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In situ PEGylation of extracellular DNA using functional peptides for anti-inflammatory therapy

Research Project

Project/Area Number 21K19923
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 90:Biomedical engineering and related fields
Research InstitutionTokyo Medical and Dental University (2022)
Kyoto Prefectural University of Medicine (2021)

Principal Investigator

Uchida Satoshi  東京医科歯科大学, 難治疾患研究所, 教授 (20710726)

Co-Investigator(Kenkyū-buntansha) 大庭 誠  京都府立医科大学, 医学(系)研究科(研究院), 教授 (20396716)
Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsダメージ関連分子パターン / ペプチド / ポリエチレングリコール / 炎症 / ペプチド医薬 / 炎症性疾患 / 薬物動態
Outline of Research at the Start

新型コロナウイルス肺炎をはじめとした炎症の病気では、炎症によって死んだ細胞から放出されたDNAが、炎症反応を悪化させる。本研究では、精密設計したペプチドを投与して、そのDNAを捕捉することで、炎症を軽減させる。様々なペプチドを設計し、その効果を培養細胞で調べ、高機能なペプチドを同定する。さらに、そのペプチドを、肺炎、肝炎などのモデルマウスに投与し、治療効果や安全性を検証する。

Outline of Final Research Achievements

In inflammatory diseases, DNA and RNA released from the damaged cells stimulate innate immune receptors, exacerbating inflammation and damaging tissues. The DNA and RNA are called damage-associated molecular patterns (DAMPs). Our study have developed PEGylated oligopeptides to capture DAMPs to alleviate the inflammation in a safe manner. Indeed, PEGylated oligopeptides successfully rescued the model mice of inflammation from death.

Academic Significance and Societal Importance of the Research Achievements

現在のバイオ医薬品は特定の標的タンパク質と相互作用し機能するが、そのために複雑な構造が必要となり、経済的コストが課題となる。これに対して、本研究の手法は、物理化学的に原因物質を除去するというコンセプトであり、単純な設計が可能である。本研究では、炎症性疾患に対する安全かつ効果的な治療法を開発しただけでなく、新たな薬剤設計のコンセプトを提唱したことが学術的意義である。そのことが、薬剤のコストダウンにつながる点が社会的意義である。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (39 results)

All 2023 2022 2021 Other

All Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 14 results,  Open Access: 8 results) Presentation (22 results) (of which Int'l Joint Research: 4 results,  Invited: 14 results) Remarks (3 results)

  • [Journal Article] An Amphipathic Structure of a Dipropylglycine-Containing Helical Peptide with Sufficient Length Enables Safe and Effective Intracellular siRNA Delivery2023

    • Author(s)
      Makoto Oba, Mika Shibuya, Yuto Yamaberi, Hidetomo Yokoo, Satoshi Uchida, Atsushi Ueda, Masakazu Tanaka
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 71 Issue: 3 Pages: 250-256

    • DOI

      10.1248/cpb.c22-00852

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2023-03-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Block catiomers with flanking hydrolyzable tyrosinate groups enhance in vivo mRNA delivery via マ?窶苫? stacking-assisted micellar assembly2023

    • Author(s)
      Wenqian Yang, Takuya Miyazaki, Yasuhiro Nakagawa, Eger Boonstra, Keita Masuda, Yuki Nakashima, Pengwen Chen, Lucas Mixich, Kevin Barthelmes, Akira Matsumoto, Peng Mi, Satoshi Uchida, Horacio Cabral
    • Journal Title

      Science and technology of advanced materials

      Volume: 24 Issue: 1 Pages: 2170164-2170164

    • DOI

      10.1080/14686996.2023.2170164

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Complete Chemical Synthesis of Minimal Messenger RNA by Efficient Chemical Capping Reaction2022

    • Author(s)
      Naoko Abe, Akihiro Imaeda, Masahito Inagaki, Zhenmin Li, Daisuke Kawaguchi, Kaoru Onda, Yuko Nakashima, Satoshi Uchida, Fumitaka Hashiya, Yasuaki Kimura, Hiroshi Abe
    • Journal Title

      ACS Chemical Biology

      Volume: 17 Issue: 6 Pages: 1308-1314

    • DOI

      10.1021/acschembio.1c00996

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Delivery Systems of Plasmid DNA and Messenger RNA for Advanced Therapies.2022

    • Author(s)
      S. Uchida
    • Journal Title

      Pharmaceutics

      Volume: 14 Issue: 4 Pages: 810-810

    • DOI

      10.3390/pharmaceutics14040810

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effective mRNA Protection by Poly(l-ornithine) Synergizes with Endosomal Escape Functionality of a Charge-Conversion Polymer toward Maximizing mRNA Introduction Efficiency2022

    • Author(s)
      A. Dirisala, S. Uchida, J. Li, J.F.R. Van Guyse, K. Hayashi, S.V.C. Vummaleti, S. Kaur, Y. Mochida, S. Fukushima, K. Kataoka
    • Journal Title

      Macromol. Rapid Commun.

