| 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 |
|
|---|
| Project Period (FY) |
2021-07-09 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
|
|---|
| Keywords | ナノボディ / 血友病 / 低比重リポ蛋白質 / nanobody / hemophilia / low density lipoprotein / HMGB1 |
|---|
| Outline of Research at the Start |
ラクダ科動物の免疫グロブリンは重鎖のみよりなる一本鎖であり、その抗原認識部位は小 型でナノボディと呼ばれる。我々は発現クローニングによってモノクローナルナノボディを迅速かつ比較的簡便に作成する行程を構築し得た。本研究では、特定物質のリソソームにおける分解を誘導するナノボディを含むバイスペシフィックナノボディ、蛋白質複合体形成を利用した生体反応の活性化を誘導する、バイスペシフィックナノボディを用いた遺伝子治療法の開発を行う。両タイプのナノボディとも、一旦成功すれば応用範囲は極めて大きく、医療を変革させる ポテンシャルを持つ。
|
| 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.
|
| 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。
|
