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- Title
Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter.
- Authors
Kim, Y. D.; Park, K. -G.; Morishita, R.; Kaneda, Y.; Kim, S. -Y.; Song, D. -K.; Kim, H. -S.; Nam, C. -W.; Lee, H. C.; Lee, K. -U.; Park, J. -Y.; Kim, B. -W.; Kim, J. -G.; Lee, I. -K.
- Abstract
Insulin gene therapy in clinical medicine is currently hampered by the inability to regulate insulin secretion in a physiological manner, the inefficiency with which the gene is delivered, and the short duration of gene expression. To address these issues, we injected the liver of streptozotocin-induced diabetic rats with hemagglutinating virus of Japan-envelope (HVJ-E) vectors containing Epstein–Barr virus (EBV) plasmids encoding the genes for insulin and the GLUT 2 transporter. Efficient delivery of the genes was achieved with the HVJ-E vector, and the use of the EBV replicon vector led to prolonged hepatic gene expression. Blood glucose levels were normalized for at least 3 weeks as a result of the gene therapy. Cotransfection of GLUT 2 with insulin permitted the diabetic rats to regulate their blood glucose levels upon exogenous glucose loading in a physiologically appropriate manner and improved postprandial glucose levels. Moreover, cotransfection with insulin and GLUT 2 genes led to in vitro glucose-stimulated insulin secretion that involved the closure of KATP channels. The present study represents a new way to efficiently deliver insulin gene in vivo that is regulated by ambient glucose level with prolonged gene expression. This may provide a basis to overcome limitations of insulin gene therapy in humans.Gene Therapy (2006) 13, 216–224. doi:10.1038/sj.gt.3302644; published online 22 September 2005
- Subjects
INSULIN; GENE therapy; CLINICAL medicine; PLASMIDS; BLOOD sugar; DIABETES
- Publication
Gene Therapy, 2006, Vol 13, Issue 3, p216
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302644