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Development of cell-specific DDS for biopharmaceuticals using a novel human-derived membrane penetration-enhancing peptide

Research Project

Project/Area Number 17H02103
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKeio University

Principal Investigator

DOI Nobuhide  慶應義塾大学, 理工学部(矢上), 教授 (50327673)

Co-Investigator(Kenkyū-buntansha) 藤原 慶  慶應義塾大学, 理工学部(矢上), 講師 (20580989)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords抗体 / ペプチド / 核酸 / ドラッグデリバリーシステム / 細胞膜透過 / 蛋白質 / 癌 / バイオテクノロジー / 共焦点顕微鏡
Outline of Final Research Achievements

Biopharmaceuticals consisting of antibodies, peptides or nucleic acids, which have high specificity and affinity for target molecules, are attracting attention as the ultimate molecular targeted drugs with less side effects and higher therapeutic effects than conventional drugs consisting of low-molecular compounds. However, biopharmaceuticals have a drawback of low cell membrane permeability, and thus development of an efficient drug delivery system (DDS) for biopharmaceuticals has been required. In this study, we discovered a membrane penetration-enhancing peptide for efficient cytoplasmic delivery of antibodies, peptides, and nucleic acids. In addition, as a basic research, we analyzed the membrane permeation mechanism.

Academic Significance and Societal Importance of the Research Achievements

我々が発見した膜透過促進ペプチドはヒト天然タンパク質由来であり免疫原性の懸念が少ないという利点もあることから、この独自の膜透過促進ペプチドを連結した抗体/ペプチド/核酸がヒト細胞の細胞質に効率よく送達されるという本研究の成果は、将来的に、細胞内の疾患標的に作用する新しい抗体医薬の開発や、ペプチドや核酸からなる中分子医薬の効率的なデリバリーに応用することが期待できる。これにより、我が国のバイオ創薬技術の基盤強化、ひいては国民の医療・福祉の向上に大きく貢献することが期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (22 results)

All 2020 2019 2018 2017 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Microfluidic screening system based on boron-doped diamond electrodes and dielectrophoretic sorting for directed evolution of NAD(P)-dependent oxidoreductases.2020

    • Author(s)
      Goto, H., Kanai, Y., Yotsui, A., Shimokihara, S., Shitara, S., Oyobiki, R., Fujiwara, K., Watanabe, T., Einaga, Y., Matsumoto, Y., Miki, N., Doi, N.
    • Journal Title

      Lab Chip

      Volume: 20 Issue: 4 Pages: 852-861

    • DOI

      10.1039/c9lc01263j

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of spatiotemporal patterning in artificial cells by a defined protein expression system2019

    • Author(s)
      Yoshida Aoi、Kohyama Shunshi、Fujiwara Kei、Nishikawa Saki、Doi Nobuhide
    • Journal Title

      Chemical Science

      Volume: 10 Issue: 48 Pages: 11064-11072

    • DOI

      10.1039/c9sc02441g

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell-sized confinement controls generation and stability of a protein wave for spatiotemporal regulation in cells2019

    • Author(s)
      Kohyama Shunshi、Yoshinaga Natsuhiko、Yanagisawa Miho、Fujiwara Kei、Doi Nobuhide
    • Journal Title

      eLife

      Volume: 8

    • DOI

      10.7554/elife.44591

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A dual system using compartmentalized partnered replication for selection of arsenic-responsive transcriptional regulator.2018

    • Author(s)
      Aye, S.L., Fujiwara, K., Doi, N.
    • Journal Title

      J. Biochem.

      Volume: 164 Issue: 5 Pages: 341-348

    • DOI

      10.1093/jb/mvy055

    • NAID

      40021724808

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Engineering of DNA polymerase I from Thermus thermophilus using compartmentalized self-replication.2018

    • Author(s)
      Aye, S.L., Fujiwara, K., Ueki, A., Doi, N.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 499 Issue: 2 Pages: 170-176

    • DOI

      10.1016/j.bbrc.2018.03.098

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Artificial Cell Fermentation as a Platform for Highly Efficient Cascade Conversion2017

