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KAKEN_15K12545seika.pdf
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Download
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膜透過促進ペプチドとpH応答性低分子抗体を組み合わせた細胞選択的膜透過技術の開発
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マク トウカ ソクシン ペプチド ト pH オウトウセイ テイブンシ コウタイ オ クミアワセタ サイボウ センタクテキ マク トウカ ギジュツ ノ カイハツ
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Maku toka sokushin pepuchido to pH otosei teibunshi kotai o kumiawaseta saibo sentakuteki maku toka gijutsu no kaihatsu
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Fusogenic peptides combined with pH-dependent antibody fragments for cell-specific intracellular drug delivery
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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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新倉, 啓介
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ニイクラ, ケイスケ
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Niikura, Keisuke
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慶應義塾大学・理工学研究科・大学院生
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Research team member
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須藤, 慧
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スドウ, ケイ
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Sudo, Kei
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慶應義塾大学・理工学研究科・大学院生
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Research team member
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岩城, 洸汰
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イワキ, コウタ
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Iwaki, Kota
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慶應義塾大学・理工学部・学部生
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Research team member
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2017
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科学研究費補助金研究成果報告書
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2016
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受精や胎盤形成における細胞膜融合に関与するタンパク質の部分ペプチドが, 様々な高分子の人為的な膜透過を促進するツールとして利用できる可能性を提唱し, 従来の細胞膜透過性ペプチドによるタンパク質の細胞質送達効率を数十倍向上させることができ, かつ, 免疫原性の懸念がないヒト由来の膜透過促進ペプチドを発見した。また, 我々が開発したPURE mRNAディスプレイ法を用いて, 膜抗原に中性pH(細胞外)で結合し酸性pH(エンドソーム内)で解離するpH応答性の一本鎖抗体の試験管内進化に成功した。膜透過促進ペプチドとpH応答性抗体とを融合することで, バイオ医薬の細胞選択的なデリバリーシステムへの応用が期待できる。
Here we focused on fusogenic peptides (FPs) from proteins involved in membrane fusion (e.g., gamete recognition and fusion, and placental morphogenesis) as a tool for promoting the membrane penetration of biomacromolecules. We identified novel human-derived FPs that possessed strong intracellular uptake activities with potentially low immunogenicity. In addition, we succeeded the directed evolution of a pH-dependent antibody fragments, which binds to an antigen at a neutral pH (extracellular environment) but dissociates from the antigen at an acidic pH (endosomal environment), by using our PURE mRNA display system. Our human-derived FPs that fused with pH-dependent antibodies would be useful for the cell-specific intracellular delivery of therapeutic proteins and nucleic acids.
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研究種目 : 挑戦的萌芽研究
研究期間 : 2015～2016
課題番号 : 15K12545
研究分野 : タンパク質(抗体・ペプチド)の進化工学
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