Development of bi-specific nanobody capable of thrapeutic application

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19493
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Tohoku University
• Principal Investigator: Horiuchi Hisanori 東北大学, 加齢医学研究所, 教授 (90291426)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: ナノボディ / 血友病 / 低比重リポ蛋白質

Outline of Final Research Achievements

Immunoglobulin of camel family is a single strand peptide. Its variable region is called ‘nanobody’. LDL is endocytosed via LDL receptor and degraded in lysosomes. Administration of a bi-specific nanobody that contains anti-LDL nanobody and anti HMGB-1, an alarmin, nanobody would induce HMGB-1 degradation through LDL receptor inside cells. It would become a novel type of treatment of a cytokine storm. On the other hand, hemophilia A is caused by genetic defect of a coagulation factor VIII (FVIII). The function of FVIII is a scaffold for FIXa and FX. Thus, bispecific nanobody for FIXa and FX would become a drug for hemophilia. In the study, we have established and improved a method to make a specific nanobody from a nanobody library. Then, we have tried to make nanobodies against proteins described above. We will further advance the research and will evaluate the effect of these bispecific nanobodies in a body.

Free Research Field

生化学、内科

Academic Significance and Societal Importance of the Research Achievements

ナノボディは分子生物学的手法によって作成できるので、モノクローナル抗体の作成に比べて、作成は比較的容易であり、今後大きな発展が期待できよう。多くの医薬品が作成されると期待される。個体レベルで有効なバイスペシフィックナノボディを作成できれば、抗炎症や、血用病などを含め、多くの医療分野に革新的な進歩をもたらすだろう。