Table 1.
iPSC disease models employing isogenic control lines generated by CRISPR/Cas9. The table lists a number of diseases, the mutation that was reverted or introduced, the differentiated cell type analysed and the molecular or cellular phenotypes observed
| Disease | Editing | Cell type | Phenotype | References |
|---|---|---|---|---|
| Neurological disorders | ||||
| Fragile X syndrome | Removal of triplet repeat (FMR1) | NPC neurons | DNA methylation, gene expression changes | (Boland et al. 2017; Xie et al. 2016) |
| Tetrahydrobiopterin metabolism disorder, Parkinson’s disease | Correction of dopamine synthesis (PHPS, DHPR) | DA neurons | Metabolic (dopamine, BH4), protein expression changes | (Ishikawa et al. 2016) |
| Parkinson’s disease (PD) | Correction of coding point mutations (SNCA) | Cortical neurons | Accumulation of ER-associated degradation substrates | (Chung et al. 2013; Soldner et al. 2011) |
| Correction of coding mutation (LRRK2) | Dopaminergic neurons | Gene expression changes | (Reinhardt et al. 2013) | |
| Alzheimer’s disease (AD) | Point mutations (APP, PSEN1) | Cortical neurons | Protein (Aβ) secretion | (Paquet et al. 2016) |
| Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) | Correction of point mutations | Spinal motor neurons | Proteasome impairment | (Murakami et al. 2017) |
| Frontotemporal lobar degeneration tauopathy (FTLD-Tau) | Correction of intronic or exonic point mutation (MAPT) | Neurons | Accumulation and release of misfolded tau, cell death, electrical stimulation of calcium transients | (Imamura et al. 2016) |
| Huntington disease (HD) | Correction of expanded CAG repeat (HTT) | Forebrain neurons | Neural rosette formation, mitochondrial respiration, gene expression changes | (Xu et al. 2017) |
| Immunodeficiency, centromeric instability, facial abnormalities (ICF) syndrome | Knockout (DNMT3B) | iPSC | Gene expression, DNA methylation changes | (Horii et al. 2013) |
| Other diseases | ||||
| Chronic granulomatous disease (CGD) | Repair of intronic point mutation, exon 5 replacement (CYBB) | Phagocytes | Oxidative burst function (ROS release) | (Flynn et al. 2015; Sweeney et al. 2017) |
| Duchenne muscular dystrophy (DMD) | Exon skipping, frameshift, exon knock-in, deletion (Dystrophin) | Skeletal muscle | Membrane integrity, protein expression, electrical contraction (Ca overflow) changes | (Li et al. 2015; Young et al. 2016) |
| Barth syndrome | Knockout (TAZ) | Cardiomyocytes | Metabolic and structural changes in muscle, myocardial contraction defects | (Wang et al. 2014a, b) |
| Monocytic and dendritic cell immunodeficiency | Knockout (IRF8) | Dendritic cells | Differentiation, cytokine release, migration, antigen presentation | (Sontag et al. 2017) |
| β-thalassemia | Correction of coding mutation (HBB) | Erythroblast | Gene expression changes, hematopoietic differentiation, reactive oxygen species production | (Niu et al. 2016; Song et al. 2015) |
| Hemophilia A | Reversion of chromosomal inversion | Endothelin cells | Restoration of factor VIII expression, rescue of lethality in mouse xenograft model | (Park et al. 2015) |
| Severe combined immunodeficiency (SCID) | Repair of loss of function mutation (JAK3) | T-cells | Restoration of correct T-cell development | (Chang et al. 2015) |
| Sickle Cell Anaemia | Reversion of point mutation (HBB) | Erythrocytes | HBB expression | (Huang et al. 2015) |