Key Inclusion Criteria: Diagnosis of Transfusion Dependent B-Thalassemia as defined by: * Documented homozygous β-thalassemia or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE) based on historical data in medical records, and * History of at least 100 mL/kg/year or 10 U/year of packed red blood cell (RBC) transfusions in the 2 years prior to signing informed consent * Clinically stable and eligible to undergo autologous HSCT * Karnofsky Performance Status ≥ 70 Key Exclusion Criteria: * Available 10/10 human leukocyte antigen (HLA)-matched related donor * Prior HSCT or contraindications to autologous HSCT * Participants with associated a history of α-thalassemia and \> 1 alpha chain deletion, or alpha multiplications as documented in medical records * Participants with a history of other inherited hemoglobinopathy or thalassemic mutation (Hb S, C, D or other) as documented in medical records * Prior receipt of gene therapy * Inadequate bone marrow function, as defined by white blood cell count of \< 3 x 10\^9/L or a platelet count \< 100 x 10\^9/L (without hypersplenism), per investigator judgement * Inadequate organ function * Advanced liver disease * Any prior or current malignancy, or immunodeficiency disorder, * Immediate family member with a known or suspected Familial Cancer Syndrome * Clinically significant and active bacterial, viral, fungal, or parasitic infection