治療のように、何回も侵襲を受け、しかも高価な抗体費用を負担することなく、一回の遺伝子投与だけで、完全な治療効果を得ることができるという、全く新しいタイプの関節リウマチ治療薬の実用化を目指した。まずリウマチモデルラットを用いた遺伝子治療実験を行って成果を挙げている。
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