2000 Fiscal Year Final Research Report Summary
Gene therapy in the Gunn rat model of Crigler-Najjar syndrome type-1
| Project/Area Number |
11670491
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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 |
Gastroenterology
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| Research Institution | Mie University |
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Principal Investigator |
IMOTO Ichiro Mie University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90176511)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAKI Sigenori Mie University, Hospital, Assistant, 医学部・附属病院, 助手 (80260602)
ADACHI Yukihiko Mie University, Faculty of Medicine, Professor, 医学部, 教授 (50111026)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Crigler-Najjar syndrome / Gunn rat / gene therapy / HEP / VLP / UGT1A1 |
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| Research Abstract |
Crigler-Najjar type 1 (CN type 1) is an autosomal recessive disorder characterizedby nonhemolytic jaundice resulting from mutations of the gene encoding bilirubin-UDP-glucoronosyltransferase (UGT1A1). Our objective of this study was to complement this deficiency in vivo using liver-directed gene therapy. Firstly, an expression plasmid for lac Z gene or strctural proteins of hepatitis C virus was injected into the mouse liver had been electroporated between two electrodes. The β-galactosidase activity was observed 14 days after and HCV proteins were expressed 16 weeks after plasmid injection in the hepatocytes. Secondly, an expression plasmid for human UGT1A1 was transferred into the liver of Gunn rat model of CN type 1. UGT1A1 activity of the liver was observed 2 days after plasmid injection. Thirdly, virus-like particles (VLP) of hepatis E virus (HEV) were generated by the recombinant capsid protein (open reading frame 2). The expression plasmids encapsulated in the VLP were efficiently tranferred and expressed in human hepatoma cells and mouse small intestine.
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Research Products
(8 results)
