| Project/Area Number |
08557082
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Nagoya university |
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Principal Investigator |
YOSHIDA Jun School of Medicine, Nagoya university Professor, 医学部, 教授 (40158449)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNO Masaaki School of Medicine, Research Assistant, 医学部, 助手 (70283439)
SEO Hisao Research Institute of Environmental Medicine, Professor, 環境医学研究所, 教授 (40135380)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1996: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | LIPOSOME / CLINICAL RESEARCH / BRAIN TUMOR / GENE-REGULATION / DRUG / 遺伝子 / 安全性 / 純度検定 |
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| Research Abstract |
We have promoted the development of cationic liposomes for human gene therapy against malignant tumors. A lot of kinds of cationic liposomes were made and performed the evaluation of the transduction efficiency. As a result, we confirmed TMAG-liposomes and DDAB-liposomes were very useful to transfer the foreign genes to. The former is a cationic liposome composed in a molar ratio of 1 : 2 : 2 as N- (alpha-trimethylammonioacetyl)- didodecyl-D-glutamate chloride (TMAG) : dilauroyl phosphatidylcholine (DLPC) : diolenyl phosphatidyl ethanolamine (DOPE) . The latter is a cationic liposome composed in a molar ratio of 1 : 2 : 2 or 1 : 1 : 1 as dimethyl-dioctadecylammonium bromide (DDAB) : dilauroyl phosphatidylcholine (DLPC) : dioleoyl phosphatidylethanolamine (DOPE) . We also found to be able to give these liposomes cell - or tissue-specificity by conjugating with a monoclonal antibody or asialoglycoprotein. In contrast, we also confinned that adeno-associated virus (AAV) vector-associated liposomes were more effective for in vitro gene transfer to human glioma cells than are liposomes containing plasmid DNA.Using vector-associated liposomes increased transduction efficiency more than 1O-fold compared to liposomes containing plasmid DNA and more than 6-fold compared to AAV alone. From these results, AAV vector-associated liposomes appear to be good candidates for in vivo gene delivery to malignant tumors. Furthermore, we investigated the effectiveness of the combination of cationic liposomes containing the plasmids driven by heat shock protein promoter and small iron ball magnetite, and induced remarkable antitumor effect.
On the other hand, we established human gene therapy vector producing facility in Nagoya University Hospital and confirmed that liposomes for clinical research could prepared in the facility.
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