The purpose of this study is to determine the optimum effective dose of recombinant plasmid DNA [pVGI.1(VEGF2)] gene therapy administered using an experimental cardiac direct injection catheter (Stiletto™) system needed to benefit patients with severe Angina Pectoris.

Inclusion Criteria:

• Are willing and able to give informed consent
• Have CCS class III or IV angina refractory to optimized medical therapy
• Experience signs or symptoms of angina during the exercise tolerance test (ETT)
• Have identified area(s) of reversible ischemic myocardium
• Have procedurally acceptable targeted treatment zones

Exclusion Criteria:

• Have exercise-limited non-cardiac chest discomfort
• Unwilling or unable to undergo exercise testing
• Able to exercise greater than 6 minutes on the treadmill
• Are candidates for conventional revascularization procedures
• Are or have been enrolled within 30 days, in another experimental study
• Have had the most recent angiogram more than 6 Months prior to screening
• Previously received an investigational angiogenic agent
• Have another disease severe enough to limit exercise test or place patient at risk
• Have uncontrolled: atrial fibrillation, atrial flutter, and/or significant arrhythmias
• Have evidence of left ventricular aneurysm or ventricular thrombus
• Are unwilling or unable to undergo cardiac catheterization or nuclear testing procedures
• Have had a Q-wave MI, within 60 days
• Have severe aortic valve stenosis or have a mechanical aortic or mitral valve
• Have unstable angina or an acute non-Q-wave myocardial infarction within 14 days
• Have had a documented stroke or transient ischemic attack within 60 days
• Are pacemaker dependent
• Have a recent history of active diabetic retinopathy or age-related wet macular degeneration
• Have a history of cancer within the last 5 yrs. or have current evidence of a malignant neoplasm
• Have a history of alcohol or drug abuse within 90 days
• Are pregnant or lactating
• Have reproductive potential and are unwilling to use condoms for contraception for 1 year after treatment - both male and female
• Are unable to return to the clinic for the scheduled follow-up appointments
• Are taking medications which may produce an undue risk
• Have areas of LV wall less than 6mm thick