RNAi for the treatment of refractory pulmonary diseases

• Project/Area Number: 25461189
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Mie University
• Principal Investigator: Kobayashi Tetsu 三重大学, 医学部附属病院, 准教授 (20437114)
• Co-Investigator(Kenkyū-buntansha): GABAZZA ESTEBAN 三重大学, 医学系研究科, 教授 (00293770) ; TAGUCHI OSAMU 三重大学, 保健管理センター, 教授 (90197244)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: siRNA / RNAi / TGF / 肺線維症 / TGF-β

Outline of Final Research Achievements

The nucleic acid innovative drug development is expected as a new therapeutic method for the refractory disease.We make the original nucleic acid as Japan original and aim at the innovative drug development to respiratory disease with the administration of the trans-airway.As a result of designing a nucleic acid using a mouse disease model, and having tested it, control of the disease clinical condition was found to be possible by a trans-airway nucleic acid medication.These results suggest that intra-tracheal instillation of RNAi agents may be useful for the therapy of pulmonary diseases.

Research Products

• [Journal Article] irculating fibrocytes correlate with the asthma control test score. (2016)
  • Author(s): Kobayashi H, Naito M, Masuya M, Maruyama M, Urata K, Takahashi Y, Tomaru A,Fujiwara K, Ohnishi M, Takagi T, Kobayashi T,D'Alessandro-Gabazza C, Urawa M,Gabazza EC, Taguchi O, Takei Y.
  • Journal Title: Allergol Immunopathol (Madr). Volume: 44 Issue: 3 Pages: 152-154
  • DOI: 10.1016/j.aller.2015.09.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Activated protein C modulates the proinflammatory activity of dendritic cells. (2015)
  • Author(s): Matsumoto T, Matsushima Y, Toda M, Roeen Z, D'Alessandro-Gabazza CN, Hinneh JA, Harada E, Yasuma T, Yano Y, Urawa M, Kobayashi T, Taguchi O, Gabazza EC.
  • Journal Title: J Asthma Allergy Volume: 8 Pages: 29-37
  • DOI: 10.2147/jaa.s75261
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Thrombomodulin inhibits the activation of eosinophils and mast cells. (2015)
  • Author(s): Roeen Z, Toda M, D'Alessandro-Gabazza CN, Onishi M, Kobayashi T, Yasuma T, Urawa M, Taguchi O, Gabazza EC.
  • Journal Title: Cell Immunol. Volume: 293 Issue: 1 Pages: 34-40
  • DOI: 10.1016/j.cellimm.2014.11.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels. (2014)
  • Author(s): Kobayashi T, Kim H, Liu X, Sugiura H, Kohyama T, Fang Q, Wen FQ, Abe S, Wang X, Atkinson JJ, Shipley JM, Senior RM, Rennard SI.
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: 306(11) Issue: 11 Pages: 1006-1015
  • DOI: 10.1152/ajplung.00015.2014
  • Peer Reviewed / Open Access
• [Journal Article] Synthesis of18O-labeled RNA for application to kinetic studies and imaging. (2013)
  • Author(s): Hamasaki T, Matsumoto T, Sakamoto N, Shimahara A, Kato S, Yoshitake A, Utsunomiya A, Yurimoto H, Gabazza EC, Ohgi T.
  • Journal Title: Nucleic Acids Res. Volume: 41 Issue: 12 Pages: e126-e126
  • DOI: 10.1093/nar/gkt344
  • Peer Reviewed
• [Journal Article] Thrombin-activatable fibrinolysis inhibitor protects against acute lung injury by inhibiting the complement system. (2013)
  • Author(s): Naito M, Taguchi O, Kobayashi T, Takagi T, D'Alessandro-Gabazza CN, Matsushima Y, Boveda-Ruiz D, Gil-Bernabe P, Matsumoto T, Chelakkot-Govindalayathil AL, Toda M, Yasukawa A, Hataji O, Morser J, Takei Y, Gabazza EC.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 49 Issue: 4 Pages: 646-653
  • DOI: 10.1165/rcmb.2012-0454oc
  • Peer Reviewed
• [Presentation] RNA新時代 (2015)
  • Author(s): 小林 哲
  • Organizer: 第１２回呼吸器バイオマーカー研究会
  • Place of Presentation: 東京（大手町サンケイプラザ）
  • Year and Date: 2015-11-28
  • Invited
• [Presentation] 気道リモデリングとその制御方法の試み (2015)
  • Author(s): 小林 哲
  • Organizer: 第四回神奈川気道炎症病態研究会
  • Place of Presentation: 神奈川県横浜市（ベイシェラトンホテル）
  • Year and Date: 2015-10-31
  • Invited
• [Presentation] ＩＰＦに対するRNAi創薬の可能性 (2015)
  • Author(s): 小林 哲
  • Organizer: 日本呼吸器学会総会
  • Place of Presentation: 東京（国際フォーラム）
  • Year and Date: 2015-04-18
  • Invited
• [Presentation] マウス疾患モデルを用いた線維化マーカーの探索 (2014)
  • Author(s): 小林 哲
  • Organizer: 第１１回呼吸器バイオマーカー研究会
  • Place of Presentation: 東京、都市センターホテル
  • Year and Date: 2014-11-29
• [Presentation] 肺線維化マウスを用いた細菌叢の検討 (2014)
  • Author(s): 小林哲
  • Organizer: 第１７回間質性肺炎細胞分子病態研究会
  • Place of Presentation: 東京、砂防会館別館
  • Year and Date: 2014-08-23
• [Presentation] ＲＮＡ ｉｎｔｅｒｆｅｒｅｎｃｅ ｆｏｒ ｔｈｅ ｔｒｅａｔｍｅｎｔ ｏｆ ｉｎｔｒａｃｔａｂｌｅ ｐｕｌｍｏｎａｒｙ ｄｉｓｅａｓｅｓ (2013)
  • Author(s): Ｔｅｔｓｕ Ｋｏｂａｙａｓｈｉ
  • Organizer: Ａｍｅｒｉｃａｎ Ｔｈｒａｃｉｃ Ｓｏｃｉｅｔｙ ｉｎｔｅｒｎａｔｉｏｎａｌ ｃｏｎｆｅｒｅｎｃｅ ２０１３
  • Place of Presentation: Ｐｈｉｌａｄｅｌｐｈｉａ
• [Presentation] 呼吸器疾患におけるRNAiを用いた創薬の可能性
  • Author(s): 小林 哲
  • Organizer: 第16回間質性肺炎細胞分子病態研究会
  • Place of Presentation: 東京
• [Presentation] 呼吸器疾患におけるRNAiを用いた治療開発の可能性
  • Author(s): 小林 哲
  • Organizer: 第53回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
• [Book] Annual Review 2016 呼吸器 (2016)
  • Author(s): 小林 哲、ガバザ エステバン
  • Total Pages: 6
  • Publisher: 中外医学社