Human induced pluripotent stem cells for monogenic disease modelling and therapy

Table 1 Models of monogenic dominant diseases

Diseases	Genetic defects	Target cells for reprogramming	Delivery methods	Disease relevant cells	Ref.
Huntington’s disease (OMIM #143100)	Expanded CAG repeat in HTT gene	HF	Lentiviral vectors (O, S, K, M, NANOG and LIN28)	Neurons	[79]
		HF	Retroviral vectors (O, S, K, M)	Astrocytes	[80]
		HF	Lentiviral vectors (O, S, K, M)	Neurons	[81]
		HF	Retroviral vectors (O, S, K, M)	Neurons	[82]
		HF	Retroviral vectors (O, S, K, M)	GABAergic neurons	[83]
		HF	Retroviral vectors (O, S, K, M)	Striatal neurons	[84]
Marfan syndrome (OMIM #154700)	FBN1 mutations	HF	Retroviral vectors (O, S, K, M)	Osteogenic cells chondrogenic cells	[87]
Myotonic dystrophy type 1 (OMIM #160900)	Expanded CTG repeat in DMPK gene	HF	Retroviral vectors (O, S, K, M)	NS	[92]
		HF	Retroviral vectors (O, S, K, M)	NSC	[94]
Achondroplasia (OMIM #100800)	FGFR3 mutations	HF	Episomal plasmid vectors (O, S, K, M, LIN28 and p53 shRNA)	Chondrocytes	[97]
Familial hypercholesterolemia (OMIM #143890)	LDLR mutations	HF	Retroviral vectors (O, S, K, M)	HLC	[99]
		HF	Lentiviral vectors (O, S, NANOG, LIN28)	Hepatocytes	[100]
		HF	Retroviral vectors (O, S, K, M)	HLC	[101]
Timothy syndrome (OMIM #601005)	CACNA1C mutations	HF	Retroviral vectors (O, S, K, M)	Cardiac myocytes	[102]
		HF	Retroviral vectors (O, S, K, M)	Cortical neuronal precursor cells and neurons	[103]
		HF	Retroviral vectors (O, S, K, M)	Cortical neuronal precursor cells and neurons	[104]

NS: Neurosphere; NSC: Neural stem cell; HLC: Hepatocyte-like cells; HF: Human fibroblasts; O: OCT4; S: SOX2; K: KLF4; M: C-MYC.

Table 2 Models of monogenic recessive diseases

Diseases	Genetic defects	Target cells for reprogramming	Delivery methods	Disease relevant cells	Ref.
Spinal muscular atrophy (OMIM #253300)	SMN1 mutations	HF	Lentiviral vectors (O, S, NANOG, LIN28)	Neurons/astrocytes/motor neurons	[109]
		HF	Retroviral vectors (O, S, K, M)	Motor neurons	[110]
		HF	Lentiviral vectors (O, S, NANOG, LIN28)	Motor neurons	[112]
		HF	Retroviral vectors (O,S, K, M)	GABAergic neurons	[113]
β-thalassaemia (OMIM #613985)	Point mutations or deletions in the β-globin (HBB) gene	HF/AF/CVS	Retroviral vectors (O, S, K, M)	Hematopoietic cells	[116]
		AF	Lentiviral vectors (O, S, K, M)	Hematopoietic cells	[118]
		HF/MSCs	Lentiviral vectors (O, S, K, M)	Erythroid cells	[119]
		HF	PiggyBac transposon	Hematopoietic cells	[120]
Cystic fibrosis (OMIM #219700)	CFTR mutations	HF	Lentiviral vectors (O, S, K, M)	Mature airway epithelial cells	[126]
		HF	Modified RNAs (RiPSC)	Mature airway epithelial cells	[127]
		HF	Retroviral vectors (O, S, K, M)	Mature airway epithelial cells	[128]
		HF	Retroviral vectors (O, S, K, M)	CLCs	[130]
Sickle cell disease (OMIM #603903)	HBB mutations	HF	Retroviral vectors (O, S, K, M)	Erythrocytes	[135]
		HF	Lentiviral vectors (O, S, K, M)	None	[136]
Hutchinson-gilford progeria syndrome (OMIM #176670)	LMNA mutations	HF	Retroviral vectors (O, S, K, M)	Neural progenitors, endothelial cells, fibroblasts, VSMCs, and MSCs	[137]
		HF	Retroviral vectors (O, S, K, M)	Vascular SMCs	[138]
		HF	Retroviral vectors (O, S, K, M)	MSCs and osteogenic cells	[139]
Niemann–pick disease type C1 (OMIM #257220)	NPC1 mutations	HF	Retroviral vectors (O, S, K, M)	Neurons	[140]
		HF	Lentiviral vectors (O, S, K, M)	Neurons	[141]
		HF	SeV vectors (O, S, K, M)	HLCs and neural progenitors	[142]

CLCs: Cholangiocytes; VSMCs: Vascular smooth muscular cells; MSCs: Mesenchymal stem cells; SMCs: Smooth muscle cells; MSCs: Mesenchymal stem cells; HLCs: Hepatocyte-like cells; SeV: Sendai virus; AF: Amniotic fluid cells; CVS: Chorionic villus; HF: Human fibroblasts; O: OCT4; S: SOX2; K: KLF4; M: C-MYC.

Table 3 Models of monogenic X-linked recessive diseases

Diseases	Genetic defects	Target cells for reprogramming	Delivery methods	Disease relevant cells	Ref.
Fragile X syndrome (OMIM #300624)	FMR1 silencing	HF	Retroviral vectors (O, S, K, M)	Neurons	[146]
		HF	Retroviral vectors (O, S, K, M)	Forebrain Neurons	[147]
		HF	Sendai virus	NPC	[148]
Duchenne muscular dystrophy (OMIM #310200)	Dystrophin gene mutations	HF	Retroviral vectors (O, S, K, M)	Myogenic cells	[154]
		HF	Retroviral vectors (O, S, K, M)	CMs	[155]
		HF	Retroviral vectors (O, S, K, M)	Neurons	[156]
Wiskott-aldrich syndrome (OMIM #301000)	WASP mutations	HF	Retroviral vectors/sendai virus vectors (O, S, K, M)	Megakaryocytes	[157]
Rett syndrome (OMIM #312750)	MeCP2/CDKL5 mutations	HF	Retroviral vectors (O, S, K, M)	Neurons	[158]
		HF	Retroviral vectors (O, S, K, M)	NPCs/mature neurons	[159]
		HF	Retroviral vectors (O, S, K, M)	NPCs/mature neurons	[160]
Hemophilia A (OMIM #306700)	Deficiency of factor VIII	Urine cells	Episomal vectors (O, S, K, SV40LT)	Hepatocytes	[161]

NPC: Neural progenitor cells; CMs: Cardiomyocytes; HF: Human fibroblasts; O: OCT4; S: SOX2; K: KLF4; M: C-MYC.