These strategies are clearly complementary to each other, and can provide information on potential epistatic interactions with other alleles present in specific genetic backgrounds. It is also worth considering that modification of a “WT” cell line is often simpler technically, since both the genome editing and subsequent downstream differentiation and analysis can be optimised for a particular cell type. Additionally, the “WT” cells can be thoroughly characterised beforehand, and different genetically edited lines involved in the same disease can be directly compared. In the case of patient-derived cells, each cell line will behave somewhat differently, and therefore it is often more difficult to perform such manipulations, especially at higher throughput.
