Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischaemic limb

Angiogenesis induced in muscle by a recombinant adenovirus expressing functional isoforms of basic fibroblast growth factor

“…A phase I clinical trial in patients with critical limb ischemia indicated that intramuscular gene transfer of naked plasmid DNA encoding VEGF 165 is sufficient to induce therapeutic angiogenesis. 7,38 Recombinant adenoviruses have been recently used to transfer different genes coding potent angiogenic factors. Angiogenesis was evaluated with a recombinant Ad expressing aFGF or VEGF either mixed with Matrigel and injected in subcutaneous position or after injection in rat adipose tissue.…”

“…This strategy has been used both in animal models of hindlimb and myocardial ischemia and more recently in clinical trials to induce therapeutic angiogenesis. [7][8][9] However, the wide cellular spectrum and the pleiotropic function of bFGF make its continuous and local production following gene transfer preferable, over administration of repetitive and large doses of the recombinant protein. Different strategies have been suggested to date to express therapeutic transgenes in fully differentiated tissues.…”

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

“…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.…”

Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts improves survival and vascularization in a model of acute skin flap ischemia

“…Direct intramuscular injections of 'naked' DNA coding for VEGF 165 can promote development of collateral vessels and improve blood perfusion in pre-clinical and clinical studies of limb ischemia. 19,20 Gene Therapy…”