| Project/Area Number |
14380391
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KATAOKA Kazunori The University of Tokyo, School of Engineering, Professor, 大学院・工学系研究科, 教授 (00130245)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASAKI Yuichi The University of Tokyo, School of Engineering, Assistant Professor, 大学院・工学系研究科, 講師 (00322678)
SHIBA Mariko Nationa Cardiovascular Center, Research Institute, laboratory Chief, 室長 (70271575)
原田 敦史 東京大学, 大学院・工学研究科, 助手 (50302774)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2002: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | polymeric micelle / gene delivery / block copolymer / nanocapsul / DNA / Biocompartibility / polyethylene glycol |
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| Research Abstract |
We investigated intelligent polymeric micelle nanocapsuls formed through the complexation of block copolymers and plasmid DNA, as non-viral gene vectors. The block copolymers are composed of a hydrophilic polyethylene glycol (PEG) and positively charged polyamino acids. To enhance the efficacy of gene expression, in particular in vivo system, novel strategy for the active targeting which can be realized through the introduction of pilot moiety on the surface of polymeric micelles should be established. For this purpose, we developed a synthetic scheme for block copolymers to employ multi-intelligent functions, i.e., prolonged circulation inside the blood vessel tubes, enhanced permeation from the blood vessel tubes toward tissues, selective transfection to the targeting tissues, enhanced cellular uptake due to the pilot moieties, smooth release of plasmid DNA inside the cells, etc.
In addition, a wide adaptability for the length of plasmid DNA and also the environmental responsibility of the polymeric micelle nanocapsuls that should be essential to overcome the efficacy of viral gene delivery system were experimentally conformed. This system exhibits highly transfection potency not only in in vitro system but also in preliminary in vivo experiments. This multi-intelligent polymeric micelle nanocapsuls can be treated as an universal platform of non-viral gene delivery system.
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