| Project/Area Number |
11670779
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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 | Osaka City University |
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Principal Investigator |
MATSUOKA Osamu Osaka City University Medical School, Lecturer, 大学院・医学研究科, 講師 (20117972)
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| Co-Investigator(Kenkyū-buntansha) |
AYATA Minoru Osaka City University Medical School, Research associate, 大学院・医学研究科, 助手 (90222702)
OGURA Hisashi Osaka City University Medical School, Professor, 大学院・医学研究科, 教授 (10115222)
HATTORI Hideshi Osaka City University Medical School, Lecturer, 大学院・医学研究科, 講師 (70244639)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Subacute sclerosing panencephalitis / SSPE virus / Gene therapy |
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| Research Abstract |
Subacute sclerosing panencephalitis (SSPE) is a progressive and degenerative disease of the central nervous system of children and adolescents. It is caused by slow virus infection of measles virus which invaded at acute measles. SSPE is rare but lethal ; no curable treatment has not yet been established. We planed to kill SSPE virus-infected cells selectively transfected with plasmid containing E. coli-derived cytosine deaminase (CD) gene by treating with 5-fluorocytosine (5-FC) as a prodrug.
First of all, we tried to develop a way of selective transfection of GFP (green fluorescent protein) gene-containing plasmid DNA, using cationic lipids or calcium phosphate precipitation method. In spite of trials under the various conditions, we did not find any conditions for selective transfection to the virus-infected cells. Therefore, a new method is needed to pursue the above issue. It might be possible to utilize measles virus antibody conjugated with plasmid DNA or measles virus minigenome containing CD gene which can express only in measles virus-infected cells. The latter system is now under investigation.
On the other hand, in order to develop assessment system for effect of the gene therapy, pseudovirions prepared from SSPE virus-infected cells by treating with cytochalasin D were infected intracerebrally in young hamsters. The SSPE virus Osaka-1, -2, and -3 strains showed strong neurovirulence ; all hamsters became ill by inoculation of less than one hundred plaque forming units from four to sixteen days and most died within 1-2 weeks after onset. Therefore, estimation of the gene therapy was possible to work.
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