2022 Fiscal Year Final Research Report
Development of Antibody Drug Delivery System to the Brain
Project/Area Number |
20H04525
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 90120:Biomaterials-related
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Research Institution | The University of Tokyo |
Principal Investigator |
Anraku Yasutaka 東京大学, 大学院工学系研究科(工学部), 特任准教授 (60581585)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 薬剤送達システム / スマートベシクル / 血液脳関門 / 抗体医薬 / 高分子 |
Outline of Final Research Achievements |
We aimed to develop a drug delivery system (DDS) that can penetrate the blood-brain barrier (BBB), infiltrate the brain parenchyma, and exhibit functionality by responding to the brain's internal environment, with the goal of establishing an innovative therapeutic approach for central nervous system (CNS) disorders. We constructed this system based on the self-assembly of high-performance polymer materials with excellent biocompatibility. We also developed a novel smart vesicle (IgG@SV) loaded with antibody therapeutics in the water phase. IgG@SV maintains its structure stably in an environment mimicking blood and undergoes structural dissociation in an environment mimicking the brain after BBB passage, thereby releasing the encapsulated IgG. When we intravenously administered IgG@SV to an Alzheimer's disease mouse model, we confirmed that it can efficiently deliver the IgG into the brain, achieving a 25-fold higher efficiency compared to the administration of IgG alone.
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Free Research Field |
薬剤送達システム
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Academic Significance and Societal Importance of the Research Achievements |
有効な治療法が未確立である脳神経系変性疾患に対して、抗体医薬の脳内送達に基づく分子治療という抜本的解決策を提供するものであり大きな意義を有している。また高分子/材料設計の観点からは、生体適合性・標的指向性・環境応答性という異なる機能を空間的に制御された形で構造内部に配置する仕掛けを創り込むなど、独創性に秀でた生体材料設計プロセスを当該分野にもたらす意義を有している。産業的側面から考えても、細胞レベルでは十分な効果が得られるのに対し、BBB通過できずに治療効果が得られず開発が中断された薬剤が多い中、本システムは開発が中止された薬剤についても再チャレンジの機会が得られる経済的価値は計り知れない。
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