| Project/Area Number |
16590114
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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 |
Medical pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
ARIMA Hidetoshi Kumamoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (50260964)
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| Co-Investigator(Kenkyū-buntansha) |
KAI Hirofumi Kumamoto University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・医学薬学研究部, 教授 (30194658)
HIRAYAMA Fumitoshi Kumamoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 助教授 (90094036)
UEKAMA Kaneto Kumamoto University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・医学薬学研究部, 教授 (90040328)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | siRNA / cyclodextrin / dendrimer / conjugate / carrier / delivery / multifunctionalization / RNAi効果 / Lipofectamine 2000 |
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| Research Abstract |
RNA interference (RNAi) is the mechanism of gene silencing-mediated messenger RNA degradation by small interference RNA (siRNA), which becomes a powerful tool for genetic analysis and novel gene therapy. However, one of the major obstacles for siRNA delivery is the difficulty to cross the biological membrane due to its hydrophilicity and high molecular weight. We evaluated the potential use of the starburst polyamidoamine dendrimer (generation 3) conjugate with α-cyclodextrin having an average degree of substitution of 2.4 (α-CDE conjugate) as a siRNA carrier for RNAi. The ternary complex composed of pGL2 control vector (pDNA)/pGL2 siRNA/α-CDE conjugate showed higher pGL2 siRNA sequence-specific gene silencing effects without off-target effects than those of commercial transfection reagents such as Lipofectamine^<TM>2000 (LP), TransFast^<TM> (TF) and Lipofectin^<TM> (LF). In the binary complex (siRNA/carrier) system, the similar inhibitory effects of α-CDE conjugate were observed without cytotoxicity. These superior RNAi effects of α-CDE conjugate to the other commercial transfection reagents could be attributed to stable complex formation and cytoplasmic distribution of siRNA after transfection. These results suggest that α-CDE conjugate has the potential to be a novel carrier for siRNA.
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