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Table 2 Summary of the applications of CRISPR/Cas9 on hiPSCs for the identifications of therapeutic strategies

From: Application of CRISPR/Cas9 to human-induced pluripotent stem cells: from gene editing to drug discovery

 

Research field

hiPSCs-derived cells

CRISPR/Cas9 gene editing

Outcome

Ref.

Drug development

Evaluation of PEPT1-mediated intestinal absorption

Intestinal epithelial-like cells

Peptide transporter 1 (PEPT1)-knock-out iPSCs

Setting the basis for the development of peptide and peptide-mimetic drugs as possible substrates of PEPT1

[65]

Multiple-system atrophy (OMIM #146500)

Neurons

Correction of COQ2 mutation

Identification of Q10 as possible therapeutic target

[66]

Monitoring of protein dosage

FOXG1 syndrome

Interneurons

Tag FOXG1 gene with small molecule-assisted shut-off (sMASh)

Demonstration of FOXG1 dose-control

[67]

Gene therapy

Beta-thalassemia (OMIM #613985)

Hematopoietic stem cells

Correction of HBB mutation

Corrected-hematopoietic stem cells transplantation as therapeutic strategy

[68, 69]

Recessive dystrophic epidermolysis bullosa (OMIM #226600)

Keratinocytes and fibroblasts

Correction of COL7A1 mutation

Restoration of the regular collagen type VII expression

[70]

Duchenne muscular dystrophy (OMIM #310200)

Skeletal muscle cells

DMD exon 44 knock-in

Restoration of full protein coding-region

[71]

Drug screening

mtDNA depletion syndrome (OMIM #251880)

Hepatocytes

Inducing DGUOK knock-out

Identification of compound able to restore mithocondrial function

[72]

Alzheimer’s disease (OMIM #104300)

Neurons

Correction of PSEN1 G384A mutation

Identification of a synergistic combination of bromocriptine, cromolyn and topiramate as an anti-Aβ cocktail

[73]

Immune response strategy

HIV infection

Macrophages

Introduction of 32bp-depletion in CCR5 gene

Generation of immune cells resistant to HIV-infection

[74]

HIV infection

Monocytes/macrophages

Engineer hiPSCs to express a CRISPR/Cas9 system directed against the reverse-transcribed products of the viral RNA genome

Stable expression of HIV-targeted CRISPR/Cas9 in hiPSCs-derived reservoir cells

[75]

SARS-Cov-2 infection

Pneumocytes type II

Regulation of genes involved in viral infection

Building a cell platform to test the capacity of candidate antiviral compounds

[76]

Solid tumors

Natural killer

hiPSCs were edited with CRISPR/Cas9 to repress ADAM17 expression

Obtaining natural killer cells directed against tumor cells

[77]