Extended Data Fig. 6: Engineered HSPCs retain function and are shielded from CIM053-SG3376 in vivo and display a good safety profile.

a, Quantification of the human chimerism (%BC8⁺mCD45⁻) in the spleen and blood of all primary host mice. b, Multi-lineage differentiation in the spleen of all primary host mice. c, Quantification of long-term haematopoietic stem cells (LT-HSC) (%BC8⁺mCD45⁻CD34⁺CD38⁻CD90⁺CD45RA⁻) in the bone marrow of secondary host mice. d, Quantification of the human chimerism (%BC8⁺mCD45⁻) in the spleen and blood of all secondary host mice. e, Multi-lineage differentiation in the spleen and blood of all secondary host mice. (8 mice per group in all panels, plotting mean values +/− SD) (Ordinary two-way ANOVA tests (alpha 0.05) were employed to assess statistical difference between groups). f, Scatterplot representing co-relation between two technical replicates for CHANGE-seq-BE read counts. Top 50 potential off-target sites highlighted in blue were used for rhAmpSeq analysis and other possible off-targets are in plotted in grey. g, Scatterplots depicting A > G base editing percentages across positions 4 to 10 within the editing window for the top 50 rhAmpSeq sites. The plots are organized based on chromosomal coordinates and categorized by sample types, with cultured cells in the top-left, primary transplant bone marrow in the top-right, primary transplant spleen in the bottom-left, and secondary transplant spleen in the bottom-right (2 different donors for cultured cells, 2 hosts for sg49.3+Saline, 1 host for sgNTC+Saline and sg49.3 + CIM053-SG3376).

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