Safety and Efficacy Study Using Gene Therapy for Critical Limb Ischemia

Inclusion Criteria: * Male or female, between 18 and 90 years of age; * Diagnosis of critical limb ischemia (Rutherford Class 4 or 5), including: * A resting ankle systolic pressure (in either the dorsalis pedis or posterior tibial arteries) of ≤ 70 mmHg in the affected limb; or * A resting toe systolic pressure of ≤ 50 mmHg in the affected limb; or * For patients in which measurement of ankle systolic pressure is not feasible (e.g. vessel calcification and non-compressibility); TcPO2 ≤ 30 mmHg; * Poor or suboptimal candidate for bypass graft surgery or percutaneous angioplasty; * Pain at rest, and/or ischemic ulcers, and/or focal gangrene (\< 3 cm2) for a minimum of 2 weeks, * Significant stenosis (≥ 75%) of one or more of the following arteries: superficial femoral, popliteal, or two or more infra-popliteal arteries as verified by angiography within 12 months prior to enrollment; * Be willing to maintain current drug therapy for peripheral arterial disease throughout the course of the study including an anti-platelet and statin treatment unless not tolerated; * Clinically stable on optimized medical regimen for \>30 days * Be capable of understanding and complying with the protocol and signing the informed consent document prior to being subjected to any study related procedures; * Women who are surgically sterile or at least 1 year postmenopausal or who have been practicing adequate contraception for at least 12 weeks prior to entering the study. If the subject is of child-bearing potential, she must have a negative urine pregnancy test result prior to study enrollment and must agree to repeat pregnancy screening tests during the study. If the subject or the subject's partner(s) is of child bearing potential, the subject and the subject's partner(s) must agree to use a "double barrier" method of birth control while participating in this study. Exclusion Criteria: * Subjects who have undergone a successful revascularization procedure or sympathectomy within 12 weeks prior to study entry. A clinically unsuccessful revascularization procedure is defined as one in which: * the target vessel re-occludes (≥50%, as verified by a second angiogram. Duplex ultrasonography can be used to determine vessel patency if the patient cannot tolerate a second angiogram), or * the target vessel remains patent, but there is no resolution of symptoms 6 weeks after the procedure (e.g. no evidence of ulcer healing, no improvement in pressures, no reduction in resting pain); * …