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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)216-224
Number of pages9
JournalGene Therapy
Volume13
Issue number3
DOIs
StatePublished - Feb 2006

Keywords

  • Diabetes
  • EBV
  • GLUT 2
  • HVJ-E
  • Insulin

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