Project/Area Number |
12557207
|
Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 展開研究 |
Research Field |
Physical pharmacy
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Research Institution | Nagoya City University |
Principal Investigator |
NAKANISHI Mamoru Nagoya City University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (90090472)
|
Co-Investigator(Kenkyū-buntansha) |
HANDA Tetsuro Kyoto University, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (00025719)
HIRASHIMA Naohide Nagoya City University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究科, 助教授 (10192296)
OHWADA Tomohiko The University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学系研究科, 教授 (20177025)
TOKUYAMA Satoru NOF Corporation, Researcher, 研究員
OKU Naoto University of Shizuoka, Professor, 薬学部, 教授 (10167322)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥4,100,000 (Direct Cost: ¥4,100,000)
|
Keywords | Gene transfection / Cationic cholesterol / Cationic liposome / Non-viral vector / Microscopy / Endocytosis / Biosurfactant / Gene therapy / 非ウイルスベクター / 膜融合 |
Research Abstract |
We will demonstrate interesting cationic liposomes with novel cationic cholesterol derivatives, a new strategy in gene transfection developed by our group and the presently accepted molecular mechanism of gene transfection. Use of confocal laser scanning microscopy and atomic force microscopy in elucidating the molecular mechanism of gene transfection by cationic liposomes is also showed using examples from our own work. As delineated, both the confocal laser scanning microscopic and the atomic force microscopic results advocate for the involvement of the sequential three steps in gene transfection mediated by the cationic liposomes: endocytotic internalization of the lipoplexes into the target cells, endosome-lysosome fusion whereby the DNA gets released from the liposomes and moves towards the nucleus of the target cells and microtubule organization apparently involved in trafficking the transfected foreign genes to lysosomes. Furthermore, our experiment also shows couple of important strategies in gene transfection namely, use of liposomes made from biosurfactans and harnessing efficient gene transfection by activating the membrane-bound receptor molecules.
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