New approaches for intracellular delivery of bioactive proteins
| Project/Area Number |
18H04017
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 47:Pharmaceutical sciences and related fields
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| Research Institution | Kyoto University |
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Principal Investigator |
Shiroh Futaki 京都大学, 化学研究所, 教授 (50199402)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2020: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2019: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2018: ¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
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| Keywords | 抗体 / 細胞 / 薬物送達 / 細胞内送達 / エンドソーム不安定化 / エンドソーム脱出 / バイオ高分子 / エンドサイトーシス / ペプチド |
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| Outline of Final Research Achievements |
Considerable research efforts have been dedicated to the delivery of antibodies and other proteins having therapeutic potentials to cell interiors. However, there were certain rooms for improvement in the efficacy. Our laboratory developed a delivery peptide L17E capable of delivering antibodies into cells. In this study, we made structure-activity-relationship analyses of L17E to improve the efficacy. New delivery peptides were developed having ability of stimulating cellular uptake. Eventually, peptides having more than 10-fold delivery efficacy compared with L17E were developed. We found a potent macropinocytosis-inducing peptide SN21 and the analog P4A. Successful intracellular delivery of antibodies and other biomacromolecules was attained using the conjugates of these peptides with the LK15 membrane-lytic peptide.
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| Academic Significance and Societal Importance of the Research Achievements |
更なる導入効率の向上や導入法の検討により、疾病に関連する細胞機能の異常とその修復に関する糸口を明らかにする新しい手法の開発が期待される。さらにこの原理に従い、新しい治療法に結びつく可能性もある。また、効率的な細胞内送達を可能にする細胞の取込機序に関しての知見も得られた。
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Report
(5 results)
Research Products
(39 results)
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[Journal Article] Discovery of a Macropinocytosis‐Inducing Peptide Potentiated by Medium‐Mediated Intramolecular Disulfide Formation2021
Author(s)
Jan Vincent V. Arafiles, Hisaaki Hirose, Yusuke Hirai, Masashi Kuriyama, Maxwell M. Sakyiamah, Wataru Nomura, Kazuhiro Sonomura, Miki Imanishi, Akira Otaka, Hirokazu Tamamura, Shiroh Futaki
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Journal Title
Angewandte Chemie, International Edition
Volume: 60
Issue: 21
Pages: 2-11
DOI
Related Report
Peer Reviewed / Open Access
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