One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid deoxyribonucleic acid by way of thoracotomy in no-option patients**Drs. Isner and Schatz are stockholders of Vascular Genetics, Inc., the sponsor of this trial.

VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

“…20,21 The only reported, major side effect was the occurrence of a remarkable edema of the leg, probably due to the potent permeabilizing activity of VEGF. 22 A series of over 20 clinical trials followed in the late 1990s and early 2000s, entailing the injection of naked plasmid DNA encoding VEGF to the myocardium of patients with severe coronary artery disease (CAD) not amenable to surgical revascularization either through a mini left anterior thoracotomy [23][24][25][26][27][28] or by a transendocardial approach using a NOGA catheter. 29 Even more recently, an open-label, uncontrolled Phase I trial with a VEGF-A 165 plasmid (the GENESIS I trial) was carried out in Argentina by direct intramyocardial injection in 10 patients.…”

Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis

“…While significant progress has been made towards inhibition of angiogenesis in a pathological context such as in cancer, therapeutic angiogenesis in diseases characterized by insufficient vascularization, such as in coronary ischemia, peripheral arterial diseases, or in diabetic sores (4,(28)(29)(30), is still at a nascent stage. We and others have previously demonstrated that HGF/SF can mount a strong angiogenic response (12), both independently of other growth factors (10) and by inducing expression of VEGF (31).…”

“…Ferrara and Kerbel recently articulated that "therapeutic angiogenesis" is an emerging and exciting frontier of cardiovascular medicine (2). However, while early preclinical studies and phase I clinical trials exhibited promising results with recombinant proteins or gene therapy, more rigorous phase II and III studies have reported conflicting outcomes (3)(4)(5)(6). A recent review of these clinical trials highlighted vector "washout" leading to inadequate duration of exposure to the angiogenic agent as a key factor that may have impaired the effectiveness of therapy (7).…”

Non‐viral gene therapy for myocardial engineering

“…Several phase I and II trials have been conducted (for example, the EUROINJECT-ONE trial). No acute complications were reported, and a one-year follow-up of a Phase I trial of direct delivery of pVEGF-C to the heart found no complications as a result of the treatment [125]. In fact, no ill-effects were reported as a result of non-viral gene therapy in any of the trials cited, either with naked or lipid-complexed plasmids [85,108,113,115,117,122,123,129].…”

“…Furthermore, if the MI has been induced by coronary artery ligation, the heart is already exposed. This technique has definite advantages, as a physician can directly observe the beating heart and select areas in need of treatment [112,122,125].…”