The proposed clinical trial is a dose escalation study of self-complementary scAAVrh74.tMCK.hSGCA to LGMD2D (alpha-sarcoglycan deficient) subjects delivered via a major lower limb artery of each leg sequentially by isolated limb perfusion (ILP). Three cohorts (Cohorts 1A, 1B, and 2) will undergo gene transfer in a dose escalation scheme to establish maximum tolerated dose (MTD) using toxicity. Two (n=2) adult wheelchair-dependent patients will be enrolled in Cohort 1A and three (n =3) ambulatory subjects will be enrolled in Cohort 1B. Three (n =3) ambulatory subjects will be enrolled in Cohort 2. The first cohort (1A) will receive a dose of 1E12 vg/kg in a single limb with delivery to the whole limb. This same dose will be delivered to both limbs in Cohort 1B. Cohort 2 will receive a total dose escalation of 3E12vg/kg per limb delivered to both extremities. The vector will be infused into an indwelling catheter in the femoral artery. This will be a one-time vector infusion to an isolated limb with a 10-minute dwell time. The total vector genome dose for each subject will be adjusted by rounding down to the closest 10 kg.