Development of a two functional super catalytic antibody for the treatment of dementia

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37010:Bio-related chemistry
• Research Institution: Institute of Systems, Information Technologies and Nanotechnologies
• Principal Investigator: Uda Taizo 公益財団法人九州先端科学技術研究所, マテリアルズ・オープン・ラボ, 特別研究員 (20232837)
• Co-Investigator(Kenkyū-buntansha): 田口 博明 鈴鹿医療科学大学, 薬学部, 教授 (20549068) ; 一二三 恵美 大分大学, 全学研究推進機構, 教授 (90254606)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: beta-amyloid / Tau protein / catalytic antibody / two functional

Outline of Final Research Achievements

This study is concerned with simultaneous decomposition of beta-amyloid (A-beta) and Tau protein (Tau). Firstly, we started to gain catalytic antibodies that can degrade A-beta and Tau. Safter that, genetically engineered scFv-like molecules in which their variable region portions were made by combining two molecules of the variable regions by a linker. Then, the FRET-antigens of A-beta and Tau were synthesized, and the degradation activity (peptidase activity) for these synthetic substrates was examined using the scFv-like molecule described above. As a result, it was found that this scFv-like molecule decomposes both antigens at the same time, achieving the intended purpose. Furthermore, when a mutation that deletes Pro95, which is present at the 95th position of this scFv-like molecule, was introduced, its enzymatic activity was improved by about 4 to 5 times, and the aggregation of beta-amyloid was completely blocked. This was a result that exceeded the intended plan.

Free Research Field

生物工学、バイオ関連化学

Academic Significance and Societal Importance of the Research Achievements

本研究は、複数の抗原を同時に分解できる高性能分子を人為的に作製することを示した点において学術的に高く評価される。また、この新型機能を有する分子薬はこれまで世間には存在しなかったために将来の新型医薬品開発へと繋げる意味合いにおいて社会的に価値がある、と考えられる。