Cell-free display technologies for development of next-generation therapeutic antibody fragments

2015 Fiscal Year Final Research Report

• Project/Area Number: 25289298
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Biofunction/Bioprocess
• Research Institution: Keio University
• Principal Investigator: DOI NOBUHIDE 慶應義塾大学, 理工学部, 准教授 (50327673)
• Co-Investigator(Kenkyū-buntansha): YANAGAWA HIROSHI 慶應義塾大学, 理工学部, 訪問教授 (40327672)
• Co-Investigator(Renkei-kenkyūsha): MATSUSHIMA KOJI 東京大学, 大学院医学系研究科, 教授 (50222427)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 蛋白質 / 進化 / バイオテクノロジー / がん / 免疫学

Outline of Final Research Achievements

In this study, we have modified cell-free display technologies previously developed in our laboratory and applied them to efficient and rapid selection of next-generation therapeutic antibody fragments with novel function such as high effector function and bispecificity. We obtained following results. (1) We selected a novel Fc receptor-binding peptide using conventional mRNA display. (2) We improved mRNA display of antibody fragments based on PURE system as a cell-free protein synthesis system and successfully applied it to in vitro selection of a novel humanized scFv against GPCR. (3) We established covalent bicistronic DNA display and applied it to directed evolution of Fab fragments with high thermostability and in vitro selection of bispecific diabodies.

Free Research Field

工学