Fig. 2: Stable HgbA production in SCD mice autologously transplanted with E6V-corrected HSPCs.

A Experimental schematic for Cas9-AAV6-based gene correction of the E6V mutation in beta-globin in Townes-SCD mouse HSPCs. B Mean HBB gene editing outcomes in mouse HSPC cultures from 8 biological replicates. C Mean HBB allelic correction frequencies in PB myeloid (nm), B cell, and T cell lineages over time in primary recipients (n = 9 mice). D Representative HPLC plots for hemoglobin tetramer analysis from PB collected at 4- and 16-weeks post-transplantation, with mouse HgbA (mHgbA), human HgbA (hHgbA), and human HgbS (hHgbS) annotated. E Mean frequency of hHgbA (of total hHgbA and hHgbS) in HSCT recipients (n = 9 mice). Dotted line represents 50% hHgbA. F Mean frequency of PB myeloid (nm) HBB allelic correction and hHgbA over time in HSCT recipients (n = 9 mice). G X–Y linear correlations between PB reticulocyte frequency and myeloid (nm) gene correction at 16-weeks post-transplantation (n = 9 mice). H Mean frequency of HBB allelic correction in PB leukocyte populations (left plot) and frequency of human HgbA in the PB as a total of human Hgb (right plot) in secondary recipients at 12-weeks post-transplantation (n = 4 mice). 1 × 10⁶ WBMCs from mouse A or mouse B (see Table 1) were transplanted into recipient mice (2 mice per primary recipient). Source data are available in the Source data file.