design: Custom SureSelect baits were designed against all predicted on- and off-target regions in the human genome (hg38) for the gRNAs utilized in this study, based on sequence homology between the gRNA protospacer and the genome. Off-targets were defined as having up to five mismatches to any on-target or one indel and up to four mismatches to any on-target. This resulted in 15,920 captured regions for the Cas9 quadruple editing scenario and 25,988 captured regions for the ABE quadruple editing scenario. In Cas9 on-target scenario, gRNAs were designed to result in a knockout (KO) of TRAC, B2M, CIITA and PVR. For the ABE setup, the KO tragets were CD3E, B2M, CIITA and PVR.