In conclusion, despite the significant and potentially therapeutic HbF increase observed in SCD patients with the optimized γ-globin lentiviral vector GGHI-mB-3D, a major limitation of our strategy, primarily regarding the precise assessment and comparison of the HbF increase in each patient and among the βSβS and βSβ+ cohorts, is the established inherent genetic and epigenetic heterogeneity per se of these patients, coupled with the lack of information regarding important HbF genetic modifiers, such XmnI, HBS1L-MYB, and BCL11A [54], in the two cohorts. This evidence concerns the gene BCL11A and Schnyder corneal dystrophy.