Functional silencing of hepatic microsomal glucose‐6‐phosphatase gene expression in vivo by adenovirus‐mediated delivery of short hairpin RNA
Copyright policy )Functional silencing of hepatic microsomal glucose‐6‐phosphatase gene expression in vivo by adenovirus‐mediated delivery of short hairpin RNA
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.
- Millennium Pharmaceuticals United States
Blood Glucose, Male, Green Fluorescent Proteins, Gene Expression Regulation, Enzymologic, Adenoviridae, Mice, RNA interference, L Cells, Adenovirus, Animals, Humans, Gene Silencing, Gene Transfer Techniques, Gene silencing, Liver Glycogen, Rats, Mice, Inbred C57BL, Luminescent Proteins, MicroRNAs, Glucose-6-Phosphatase, Microsomes, Liver, Short hairpin RNA, Glucose-6-phosphatase
Blood Glucose, Male, Green Fluorescent Proteins, Gene Expression Regulation, Enzymologic, Adenoviridae, Mice, RNA interference, L Cells, Adenovirus, Animals, Humans, Gene Silencing, Gene Transfer Techniques, Gene silencing, Liver Glycogen, Rats, Mice, Inbred C57BL, Luminescent Proteins, MicroRNAs, Glucose-6-Phosphatase, Microsomes, Liver, Short hairpin RNA, Glucose-6-phosphatase
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