Development of novel gene medicine for rheumatoid arthritis

• Project/Area Number: 23790186
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Nagasaki University
• Principal Investigator: KODAMA Yukinobu 長崎大学, 医歯(薬)学総合研究科, 助教 (50448510)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 遺伝子デリバリー / 関節リウマチ / メトトレキセート / コンドロイチン硫酸 / メトトレキサート

Research Abstract

In this study, we developed the novel delivery system which enables delivery of both gene and drugs to rheumatoid arthritis. We successfully prepared the pDNA-PEI-MTX complexes (MTX complexes) by optimization of the mix ratio and preparation process. MTX complexes showed high gene expression in human fibroblast-like synoviocytes from RA patients (HFLS-RA). We also developed siRNA-PEI-CS (CS complexes). CS complexes showed high silencing effect comparable to commercial vector (lipofectamine).

Research Products

• [Journal Article] Secure splenic delivery of plasmid DNA and its application to DNA vaccine (2013)
  • Author(s): Kurosaki T, Kodama Y, Muro T, Higuchi N, Nakamura T, Kitahara T, Miyakoda M, Yui K, Sasaki H
  • Journal Title: Biol Pharm Bull Volume: 36(11) Pages: 1800-6
  • NAID: 130003382044
  • Peer Reviewed
• [Journal Article] Ternary complex of plasmid DNA with protamine andγ-polyglutamic acid for biocompatible gene delivery system (2013)
  • Author(s): Kanda K, Kodama Y, Kurosaki T, Imamura M, Nakagawa H, Muro T, Higuchi N, Nakamura T, Kitahara T, Honda M, Sasaki H
  • Journal Title: Biol Pharm Bull Volume: 36(11) Pages: 1794-9
  • Peer Reviewed
• [Journal Article] Safe and effective delivery of small interfering RNA with polymer- and liposomes-based complexes (2013)
  • Author(s): Kodama Y, Harauchi S, Kawanabe S, Ichikawa N, Nakagawa H, Muro T, Higuchi N, Nakamura T, Kitahara T, Sasaki H
  • Journal Title: Biol Pharm Bull. Volume: 36(6) Pages: 995-1001
  • NAID: 130003361445
  • Peer Reviewed
• [Journal Article] Safe and Effective Delivery of Small Interfering RNA with Polymer- and Liposomes-Based Complexes (2013)
  • Author(s): Yukinobu Kodama, Satoe Harauchi, Saki Kawanabe, Nobuhiro Ichikawa, Hiroo Nakagawa, Takahiro Muro, Norihide Higuchi, Tadahiro Nakamura, Takashi Kitahara, Hitoshi Sasaki
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 36 Pages: 995-1001
  • NAID: 130003361445
  • Peer Reviewed
• [Journal Article] Development of effective cancer vaccine using targeting system of antigen protein to APCs (2012)
  • Author(s): Kurosaki T, Kitahara T, Nakamura T, Nishida K, Fumoto S, Kodama Y, Nakagawa H, Higuchi N, Sasaki H
  • Journal Title: Pharm Res Volume: 29(2) Pages: 483-9
  • NAID: 120006985292
  • Peer Reviewed
• [Journal Article] Secure and effective gene vector of polyamidoamine dendrimer pharmaceutically modified with anionic polymer (2011)
  • Author(s): Kurosaki T, Yamashita Y, Aki K, Harasawa H, Nakagawa H, Kodama Y, Higuchi N, Nakamura T, Kitahara T, Sasaki H
  • Journal Title: J Pharm Sci Volume: 100(11) Pages: 4855-63
  • Peer Reviewed
• [Journal Article] Nanoparticles electrostatically coated with folic acid for effective gene therapy (2011)
  • Author(s): Kurosaki T, Morishita T, Kodama Y, Sato K, Nakagawa H, Higuchi N, Nakamura T, Hamamoto T, Sasaki H, Kitahara T
  • Journal Title: Mol Pharm Volume: 8(3) Pages: 913-9
  • Peer Reviewed
• [Presentation] 樹状細胞標的型ナノデバイスを用いたマラリアDNAナノワクチンの開発 (2013)
  • Author(s): 西垣和香、兒玉幸修、北原隆志、佐々木均
  • Organizer: 第30回日本薬学会九州支部大会
  • Place of Presentation: 佐世保
  • Year and Date: 2013-12-08
• [Presentation] Dendrigraft poly-L-lysineを用いた生体内分解型遺伝子ベクターの開発 (2013)
  • Author(s): 塩川裕美、兒玉幸修、北原隆志、佐々木均
  • Organizer: 日本薬剤学会第28年会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-05-25
• [Presentation] ポリヌクレオチド被膜型複合体による脾臓指向性新規遺伝子ベクターの開発 (2013)
  • Author(s): 矢次結衣子、兒玉幸修、大久保智佳子、北原隆志、佐々木均
  • Organizer: 日本薬剤学会第28年会
  • Place of Presentation: 名古屋
  • Year and Date: 2013-05-25
• [Presentation] Fetuin被膜型複合体による新規遺伝子ベクターの構築 (2013)
  • Author(s): 兒玉幸修、北原隆志、江頭かの子、中嶋幹郎、樋口則英、中村忠博、佐々木均
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] 静電的自己組織化を基盤としたアニオン性siRNAベクターの開発 (2012)
  • Author(s): 塩川裕美、兒玉幸修、原内智慧、北原隆志、佐々木均
  • Organizer: 第29回日本薬学会九州支部大会
  • Place of Presentation: 熊本
  • Year and Date: 2012-12-08
• [Presentation] ホスファチジルセリンアナログを用いた脾臓指向性遺伝子導入ベクターの開発 (2012)
  • Author(s): 大久保智佳子、仲宗根ちひろ、黒崎友亮、兒玉幸修、北原隆志、佐々木均
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-24
• [Presentation] 肝細胞選択的なグリチルリチン含有遺伝子ベクターの開発 (2012)
  • Author(s): 原内智慧、川鍋早紀、黒崎友亮、兒玉幸修、北原隆志、佐々木均
  • Organizer: 日本薬剤学会第27年会
  • Place of Presentation: 神戸
  • Year and Date: 2012-05-24
• [Presentation] 制癌剤と遺伝子同時送達を目的としたメトトレキサート被膜型遺伝子ベクターの開発 (2012)
  • Author(s): 兒玉幸修、黒崎友亮、江頭かの子、中嶋幹郎、中川博雄、樋口則英、中村忠博、北原隆志、佐々木均
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 2012-03-31
• [Presentation] 制癌剤と遺伝子同時送達を目的としたメトトレキサート被膜型遺伝子ベクターの開発 (2012)
  • Author(s): 兒玉幸修
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学（北海道）
• [Presentation] Polyplex of pDNA with poly-L-lysine, poly-L-histidine, andγ-polyglutamic acid for biocompatible gene delivery system (2011)
  • Author(s): Yukinobu Kodama, Tomoaki Kurosaki, Kanoko Egashira, Tadahiro Nakamura, Takashi Kitahara, Hitoshi Sasaki
  • Organizer: 日本薬物動態学会第26回年会
  • Place of Presentation: 広島
  • Year and Date: 2011-11-17