Table 1 Base substitution in hPSCs with base editing tools
From: Gene editing with ‘pencil’ rather than ‘scissors’ in human pluripotent stem cells
Disease | Cell type | Editing tool | Mutations | Phenotype | Reference | |
|---|---|---|---|---|---|---|
Long QT (LQT) | hESCs, hiPSCs | ABE | L114P, R190Q | KCNQ1 | Prolonged QT beating interval | Qi et al. [72] |
Y616C, Y475C | KCNH2 | |||||
GNE myopathy | hESCs, hiPSCs | ABE | I329T, I588T | GNE | Reduced sialic acid production in hPSCs and myoblasts | Park et al. [9] |
CBE | R160Q, V727M | |||||
Recessive Dystrophic Epidermolysis Bullosa (RDEB) | Patient-derived iPSC | ABE | R185* (*non-sense mutation) | COL7A1 | Deposition of C7 at the dermal–epidermal junction | Osborn et al. [74] |
Duchenne muscular dystrophy (DMD) | Patient-derived iPSC | ABE | Exon 50 skipping | DMD | Restoration of dystrophin protein level in differentiated cardiomyocyte | Chemello et al. [76], Yuan et al. [75], Wang et al. [79] Eberherr et al. [77] |
PE | Exon 52 reframing | |||||
(GT insertion) | ||||||
CBE | Modulating mRNA splicing | |||||
DMD hiPSCs established by CRISPR-Cas9 gene editing | ABE | Exon 55 skipping | ||||
STAT3-Hyperimmuno-globulin | Patient-derived iPSC | ABE | R382W | STAT3 | Restoration of STAT3 downstream signaling | |
E syndrome (STAT3-HIES) | ||||||
Parkinson’s disease (PD) | Patient-derived iPSC | ABE | G2019S | LRRK2 | Reduced LPRRK2 kinase activity, decreased phospho-α-synuclein expression, mitigated neurite shrinkage, apoptosis and restored impaired neurite outgrowth in differentiated dopaminergic neuron | Chang et al. [78] |
iPSCs, hESCs | PE | G2019S A30P | LRRK2 SNCA | n.a | Li et al. [80] | |
Dilated cardiomyopathy (DCM) | iPSCs | ABE | R634Q | RBM20 | Normal distribution of RBM20 in cardiomyocytes, TTN splicing pattern, and expression of N2B | Nishiyama et al. [81] |
PE | R636S | |||||