Comparison of Minicircle with Conventional Plasmid for the Non-viral Vascular Endothelial Growth Factor (VEGF) Gene Therapy

Abstract

Background: Delayed wound healings in diabetic patients are related with t he impairment of the expressions of various growth factors. Treatments using growth factors have been attempted on diabetic foot ulcer. VEGF (vascular endothelial growth factor) accelerates neo-angiogenes is on the early phase of the wound healing and exerts chemo-attractive effe ct for the other growth factors and cytokines. Non-viral gene transfer strategies are attractive tool for the gene therapy due to the safety and the versatility, but the low efficiency has been the serious problem. Methods: We performed the VEGF gene therapy using reconstructed minicircle MINI-pβ VEGF DNA with a polymeric carrier, polyethylenimine (PEI, 25 kDa) in HEK293, CHO, and NIH3T3 cell lines, and compared its efficiency with the conventional VEGF plasmid pβVEGF. Results: The levels of expressed VEGF were higher in the groups using BP EI (branched PEI) as a gene carrier than naked plasmid transfer in all cell lines (P < 0.05). The minicircle MINI-pβVEGF DNA showed much higher VEGF expression than conventional plasmid pβVEGF (P < 0.05). Conclusion: Minicircle DNA MINI-pβVEGF showed much higher transfection efficiency than conventional plasmid pβ VEGF. It might be used in actual human clinical trial due to it s higher efficiency and possible safety for the treatment of diabetic foot ulcer. (J Kor Diabetes Assoc 31:465~471, 2007)