| Project/Area Number |
17590043
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
MAITANI Yoshie Hoshi University, Medicinal chemistry, Professor, 医薬品化学研究所, 教授 (10231581)
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| Co-Investigator(Kenkyū-buntansha) |
TOMA Kazunori The Noguchi Institute, Researcher, 研究部, 研究員 (30311260)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | gene vector / cell penetrating peptide / liposome / non-endocytosis / gene therapy / oligo-arginine |
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| Research Abstract |
The success of gene therapy is depended on gene delivery system using non-viral vector with high transfection efficiency and less toxicity.
In this study, we synthesized oligoarginine conjugated-lipid (Arg), developed two kinds of Arg based particles; Arg conjugated-lipid complex with plasmid DNA (Arg/DNA), and Arg conjugated-lipid coating plasmid DNA compacted with protamine (ArgPD), and optimized the charge ratio (+/-)of vector and plasmid DNA in human cervical carcinoma HeLa cells and tumor via intratumoral transfection.
The transfection efficiencies in HeLa cells resulted in efficient DNA transfer when arginine 10 conjugated-lipid vector (Arg10) effectively transfected gene, especially positive-charged Arg10PD. In tumor transfection by intratumoral injection, negative-charged particles showed higher transfection efficiency compared with positive-charged ones. In Arg4PD and Arg10PD with similar negative-charged, Arg4PD showed 13-fold higher transfection efficiency than Arg10PD. This suggested that shorter oligoarginine length is effective for intratumoral gene delivery. Arg4 conjugated-lipid has a potential of non-viral vector for intratumoral injection. The mechanism of gene transfer by Arg 4 and Arg10 vectors was different. The former was penetrated via endocytosis and the latter was via macropinocytosis.
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