CRISPRCas9-mediated HDR was improved in activated T cells and HSPCs using protected ssODN templates. HDR efficiency was measured in three different loci in activated T cells ( n = 10, P = 0.0006 for CXCR4 , n = 6, P = 6.6 x 10 -6 for FANCD2 and n = 6, P = 9.3 x 10 -5 for UROS loci n indicates the number of biologically independent experiments). Black dots represent measurements with unprotected (un) ssODN templates, and blue dots represent measurements with 5 and 3 protected (PT) ssODN templates.