Korean Diabetes Journal 2003;27(5):405-413.
Published online October 1, 2003.
Insulin Gene Therapy Using HVJ-liposome and Epstein-Barr Virus Plasmid in Murine Streptozotocin Induced Diabetes.
Yong Deuk Kim, Keun Gyu Park, Seong Wook Han, Jong Doek Ahn, Hyo Jung Lee, Mi Jung Kim, Hye Soon Kim, Nam Hee Park, In Kyu Lee
1Department of Internal Medicine, Keimyung University, School of Medicine, Daegu, Korea.
2Institute for Medical Science, Keimyung University, School of Medicine, Daegu, Korea.
3Department of Chest Surgery, Keimyung University, School of Medicine, Daegu, Korea.
Abstract
BACKGROUND
Despite improvement in insulin preparation and delivery, the use of insulin therapy alone to maintain normal glucose concentration and prevent the development of diabetic complication is not easy. Therefore, there has been considerable interest in developing gene therapy to supply insulin. We investigated that the administration of hemagglutinating virus of Japan (HVJ)- liposome complex, containing human insulin construct into the portal vein to control the blood glucose level in murine streptozotocin (STZ)-induced diabetes. METHODS: Human insulin gene was delivered to STZ-induced diabetic rats through the portal vein using HVJ-liposome containing Epstein-Barr virus (EBV) replicon-based plasmid (pEB). Blood glucose and body weight were measured after insulin gene delivery. The animals were sacrificed 28 days later and the livers were collected for immuno-histochemical staining of insulin. In addition plasma insulin and C-peptide levels were measured. RESULTS: Significant decrease in blood glucose levels and an increase in insulin and C-peptide levels were observed in the insulin gene transfection group as compared to the control group. Immunohistochemical staining of insulin also showed significant differences between these two groups. CONCLUSION: This study demonstrated the possibility of insulin gene therapy through the portal vein using pEB and HVJ-liposome method to produce a sustained improvement of diabetic glucose metabolism.
Key Words: Insulin gene therapy, pEB (Epstein-Barr virus replicon-based plasmid, HVJ (hemagglutinating virus of Japan)-liposome


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