      Volume: - Issue: 12 Pages: 2100754-2100754

    • DOI

      10.1002/marc.202100754

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Microglial Immunoregulation by Apoptotic Cellular Membrane Mimetic Polymeric Particles2022

    • Author(s)
      Nakagawa Yasuhiro、Lee Jeonggyu、Liu Yihua、Abbasi Saed、Hong Taehun、Cabral Horacio、Uchida Satoshi、Ebara Mitsuhiro
    • Journal Title

      ACS Macro Letters

      Volume: 11 Issue: 2 Pages: 270-275

    • DOI

      10.1021/acsmacrolett.1c00643

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell-Penetrating Peptides: Emerging Tools for mRNA Delivery2022

    • Author(s)
      H. Yokoo, M. Oba, S. Uchida
    • Journal Title

      Pharmaceutics

      Volume: 14 Issue: 1 Pages: 78-78

    • DOI

      10.3390/pharmaceutics14010078

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bridging mRNA and polycation using RNA oligonucleotide derivatives improves the robustness of polyplex micelle for efficient mRNA delivery.2021

    • Author(s)
      N. Yoshinaga, S. Uchida, A. Dirisala, M. Naito, K. Koji, K. Osada, H. Cabral, K. Kataoka,
    • Journal Title

      Advanced Healthcare Materials,

      Volume: - Issue: 9 Pages: 2102016-2102016

    • DOI

      10.1002/adhm.202102016

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Size-controlled bimodal in vivo nanoprobes as near-infrared phosphors and positive contrast agents for magnetic resonance imaging2021

    • Author(s)
      K. Okubo, R. Takeda, S. Murayama, M. Umezawa, M. Kamimura, K. Osada, I. Aoki, K. Soga,
    • Journal Title

      Science and Technology of Advanced Materials

      Volume: 22 Issue: 6 Pages: 160-172

    • DOI

      10.3390/pharmaceutics13060800

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A helix foldamer oligopeptide improves intracellular stability and prolongs protein expression of the delivered mRNA2021

    • Author(s)
      S. Uchida, Y. Yamaberi, M. Tanaka, M. Oba
    • Journal Title

      Nanoscale

      Volume: 13 Issue: 45 Pages: 18941-18946

    • DOI

      10.1039/d1nr03600a

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer2021

    • Author(s)
      J. Li, Z. Ge, K. Toh, X. Liu, A. Dirisala, W. Ke, P. Wen, H. Zhou, Z. Wang, S. Xiao, J.F.R. Van Guyse, T.A. Tockary, J. Xie, D. Gonzalez-Carter, H. Kinoh, S. Uchida, Y. Anraku, K. Kataoka
    • Journal Title

      Adv. Mater.

      Volume: 33 Issue: 49 Pages: 2105254-2105254

    • DOI

      10.1002/adma.202105254

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Bioinspired Silicification of mRNA-Loaded Polyion Complexes for Macrophage-Targeted mRNA Delivery2021

    • Author(s)
      R. Kamegawa, M. Naito, S. Uchida, H.J. Kim, B.S. Kim, K. Miyata
    • Journal Title

      ACS Applied Bio Materials

      Volume: 4 Issue: 11 Pages: 7790-7799

    • DOI

      10.1021/acsabm.1c00704

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A proton/macromolecule-sensing approach distinguishes changes in biological membrane permeability during polymer/lipid-based nucleic acid delivery2021

    • Author(s)
      Boonstra Eger、Hatano Hiroaki、Miyahara Yuji、Uchida Satoshi、Goda Tatsuro、Cabral Horacio
    • Journal Title

      Journal of Materials Chemistry B

      Volume: 9 Issue: 21 Pages: 4298-4302

    • DOI

      10.1039/d1tb00645b

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multifunctional Immunoadjuvants for Use in Minimalist Nucleic Acid Vaccines2021

    • Author(s)
      S. Abbasi, S. Uchida
    • Journal Title

      Pharmaceutics

      Volume: 13 Issue: 5 Pages: 644-644

    • DOI

      10.3390/pharmaceutics13050644

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] mRNA分子設計に着目したDDSとワクチン2023

    • Author(s)
      内田 智士
    • Organizer
      日本薬学会第143回年会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] mRNA医薬の再生医療分野への展開とバイオマテリアル2023

    • Author(s)
      内田 智士
    • Organizer
      第22回再生医療学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] mRNAワクチン、医薬における免疫と医用高分子2023

