Construction of artificial poly-clonal gamma globulin to control HCV infection and development of assay system

• Project/Area Number: 20590117
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: National Institute of Biomedical Innovation
• Principal Investigator: KAMEOKA Yousuke National Institute of Biomedical Innovation, 難病・疾患資源研究部・難病資源研究室 (00224692)
• Co-Investigator(Kenkyū-buntansha): OOSHIMA Masamiti 国立感染症研究所, 免疫部, 室長 (10272428) ; SUZUKI Kazuo 千葉大学, 医学研究科, 特任教授 (20192130)
• Project Period (FY): 2008 – 2011
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: ゲノム創薬 / 人体抗体 / C型肝炎 / HCV / 感染制御

Research Abstract

178 clones of artificial poly-clonal gamma globulin, which consist of VH, CH1 and hinge region, was constructed from cDNA originated from peripheral blood. The expressed recombinant proteins in E. coli, were extracted, purified and recovered in milligram order. SCGK/J mouse, which is an inflammatory disease model, although the strain is not a model of hepatic disease, were examined for therapeutic treatment with the recombinant poly-clonal gamma globulin. After the therapeutic treatment in some dose of recombinant protein, hemogram and some cytokines were assayed. The level of peripheral blood lymphocyte and some inflammatory cytokines were decreased in dose dependent manner, and some suppressive cytokines were increased. It was suggested that the recombinant poly-clonal gamma globulin, constructed in this study, would be possible to apply to the therapy for hepatic inflammatory disease.

