This is an open label, non-randomized, 2-center, phase 1/2 trial of a single infusion of sickle allele modified CD34+ HSPCs in subjects with severe SCD. The primary endpoint of the trial will determine the safety of CRISPR_SCD001 through a 3+3 design with staggered enrollment and a pause in enrollment for safety review after each of the first 3 patients has had drug product infused. After safety is assessed in the 3rd patient, enrollment of the next 3 patients will not be staggered. The first six subjects will be adults. If CRISPR_SCD001 is determined to be safe in the first six subjects, the trial will continue to enroll 3 adolescents 12 - 18 years of age to evaluate the safety in younger patients. The younger age cohort also will follow staggered enrollment.