    • Author(s)
      Fujiwara Kei、Adachi Takuma、Doi Nobuhide
    • Journal Title

      ACS Syntheitc Biology

      Volume: 7 Issue: 2 Pages: 363-370

    • DOI

      10.1021/acssynbio.7b00365

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human-derived fusogenic peptides for the intracellular delivery of proteins.2017

    • Author(s)
      Sudo, K., Niikura, K., Iwaki, K., Kohyama, S., Fujiwara, K., Doi, N.
    • Journal Title

      J. Control. Release

      Volume: 255 Pages: 1-11

    • DOI

      10.1016/j.jconrel.2017.03.398

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ヒト由来膜融合ペプチドによるバイオ医薬のDDS.2017

    • Author(s)
      土居信英
    • Journal Title

      細胞

      Volume: 49 Pages: 602-605

    • Related Report
      2017 Annual Research Report
  • [Presentation] Application of a human-derived fusogenic peptide to intracellular delivery of therapeutic peptides.2019

    • Author(s)
      Kikuchi, M., Iwaki, K., Fujiwara, K., Doi, N.
    • Organizer
      The Cold Spring Harbor Asia conference on Chemical Biology and Drug Discovery
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ペプチド医薬の細胞質送達に向けたヒト由来膜透過促進ペプチドの応用2019

    • Author(s)
      菊地萌希,岩城洸汰,藤原慶,土居信英
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト・シンシチン1由来膜透過促進ペプチドのアラニンスキャニング変異解析2019

    • Author(s)
      鈴木麻友子,岩城洸汰,須藤慧,藤原慶,土居信英
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] LDL受容体を標的とする細胞選択的なタンパク質のデリバリーのためのヒト由来膜透過促進ペプチドの最適化2019

    • Author(s)
      前村帆南,岩城洸汰,藤原慶,土居信英
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト由来膜透過促進ペプチドS19を利用したsiRNAデリバリー2019

    • Author(s)
      中村桃子,藤原慶,土居信英
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト由来膜透過促進ペプチドを利用したDDSの可能性2019

    • Author(s)
      土居信英
    • Organizer
      第21回ヒューマンサイエンス総合研究ワークショップ
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒト由来膜融合ペプチドと積み荷タンパク質の連結様式がその細胞質送達活性に与える影響2018

    • Author(s)
      岩城洸汰,菊地萌希,須藤慧,藤原慶,土居信英
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] タンパク質の細胞質送達を促進するヒト由来ペプチドの発見とDDSへの応用2018

    • Author(s)
      土居信英
    • Organizer
      LIP横浜オープンイノベーションカンファレンスIII
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒト由来膜透過促進ペプチドによるバイオ医薬の効率的な細胞質送達の可能性評価2018

    • Author(s)
      菊地萌希,岩城洸汰,漆島穣一,須藤慧,藤原慶,土居信英
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒトSyncytin1由来膜融合ペプチドによるタンパク質の細胞質送達機構の解析2017

    • Author(s)
      岩城洸汰,須藤慧,光山隼史,藤原慶,土居信英
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] mRNAディスプレイ法によるヒト抗GPCR単一ドメイン抗体の試験管内選択2017

    • Author(s)
      漆島穣一,海野佑樹,須藤慧,藤原慶,土居信英
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Book] ドラッグデリバリーシステム - バイオ医薬品創成に向けた組織、細胞内、核内送達技術の開発-2018

    • Author(s)
      土居信英
    • Total Pages
      280
    • Publisher
      シーエムシー出版
    • Related Report
      2018 Annual Research Report
  • [Book] 医療・診断をささえるペプチド科学 - 再生医療・DDS・診断への応用 -2017

    • Author(s)
      土居信英
    • Total Pages
      7
    • Publisher
      シーエムシー出版
    • ISBN
      9784781312675
    • Related Report
      2017 Annual Research Report
  • [Remarks] プレスリリース:タンパク質の細胞質送達を促進するヒト由来ペプチドを発見

    • URL

      https://www.keio.ac.jp/ja/press-releases/2017/4/6/28-20259/index.html

    • Related Report
      2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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