Genomic Editing Tools to Model Human Diseases with Isogenic Pluripotent Stem Cells

Gene correction of HAX1 reversed Kostmann disease phenotype in patient-specific induced pluripotent stem cells

“…This provides optimal experimental conditions for iPSC disease modeling as patient-specific or clonal variability between different iPSC lines can be largely excluded. 52,53 Furthermore, this strategy allows for confidence in genetic causality without the necessity of animal models. [54][55][56] Our CRISPR-Cas9-and homology-directed repair-based 1-step cell transfection and screening protocol allowed the generation and identification of corrected clones in less than 3 weeks with no detectable chromosomal aberrations or mutations at the sgRNA's top predicted 5 off-target sites.…”

Urine-derived induced pluripotent stem cells as a modeling tool to study rare human diseases

“…Reliable control iPSC clones could be generated via gene editing to eliminate any potential confounding effects of variations in genetic background. In other words, isogenic iPSCs may differ only at specific loci while all other locations remain identical (74,75).…”

Reprogramming patient-derived cells to study the epilepsies

“…Genome editing techniques, such as the clustered regularly interspaced short palindromic repeat (CRISPR) system, have quickly become the standard for correcting mutant iPSCs for isogenic controls or generating mutant iPSCs from wild type cells (reviewed in 95 ). Genomic background strongly affects the penetrance of epilepsy phenotypes, and the use of genome-editing technology preserves such relations in isogeneic control lines, allowing for in-depth studies of relevant factors in comparison with unrelated human iPSC lines.…”