HSPCs are amenable to both CRISPR/Cas9 and ABE/Cas9-mediated CD33 editing, engrafting long-term and maintaining multilineage potential. (A) CFC assay of transplanted HSPCs. Sorted on (1) CD34⁺, (2) CD34⁺CD90⁺, (3) CD34⁺CD90⁻, and (4) CD34⁺CD45RA⁺. (B) Editing of single colonies collected from CFC assay. (C) Schematic of BM transplant and tracking of hematologic recovery. (D) Representative table of transplant information. (E) Hematologic recovery of A17039 and A18038 as measured by time to recovery of platelets and neutrophils. Vertical dashed line represents day of transplant. Horizontal lines represent threshold of recovery (solid line) and healthy blood ranges (dashed lines). (F) Recovery of total WBC compartment with CD33-edited cells (top) and the granulocyte compartment with CD33-modified cells (bottom) measured by ddPCR/NGS or FACS, respectively. BFU-E, burst forming unit erythroid; G, granulocyte; GEMM, granulocyte, erythrocyte, macrophage, megakaryocyte; GM, granulocyte, macrophage; M, macrophage; QC, quality control; WBC, white blood cell; WT, wild type.