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Design of systemic siRNA delivery system based on quantitative analyses of intracellular trafficking

Research Project

Project/Area Number 23790038
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionHokkaido University

Principal Investigator

HAYASHI Yasuhiro  北海道大学, 大学院・薬学研究院, 特任助教 (30548178)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords核酸デリバリー / 細胞内動態 / 肝臓 / 急性肝炎 / 2型糖尿病 / DDS / siRNA / pDNA
Research Abstract

In this study, comparative analyses between in vitro and in vivo settings were examined in order to develop an efficient in vivo nucleic acid delivery system. We focused on three main intracellular trafficking processes; accumulation, endosome escape, and decondensation process in tissues or cells. We found that the accumulation process is a key factor in achieving in vivo nucleic acid activity at low dose. In addition, nucleic acid activity was increased by improving nucleic acid decondensation process in cytoplasm. Lastly, we have succeeded to prevent acute liver hepatitis and the symptoms of type 2 diabetes and obesity in mice by using the in vivo nucleic acid delivery system.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (40 results)

All 2013 2012 2011 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (30 results) Book (5 results)

  • [Journal Article] The transfection activity of R8-modified nanoparticles and siRNA condensation using pH sensitive stearylated-octahistidine2013

    • Author(s)
      Toriyabe N, Hayashi Y, Harashima H.
    • Journal Title

      Biomaterials. (Elsevier)

      Volume: 34 Issue: 4 Pages: 1337-43

    • DOI

      10.1016/j.biomaterials.2012.10.043

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pretreatment of hepatocyte growth factor gene transfer mediated by octaarginine peptide-modified nanoparticles ameliorates LPS/D-galactosamine-induced hepatitis2012

    • Author(s)
      Hayashi Y
    • Journal Title

      Nucleic Acid Therapy

      Volume: 22 Issue: 5 Pages: 360-363

    • DOI

      10.1089/nat.2012.0352

    • NAID

      120004883876

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Non-linear pharmacokinetics of octaarginine-modified lipid nanoparticles: barriers from in vitro to in vivo2012

    • Author(s)
      Hayashi Y
    • Journal Title

      Journal of Controlled Release

      Volume: 161 Issue: 3 Pages: 757-762

    • DOI

      10.1016/j.jconrel.2012.05.036

    • NAID

      120004756332

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Octaarginine- and pH sensitive fusogenic peptide-modified nanoparticles for liver gene delivery.2011

    • Author(s)
      Khalil IA, Hayashi Y, Mizuno R, Harashima H.
    • Journal Title

      J Control Release.

      Volume: 156(3) Issue: 3 Pages: 374-80

    • DOI

      10.1016/j.jconrel.2011.08.012

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cell penetrating peptide-mediated systemic siRNA delivery to the liver2011

    • Author(s)
      Hayashi Y, Yamauchi J, Khalil IA, Kajimoto K, Akita H, Harashima H
    • Journal Title

      Int J Pharm

      Volume: 419(1-2) Issue: 1-2 Pages: 308-313

    • DOI

      10.1016/j.ijpharm.2011.07.038

    • NAID

      120003504743

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Mogat1 siRNA 搭載型 in vivo デリバリー システムを用いた2型糖尿病予防効果の検証2012

    • Author(s)
      末光永理奈、林泰弘 、梶本和昭、佐藤悠介、Afsana Akhter、櫻井遊、畠山浩人、兵藤守、加地範匡、馬場嘉信、原島秀吉
    • Organizer
      日本薬学会北海道支部第139回例会
    • Place of Presentation
      札幌・学術交流会館
    • Year and Date
      2012-12-08
    • Related Report
      2012 Final Research Report
  • [Presentation] Identifying therapeutic targets for type 2 diabetes in combination with a DNA microarray and the non-viral delivery of siRNA2012

