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Cardiovascular gene therapy with vascular endothelial growth factors
Authors:Seppo Ylä  -Herttuala
Affiliation:A.I. Virtanen Institute, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland; Gene Therapy Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland; Research Unit, Kuopio University Hospital, P.O. Box 1777, FI-70211 Kuopio, Finland
Abstract:Therapeutic angiogenesis with vascular endothelial growth factors (VEGFs) is a promising approach for the treatment of ischemic myocardium and peripheral skeletal muscles. Preclinical studies in large animals have clearly demonstrated safety and efficacy of VEGF gene therapy in clinically relevant disease models. However, first clinical trials with intravascular delivery of VEGF vector constructs have only resulted in limited benefits to the patients. Second generation VEGF-based gene therapy trials are based on direct intramyocardial and intraskeletal muscle injections in order to achieve better transfection efficiency and more targeted effects. Phase I/II studies are currently ongoing to test safety, feasibility and efficacy of these improved approaches in patients with severe cardiovascular diseases.
Keywords:VEGF, vascular endothelial growth factor   AAV, adeno-associated virus   CRP, C-reactive protein   lacZ, beta-galactocidase   MRI, magnetic resonance imaging   Adv, adenovirus   SPECT, single-photon emission computed tomography   PET, positron emission tomography   18F-FDG, 18F-fluorodeoxyglucose   GMP, good manufacturing practice
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