Data supporting "Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques"

Abstract: For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of longterm engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDRedited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via 53BP1 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs.Data Summary:All data is organized by the corresponding manuscript figure and panel.Supporting scripts and barcodetrackR app required to generate Fig. 3C-E, Fig. 6,Fig. S4A and Fig. S6 are linked to this repository under "Related Materials".Any additional information required to reanalyze the data reported in this repository and corresponding paper is available from the lead contact upon request ([e-mail]).