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Development of the nanoDDS platform for the penetrarion or intracellular delivery: Develioment of the rapid ligand-identification system and in vivo control of intracellular trafficking

Research Project

Project/Area Number 17K19473
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pharmaceutical Sciences and related fields
Research InstitutionChiba University

Principal Investigator

Akita Hidetaka  千葉大学, 大学院薬学研究院, 教授 (80344472)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsリガンド / 脂質様材料 / DDS / 脂質 / ナノバイオ / ナノマシン
Outline of Final Research Achievements

In this project, we have established a method for the rapid identification of targeting ligand by using a phage display library. Also, we developed a lipid-like materials that can deliver the nucleic acids via intravenous administration. As to the first project, the extracellular domain of membrane-translocating protein was fixed onto the beads, and its binding antibody was identified from the phage library that encoded a randomized domain antibody. In the second project, the lipid-like materials that mounts ternary amine and disulfide bonging as a pH-triggered protonation unit and reductive environment-triggered cleavable unit, respectively was developed as a nucleic acid delivery system. We clarified that an oleic acid is useful for the application via intravenous administration. As one example, the application to the siRNA delivery system was also demonstrated.

Academic Significance and Societal Importance of the Research Achievements

本方法は、これまで困難であった膜蛋白質の細胞外ドメインに結合する抗体を簡便かつ迅速に同定する方法として、広く応用できる。また、本研究で開発した脂質用材料は中性な核酸搭載ナノ粒子の調製を可能とし、細胞内に取り込まれた後には効率的にエンドソーム脱出をし、さらに自己崩壊することで搭載分子を細胞内に導入できることから、リガンドを搭載することで、様々な受容体を標的とするナノ粒子製剤として発展させることできる。本材料に関しては国際的な供給も開始しており、様々な創剤技術として発展が期待される。

Report

(2 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (16 results)

All 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] The delivery of mRNA to colon inflammatory lesions by lipid-nano-particles containing environmentally-sensitive lipid-like materials with oleic acid scaffolds.2018

    • Author(s)
      Tanaka H, Watanabe A, Konishi M, Nakai Y, Yoshioka H, Ohkawara T, Takeda H, Harashima H, Akita H.
    • Journal Title

      Heliyon

      Volume: 4 Issue: 12 Pages: e00959-e00959

    • DOI

      10.1016/j.heliyon.2018.e00959

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A hepatic pDNA delivery system based on an intracellular environment sensitive vitamin E-scaffold lipid-like material with the aid of an anti-inflammatory drug.2018

    • Author(s)
      Togashi R, Tanaka H, Nakamura S, Yokota H, Tange K, Nakai Y, Yoshioka H, Harashima H, Akita H
    • Journal Title

      Journal of Controlled Release

      Volume: 279 Pages: 262-270

    • DOI

      10.1016/j.jconrel.2018.04.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In Vivo Introduction of mRNA Encapsulated in Lipid Nanoparticles to Brain Neuronal Cells and Astrocytes via Intracerebroventricular Administration.2018

    • Author(s)
      Tanaka H, Nakatani T, Frihata T, Tange K, Nakai Y, Yoshioka H, Harashima H, Akita H.
    • Journal Title

      Mol Pharm

      Volume: 15 Issue: 5 Pages: 2060-2067

    • DOI

      10.1021/acs.molpharmaceut.7b01084

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Development of RNA vaccine platform based on an intracellular environment-responsive lipid like material with vitamin E-scaffold2018

    • Author(s)
      Jessica Anndita、Naho Tateshita、Hiroki Tanaka、Naoya Miura, Yu Sakurai、Kota Tange 、Yuta Nakai、Hiroki Yoshioka、Hidetaka Akita
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 凍結乾燥ワンポット法を用いたsiRNA搭載ナノ粒子の開発2018

    • Author(s)
      白根大貴、田中浩揮、櫻井遊、丹下耕太、中井悠太、吉岡宏樹、秋田英万
    • Organizer
      日本薬学会 第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cytoplasmic delivery of exogenous IVT-mRNA using self-degradable lipid-like material.2018

    • Author(s)
      Hiroki Tanaka, Manami Konishi, Nae Takada, Tatsunari Takahashi, Yuta Nakai, Kota Tange, Hiroki Yoshioka, Shinya Tamagawa, Hidetaka Akita
    • Organizer
      第20回武田科学振興財団生命科学シンポジウム RNAネオバイオロジー
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intracellular environment-responsive material (ssPalm), as a technology for the DNA/RNA-based immune-engineering2018

    • Author(s)
      Hidetaka Akita
    • Organizer
      THE 12th SUGIYAMA LABORATORY (RIKEN) OPEN SYMPOSIUM
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of DNA/RNA vaccine platform based on the intracellular environment-responsive lipid-like material2018

    • Author(s)
      Hidetaka Akita
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of mRNA nanocarriers based on environment- responsive materials for the application to cancer vaccines2018

    • Author(s)
      Naho Tateshita, Hidetaka Akita
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞内環境応答性脂質様材料を基盤とするin vivoメッセンジャーRNA送達システムの開発2018

    • Author(s)
      小西真奈美、田中浩揮、高橋達也、高田奈依、中井悠太、丹下耕太、吉岡宏樹、玉川晋也、秋田英万
    • Organizer
      第12回 次世代を担う若手医療薬科学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of self-hydrolyzable lipid-like material equipped with environment sensing motifs2018

    • Author(s)
      Hiroki Tanaka, Manami Konishi, Nae Takata, Tatunari, Takahashi, Yuta Nakai, Hiroki Yoshioka, Hidetaka Akita
    • Organizer
      18th Symposium for Gene, Design and Delivery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞内環境応答性材料ssPalmを基盤とした遺伝子・核酸デリバリーとイムノエンジニアリングへの応用2018

    • Author(s)
      秋田英万
    • Organizer
      第27回 日本癌転移学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 還元環境依存的な粒子内分解機構を搭載した自己崩壊型RNA送達システムの開発2018

    • Author(s)
      高田奈依、田中浩揮、高橋達成、小西真奈美、中井悠太、丹下耕太、吉岡宏樹、玉川晋也、秋田英万
    • Organizer
      日本核酸医薬学会第4回年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 凍結乾燥ワンポット法によるsiRNA 搭載型中性脂質ナノ粒子の開発と機能評価2018

    • Author(s)
      白根 大貴, 田中 浩揮, 丹下 耕太, 中井 悠太, 吉岡 宏樹, 秋田英万
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Book] ドラッグキャリア設計入門~DDSからナノマシンまで~2018

    • Author(s)
      秋田 英万
    • Total Pages
      21
    • Publisher
      丸善出版
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 細胞内動態を改善した新規カチオン性脂質2018

    • Inventor(s)
      秋田英万、田中浩揮、高田奈依、高橋達也、小西真奈美
    • Industrial Property Rights Holder
      秋田英万、田中浩揮、高田奈依、高橋達也、小西真奈美
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas

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Published: 2017-07-21   Modified: 2020-03-30  

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