Figure 4.

Single BFU-E clonal analyses

(A) Total editing and indel type by HBG-113 or BCL11A-ee locus and by reaction arm in individual BFU-Es. Defined indels are included where frequency was reported as ≥10%, and the difference between sum of defined indels and total reported editing efficiency is presented as undefined indels. (B) Indel patterns observed in BFU-Es following editing at HBG-113 demonstrating a high frequency of 13-nucleotide and small deletions. (C) Indel patterns observed in BFU-Es following editing at BCL11A-ee demonstrating a high frequency of single nucleotide insertion. (D) Number of BFU-Es from each arm edited at one or both loci. (E) HbF percentage of total hemoglobin plotted against editing efficiency in unedited, single- and dual-edited BFU-Es. Reported editing of <5% taken to represent colonies with no editing. (F) HbF percentage of total hemoglobin for reactions with no editing or single HBG-113 editing, plotted against total HBG-113 editing and 13-nucleotide deletion frequency. Reported editing of <5% taken to represent colonies with no editing. (G) HbF percentage of total hemoglobin in BFU-Es with editing of over half available alleles at both HBG-113 and BCL11A-ee, compared with those with over half available alleles edited only at one locus (mean ± SD). BCL11A, BCL11A-ee; HBG, HBG-113.