Research Products

• [Journal Article] Ancient genome-wide admixture extends beyond the current hybrid zone between Macaca fascicularis and M. mulatta. (2010)
  • Author(s): Osada N, Uno Y, Mineta K, Kameoka Y, Takahashi I, Terao K.
  • Journal Title: Mol Ecol. 19(14) Pages: 884-95
• [Journal Article] Ancient genome-wide admixture extends beyond the current hybrid zone between Macaca fascicularis and M.mulatta. (2010)
  • Author(s): Osada N, Uno Y, Mineta K, Kameoka Y, Takahashi I, Terao K.
  • Journal Title: Mol Ecol. Volume: 19(14) Pages: 2884-2895
  • Peer Reviewed
• [Journal Article] Collection of Macaca fascicularis cDNAs derived from bone marrow, kidney, liver, pancreas, spleen, and thymus. (2009)
  • Author(s): Osada N, Hirata M, Tanuma R, Suzuki Y, Sugano S, Terao K, Kusuda J, Kameoka Y, Hashimoto K, Takahashi I.
  • Journal Title: BMC Res Notes. 2 Pages: 199-199
• [Journal Article] IL-10 is a negative regulatory factor of CAWS-vasculitis in CBA/J mice as assessed by comparison with Bruton's tyrosine kinase-deficient CBA/N mice. (2009)
  • Author(s): Miura NN, Komai M, Adachi Y, Osada N, Kameoka Y, Suzuki K, Ohno N.
  • Journal Title: The Jounal of Immunology 183 Pages: 3417-3424
• [Journal Article] Collection of Macaca fascicularis cDNAs derived from bone marrow, kidney, liver, pancreas, spleen, and thymus. (2009)
  • Author(s): Osada N, Hirata M, Tanuma R, Suzuki Y, Sugano S, Terao K, Kusuda J, Kameoka Y, Hashimoto K, Takahashi I.
  • Journal Title: BMC Res Notes. 2:199
  • Peer Reviewed
• [Journal Article] Development of an integrative database with 499 novel microsatellite markers for Macaca fascicularis. (2008)
  • Author(s): Higashino A, Osada N, Suto Y, Hirata M, Kameoka Y, Takahashi I, Terao K.
  • Journal Title: BMC Genet. 26(6)
• [Journal Article] Large-scale analysis of Macaca fascicularis transcripts and inference of genetic divergence between M.fascicularis and M.mulatta. (2008)
  • Author(s): Osada N, Hashimoto K, Kameoka Y, Hirata M, Tanuma R, Uno Y, Inoue I, Hida M, Suzuki Y, Sugano S, Terao K, Kusuda J, Takahashi I.
  • Journal Title: BMC Genomics 92 Pages: 90-90
• [Journal Article] Preparedness for the spread of influenza: prohibition of traffic, school closure, and vaccination of children in the commuter towns of Tokyo. (2008)
  • Author(s): Yasuda H, Yoshizawa N, Kimura M, Shigematsu M, Matsumoto M, Kawachi S, Oshima M, Yamamoto K, Suzuki K.
  • Journal Title: J Urban Health. 85 Pages: 619-635
• [Journal Article] A comparative study of the diagnostic accuracy of ELISA systems for the detection of anti-neutrophil cytoplasm antibodiesavailable in Japan and Europe. (2008)
  • Author(s): T.Ito-Ihara, E.Muso, S.Kobayashi, K.Uno, N.Tamura, Y.Yamanishi, A.Fukatsu, R.A.Watts, D.G.I.Scott, D.R.W.Jayne, K.Suzuki, H.Hashimoto.
  • Journal Title: Clin.Exp.Rheumatol. 26(6) Pages: 1027-33
• [Journal Article] Role of F4/80+Mac-1high adherent non-parenchymal liver cells in concanavalin A-induced hepatic injury in mice. (2008)
  • Author(s): Ayako Mabuchi, Tomokazu Nagao, Osamu Koshio, Toshiyuki Ishiwata, Akihiko Yano, Kazuo Suzuki, Kozo Yokomuro, Antony M Wheatley.
  • Journal Title: Hepatology Res. 38 Pages: 1040-1049
• [Journal Article] MPO-ANCA induces IL-17 production by activated neutrophils in vitro via classical complement pathway-dependent manner. (2008)
  • Author(s): Akiyoshi Hoshino, Tomokazu Nagao, Noriko Nagi-Miura, Naohito Ohno, Masato Yasuhara, Kenji Yamamoto, Toshinori Nakayama, Kazuo Suzuki.
  • Journal Title: J.Autoimmunity 31 Pages: 79-89
• [Journal Article] Large-scale analysis of Macaca fascicularis transcripts and inference of genetic divergence between M. fascicularis and M. mulatta (2008)
  • Author(s): Osada N, Hashimoto K, Kameoka Y, Hirata M, Tanuma R, Uno Y, Inoue I, Hida M, Suzuki Y, Sugano S, Terao K, Kusuda J, Takahashi I.
  • Journal Title: BMC Genomics 9 Pages: 90-90
  • Peer Reviewed
