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Development of Novel mRNA Delivery Systems based on Flexible Biodegradable Block Copolymers

Research Project

Project/Area Number 20J13458
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionThe University of Tokyo

Principal Investigator

楊 文セイ  東京大学, 工学系研究科, 特別研究員(DC2)

Project Period (FY) 2020-04-24 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2020: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsNanomedicine / Polymeric micelles / messenger RNA
Outline of Research at the Start

本研究ではmRNAの安定化とポリマーの生分解性に焦点を当てた検討から着手し、機能性アミノ酸を導入することにより、mRNAに安定効果もあり、かつ標的細胞、部位、至るところの毒性を減低する。本研究は、ポリマー生分解性とmRNA 安定化効果の両方を兼ね備えたシステムを構築する際の優れた設計指針となり、この技術により多種ヌクレオチト薬剤を全身へ送達することが可能となり、がんを含めて様々難治療疾患の治療や診断への展開が期待できる。

Outline of Annual Research Achievements

Here, we focused on the development of nanocarriers for safe and stable systemic delivery of mRNA. Thus, we have developed a library of polymers, and chemically modified with amino acids which could stable mRNA by hydrophobic interaction and π-π interaction. We confirmed that these polymers were biodegradable in physiological conditions. Polymeric micelles prepared by polymers with π-π interaction were found to be safe in vitro after incubation with 50% Fetal Bovine Serum, could achieve a highest mRNA expression in vitro. We found that micelles with π-π interaction with mRNA showed higher protein expression in the lung of mouse after 24 h intratracheal administration. Moreover, these micelles maintained over 10% of loaded mRNA in mice blood after 10 mins of intravenous administration.

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (7 results)

All 2021 2020

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Effect of PEG-Polycation Chain Flexibility on the Assembly of siRNA-Loaded Polyion Complexes and their in Vitro Performance2021

    • Author(s)
      Wenqian Yang, Takuya Miyazaki, Pengwen Chen, Taehun Hong, Mitsuru Naito, Yuji Miyahara, Akira Matsumoto, Kazunori Kataoka, Kanjiro Miyata and Horacio Cabral
    • Journal Title

      Science and Technology of Advanced Materials

      Volume: 22 Issue: 1 Pages: 850-863

    • DOI

      10.1080/14686996.2021.1976055

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Influence of PEG-Polycation Chain Flexibility on the Assembly of siRNA into Polyion Complexes2021

    • Author(s)
      Wenqian Yang, Takuya Miyazaki, Pengwen Chen, Taehun Hong and Horacio Cabral
    • Organizer
      The 12th International Conference on the Science and Technology for Advanced Ceramics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhanced cancer immunotherapy by tumor-targeted Interleukin-12-loaded polymeric micelles2021

    • Author(s)
      Pengwen Chen, Wenqian Yang, Kazunori Igarashi, Taehun Hong, Kazunori Kataoka, Horacio Cabral
    • Organizer
      Materials Research Meeting (MRM2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhanced mRNA Delivery by Polyion Complex Micelles from Flexible Block Ionomers2021

    • Author(s)
      Horacio Cabral, Takuya Miyazaki, Wenqian Yang, Satoshi Uchida
    • Organizer
      Materials Research Meeting (MRM2021)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bioinspired design of stable siRNA-loaded polyion complex micelles from strong Tryptophan/Tyrosine-RNA interactions for siRNA delivery2020

    • Author(s)
      Wenqian Yang, Takuya Miyazaki, Yasuhiro Nakagawa, Satoshi Uchida, Kazunori Kataoka and Horacio Cabral
    • Organizer
      69th SPSJ (Society of Polymer Science, Japan) Annual Meeting
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effect of PEG-Polycation Chain Flexibility on siRNA loaded Polyion Complex Micelles Assembly2020

    • Author(s)
      Wenqian Yang, Takuya Miyazaki, Yasuhiro Nakagawa, Pengwen Chen, Taehun Hong and Horacio Cabral
    • Organizer
      3rd GLowing Polymer Symposium in KANTO (GPS-K 2020)
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of PEG-Polycation Chain Flexibility on siRNA loaded Polyion Complex Micelles Assembly2020

    • Author(s)
      Wenqian Yang, Takuya Miyazaki, Teahon Hong and Horacio Cabral
    • Organizer
      2nd International online conference on nanomedicine
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research

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Published: 2020-07-07   Modified: 2024-03-26  

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