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.
引用
收藏
页码:69 / 73
页数:5
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