Key Inclusion Criteria Include: 1. Age ≥12 years to ≤35 years 2. Documented diagnosis of sickle cell disease with βS/βS, βS/β0, or βS/β+ genotypes. 3. Severe SCD defined by the occurrence of at least 4 severe VOCs in the 24 months prior to screening despite receiving hydroxyurea or other supportive care measures Key Exclusion Criteria Include: 1. HbF levels \>20%, obtained at the time of screening on or off hydroxyurea therapy 2. Previous receipt of an autologous or allogeneic HSCT or solid organ transplantation 3. Available and willing matched sibling donor 4. Definitive diagnosis of moyamoya syndrome based on screening brain MRA 5. History of overt stroke