Liver-directed gene therapy of diabetic rats using an HVJ-E vector containing EBV plasmids expressing insulin and GLUT 2 transporter View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2006-02

AUTHORS

B-W Kim, C-W Nam, D-K Song, H C Lee, H-S Kim, I-K Lee, J-G Kim, J-Y Park, K-G Park, K-U Lee, R Morishita, S-Y Kim, Y D Kim, Y Kaneda

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 K(ATP) 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. More... »

PAGES

216

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.gt.3302644

DOI

http://dx.doi.org/10.1038/sj.gt.3302644

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022857120

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16177820


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