New approaches for intracellular delivery of bioactive proteins

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H04017
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kyoto University
• Principal Investigator: Shiroh Futaki 京都大学, 化学研究所, 教授 (50199402)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 抗体 / 細胞 / 薬物送達

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.

Free Research Field

生体機能化学

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。