Fusogenic peptides combined with pH-dependent antibody fragments for cell-specific intracellular drug delivery
| Project/Area Number |
15K12545
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Keio University |
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Principal Investigator |
DOI Nobuhide 慶應義塾大学, 理工学部(矢上), 准教授 (50327673)
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| 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
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| 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 / 蛋白質 / 進化 / バイオテクノロジー / 免疫学 / 共焦点顕微鏡 |
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| 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.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Human-derived fusogenic peptides for the intracellular delivery of proteins.2017
Author(s)
Sudo, K., Niikura, K., Iwaki, K., Kohyama, S., Fujiwara, K., Doi, N.
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Journal Title
J. Control. Release
Volume: 255
Pages: 1-11
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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