Development of siRNA delivery system with programmed tumor activation

• Project/Area Number: 20890003
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: Hokkaido University
• Principal Investigator: HATAKEYAMA Hiroto Hokkaido University, 大学院・薬学研究院, 特任助教 (70504786)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥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)
• Keywords: ドラッグデリバリー / siRNA / がん治療 / siRNAデリバリー / 多機能性エンベロープ型ナノ構造体 / 核酸医薬 / ドラッグデリバリーシステム / 膜融合ペプチド / 細胞内動態制御 / 膜融合性ペプチド

Research Abstract

siRNA is considered to be a potential therapeutic tool for cancer. To realize siRNA therapy, brilliant DDS carriers should be essential. Therefore, we developed efficient carriers by controlling intracellular trafficking of carriers and release of siRNA in cytosol. Fusogenic peptide accelerated the endosomal escape of the carrier, resulting in enhanced gene knockdown in vitro and in vivo. The superior polycation which exhibited higher activity than the conventional was successfully discovered through screening.

Research Products

• [Journal Article] Ornithine and tryptophan analogs as efficient polycations for siRNA delivery to tumor cells. (2010)
  • Author(s): Y.Sato, H.Hatakeyama, et al.
  • Journal Title: Biol.Pharm.Bull. (In press)
  • Peer Reviewed
• [Journal Article] Harashima. A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. (2009)
  • Author(s): H. Hatakeyama, E. Ito, H. Akita, M. Oishi, Y. Nagasaki, S. Futaki, H
  • Journal Title: J. Control. Release 139 Pages: 127-132
  • Peer Reviewed
• [Journal Article] Oishi, Y. Nagasaki, S. Futaki, H. Harashima. Efficient siRNA delivery to tumor cells using the combination of octaarginine, GALA and tumor-specific, cleavable PEG system (2009)
  • Author(s): Y. Sakurai, H. Hatakeyama, H. Akita, M
  • Journal Title: Biol. Pharm. Bull. 32 Pages: 928-932
  • Peer Reviewed
• [Journal Article] Efficient siRNA delivery to tumor cells using the combination of octaarginine, GALA and tumor-specific, cleavable PEG system. (2009)
  • Author(s): Y.Sakurai, H.Hatakeyama, et al.
  • Journal Title: Biol.Pharm.Bull. 32 Pages: 127-132
  • Peer Reviewed
• [Journal Article] pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. (2009)
  • Author(s): H.Hatakeyama, et al.
  • Journal Title: J.Control.Release 139 Pages: 127-132
  • Peer Reviewed
• [Journal Article] 多機能性エンベロープナノ構造体の開発-血管をキーワードとして (2008)
  • Author(s): 畠山浩人, Diky Mudhakir, 秋田英万, 原島秀吉.
  • Journal Title: 血管医学(メディカルレビュー社) 9(2) Pages: 181-187
• [Journal Article] 多機能性エンベロープ型ナノ構造体による人工遺伝子デリバリーシステムの創製 (2008)
  • Author(s): 畠山浩人, 秋田英万, 小暮健太朗, 原島秀吉
  • Journal Title: 化学工業(化学工業社) 59(4) Pages: 263-268
• [Journal Article] Ornithine and tryptophan analogs as efficient polycations for siRNA delivery to tumor cells.
  • Author(s): Y. Sato, H. Hatakeyama, H. Harashima.
  • Journal Title: Biol. Pharm. Bull. (in press)
  • Peer Reviewed
• [Presentation] A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhanced the gene silencing of siRNA-containing nanoparticles in vitro and in vivo (2009)
  • Author(s): H.Hatakeyama, et al.
  • Organizer: Joint Symposium of OTS-Antisense 2009
  • Place of Presentation: Fukuoka, the Centennial Hall Kyushu University.
  • Year and Date: 2009-11-04
• [Presentation] Development of efficient siRNA delivery system to tumor cells by combining octaarginine, GALA and enzymatically-cleavable PEG-lipid. (2009)
  • Author(s): Y. Sakurai, H. Hatakeyama, et al
  • Organizer: The Asian Federation for Pharmaceutical Sciences 2009
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 2009-10-15
• [Presentation] Development of efficient siRNA delivery system to tumor cells by combining octaarginine, GALA and enzymatically-cleavable PEG-lipid (2009)
  • Author(s): Y.Sakurai, H.Hatakeyama, et al.
  • Organizer: The Asian Federation for Pharmaceutical Sciences 2009
