Functional silencing of hepatic microsomal glucose‐6‐phosphatase gene expression in vivo by adenovirus‐mediated delivery of short hairpin RNA

FEBS Letters

Huang, Alan¹  Su, Nancy¹  White, David W¹  Wang, Xinzhong¹  Chen, Yan¹  Zhao, Shanchuan¹ 

[1] Millennium Pharmaceuticals, 75 Sidney St., Cambridge, MA 02139, USA

关键词: RNA interference;    Short hairpin RNA;    Gene silencing;    Glucose-6-phosphatase;    Adenovirus;   

DOI  :  10.1016/S0014-5793(03)01499-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown