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KAKEN_25289298seika.pdf
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無細胞ディスプレイ技術による次世代低分子抗体医薬の開発
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ムサイボウ ディスプレイ ギジュツ ニ ヨル ジセダイ テイブンシ コウタイ イヤク ノ カイハツ
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Musaibo disupurei gijutsu ni yoru jisedai teibunshi kotai iyaku no kaihatsu
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Cell-free display technologies for development of next-generation therapeutic antibody fragments
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土居, 信英
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ドイ, ノブヒデ
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Doi, Nobuhide
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慶應義塾大学・理工学部・准教授
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Research team head
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科研費研究者番号 : 50327673
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柳川, 弘志
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ヤナガワ, ヒロシ
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Yanagawa, Hiroshi
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慶應義塾大学・理工学部・訪問教授
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Research team member
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科研費研究者番号 : 40327672
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松島, 綱治
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マツシマ, コウジ
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Matsushima, Koji
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東京大学・大学院医学系研究科・教授
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Research team member
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科研費研究者番号 : 50222427
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2016
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科学研究費補助金研究成果報告書
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2015
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本研究では, 以前に当研究室で開発された無細胞ディスプレイ技術を応用・発展させることにより, 高いエフェクター機能や二重特異性などの新たな機能を付与した次世代低分子抗体医薬を簡便かつ迅速に開発できるシステムを確立することを目指し, 以下の成果を得た。(1) 従来のmRNAディスプレイ法を用いて, 新規のFc受容体結合ペプチドを同定した。(2) 無細胞翻訳系としてPUREシステムを用いたmRNAディスプレイ法を確立し, 抗GPCRヒト一本鎖抗体の試験管内選択に成功した。(3) 共有結合型DNAディスプレイ法を確立し, 耐熱性Fab抗体の試験管内進化と二重特異性Diabody抗体の試験管内選択に応用した。
In this study, we have modified cell-free display technologies previously developed in our laboratory and applied them to efficient and rapid selection of next-generation therapeutic antibody fragments with novel function such as high effector function and bispecificity. We obtained following results. (1) We selected a novel Fc receptor-binding peptide using conventional mRNA display. (2) We improved mRNA display of antibody fragments based on PURE system as a cell-free protein synthesis system and successfully applied it to in vitro selection of a novel humanized scFv against GPCR. (3) We established covalent bicistronic DNA display and applied it to directed evolution of Fab fragments with high thermostability and in vitro selection of bispecific diabodies.
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研究種目 : 基盤研究(B)(一般)
研究期間 : 2013～2015
課題番号 : 25289298
研究分野 : 工学
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