title: Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer.
abstract: BACKGROUND
  The development of an efficient method to improve the wound healing process is urgently required for diabetic patients suffering a threat of limb amputations. Various growth factors have been proposed for treatment; however, more research still has to be carried out to maintain their curative effect. In the present study, we describe a simple nonviral gene therapy method for improving wound healing.
  
  
  METHODS
  Minicircle plasmid DNA encoding vascular endothelial growth factor (VEGF) was combined with an arginine-grafted cationic dendrimer, PAM-RG4. The formed complexes were injected subcutaneously into the skin wounds of diabetic mice.
  
  
  RESULTS
  Actively proliferating cells in wound tissue were efficiently transfected, resulting in a high level of VEGF expression. Within 6 days after injection, skin wounds in the diabetic mice were generally healed and displayed a well-ordered dermal structure, which was confirmed by histological staining.
  
  
  CONCLUSIONS
  This simple and effective gene therapy method may represent a powerful tool for the treatment of diabetic foot ulcers and other diseases that are refractory to treatment.
authors.affiliation: Department of Internal Medicine, Pusan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Min J
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Songhie
authors.initials: S
authors.lastname: An
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Choi
authors.forename: Kihoon
authors.initials: K
authors.lastname: Nam
authors.forename: Hye S
authors.initials: HS
authors.lastname: Jung
authors.forename: Chang S
authors.initials: CS
authors.lastname: Yoon
authors.forename: Jung H
authors.initials: JH
authors.lastname: Ko
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Jun
authors.forename: Tae K
authors.initials: TK
authors.lastname: Kim
authors.forename: Soo J
authors.initials: SJ
authors.lastname: Jung
authors.forename: Jeong H
authors.initials: JH
authors.lastname: Park
authors.forename: Yan
authors.initials: Y
authors.lastname: Lee
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Park
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry; D002412:Cations; D004270:DNA, Circular / Q000008:administration & dosage*; D050091:Dendrimers / Q000737:chemistry*; D048909:Diabetes Complications / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D012867:Skin / Q000098:blood supply / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing
chemical_list: D002412:Cations; D004270:DNA, Circular; D050091:Dendrimers; D042461:Vascular Endothelial Growth Factor A; D001120:Arginine