Development of functional mutant protein with antagonistic activity as an anti-inflammatory drug
Project/Area Number |
20890300
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Research Category |
Grant-in-Aid for Young Scientists (Start-up)
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Allocation Type | Single-year Grants |
Research Field |
Medical pharmacy
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Research Institution | National Institute of Biomedical Innovation |
Principal Investigator |
ABE Yasuhiro National Institute of Biomedical Innovation, 創薬基盤研究部バイオ創薬プロジェクト, 研究員 (20509898)
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Research Collaborator |
角田 慎一
鎌田 春彦
井上 雅己
山根 美紀
長野 一也
野村 鉄也
萱室 裕之
河原 倫之
有田 修平
古屋 剛
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Project Period (FY) |
2008 – 2009
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Project Status |
Completed (Fiscal Year 2009)
|
Budget Amount *help |
¥3,302,000 (Direct Cost: ¥2,540,000、Indirect Cost: ¥762,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,742,000 (Direct Cost: ¥1,340,000、Indirect Cost: ¥402,000)
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Keywords | 蛋白質 / 自己免疫疾患 / アンタゴニスト / ファージ表面提示法 / バイオコンジュゲーション |
Research Abstract |
Blocking the binding of TNF to TNF receptor subtype 1 (TNFR1) is believed to be a promising strategy for the treatment of autoimmune disease. Recently, we generated the TNFR1-selective mutant TNF with antagonistic activity (R1antTNF) using phage display technique. In this study, the anti-inflammatory effects of R1antTNF have been investigated. First, to improve the in vivo stability, polyethylene glycol-modified R1antTNF (PEG-R1antTNF) was prepared. In the autoimmune disease model, the clinical score of the mice given PEG-R1antTNF was improved. These results suggest that selective blocking of TNFR1 by PEG-R1antTNF could be an effective therapeutic strategy against autoimmune disease.
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Report
(3 results)
Research Products
(38 results)
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[Journal Article] Creation of an improved mutant TNF with TNFR1-selectivity and antagonistic activity by phage display technology2010
Author(s)
Nomura T., Abe Y., Kamada H., Inoue M., Kawara T., Arita S., Furuya T., Minowa K., Yoshioka Y., Shibata H., Kayamuro H., Yamashita T., Nagano K., Yoshikawa T., Mukai Y., Nakagawa S., Tsunoda S., Tsutsumi Y
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Journal Title
Pharmazie 65(2)
Pages: 93-96
Related Report
Peer Reviewed
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[Journal Article]2010
Author(s)
Nomura T., Abe Y., Yoshioka Y., Nakagawa S., Tsunoda S., Tsutsumi Y
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Journal Title
Yakugaku Zasshi 130(1)
Pages: 63-8
Related Report
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[Journal Article] Creation of an improved mutant TNF with TNFR1-selectivity and antagonisitic activity by phage display technology.2010
Author(s)
Nomura T., Abe Y., Kamada H., Inoue M., Kawara T., Arita S., Furuya T., Minowa K., Yoshioka Y., Shibata H., Kayamuro H., Yamashita T., Nagano K., Yoshikawa T., Mukai Y., Nakagwa S., Tsunoda S., Tsutsumi Y.
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Journal Title
Pharmazie 65(2)
Pages: 93-6
Related Report
Peer Reviewed
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[Journal Article] The treatment of established murine collagen-induced arthritis with a TNFR1-selective antagonistic mutant TNF2009
Author(s)
Shibata H., Yoshioka Y., Abe Y., Ohkawa A., Nomura T., Minowa K., Mukai Y., Nakagawa S., Taniai M., Ohta T., Tsunoda S., Kamada H., Tsutsumi Y
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Journal Title
Biomaterials 30(34)
Pages: 6638-6647
Related Report
Peer Reviewed
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[Journal Article] Novel protein engineering strategy for creating highly receptor-selective mutant TNFs2009
Author(s)
Nomura T., Abe Y., Kamada H., Inoue M., Kawara T., Arita S., Furuya T., Yoshioka Y., Shibata H., Kayamuro H., Yamashita T., Nagano K., Yoshikawa T., Mukai Y., Nakagawa S., Taniai M., Ohta T., Tsunoda S., Tsutsumi Y
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Journal Title
Biochem. Biophys. Res. Commun 388(4)
Pages: 667-71
Related Report
Peer Reviewed
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[Journal Article] Structure-function relationship of tumor necrosis factor (TNF) and its receptor interaction based on 3D structural analysis of a fully active TNFR1-selective TNF mutant2009
Author(s)
Mukai Y., Shibata H., Nakamura T., Yoshioka Y., Abe Y., Nomura T., Taniai M., Ohta T., Ikemizu S., Nakagawa S., Tsunoda S., Kamada H., Yamagata Y., Tsutsumi Y
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Journal Title
J. Mol. Biol 385
Pages: 1221-1229
Related Report
Peer Reviewed
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[Journal Article] Novel protein engineering strategy for creating highly receptor-selecive mutant TNFs.2009
Author(s)
Nomura T., Abe Y., Kamada H., Inoue M., Kawara T., Arita S., Furuya T., Yoshioka Y., Shibata H., Kayamuro H., Yamashita T., Nagano K., Yoshikawa T., Mukai Y., Nakagawa S., Taniai M., Ohta T., Tsunoda S., Tsutsumi Y.