  • Place of Presentation: Fukuoka, the Centennial Hall Kyushu University.
  • Year and Date: 2009-10-15
• [Presentation] 血清耐性MENDを用いたがん選択的siRNAデリバリーシステムの機能評価 (2009)
  • Author(s): 櫻井遊, 畠山浩人, 秋田英万, 大石基, 長崎幸夫, 二木史朗, 原島秀吉
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-28
• [Presentation] 膜融合性ペプチドを用いた腫瘍選択的siRNAデリバリーシステムの開発 (2009)
  • Author(s): 畠山浩人, 他
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2009-03-28
• [Presentation] 血清耐性MENDを用いたがん選択的siRNAデリバリーシステムの機能評価 (2009)
  • Author(s): 櫻井遊, 畠山浩人, 他
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都、国立京都国際会館
  • Year and Date: 2009-03-28
• [Presentation] A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhanced the gene silencing of siRNA-containing nanoparticles in vitro and in vivo (2009)
  • Author(s): H. Hatakeyama, E. Ito, H. Akita, M. Oishi, Y. Nagasaki, S. Futaki, H. Harashima
  • Organizer: Joint Symposium of OTS-Antisense 2009
  • Place of Presentation: Fukuoka, Japan.
• [Presentation] 膜融合性ペプチドを用いたsiRNAデリバリーシステムの開発 (2008)
  • Author(s): 伊東恵里佳, 畠山浩人, 他
  • Organizer: 北海道支部第131回例会
  • Place of Presentation: 北海道、北海道薬科大学
  • Year and Date: 2008-11-29
• [Presentation] 腫瘍選択的活性化型血清耐性MENDによるsiRNA送達システムの構築 (2008)
  • Author(s): 櫻井遊, 畠山浩人, 他
  • Organizer: 北海道支部第131回例会
  • Place of Presentation: 北海道、北海道薬科大学
  • Year and Date: 2008-11-29
• [Presentation] Systemic siRNA Delivery Using a Maltifunctional Nanodevice with Programmed Tumor Activation. (2008)
  • Author(s): H. Hatakeyama, et al
  • Organizer: 11th LIPOSOME RESEARCH DAYS CONFERENCE
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2008-07-22
• [Presentation] Systemic siRNA Delivery Using a Maltifunctional Nanodevice with Programmed Tumor Activation (2008)
  • Author(s): H. Hatakeyama, et.al.
  • Organizer: 11th LIPOSOME RESEARCH DAYS CONFERENCE
  • Place of Presentation: 神奈川、横浜シンポジア
  • Year and Date: 2008-07-22
• [Presentation] 腫瘍選択的活性化をプログラムしたsiRNAデリバリーシステムの開発 (2008)
  • Author(s): 畠山浩人, 他
  • Organizer: 第24回日本DDS学会
  • Place of Presentation: 東京、六本木アカデミーヒルズ
  • Year and Date: 2008-06-30
• [Presentation] Development of systemic siRNA delivery for tumor with specific ally tumor activation system (2008)
  • Author(s): H. Hatakeyama, et.al.
  • Organizer: The 11th Annual Meeting of the American Society of Gene Therapy
  • Place of Presentation: 米国、ボストン、Hynes Convention Center
  • Year and Date: 2008-06-01
• [Presentation] evelopment of systemic siRNA delivery for tumor with specifically tumor activation system (2008)
  • Author(s): H. Hatakeyama, H. Akita, E. Ito, M. Oishi, Y. Nagasaki, H. Harashima
  • Organizer: he 11th Annual Meeting of the American Society of Gene Therapy
  • Place of Presentation: Boston, MA, USA
• [Book] A Novel Nonviral Gene Delivery System: Multifunctional Envelope-Type Nano Device (2009)
  • Author(s): H. Hatakeyama, H. Akita, K. Kogure, H. Harashima
  • Publisher: Adv Biochem Eng Biotechnol
• [Book] Advances in biochemical engineering/biotechnology (2009)
  • Author(s): A Novel Nonviral Gene Delivery System : Multifunctional Envelope-Type Nano Device.
  • Total Pages: 187
  • Publisher: Springer Verlag
• [Book] 細胞内動態の制御を可能とする多機能性エンベロープ型ナノ構造体による遺伝子導入(遺伝子医学MOOK別冊「ますます重要になる細胞周辺環境(細胞ニッチ)の最新科学技術」)
  • Author(s): 畠山浩人, 原島秀吉
• [Patent(Industrial Property Rights)] 機能性ポリペプチド及び当該ポリペプチドで修飾された脂質膜構造体 (2010)
  • Inventor(s): 原島秀吉, 秋田英万, 畠山浩人, 他
  • Industrial Property Rights Holder: 国立大学法人北海道大学
  • Industrial Property Number: 2010-039667
  • Filing Date: 2010-02-25
• [Patent(Industrial Property Rights)] の別:国内名称:腫瘍組織で選択的に分解性を示す血中滞留性素子 (2008)
  • Inventor(s): 秋田英万, 畠山浩人, 原島秀吉
  • Industrial Property Rights Holder: 国立大学法人北海道大学
  • Filing Date: 2008-12-12
• [Patent(Industrial Property Rights)] 腫瘍組織で選択的に分解性を示す血中滞留性素子 (2008)
  • Inventor(s): 原島秀吉, 畠山浩人, など
  • Industrial Property Rights Holder: 北海道大学, 塩野義製薬(株)
  • Filing Date: 2008-12-12
  • Overseas