• [Journal Article] Preparedness for the spread of influenza : prohibition of traffic, school closure, and vaccination of children in the commuter towns of Tokyo (2008)
  • Author(s): Yasuda H, Yoshizawa N, Kimura M, Shigematsu M, Matsumoto M, Kawachi S, Oshima M, Yamamoto K, Suzuki K.
  • Journal Title: J Urban Health 85 Pages: 619-635
  • Peer Reviewed
• [Journal Article] A comparative study of the diagnostic accuracy of ELISA systems for the detection of anti-neutrophil cytoplasm antibodies available in Japan and Europe (2008)
  • Author(s): T. Ito-Ihara, E. Muso, S. Kobayashi, K. Uno, N. Tamura, Y. Yamanishi, A. Fukatsu, R. A. Watts, D. G. I. Scott, D. R. W. Jayne, K. Suzuki, H. Hashimoto
  • Journal Title: Clin. Exp. Rheumatol 26(6) Pages: 1027-33
  • Peer Reviewed
• [Journal Article] Role of F4/80+Mac-1high adherent non-parenchymal liver cells in concanavalin A-induced hepatic injury in mice (2008)
  • Author(s): Ayako Mabuchi, Tomokazu Nagao, Osamu Koshio, Toshiyuki Ishiwata, Akihiko Yano, Kazuo Suzuki, Kozo Yokomuro, Antony M Wheatley
  • Journal Title: Hepatology Res. 38 Pages: 1040-1049
  • Peer Reviewed
• [Journal Article] MPO-ANCA induces IL-17 production by activated neutrophils in vitro via classical complement pathway-dependent manner (2008)
  • Author(s): Akiyoshi Hoshino, Tomokazu Nagao, Noriko Nagi-Miura, Naohito Ohno, Masato Yasuhara, Kenji Yamamoto, Toshinori Nakayama, Kazuo Suzuki
  • Journal Title: J. Autoimmunity 31 Pages: 79-89
  • Peer Reviewed
• [Presentation] ヒトmonovalent-hScFvの評価検討 (2011)
  • Author(s): 亀岡洋祐、小浦美奈子、内田敬子、竹内喜久子、松田潤一郎、長尾朋和、宇野賀津子、大野尚仁、鈴木和男
  • Organizer: MPO研究会
  • Place of Presentation: 仙台
• [Presentation] 培養により形質転換したヒト間葉系幹細胞のトランスクリプト-ム解析 (2010)
  • Author(s): 竹内昌男、東濃篤徳、竹内喜久子、牧野初音、田沼玲子、平田誠、高橋一朗、梅澤明弘、亀岡洋祐
  • Organizer: 第33回日本分子生物学会年会・日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] 長期培養により形質転換したヒト間葉系幹細胞のトランスクリプトーム解析 (2010)
  • Author(s): 竹内昌男、東濃篤徳、竹内喜久子、牧野初音、田沼玲子、平田誠、高橋一朗、梅澤明弘、亀岡洋祐
  • Organizer: 第33回日本分子生物学会年会・日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] 次世代シークエンサーを用いたカニクイザルにおける遺伝子発現解析 (2010)
  • Author(s): 東濃篤徳、長田直樹、坂手龍一、平田誠、亀岡洋祐、保富康弘、高橋一朗
  • Organizer: 第33回日本分子生物学会年会・日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 世代シークエンサーを用いたカニクイザルにおける遺伝子発現解析 (2010)
  • Author(s): 東濃篤徳、長田直樹、坂手龍一、平田誠、亀岡洋祐、保富康弘、高橋一朗
  • Organizer: 第33回日本分子生物学会年会・日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] Possible role for the leader peptide of myeloperoxidase. (2009)
  • Author(s): Yosuke Kameoka, Tsuyoshi Kasama, Toshiko Ito-Ihara, Eri Muso, Kazuo
  • Organizer: the 6th International Human Peroxidase meeting
  • Place of Presentation: Chapel Hill, NC, USA
• [Presentation] モノバレントVH-CH1-h型人工ガンマグロブリンの多様性と結合性の検討 (2009)
  • Author(s): 亀岡洋祐、内田敬子、田中早苗、平田誠、田沼玲子、竹内昌男、竹内喜久子、長田直樹、高橋一朗1、三浦典子、大野尚仁、鈴木和男
  • Organizer: 第15回MPO研究会
  • Place of Presentation: 下野市 自治医大
• [Presentation] 改良型人工ガンマグロブリンの多様性と結合性の検討 (2009)
  • Author(s): 亀岡洋祐、内田敬子、田中早苗、平田誠、田沼玲子、竹内昌男、竹内喜久子、長田直樹、高橋一朗、三浦典子、大野尚仁、鈴木和男
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] ヒト間葉系幹細胞の長期培養による形質転換 (2009)
  • Author(s): 竹内昌男、竹内喜久子、亀岡洋祐、小原有弘、長田直樹、高橋一朗、牧野初音、梅澤明弘
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] モノバレントVH-CH1-h型人エガンマグロブリンの多様性と結合性の検討 (2009)
  • Author(s): 亀岡洋祐、内田敬子、田中早苗、平田誠、田沼玲子、竹内昌男、竹内喜久子、長田直樹、高橋一朗1、三浦典子、大野尚仁、鈴木和男
  • Organizer: 第15回MPO研究会
  • Place of Presentation: 下野市 自治医大
• [Presentation] カニクイザル骨髄,脾臓,膵臓由来cDNAライブラリーの解析 (2008)
  • Author(s): 長田直樹、亀岡洋祐、平田誠、田沼玲子、鈴木穣、菅野純夫、高橋一朗
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] 人工ガンマグロブリンの多様性の検討 (2008)
  • Author(s): 亀岡洋祐、古谷昌弘、大島正道、平田 誠、田沼玲子、長田直樹、高橋一朗、鈴木和男
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
• [Presentation] MPOリーダーペプチドは活性制御に関与するかII (2008)
  • Author(s): 亀岡洋祐、猪原登志子、武曾恵理、橋本雄之、鈴木和男
  • Organizer: MPO研究会
  • Place of Presentation: 東京
• [Presentation] カニクイザル骨髄, 脾臓, 膵臓由来cDNAライブラリーの解析 (2008)
  • Author(s): 長田直樹, 亀岡洋祐, 平田誠, 田沼玲子, 鈴木穣, 菅野純夫, 高橋一朗
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