    • Author(s)
      Y. Hayashi.
    • Organizer
      The15th Hokkaido University-Seoul National University joint symposium.
    • Place of Presentation
      学術交流会館・Sapporo,Japan.
    • Year and Date
      2012-12-07
    • Related Report
      2012 Final Research Report
  • [Presentation] The new pH sensitive polycation improves the transfection activity of R8-nanoparticles by facilitatingsiRNA condensation2012

    • Author(s)
      N. Toriyabe, Y. Hayashi, H. Harashima.
    • Organizer
      72nd FIP World Congress 2012.
    • Place of Presentation
      RAI Amsterdam, Amsterdam, Netherlands.
    • Related Report
      2012 Final Research Report
  • [Presentation] An integrated strategywith DNA microarray and non-viral in vivo siRNA delivery to discover novel therapeutic targets for type 2 diabetes2012

    • Author(s)
      Y. Hayashi, K. Kazuaki, Y. Sato, E.Suemitsu, A. Akhter, Y. Sakurai, H. Hatakeyama, M. Hyodo, N. Kaji, Y. Baba, H. Harashima.
    • Organizer
      10th Annual discovery on target.
    • Place of Presentation
      Copley Marriott Hotel, Boston, MA, USA.
    • Related Report
      2012 Final Research Report
  • [Presentation] 新規pH応答性ポリカチオンを用いた"細胞質"動態制御型siRNAキャリア-の有用性と評価2012

    • Author(s)
      鳥谷部尚之、林泰弘、原島秀吉
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2012
    • Place of Presentation
      仙台・仙台市民会館
    • Related Report
      2012 Final Research Report
  • [Presentation] Hepatocyte growth factor 遺伝子搭載ナノキャリアによる急性肝炎の予防効果の検証2012

    • Author(s)
      林泰弘 、水野諒一、Khalil IA、秋田英万、原島秀吉
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2012
    • Place of Presentation
      仙台・仙台市民会館
    • Related Report
      2012 Final Research Report
  • [Presentation] Gene therapy for LPS/D-GalN-induced hepatitis by octaarginine peptide-modifiednanoparticles2012

    • Author(s)
      R. Mizuno, Y. Hayashi, IA. Khalil, H.Harashima.
    • Organizer
      The 39^th Annual Meeting& Exposition of the Controlled Release Society.
    • Place of Presentation
      Centre des Congres de Quebec, Quebec, Canada.
    • Related Report
      2012 Final Research Report
  • [Presentation] In vitro / in vivo correlation analysis using siRNA-loaded lipid nanoparticles2012

    • Author(s)
      Y. Noguchi, Y. Hayashi, H. Harashima.
    • Organizer
      The 39th Annual Meeting& Exposition of the Controlled Release Society.
    • Place of Presentation
      Centre des Congres de Quebec, Quebec, Canada.
    • Related Report
      2012 Final Research Report
  • [Presentation] ナノキャリアを用いたin vitro/in vivo活性相関解析2012

    • Author(s)
      野口裕生、林泰弘 、原島秀吉
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌・北海道大学
    • Related Report
      2012 Final Research Report
  • [Presentation] The new pH sensitive polycation improves the transfection activity of R8-nanoparticles by facilitating siRNA condensation2012

    • Author(s)
      N. Toriyabe
    • Organizer
      72nd FIP World Congress 2012
    • Place of Presentation
      RAI convention center (Amsterdam, Netherlands)
    • Related Report
      2012 Annual Research Report
  • [Presentation] An integrated strategy with DNA microarray and non-viral in vivo siRNA delivery to discover novel therapeutic targets for type 2 diabetes2012

    • Author(s)
      Yasuhiro Hayashi
    • Organizer
      10th Annual discovery on target
    • Place of Presentation
      Marriott Hotel (Boston, U.S.A)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規pH応答性ポリカチオンを用いた細胞質動態制御型siRNAキャリアーの有用性と評価2012

    • Author(s)
      鳥谷部尚之
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2012
    • Place of Presentation
      仙台市民会館(仙台市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Hepatocyte growth factor遺伝子搭載ナノキャリアによる急性肝炎の予防効果の検証2012

