Gene therapy progress and prospects: therapeutic angiogenesis for limb and myocardial ischemia

Peptide-matrix-mediated gene transfer of an oxygen-insensitive hypoxia-inducible factor-1α variant for local induction of angiogenesis

“…As an alternative to local administration of one, or even multiple, growth factors, the approach of delivering HIF-1␣, a transcription factor that is responsible for regulation of a number of proangiogenic signals has been presented (5,11,12). HIF-1␣ is known to play an important role in tissue response to hypoxia, and two variants have been designed that provide signaling even under conditions of normoxia.…”

“…A key challenge in angiogenesis remains the induction of mature, stable vessels. To do so, several strategies have been followed (5), including multiple growth factor delivery (6,7) and delivery of growth factors at ultralow levels (8)(9)(10)). …”

In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents

“…Therapeutic strategies may therefore be designed to enhance or decrease vessel growth. Angiogenic agents have been used to treat ischemic disorders such as peripheral vascular disease and coronary artery disease (reviewed in Khan et al, 2003;Zhou et al, 2007). Anti-angiogenic agents have been used as treatments for cancer, diabetic retinopathy, macular degeneration, psoriasis and other diseases (reviewed in Liekens et al, 2001;Quesada et al, 2006).…”

Effective treatment of vascular endothelial growth factor refractory hindlimb ischemia by a mutant endothelial nitric oxide synthase gene

“…1 Local delivery of genes encoding angiogenic factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor or hepatocyte growth factor emerged as a promising new therapeutic approach for ischemic cardiovascular disease. 2 However, clinical results so far are lacking unequivocal proof for efficacy by therapeutic angiogenesis. It may be due to inefficient gene delivery or because of some patients are refractory to exogenously administered growth factors.…”

“…It may be due to inefficient gene delivery or because of some patients are refractory to exogenously administered growth factors. 2 Gene expression following naked plasmid DNA delivery is generally very low compared to viral vectors, therefore its suitability for clinical therapeutic application is questionable. 3 Transfection efficiency achieved by plasmid DNA delivery has been significantly improved by the application of electroporation.…”