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Efficient induction of in vivo RNA interference by designing exosome-tropic siRNA derivatives

Research Project

Project/Area Number 26670266
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Applied pharmacology
Research InstitutionKyoto University

Principal Investigator

Takahashi Yuki  京都大学, 薬学研究科(研究院), 助教 (00547870)

Co-Investigator(Kenkyū-buntansha) TAKAKURA Yoshinobu  京都大学, 大学院薬学研究科, 教授 (30171432)
NISHIKAWA Makiya  京都大学, 大学院薬学研究科, 准教授 (40273437)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsエキソソーム / ラジオアイソトープ / DDS / SELEX法
Outline of Final Research Achievements

In the current study, for the goal of the development of drug delivery system by using exosomes, a method to quantitatively evaluate in vivo tissue distribution of exosomes was developed, and three ultracentrifugation-based exosome collection methods were compared to one another. We selected a biotin binding protein (streptavidin: SAV) and an exosome-tropic protein (lactadherin: LA) to obtain a fusion protein SAV-LA. Radio-labeled exosomes were prepared by using SAV-LA and radioactive biotin derivatives, and tissue distribution of the exosomes was quantitatively evaluated by using the labeled exosomes. By comparing the three ultracentrifugation-based exosome collection methods, we concluded that a density gradient ultracentrifugation method was the best method to collect exosomes with minimal aggregates and in a good quality.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (10 results)

All 2016 2015 2014

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation.2016

    • Author(s)
      Yamashita T, Takahashi Y, Nishikawa M, Takakura Y.
    • Journal Title

      European Journal of Pharmaceutics and Biopharmaceutics

      Volume: 98 Pages: 1-8

    • DOI

      10.1016/j.ejpb.2015.10.017

    • NAID

      120005697969

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Quantitative Analysis of Tissue Distribution of the B16BL6-Derived Exosomes Using a Streptavidin-Lactadherin Fusion Protein and Iodine-125-Labeled Biotin Derivative After Intravenous Injection in Mice.2015

    • Author(s)
      Morishita M, Takahashi Y, Nishikawa M, Sano K, Kato K, Yamashita T, Imai T, Saji H, Takakura Y.
    • Journal Title

      J Pharm Sci.

      Volume: 104 Issue: 2 Pages: 705-713

    • DOI

      10.1002/jps.24251

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice.2015

    • Author(s)
      Imai T, Takahashi Y, Nishikawa M, Kato K, Morishita M, Yamashita T, Matsumoto A, Charoenviriyakul C, Takakura Y.
    • Journal Title

      J Extracell Vesicles.

      Volume: 4 Issue: 1

    • DOI

      10.3402/jev.v4.26238

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 核酸医薬のDDSへの応用を目的とした体内動態制御型核酸搭載exosomeの開発2015

    • Author(s)
      高橋有己、西川元也、高倉喜信
    • Organizer
      第31回 日本DDS学会学術集会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Exosome回収方法がexosomeの特性に及ぼす影響の評価2015

    • Author(s)
      山下拓真、高橋有己、西川元也、高倉喜信
    • Organizer
      日本薬剤学会 第30年会
    • Place of Presentation
      長崎ブリックホール(長崎県 長崎市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 抗腫瘍免疫の増強を目的としたCpG DNA修飾癌細胞由来exosomeの開発2015

    • Author(s)
      森下将輝、高橋有己、西川元也、高倉喜信
    • Organizer
      日本薬剤学会 第30年会
    • Place of Presentation
      長崎ブリックホール(長崎県 長崎市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Streaptavidin-biotin結合に基づいたexosome放射標識法によるexosome体内動態の定量的解析2014

    • Author(s)
      森下将輝、高橋有己、佐野紘平、西川元也、佐治英郎、高倉喜信
    • Organizer
      日本DDS学会第30年会
    • Place of Presentation
      慶應義塾大学(東京)
    • Year and Date
      2014-07-30 – 2014-07-31
    • Related Report
      2014 Research-status Report
  • [Presentation] SELEX法を利用したexosome移行性RNAの探索2014

    • Author(s)
      篠塚春香、高橋有己、加藤佳奈、西川元也、高倉喜信
    • Organizer
      日本DDS学会第30年会
    • Place of Presentation
      慶應義塾大学(東京)
    • Year and Date
      2014-07-30 – 2014-07-31
    • Related Report
      2014 Research-status Report
  • [Presentation] 静脈内投与されたB16BL6由来エキソソームのマウスにおけるマクロファージ依存的消失挙動2014

    • Author(s)
      山下拓真、今井貴文、高橋有己、森下将輝、西川元也、高倉喜信
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮ソニックシティビル(さいたま市)
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Research-status Report
  • [Presentation] Quantitative analysis of the distribution and clearance of mouse melanoma B16-BL6-derived exosomes in mice.2014

    • Author(s)
      Takahashi Y, Imai T, Nishikawa M, Kato K, Morishita M, Takakura Y.
    • Organizer
      International Society for Extracellular Vesicles 2014
    • Place of Presentation
      Rotterdam(オランダ)
    • Year and Date
      2014-04-30 – 2014-05-04
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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