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Journal Title
Biochem Biophys Res Commun 388(4)
Pages: 667-71
Related Report
Peer Reviewed
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[Journal Article] The treatment of established murine collagen-induced arthritis with a TNFR1-selective antagonistic mutant TNF.2009
Author(s)
Shibata H., Yoshioka Y., Abe Y., Ohkawa A., Nomura T., Minowa K., Mukai Y., Nakagawa S., Taniai M., Ohta T., Tsunoda S., Kamada H., Tsutsumi Y.
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Journal Title
Biomaterials 30(34)
Pages: 6638-47
Related Report
Peer Reviewed
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[Journal Article] Structure-function relationship of tumor necrosis factor (TNF) and its receptor interaction based on 3D structural analysis of a fully active TNFR1-selective TNF mutant2009
Author(s)
Mukai Y, Shibata H, Nakamura T, Yoshioka Y, Abe Y, Nomura T, Taniai M, Ohta T, Ikemizu S, Nakagawa S, Tsunoda S, Kamada H, Yamagata Y, Tsutsumi Y
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Journal Title
Journal of Molecular Biology 385
Pages: 1221-9
Related Report
Peer Reviewed
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[Journal Article] The therapeutic effect of TNFR1-selective antagonistic mutant TNF-αin murine hepatitis models2008
Author(s)
Shibata H., Yoshioka Y., Ohkawa A., Abe Y., Nomura T., Mukai Y., Nakagawa S., Taniai M., Ohta T., Mayumi T., Kamada H., Tsutsumi Y
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Journal Title
Cytokine 44(2)
Pages: 229-233
Related Report
Peer Reviewed
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[Journal Article] Organelle-targeted delivery of biological macromolecules using the protein transduction domain: Potential applications for peptide aptamer delivery into the nucleus2008
Author(s)
Yoshikawa T., Sugita T., Mukai Y., Yamanada N., Nagano K., Nabeshi H., Yoshioka Y., Nakagawa S., Abe Y., Kamada H., Tsunoda S., Tsutsumi Y
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Journal Title
J. Mol. Biol 380(5)
Pages: 777-782
Related Report
Peer Reviewed
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[Journal Article] Simple and highly sensitive assay system for TNFR2-mediated soluble-and transmembrane-TNF activity2008
Author(s)
Abe Y., Yoshikawa T., Kamada H., Shibata H., Nomura T., Minowa K., Kayamuro H., Katayama K., Miyoshi H., Mukai Y., Yoshioka Y., Nakagawa S., Tsunoda S., Tsutsumi Y
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Journal Title
J. Immunol. Methods 335(1-2)
Pages: 71-8
Related Report
Peer Reviewed
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[Journal Article] Simple and highly sensitive assay system for TNFR2-mediated soluble- and transmembrane-TNF activity2008
Author(s)
Abe Y, Yoshikawa T, Kamada H, Shibata H, Nomura T, Minowa K, Kayamuro H, Katayama K, Miyoshi H, Mukai Y, Yoshioka Y, Nakagawa S, Tsunoda S, Tsutsumi Y
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Journal Title
Journal of Immunological Methods 335(1-2)
Pages: 71-78
Related Report
Peer Reviewed
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[Journal Article] Organelle-targeted delivery of biological macromolecules using the protein transduction domain : potential applications for Peptide aptamer delivery into the nucleus2008
Author(s)
Yoshikawa T, Sugita T, Mukai Y, Yamanada N, Nagano K, Nabeshi H, Yoshioka Y, Nakagawa S, Abe Y, Kamada H, Tsunoda S, Tsutsumi Y.
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Journal Title
Journal of Molecular Biology 380(5)
Pages: 229-33
Related Report
Peer Reviewed
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[Journal Article] The therapeutic effect of TNFR1-selective antagonistic mutant TNF-<alpha> in murine hepatitis models2008
Author(s)
Shibata H, Yoshioka Y, Ohkawa A, Abe Y, Nomura T, Mukai Y, Nakagawa S, Taniai M, Ohta T, Mayumi T, Kamada H, Tsutsumi Y
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Journal Title
Cytokine 44(2)
Pages: 229-233
Related Report
Peer Reviewed
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[Presentation] Evaluation of safety and efficacy of TNFR1-selective antagonistic mutant TNF as a novel anti-inflammatory drug2009
Author(s)
Abe Y., Shibata H., Nomura T., Kayamuro H., Yoshikawa T., Yoshioka Y., Nakagawa S., Kamada H., Tsunoda S., Tsutsumi Y
Organizer
Society of Toxicology 48th Annual Meeting, ToxExpo
Place of Presentation
Baltimore (U.S.A. )
Related Report
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[Presentation] Fine tuning of receptor-selectivity for tumor necrosis factor-□ using a phage display system with one-step competitive-subtractive panning2008
Author(s)
Abe Y., Shibata H., Nomura T., Kayamuro H., Mukai Y., Yoshikawa T., Yoshioka Y., Taniai M., Ohta T., Nakagawa S., Kamada H., Tsunoda S., Tsutsumi Y
Organizer
7th Joint Conference of the Intenational Society for Interderon and Cytokine Research and International Cytokine Society
Place of Presentation
Montreal/Quebec (CANADA)
Related Report
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[Presentation] Fine tuning of receptor-selectivity for tumor necrosis factor-α using a phage display system with one-step competitive-subtractive panning2008
Author(s)
Abe Y., Shibata H., Nomura T., Kayamuro H., Mukai Y., Yoshikawa T., Yoshioka Y., Taniai M., Ohta T., Nakagawa S., Kamada H., Tsunoda S., Tsutsumi Y.
Organizer
7th Joint Conference of the Intenational Society for Interderon and Cytokine Research and International Cytokine Society
Place of Presentation
Montreal/Quebec (CANADA)
Related Report
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