Rapidly developing genome editing technologies now enable the introduction of genetic changes into iPSCs in a site-specific manner, including correction of disease-causing gene mutations in patient-derived iPSCs and introduction of specific mutations into non-disease affected wild type (WT) iPSCs. These approaches allow the generation of genetically matched, isogenic iPSC lines with the introduced mutation as the sole variable, ensuring the reliable identification of the true pathology while avoiding the confusion with any disparities in genetic background or epiphenomena resulting from possible line-to-line variations. The isogenic iPSC controls will be especially important when modeling sporadic or polygenic diseases, in which phenotypic differences are expected to be small14.
