Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer

Abstract

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.

Nanomaterials for Wound Healing: Scope and Advancement

“…Furthermore, less immature blood vessel formation resulted in diabetic wound recovery comparable to wound healing for normal mice [38]. For example, arginine-grafted cationic dendrimer was tested for wound healing in diabetic and normal mice as a vehicle to deliver minicircle plasmid DNA encoding VEGF.…”

Nonviral Gene Therapy—The Challenge of Mobilizing DNA

“…Using similar VEGF-encoding minicircles (with expression driven by a β-actin promoter) Kwon et al treated skin wounds of diabetic mice by subcutaneous injection of minicircles complexed with a cationic dendrimer carrier. However, in this study, only dendrimer-complexed minicircles, and not naked minicircles, resulted in VEGF production after injection, leading to a marked increase in the healing rate of wounds in mice with streptozotocin-induced diabetes (Kwon et al 2012).…”

Minicircle DNA vectors for gene therapy: advances and applications

“…Although this process seems straightforward, it is not as efficient as that mediated by some viral vectors [84], a fact that accounts for the lower transgene expression efficiency of the nonviral counterparts. Various efforts have been put forward to improve the nuclear uptake of naked nonviral expression cassettes these include: i) the conjugation to NLS-containing peptides; ii) DNA complexes with nuclear 6 days after injection of mcDNA diabetic mice skin wounds were healed and with skin-like structure [118] Wound proteins; iii) small molecule ligands (e.g., dexamethasone, alltrans-retinoic acid); iv) inclusion of nuclear-targeting sequences in DNA vectors [69,85]. Using the latter strategy, Breuzard et al have developed a pDNA vector with a kb optimized insert (3NF) to promote NF-kb-mediated nuclear import.…”