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Designing PEGylated proteins for reducing PEG-specific immunogenicity

Research Project

Project/Area Number 17KK0105
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionJikei University School of Medicine

Principal Investigator

Shiraishi Koichi  東京慈恵会医科大学, 医学部, 准教授 (40426284)

Project Period (FY) 2018 – 2021
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Keywordsポリエチレングリコール / 免疫原性 / 抗PEG抗体 / PEG修飾 / タンパク質 / PEG化タンパク質 / PEG化 / 免疫原性低減 / たんぱく質 / 抗原性低減 / 高分子化学 / 抗体
Outline of Final Research Achievements

PEGs have been known as a bio-inert polymer, and conjugation of PEG on proteins, which is called PEGylation, is the most frequently used method for protein modification. Nowadays, PEG has been used for coverages of lipid nanoparticles for mRNA delivery. PEG reduces proteins’ immunogenicity, however, PEG-specific antibodies have been observed in patients, who received repeated injection of PEGylated therapeutics. Therefore, there is the issue that PEG-specific antibodies have been induced after injections of PEGylated therapeutics to be overcome. We have previously suggested a new PEGylation method to reduce PEG-related immunogenicity, and the current study examined the new PEGylation onto proteins. Our suggested PEGylation reduced PEG-related antibody responses, whereas a classic PEGylation exhibited PEG-related antibody responses. Our PEGylation method will be a promising new method for protein modification.

Academic Significance and Societal Importance of the Research Achievements

ポリエチレングリコール(PEG)は生体親和性の高い高分子として知られ、タンパク質製剤へのPEG化はタンパク質製剤の免疫原性を低減させ、安定性向上、半減期の延長など製剤としての治療効率の向上に貢献している。また、PEG化はmRNAワクチン脂質ナノ粒子にも用いられている。一方、PEGをタンパク質製剤に付加することで、PEGに対する抗体産生が知られるようになり、実際、PEG化製剤において、抗PEG抗体が治療効果が低下させることが報告されている。本研究は抗PEG抗体の産生を低減する新たなPEG化手法を提案し、実践し、特許申請を行った。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2021 2018

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] ユトレヒト大学(オランダ)2018

    • Year and Date
      2018-11-15
    • Related Report
      2021 Annual Research Report
  • [Journal Article] 分子プローブ開発の視点から見出されるポリエチレングリコール(PEG)における免疫応答2021

    • Author(s)
      白石貢一
    • Journal Title

      JSMI Report

      Volume: 14 Pages: 10-16

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Presentation] Wavering PEGs toward specific antibodies2021

    • Author(s)
      Koichi Shiraishi
    • Organizer
      The 43rd JSB and 8th ABMC
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 生体親和性高分子が誘導する特異的相互作用の解明2021

    • Author(s)
      白石貢一
    • Organizer
      第15回日本分子イメージング学会
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] PEG修飾タンパク質若しくはPEG修飾疎水性物質、又はその製造方法2021

    • Inventor(s)
      白石貢一
    • Industrial Property Rights Holder
      白石貢一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-073670
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] PEG修飾タンパク質若しくはPEG修飾疎水性物質、又はその製造方法2021

    • Inventor(s)
      白石貢一
    • Industrial Property Rights Holder
      学校法人慈恵大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Research-status Report

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Published: 2018-01-25   Modified: 2023-01-30  

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