    • Author(s)
      林泰弘
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2012
    • Place of Presentation
      仙台市民会館(仙台市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Gene therapy for LPS/D-GalN-induced hepatitis by octaarginine peptide-modified nanoparticles2012

    • Author(s)
      Ryoichi Mizuno
    • Organizer
      The 39th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Centre des congress de Quebec (Quebec, Canada)
    • Related Report
      2012 Annual Research Report
  • [Presentation] In vitro/in vivo correlation analysis using siRNA-loaded lipid nanoparticles2012

    • Author(s)
      Yuki Noguchi
    • Organizer
      The 39th Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Centre des congress de Quebec (Quebec, Canada)
    • Related Report
      2012 Annual Research Report
  • [Presentation] R8-MENDを用い in vitro/in vivoにおけるsiRNAの定量的解析2011

    • Author(s)
      野口裕生、林泰弘 、原島秀吉
    • Organizer
      第137回日本薬学会北海道支部例会
    • Place of Presentation
      札幌・学術交流会館
    • Year and Date
      2011-12-03
    • Related Report
      2012 Final Research Report
  • [Presentation] オクタアルギニン(R8)とGALAを用いた肝臓への遺伝子送達キャリアの構築2011

    • Author(s)
      水野諒一、林泰弘、Khalil Ikramy、原島秀吉
    • Organizer
      日本薬学会北海道支部第136年会
    • Place of Presentation
      札幌・学術交流会館
    • Year and Date
      2011-05-21
    • Related Report
      2012 Final Research Report
  • [Presentation] Octaarginine peptide-based nanoparticle system forliver-targeted nucleic acid delivery2011

    • Author(s)
      Y. Hayashi, R. Mizuno, J. Yamauchi, IA.Khalil, H. Harashima.
    • Organizer
      The 9^th International Symposium for Future Drug Discovery and Medical Care.
    • Place of Presentation
      Sapporo, Japan・北海道大学医学部学友会館
    • Related Report
      2012 Final Research Report
  • [Presentation] R8ペプチドとGALAペプチドを用いた肝臓への遺伝子デリバリーシステムの開発2011

    • Author(s)
      林泰弘、水野諒一、Ikramy Khalil、原島 秀吉
    • Organizer
      第27回日本DDS 学会
    • Place of Presentation
      東京・東京大学
    • Related Report
      2012 Final Research Report
  • [Presentation] 膜透過性ペプチドを用いた肝臓へのsiRNA送達2011

    • Author(s)
      山内順、林泰弘、Ikramy Khalil、梶本和 昭、秋田英万、原島秀吉
    • Organizer
      第27回日本DDS学会
    • Place of Presentation
      東京・東京大学
    • Related Report
      2012 Final Research Report
  • [Presentation] Octaarginine- and pH Sensitive Fusogenic Peptide-Modified Nanoparticles for Liver Gene Delivery2011

    • Author(s)
      Y. Hayashi, R. Mizuno, IA. Khalil, H.Harashima.
    • Organizer
      The 14^th Annual Meeting of the American Society of Gene and Cell Therapy
    • Place of Presentation
      Washington State Convention & trade center, Seattle, WA, USA.
    • Related Report
      2012 Final Research Report
  • [Presentation] Cell Penetrating Peptide-Mediated Systemic siRNA Delivery to the Liver2011

    • Author(s)
      J. Yamauchi, Y. Hayashi, IA. Khalil, H.Akita, H. Harashima.
    • Organizer
      The 14^th Annual Meeting of the American Society of Gene and Cell Therapy
    • Place of Presentation
      Washington State Convention &trade center, Seattle, WA, USA.
    • Related Report
      2012 Final Research Report
  • [Presentation] R8ペプチドとGALAペプチドを用いた肝臓への遺伝子デリバリーシステムの開発2011

