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New strategy for intracellular delivery of biomacropharmaceuticals

Research Project

Project/Area Number 15H02497
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionKyoto University

Principal Investigator

Futaki Shiroh  京都大学, 化学研究所, 教授 (50199402)

Co-Investigator(Renkei-kenkyūsha) TAKEUCHI Toshihide  京都大学, 化学研究所, 助教 (70600120)
KAWANO Kenichi  京都大学, 化学研究所, 助教 (70732874)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥47,190,000 (Direct Cost: ¥36,300,000、Indirect Cost: ¥10,890,000)
Fiscal Year 2017: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2016: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2015: ¥27,820,000 (Direct Cost: ¥21,400,000、Indirect Cost: ¥6,420,000)
Keywords細胞内送達 / 抗体 / エンドサイトーシス / マクロピノサイトーシス / クモ毒 / 膜傷害性ペプチド / バイオ医薬品 / バイオ高分子医薬品 / エンドソーム膜不安定化ペプチド / 薬学 / 蛋白質 / 細胞 / 薬物送達
Outline of Final Research Achievements

One of the major obstacles in intracellular targeting using antibodies is their limited release from endosomes into the cytosol. We have developed an approach to deliver biomacromolecules into cells by using endosomolytic peptides derived from the cationic and membrane-lytic spider venom peptide M-lycotoxin. The delivery peptides were developed by introducing a glutamic acid into the hydrophobic face (L17E) to M-lycotoxin, enabling a marked cytosolic liberation of proteins including antibodies from endosomes. The predominant membrane-perturbation mechanism of this peptide is assumed to be the preferential disruption of negatively charged membranes (endosomal membranes) over neutral membranes (plasma membranes), and the endosomolytic peptide promotes the uptake by inducing macropinocytosis.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (20 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (12 results) (of which Int'l Joint Research: 9 results,  Invited: 12 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] ストックホルム大学(スウェーデン)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Arginine-rich cell-penetrating peptide-modified extracellular vesicles for active macropinocytosis induction and efficient intracellular delivery2017

    • Author(s)
      Nakase Ikuhiko、Noguchi Kosuke、Aoki Ayako、Takatani-Nakase Tomoka、Fujii Ikuo、Futaki Shiroh
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1991-1991

    • DOI

      10.1038/s41598-017-02014-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytosolic Antibody Delivery by Lipid-sensitive Endosomolytic Peptide2017

    • Author(s)
      Misao Akishiba, Toshihide Takeuchi, Yoshimasa Kawaguchi, Kentarou Sakamoto, Hao-Hsin Yu, Ikuhiko Nakase, Tomoka Takatani-Nakase, Fatemeh Madani, Astrid Graslund, Shiroh Futaki
    • Journal Title

      Nature Chemistry

      Volume: in press Issue: 8 Pages: 751-761

    • DOI

      10.1038/nchem.2779

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Vectorization of biomacromolecules into cells using extracellular vesicles with enhanced internalization induced by macropinocytosis2016

    • Author(s)
      I. Nakase*, K. Noguchi, I. Fujii, S. Futaki
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 34937-34937

    • DOI

      10.1038/srep34937

    • NAID

      120006223631

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Cytosolic delivery of biomacromolecules2018

    • Author(s)
      Shiroh Futaki
    • Organizer
      2018 International Symposium on Chemical Biology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ペプチドを用いた細胞内デリバリー2018

    • Author(s)
      二木史朗
    • Organizer
      第393回CBI学会講演会「中分子創薬の実現にむけて」
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 細胞内デリバリーペプチドの膜との相互作用2017

    • Author(s)
      二木史朗
    • Organizer
      17-1 バイオ・高分子研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Peptide-mediated Delivery of Biomacromolecules into Cells2017

    • Author(s)
      Shiroh Futaki
    • Organizer
      12th Australian Peptide Conference 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cytosolic antibody delivery by lipid-sensitive endosomelytic peptide2017

    • Author(s)
      Shiroh Futaki
    • Organizer
      The Second A3 Roundtable Meeting on Chemical Probe Research Hub
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Peptide Mediated Delivery of Bioactive Proteins into Cells2016

    • Author(s)
      Shiroh Futaki
    • Organizer
      8th AsiaTIDES
    • Place of Presentation
      京都
    • Year and Date
      2016-02-24
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 見る・知る・作る:ペプチドと細胞膜との相互作用2016

    • Author(s)
      二木史朗
    • Organizer
      第9回東京大学化学生命工学専攻ChemBioハイブリッドレクチャー
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Facilitated membrane translocation of arginine-rich peptides in the presence of curvature inducing peptides2016

    • Author(s)
      Shiroh Futaki
    • Organizer
      14th Chinese International Peptide Symposium & 5th Asia-pacific International Peptide Symposium (CPS-14 & APIPS-5)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Exploiting hemolytic amphiphilic peptides as a design template for cytosolic antibody2015

    • Author(s)
      Shiroh Futaki
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015 (Pacifichem 2015)
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2015-12-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Peptide mediated delivery of bioactive proteins into cells2015

    • Author(s)
      Shiroh Futaki
    • Organizer
      The 7th International Peptide Symposium
    • Place of Presentation
      Singapore
    • Year and Date
      2015-12-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel lysosomolytic peptide designed from spider venom2015

    • Author(s)
      Shiroh Futaki
    • Organizer
      7th Peptide Engineering Meeting (PEM7-2015)
    • Place of Presentation
      Pune, India
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Converting a cytotoxic, hemolytic peptide to an intracellular delivery tool of bioactive proteins2015

    • Author(s)
      Shiroh Futaki
    • Organizer
      NEA & ASIAHORCs Joint Symposium on Chemical Biology
    • Place of Presentation
      OIST
    • Year and Date
      2015-11-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 京都大学化学研究所生体機能設計化学研究領域

    • URL

      http://www.scl.kyoto-u.ac.jp/~bfdc/index.html

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Remarks] 京都大学化学研究所 生体機能設計化学 二木研究室

    • URL

      http://www.scl.kyoto-u.ac.jp/~bfdc/index.html

    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞質送達ペプチド2017

    • Inventor(s)
      二木史朗、坂本健太郎、秋柴美沙穂
    • Industrial Property Rights Holder
      二木史朗、坂本健太郎、秋柴美沙穂
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞質送達ペプチド2015

    • Inventor(s)
      二木史朗、秋柴美沙穂、川口祥正、武内敏秀
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-28
    • Related Report
      2015 Annual Research Report
    • Overseas

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Published: 2015-04-16   Modified: 2019-03-29  

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