HbF expression and functional correction in G^bG mice that underwent transplantation after reduced-intensity conditioning, separated into 2 groups: mice with HbF of 10% or more (G^bG≥10) and mice with HbF of less than 10% (G^bG<10). (A) HbF in individual BERK mice 18 weeks after transplantation of sG^bG-transduced BERK HSCs, after reduced-intensity conditioning. (B-C) Stable and high HbF expression and F-cell repopulation in long-term survivors analyzed at 11 months. (D) Box and whisker plot showing vector copy numbers in G^bG<10 and G^bG≥10 mice, with mean vector copy number denoted by the line. Symbols in panels A through C represent mouse groups: ○ = mock (HbF 0%), ▽ = G^bG<10 (HbF < 10%), and ● = G^bG≥10 (HbF ≥ 10%). (E) The proportion of ISCs was reduced (P < .04) in G^bG<10 mice, but was markedly reduced in G^bG≥10 mice (P < .001), compared with mock mice. (F) Graded deoxygenation via tonometry demonstrates significant reduction in sickling at physiologically relevant partial oxygen pressures (PO₂) in G^bG≥10 mice, whereas G^bG<10 mice RBC sickled similar to controls. (G-H) RBC deformability showed highly variable improvement in deformability in G^bG<10 mice. In contrast, RBC deformability in G^bG≥10 mice was highly significantly improved at low and high shear stress (P < .001). Symbols represent mouse groups: ○, mock; ▽, G^bG<10; ●, G^bG≥10; and ⊗, wild-type mice (C57BL/6). Gray shaded rectangles are representative of low and high shear stress through microvessels and large vessels, respectively. Error bars indicate SEM.