    • Author(s)
      林泰弘、水野諒一、Ikramy Khalil、原島秀吉
    • Organizer
      第27回日本DDS学会
    • Place of Presentation
      東京大学(文京区)
    • Related Report
      2011 Research-status Report
  • [Presentation] Octaarginine peptide-based nanoparticle system for liver-targeted nucleic acid delivery2011

    • Author(s)
      Y. Hayashi, R. Mizuno, J. Yamauchi, IA. Khalil, H. Harashima
    • Organizer
      The 9th International Symposium for Future Drug Discovery and Medical Care
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2011 Research-status Report
  • [Presentation] in vitro/in vivoにおけるsiRNAの定量的解析2011

    • Author(s)
      野口裕生、林泰弘、原島秀吉
    • Organizer
      第137回日本薬学会北海道支部例会
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2011 Research-status Report
  • [Presentation] オクタアルギニン(R8)とGALAを修飾した肝臓指向性遺伝子送達キャリアの構築2011

    • Author(s)
      水野諒一、林泰弘、Ikramy Khalil、原島秀吉
    • Organizer
      第11回アンチセンス・遺伝子・デリバリーシンポジウム2011
    • Place of Presentation
      大阪大学(吹田市)
    • Related Report
      2011 Research-status Report
  • [Presentation] 膜透過性ペプチドを用いた肝臓へのsiRNA送達2011

    • Author(s)
      山内順、林泰弘、Ikramy Khalil、梶本和昭、秋田英万、原島秀吉
    • Organizer
      第27回日本DDS学会
    • Place of Presentation
      東京大学(文京区)
    • Related Report
      2011 Research-status Report
  • [Presentation] Cell penetrating peptide-mediated systemic siRNA delivery to the liver2011

    • Author(s)
      J. Yamauchi, Y. Hayashi, IA. Khalil, H. Akita, H. Harashima
    • Organizer
      The 14th annual meeting of the american society of gene and cell therapy
    • Place of Presentation
      Washington State Convention & Trade Center (U.S.A.)
    • Related Report
      2011 Research-status Report
  • [Presentation] Mogat1 siRNA搭載型in vivoデリバリーシステムを用いた2型糖尿病予防効果の検証.

    • Author(s)
      末光永理奈
    • Organizer
      日本薬学会北海道支部第139回例会
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Identifying therapeutic targets for type 2 diabetes in combination with a DNA microarray and the non-viral delivery of siRNA

    • Author(s)
      Yasuhiro Hayashi
    • Organizer
      The 15th Hokkaido University – Seoul National University Joint Symposium
    • Place of Presentation
      北海道大学(札幌市)
    • Related Report
      2012 Annual Research Report
  • [Book] 第3章DDS用バイオマテリアル 多機能性エンベロープ型ナノ構造体による遺伝子デリバリー. 「先端バイオマテリアルハンドブック」2012

    • Author(s)
      小暮健太郎、林泰弘、原島秀吉
    • Publisher
      エヌティーエス出版
    • Related Report
      2012 Final Research Report
  • [Book] 多機能性エンベロープ型ナノ構造体の創薬への応用.細胞2012

    • Author(s)
      林泰弘 、梶本和昭、原島秀吉
    • Publisher
      ニューサイエンス社
    • Related Report
      2012 Final Research Report
  • [Book] 先端バイオマテリアルハンドブック2012

    • Author(s)
      小暮健太郎
    • Publisher
      エヌティーエス出版
    • Related Report
      2012 Annual Research Report
  • [Book] 第4編イメージングを可能とする周辺技術第18章プローブデリバリーシステム.「蛍光イメージング/MRIプローブの開発」2011

    • Author(s)
      秋田英万、山田勇磨、中村孝司、畠山浩 人、林泰弘、梶本和昭、原島秀吉
    • Publisher
      シーエムシー出版
    • Related Report
      2012 Final Research Report
  • [Book] 多機能性エンベロープ型ナノ構造体の創薬への応用2011

    • Author(s)
      林泰弘、梶本和昭、原島秀吉.
    • Publisher
      細胞
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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