Gene therapy for Crigler-Najjar syndrome type l by using a model animal
| Project/Area Number |
08671202
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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 |
内分泌・代謝学
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| Research Institution | SCIENCE UNIVERSITY OF TOKYO,Faculty of Science & Technology (1997)
Aichi Cancer Center Research Institute (1996) |
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Principal Investigator |
KOIWAI Osamu Science University of Tokyo Dep.of Applied Biological Science Asistant prof., 理工・応用生物, 助教授 (50132923)
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| Co-Investigator(Kenkyū-buntansha) |
AONO Sachiko Aichi Prefectural Colony Chief.Researcher, 発達障害研究所・周生期, 主任研究員 (20231780)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Gene therapy / Jaundice / Bilirubin / Glucuronic acid / Baculovirus / Liver / Gene expression / グルクロン酸転移酵素 / クリグラーナジャー症候群 / がんラット |
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| Research Abstract |
Crigler-Najjar syndrome typel is a hereditary disease which is caused by the defect of bilirubin UDP-glucuronosyl transferase (UDPGT) gene. We have tried the gene therapy for the Crigler-Najjar syndrome typel using a model animal, Gunn rat. Recently, it was reported that Baclrovirus specifically infects human liver cells. To apply the baculovirus system to the gene therapy, we firstly constructed the expression vector of bilirubin UDPGT cDNA and transfected to Sf9 insectcells.We could detect the bilirubin UDPGT band expressed in Sf9 cells by Western blotting. We cloud also detect high bilirubin UDPGT activity by the method of thin layr chromatography. Next we constructed a expression vector having alpha1-antitrypsin promoter which specifically works in liver cells. Now we are transfecting the expression vector to HepG2 or Huh7 cells to conferm the availability of the vector in liver cells. We have analyzed the promoter region by constructing thedeletion series of the region in detail. We clarified that HNF-1 and APS elements are essential to the expression of the bilirubin UDPGT gene.
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Report
(3 results)
Research Products
(19 results)
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[Publications] Soeda, Y., Tamamoto, K., Adachi, Y., Hayashi, K., Aono, S., Koiwai, O.and Sato, H.: "A predicted homozygous case of missense mutation in Gilbert's syndrome" Lancet. 346. 1494 (1996)
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[Publications] Koiwai, O., Aono, S., Adachi, Y., Kamisako, T., Yasui, Y., Nishizawa, M.and Sato, H.: "Crigler-Najjar syndrome type II is inherited both as a dominant and as recessive trait" Hum.Mol.Genet.5. 645-647 (1996)
Description
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