| Project/Area Number |
25000006
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| Research Category |
Grant-in-Aid for Specially Promoted Research
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
Chemistry
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| Research Institution | Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine (2016-2017)
The University of Tokyo (2013-2015) |
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Principal Investigator |
KATAOKA Kazunori 公益財団法人川崎市産業振興財団, ナノ医療イノベーションセンター, センター長 (00130245)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOTA Takanori 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (90231688)
ITAKA Keiji 東京医科歯科大学, 生体材料工学研究所, 教授 (60292926)
TSUMOTO Kouhei 東京大学, 大学院工学系研究科, 教授 (90271866)
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| Co-Investigator(Renkei-kenkyūsha) |
OSADA Kensuke 東京大学, 大学院工学系研究科, 特任准教授 (10396947)
Ishii Takehiko 東京大学, 大学院工学系研究科, 特任准教授 (80415075)
NISHIYAMA Nobuhiro 東京工業大学, 科学技術創成研究院化学生命科学研究所, 教授 (10372385)
MIYATA Kanjiro 東京大学, 大学院工学系研究科, 准教授 (50436523)
ANRAKU Yasutaka 東京大学, 大学院工学系研究科, 特任助教 (60581585)
MATSUMOTO Yu 東京大学, 大学院医学系研究科, 特任講師 (80548553)
UCHIDA Satoshi 東京大学, 大学院工学系研究科, 特任助教 (20710726)
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| Project Period (FY) |
2013 – 2017
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥555,880,000 (Direct Cost: ¥427,600,000、Indirect Cost: ¥128,280,000)
Fiscal Year 2017: ¥103,220,000 (Direct Cost: ¥79,400,000、Indirect Cost: ¥23,820,000)
Fiscal Year 2016: ¥82,290,000 (Direct Cost: ¥63,300,000、Indirect Cost: ¥18,990,000)
Fiscal Year 2015: ¥84,240,000 (Direct Cost: ¥64,800,000、Indirect Cost: ¥19,440,000)
Fiscal Year 2014: ¥98,410,000 (Direct Cost: ¥75,700,000、Indirect Cost: ¥22,710,000)
Fiscal Year 2013: ¥187,720,000 (Direct Cost: ¥144,400,000、Indirect Cost: ¥43,320,000)
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| Keywords | ブロック共重合体 / 高分子ミセル / ポリエチレングリコール / ポリアミノ酸 / 薬物送達システム / 血液脳関門（BBB） / siRNA / アンチセンス核酸 / メッセンジャーRNA / プラスミドDNA / 抗体医薬 / 遺伝子治療 / 脳-血液関門 / アルツハイマー病 / グルコーストランスポーター / 脳一血液関門 / 脳―血液関門 / グルコーストランスポ-ター |
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| Outline of Final Research Achievements |
Since the brain is protected by a highly developed biological barrier, delivery of the drug is extremely difficult. In this research, we developed a drug delivery system (DDS) of virus size (<50 nm) that overcomes such a robust biological barrier, penetrates into the brain, and delivers nucleic acid drugs to target cells such as neurons. Here, DDS was constructed on the basis of self-assembly (polymeric micelle formation) of biocompatible block copolymers. In the vascular system of the brain, drug penetration from the vascular lumen to the brain parenchyma is markedly restricted (blood-brain barrier: BBB), since the junction between the endothelial cells is extremely tight. Therefore, a glucose-bound polymeric micelle targeting glucose transporter 1 (GLUT 1), which is localized in the vascular lumen side of cerebral vascular endothelial cells, was constructed. There was observed a significant accumulation of
… More
the micelles in the brain by crossing the BBB at about 60 times the efficiency of the existing DDS by the precise molecular design of the micelles, including size and surface glucose density, and the use of active migration of GLUT1 from the vascular luminal side to the brain parenchyma side, synchronizing with a change in the blood glucose concentration. Eventually, siRNA was successfully delivered into the brain by the glucose-conjugated micelles, and the expression of enzymes involved in amyloid β (Aβ) production was reduced to about 50%. Furthermore, mRNA, known to be fragile in biological milieu, was remarkably stabilized by micelle loading, and local intracerebroventricular administration of the micelles loaded with mRNA encoding single chain antibody targeting Aβ attained significant reduction of the amount of Aβ in mouse brain. In this way, wide on/off control of disease-related genes becomes feasible, opening a new avenue to solve long-standing problems in the treatment of neurodegenerative diseases. Less
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| Assessment Rating |
Verification Result (Rating)
A
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Assessment Rating |
Result (Rating)
A: Progress in the research is steadily towards the initial goal. Expected research results are expected.
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