Designing PEGylated proteins for reducing PEG-specific immunogenicity

2021 Fiscal Year Final Research Report

• Project/Area Number: 17KK0105
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Jikei 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
• Keywords: ポリエチレングリコール / 免疫原性 / 抗PEG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.

Free Research Field

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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。