Fusogenic peptides combined with pH-dependent antibody fragments for cell-specific intracellular drug delivery

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K12545
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Keio University
• Principal Investigator: DOI Nobuhide 慶應義塾大学, 理工学部(矢上), 准教授 (50327673)
• Research Collaborator: NIIKURA Keisuke 慶應義塾大学, 理工学研究科, 大学院生 ; SUDO Kei 慶應義塾大学, 理工学研究科, 大学院生 ; IWAKI Kouta 慶應義塾大学, 理工学部, 学部生
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 膜融合ペプチド / 免疫原性 / mRNAディスプレイ / pH応答性一本鎖抗体 / 試験管内進化 / 細胞内抗体医薬 / 中分子医薬 / ドラッグデリバリーシステム

Outline of Final Research Achievements

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.

Free Research Field

タンパク質（抗体・ペプチド）の進化工学