| Project/Area Number |
17H06109
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Yokota Takanori 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (90231688)
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| Co-Investigator(Kenkyū-buntansha) |
永田 哲也 東京医科歯科大学, 大学院医歯学総合研究科, プロジェクト准教授 (50362976)
宮田 完二郎 東京大学, 大学院工学系研究科(工学部), 准教授 (50436523)
津本 浩平 東京大学, 大学院工学系研究科(工学部), 教授 (90271866)
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| Project Period (FY) |
2017-05-31 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥173,030,000 (Direct Cost: ¥133,100,000、Indirect Cost: ¥39,930,000)
Fiscal Year 2021: ¥34,580,000 (Direct Cost: ¥26,600,000、Indirect Cost: ¥7,980,000)
Fiscal Year 2020: ¥47,450,000 (Direct Cost: ¥36,500,000、Indirect Cost: ¥10,950,000)
Fiscal Year 2019: ¥29,380,000 (Direct Cost: ¥22,600,000、Indirect Cost: ¥6,780,000)
Fiscal Year 2018: ¥29,380,000 (Direct Cost: ¥22,600,000、Indirect Cost: ¥6,780,000)
Fiscal Year 2017: ¥32,240,000 (Direct Cost: ¥24,800,000、Indirect Cost: ¥7,440,000)
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| Keywords | 血液脳関門 / グルコーストランスポーター / トランスフェリン受容体 / 抗体工学 / 神経変性疾患 / ヘテロ核酸 / LDL受容体 / トランスフェリンレセプター / Glucose transporter / 核酸医薬 / リサイクリング / トランスフェリン / Glut 1/4 / Glut / 核酸 / バイオテクノロジー |
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| Outline of Final Research Achievements |
Nucleic acid therapeutics are attracting attention as next generation pharmaceuticals following antibody drugs. Their development is particularly remarkable in neurological intractable diseases. However, nucleic acid therapeutics do not migrate into the brain by systemic administration and must be required intrathecally. Therefore, antibodies were produced against glucose transporter (Glut)1, Glut4, and transferrin receptors that are highly expressed and internalized in the blood-brain barrier (BBB). In addition to confirming binding to the antigens, the antibodies obtained were evaluated for binding activity using cells, and it was confirmed that they recognize the target receptors. In addition, a new ligand that crosses the LDL receptor-related BBB was obtained, and its gene suppression effect on the central nervous system was successfully confirmed by systemic administration.
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| Academic Significance and Societal Importance of the Research Achievements |
計算科学を活用しながらGlut1/4の細胞外に位置する領域を、新規方法で作製した融合タンパク質を設計し、その融合タンパク質を活用しながらの抗体取得を行っている。生体内において重要な役割を果たしているケースが多い多重膜貫通タンパク質に対する機能性抗体の取得が効率的に行えるようになると考えられ、極めて大きな波及効果が期待される。また全身投与でリガンド結合ヘテロ核酸の脳内移行および遺伝子抑制効果を確認しており、全身投与での中枢神経疾患への治療に一歩近づいたと考えられる。
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| Assessment Rating |
Verification Result (Rating)
A+
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Assessment Rating |
Result (Rating)
B: Progress in the research is delayed than the initial goal. Further efforts are necessary.
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