| Project/Area Number |
10670774
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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 |
Pediatrics
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| Research Institution | Kurume University |
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Principal Investigator |
KOSAI Ken-ichiro Kurume University School of Medicine, Pediatrics, Assistant Professor, 医学部, 助手 (90258418)
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| Co-Investigator(Kenkyū-buntansha) |
MEKADA Eisuke Kurume University, Institute of Life Science, Professor, 分子生命科学研究所, 教授 (20135742)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Metabolic disease / Gene therapy / Chimeric vector / Liver / Retrovirus / Hepatocyte growth factor / Adenovirus / Gene transduction / HGF / アデノウイルスベクター / レトロウイルスベクター / 肝遺伝子導入法 |
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| Research Abstract |
<Aim>
Aim of this research is the development of novel gene therapy for curing genetic and/or metabolic diseases. A novel chimeric vector capable of high gene transduction and long-term gene expression is developed, and the efficacy Of hepatic gene transduction using this vector is assessed.
<summary of results>
1. Retrovirus-mediated in vivo gene transfer into the replicating liver using recombinant hepatocyte growth factor (HGF) was newly developed. 2. HGF is a key molecule to induce hepatocyte replication, which is necessary for gene transduction. A potent antiapoptotic action of HGF in hepatocyte and its molecular mechanism were newly identified. HGF inhibited Fas-induced and/or complex factors-induced apoptotic signal transduction by induction of Bc1-xl expression in hepatocyte, leading to a potent antiapoptotic action in the liver and inhibition of the onset of fulminant hepatic failure in mice. 3. The relationship among liver regenerationl transcription factor C/EBPα and cell cycle associated proteins was investigated in animals because the understanding of molecular mechanism in liver regeneration is important to achieve efficient gene transduction. The change in expression of these molecules in dependence on the age affected the degree of liver regeneration. 4. A simple and feasible method to construct high titer retroviral vector was developed. 5. Adenoviral vector expressing HGF was constructed and its function was tested.6. Aden/retro-chimeric vector, which was adenovirus expressing retroviral coding sequences, was constructed.
<Future plan and prospect>
<Future plan and prospect>
<Future plan and prospect>
The efficiency and the availability Of this chimeric vector and in the hepatic gene transduction will be carefully investigated in the mouse model of genetic and/or metabolic disease such as hemophilia B.
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