    • Author(s)
      内田 智士
    • Organizer
      第73回医用高分子研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] mRNAワクチン、医薬品の基盤技術、応用、今後の展望2023

    • Author(s)
      内田 智士
    • Organizer
      JSSX-APDD合同ワークショップ 第7回
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] mRNA医薬を用いた中枢神経系疾患の治療2022

    • Author(s)
      内田 智士
    • Organizer
      第41回日本認知症学会学術集会/第37回日本老年精神医学会[合同開催]
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 精密設計2本側鎖mRNAを基盤とした汎用的がんmRNAワクチンアジュバントの創製2022

    • Author(s)
      内田智士, Theofilus A. Tockary, Saed Abbasi, 正井三貴, 片岡一則
    • Organizer
      第44回日本バイオマテリアル学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Hybridizing antigen mRNA with short double-stranded RNA adjuvants for safe and efficient cancer vaccine2022

    • Author(s)
      Satoshi Uchida, Theofilus A. Tockary, Saed Abbasi, Miki Masai, Kazunori Kataoka
    • Organizer
      10th International mRNA Health Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mRNA 工学を基盤としたナノ DDS とワクチン2022

    • Author(s)
      内田 智士
    • Organizer
      第 17 回ナノ・バイオメディカル学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] mRNA工学を基盤とした次世代mRNAワクチンの創製2022

    • Author(s)
      内田 智士
    • Organizer
      第43回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] mRNA cancer vaccines hybridized with short double-stranded RNA adjuvants2022

    • Author(s)
      Satoshi Uchida, Theofilus A. Tockary, Saed Abbasi, Miki Masai, Kazunori Kataoka
    • Organizer
      第10回日本核酸医薬学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] mRNA工学を基盤としたmRNAデリバリーとワクチン2022

    • Author(s)
      内田 智士
    • Organizer
      第38回日本DDS学会学術集会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] Engineering polymers and mRNA for therapeutic mRNA delivery2022

    • Author(s)
      Satoshi Uchida
    • Organizer
      13th International Symposium on Polymer Therapeutics 2022
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生体適合性高分子を基盤とした遺伝子治療とmRNA創薬2022

    • Author(s)
      内田 智士
    • Organizer
      日経バイオテクセミナー 遺伝子治療が抱える課題と新展開
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] mRNAワクチンの基礎から最前線まで2022

    • Author(s)
      内田 智士
    • Organizer
      第56回緑膿菌感染症研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] RNA architectonicsを基盤としたmRNA送達とワクチン2021

    • Author(s)
      内田 智士
    • Organizer
      日本バイオマテリアル学会関西ブロック 第16回若手研究発表会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] SDGsとバイオマテリアル2021

    • Author(s)
      内田 智士
    • Organizer
      第43回日本バイオマテリアル学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 2本鎖PEG-オリゴリシンを用いた肝類洞壁一過的コーティングによるナノ医薬品の体内動態制御2021

    • Author(s)
      内田 智士
    • Organizer
      第70回高分子討論会
    • Related Report
      2021 Research-status Report
  • [Presentation] COVID-19に対するmRNAワクチン開発の動向と独自の取り組み2021

    • Author(s)
      内田 智士
    • Organizer
      JAACT2021日本動物細胞工学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] mRNA医薬、遺伝子治療薬の全身投与に向けた取り組み2021

    • Author(s)
      内田 智士
    • Organizer
      日本核酸医薬学会第6回年会
    • Related Report
      2021 Research-status Report
  • [Presentation] Polyplex micelles co-loading Cas9 mRNA and single guide RNA exhibit efficient genome editing in the mouse brain2021

    • Author(s)
      Uchida S, Abbasi S, Kataoka K
    • Organizer
      9th International mRNA Health Conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Assembling Several mRNA Strands for Facilitating mRNA Delivery with and without Using Carriers.2021

    • Author(s)
      Uchida S, Yoshinaga N, Koji K, Cabral H
    • Organizer
      24th Annual Meeting of the American Society of Gene & Cell Therapy
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 2本鎖PEGを用いた肝類洞内皮一過的コーティングによる遺伝子治療薬の標的組織集積性向上2021

    • Author(s)
      内田智士, A. Dirisala, 籐加珠子, 長田健介, 片岡一則
    • Organizer
      第37回日本DDS学会学術集会
    • Related Report
      2021 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      https://www.tmd.ac.jp/mri/anme/index.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] ホームページ(日本語)

    • URL

      https://kpu-m.medchem.jp/uchida.html

    • Related Report
      2021 Research-status Report
  • [Remarks] ホームページ(英語)

    • URL

      https://kpu-m.medchem.jp/uchida_en.html

    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2024-12-25  

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