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2023 Fiscal Year Final Research Report

Basic research on development of novel therapeutic products for hemophilia A and thrombotic disorders based on the regulation of factor VIII function in the blood coagulation

Research Project

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Project/Area Number 21K07804
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionNara Medical University

Principal Investigator

Nogami Keiji  奈良県立医科大学, 医学部, 教授 (50326328)

Project Period (FY) 2021-04-01 – 2024-03-31
Keywords第VIII因子 / トロンビン / 第IX因子 / 凝固 / 遺伝子組み換え型 / インヒビター / ノックアウトマウス
Outline of Final Research Achievements

In coagulation factor Ⅷ (FⅧ), which is involved in both bleeding and hemostasis in blood coagulation, we identified a thrombin-binding region that regulates activation by FⅧ cleavage and successfully produced a highly active gain-of-function FⅧ protein focusing on this binding region. We identified a novel FⅨa-binding region on FⅧa in the intrinsic tenase complex, and also generated a high active-sustained FVIII protein focusing on the FVIIIa-FIXa interaction. In addition, an inhibitor-binding-avoiding FⅧ protein was also generated.

Free Research Field

止血血栓学

Academic Significance and Societal Importance of the Research Achievements

血液凝固第Ⅷ因子は出血と血栓の相反する病態に関わる重要な凝固因子であるため、今回の研究における第Ⅷ因子に関連した機能構造および他の凝固因子との相互反応の解明が、凝固や血栓形成機序の解明と血友病A患者への新規第Ⅷ因子治療製剤開発への応用、また第Ⅷ因子の生体内機能を制御する抗血栓および抗凝固薬の開発に将来的に繋がり、止血血栓学の発展並びに医療に貢献できるものと思われる。

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Published: 2025-01-30  

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