Fig. 4: HSPCs with high frequency knock-in maintain edited alleles following engraftment in vivo.

a Distribution frequency of WT (gray), INDEL (blue), and KI (green) alleles in CB CD34⁺ HSPCs prior to transplantation in NBSGW mice. Cells were targeted at CCR5 with an AAV6 MOI of 625 for each linker antibody construct and treated with 0.5 µM AZD7648 (n = 2 independent biologic donors; data also shown in Fig. 2f). b Percent of KI alleles integrated with 10-1074 (blue) or Ibalizumab (purple) within the 10-1074+Ibalizumab targeted cells treated with 0.5 µM AZD7648 and shown in panel a (n = 2). c Percent human cell chimerism in the bone marrow 12 weeks post-transplantation with cells shown in panel a (treated with 0.5 µM AZD7648 and targeted as indicated). Two-tailed Mann–Whitney test (**P = 0.0040, n = 4 mice for mock and n = 8 mice for 10-1074+Ibalizumab). d Percent of human cells in the bone marrow that are CD19⁺ (B cell lineage), CD33⁺ (myeloid cell lineage), or within other lineages in mice engrafted with mock (black) or gene edited (red) HSPCs (n are the same as in c). e Percent of human alleles with knock-in from the bulk bone marrow or in positively selected bone marrow CD19⁺ cells. Knock-in frequency was measured by ddPCR. Lines connect measurements from the same mice (n are the same as in c). Two-tailed Mann–Whitney test (ns, not significant, P = 0.7178). f Percent of human alleles from the bone marrow with an INDEL at CCR5 (n are the same as in c). This analysis only includes alleles without KI. All bars represent mean and all error bars represent SD. Integration frequencies were measured by ddPCR, INDEL and wild-type frequencies were measured by ICE analysis. Source data are provided as a Source Data file.