Precise Gene Editing Preserves Hematopoietic Stem Cell Function Following Transient p53-Mediate DNA Damage Response [Clear-seq]

We analysed AAVS1 edited cells in presence and absence of GSE56 (p53 inhibitor) 14 days upon electroporation to evaluate whether p53 transient inhibition by GSE56 could aggravate the genotoxicity risk of the procedure Overall design: We deep sequenced a panel of 151 cancer-associated genes, including TP53, in cultured HSPC edited with AAVS1 HS RNP in the presence or not of GSE56 from three independent donors. We identified few low-frequency variants in all samples when comparing either editing or control treatment to each other for every donor, without any significant difference in number, type or distribution of nucleotide substitutions in HSPC edited with or without GSE56 or control cells.