β-thalassemia and sickle cell disease (SCD) are the most common monogenic diseases worldwide. About 20% of these patients may be cured by allogeneic hematopoietic stem-cell transplantations from HLA-matched donors, and recent therapies have been approved to treat both hemoglobinopathies by disrupting the gene encoding BCL11A—the transcription factor that shuts off production of fetal hemoglobin. The naturally occurring hereditary persistence of…