| Project/Area Number |
12670651
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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 |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
TOYO-OKA Teruhiko (2001) Health Service Centre, The University of Tokyo, Professor of Medicine, 保健管理センター, 教授 (00146151)
申 偉秀 (2000) 東京大学, 保健管理センター, 助手 (10211971)
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| Co-Investigator(Kenkyū-buntansha) |
SHIN Wee soo Health Service Centre, The University of Tokyo, Research Associate, 保健管理センター, 助手 (10211971)
豊岡 照彦 東京大学, 医学部・保健管理センター, 教授・所長 (00146151)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Gene therapy / Dilated cardiomyopathy / δ-Sarcoglycan / rAAV vector / Sarcolemma / Hemodynamics / Prognosis / gene delivery / cardiomyopathy / δ-sarcoglycan / AAV / liposome / athelocollagen |
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| Research Abstract |
At the end-stage of advanced heart failure, cardiac transplantation is a finally available treatment. In the present study, authors have addressed the development of new strategy using gene therapy, based on our preceding studies, employing TO-2 strain hamsters as human DCM model. We prepared reporter gene (Lac Z) or full-length δ-sargoglycan (SG) gene, both of which were driven by CMV promoter and intramurally administered to the apex of the animals under open-chest surgery. The transcript and transgene analyzed by Northern blotting and Western blotting, respectively, revealed both expressions at 10 to 40 weeks later, indicating the appreciable and long-lasting effect of the rAAV vector. Cell-exclusion analysis of Evans blue staining and δ-SG immunostaining denoted that cardiomyocytes after the efficient expression of δ-SG protein demonstrated normalized cell-permeability. Physiological indices measured in vivo by echocardiography and cardiac catheterization also indicated an improved cardiac performances. Finally, Kaplan-Meier's analysis of the animals distinctly certified an improved survival rate in a group cotransfected by Lac Z and δ-SG gene, compared with another group treated by Lac Z alone. These data have provided the first evidence for the effective gene therapy of advanced heart failure and are expected to be applicable for the treatment in human cases in future.
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