Whilst genome editing can be very effectively used to reduce the variability between patients, the process of genome editing itself can introduce artefacts from both off-target mutagenesis (Cradick et al. 2013; Fu et al. 2013; Veres et al. 2014) and clonal variability within a particular iPSC line. One method for controlling the variability introduced by the genome editing process is by re-introducing the disease mutation in the genetically corrected patient line. Similarly, introducing mutations into a consistent “WT” line can reduce the variability between patients and during iPSC derivation. The experimental strategy will depend on the specific question that is being addressed, but these criteria should be taken into account in order to maximise sensitivity for phenotypic changes, and minimise workload.
