Lower-Extremity Edema Associated with Gene Transfer of Naked DNA Encoding Vascular Endothelial Growth Factor

Abstract

Vascular endothelial growth factor may enhance vascular permeability in humans. At the doses of plasmid DNA used in this study, lower-extremity edema responded to oral diuretic therapy and did not seem to be associated with serious sequelae.

Development of safe and efficient novel nonviral gene transfer using ultrasound: enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle

“…The clinical utility of gene therapy using the VEGF gene has been recently reported for the treatment of critical limb ischemia and myocardial ischemia. [4][5][6][7][8][9][10][11] Instead of VEGF, other angiogenic growth factors such FGF, HGF and a transcription factor for angiogenesis, HIF (hypoxiainducible factor), have been considered candidates for therapeutic angiogenesis as gene therapy for the treatment of patients with critical limb ischemia. [12][13][14][15][16][17][18][19][20] Although the feasibility of therapeutic angiogenesis using these angiogenic growth factors has been reported in experimental models and human clinical trials, [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] there are still unresolved problems such as undesirable side-effects.…”

“…1 Therefore, novel therapeutic modalities are needed to treat these patients. Recently, the efficacy of therapeutic angiogenesis using VEGF (vascular endothelial growth factor) gene transfer has been reported in human patients with critical limb ischemia [4][5][6][7] and myocardial ischemia. [8][9][10][11] In addition to VEGF, the utility of gene transfer of other angiogenic growth factors such as fibroblast growth factor (FGF) or hepatocyte growth factor (HGF) has been reported to stimulate collateral formation.…”

“…Interestingly, most successful clinical trials of treating peripheral arterial disease using angiogenic growth factors have been performed by intramuscular transfection of naked plasmid DNA, [4][5][6][7][8] although in vivo gene transfer using direct injection of 'naked' DNA into cardiac and skeletal muscle is inefficient. It is apparent that a more efficient gene transfer method is required to achieve therapeutic effects.…”

Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound

“…7 Since naked plasmid DNA is safe and easy to handle as compared to viral vectors, intramuscular injection of naked plasmid DNA of angiogenic growth factors such as vascular growth factor (VEGF) has been used clinically for the treatment of ischemic cardiovascular disease. 8,9 Although some researchers have tried to apply direct injection of naked plasmid DNA into the brain, 10,11 the transfection efficiency was quite low 10 and a large amount of naked plasmid DNA was required to produce the target protein. 11 Recently, ultrasound-mediated gene transfer has been reported to augment the transfection efficiency and facilitate local gene expression.…”

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

“…The increased vascular permeability was an effect attributed to the VEGF therapy. 27 Recently, the results of a phase II clinical trial of VEGF-1 gene therapy for chronic limb ischemia were published. In the randomized, placebo-controlled, double-blinded study of catheter-based VEGF-1 gene therapy after percutaneous transluminal angioplasty (PTA), patients in the treatment groups received intra-arterial VEGF-1 by adenoviral vector or liposome/plasmid carrier while those in the control group received crystalloid solution.…”