Development of BBB-passable polymeric micelles for sustained expression of neurotrophic factors in the brain

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19888
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• 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)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 薬剤送達システム / 血液脳関門 / mRNA / 高分子ミセル / 静電相互作用

Outline of Final Research Achievements

Regeneration of brain function using neurotrophic factors derived from the brain has garnered attention as a treatment for refractory central nervous system (CNS) disorders. However, delivering an adequate quantity of proteins to the brain via systemic administration poses a significant challenge due to the presence of the blood-brain barrier (BBB), a biological barrier that severely restricts substance transport into the brain. In this research project, we successfully utilized highly efficient polymeric micelles capable of traversing the BBB to deliver mRNA with remarkably low in vivo stability to the localized region in the body through systemic administration, thereby facilitating sustained production of a substantial amount of proteins. This accomplishment holds promise for the development of a completely novel treatment approach: an innovative CNS therapy based on the regeneration of brain function.

Free Research Field

薬剤送達システム

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、脳内で所望のタンパク質を産生することによる分子治療という抜本的解決策を提供するものであり極めて大きな意義を有している。これらの方法論は、CNS疾患に留まらずアミノ酸代謝異常など広範な疾患治療に大きく貢献することが確信される。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。