HSPCs from a healthy human donor were electroporated in triplicate with Cas9 nuclease RNP targeting the BCL11A erythroid-specific enhancer, ABE8e-NRCH mRNA and an sgRNA targeting the wild-type HBB locus, or no cargo as a control. An additional set of control cells was not electroporated. a, CDKN1 transcription levels, a measure of the p53-mediated DNA damage response49, were quantified by ddPCR after reverse transcription, and were normalized to CDKN1 levels before electroporation (n = 3). b, Editing efficiencies at the targeted genomic loci in HSPCs were measured by HTS 6 days after electroporation. Adenine base editing at the synonymous bystander position 9 of the HBB protospacer is shown for ABE8e-NRCH. c, d, The indicated target sites were amplified and quantified by ddPCR to measure the fraction of missing alleles consistent with larger deletions, translocations, or other chromosomal rearrangements that result in loss of the ability to be amplified by PCR. PCR amplification of a non-targeted ACTB site was used to normalize each sample. Each DNA sample was assessed in triplicate (n = 9). Data shown as mean ± s.d., with individual values in bar graphs shown as dots. Statistical significance between edited and unedited samples was assessed by a two-tailed Student’s t-test; ns, not significant.