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Functional silencing of hepatic microsomal glucose-6-phosphatase gene expression in vivo by adenovirus-mediated delivery of short hairpin RNA
被引:12
作者:
Huang, A
[1
]
Chen, Y
[1
]
Wang, XZ
[1
]
Zhao, SC
[1
]
Su, N
[1
]
White, DW
[1
]
机构:
[1] Millennium Pharmaceut, Cambridge, MA 02139 USA
关键词:
RNA interference;
short hairpin RNA;
gene silencing;
glucose-6-phosphatase;
adenovirus;
D O I:
10.1016/S0014-5793(03)01499-6
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
An expression cassette containing mouse U6 polymerase III promoter directing expression of short hairpin RNA (shRNA) targeting murine microsomal glucose-6-phosphatase (G6P) transcript was generated. This construct was packaged into an adenoviral (AdV) backbone and viral stocks generated. Mice injected intravenously with AdV-G6PshRNA exhibited a significant reduction in postprandial glucose levels and had significantly elevated steady-state hepatic glycogen stores. Target gene silencing was confirmed by measurements demonstrating a significant reduction in both hepatic G6P transcript level and phosphohydrolase activity. These findings provide evidence that AdV delivery of expressed shRNA can be a productive tool to explore gene function in vivo. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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页码:69 / 73
页数:5
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