Review Article

Era of Genomic Medicine: A Narrative Review on CRISPR Technology as a Potential Therapeutic Tool for Human Diseases

Table 2

Application of CRISPR as a therapeutic tool for common multifactorial diseases of humans.

DiseaseManipulated geneTargetCell typeSpeciesIn vitro/in vivoDeliveryOutcomeRef

CancerHPV16 genomeExon 7HPV positive SiHa and Caski cells,
HPV negative C33
A HEK 293
HumanIn vitroLuciferase reporter pSSA Rep3-1 plasmidApoptosis and growth inhibition of cells.
No inhibition and apoptosis.
Downregulation of E7 protein and upregulation of tumor suppression protein pRb.
[65]
Pten gene and p53 gene simultaneouslyLiver cellsMouseIn vivoHydrodynamic injection to deliver of Cas9 and sgRNAsLiver tumors similar to those caused by Cre-loxP mediated deletion of p53.[66]
Pten gene onlyLiver cellsMouseIn vivoAkt phosphorylation and lipid accumulation phenocopying gene deletion using Cre-loxp deletion.[66]
AsLX1 homozygous mutationGenomic region overlapping AsLX1 mutations observed in KBM5 cellsKBM5 cell lineMouseIn vivopX458 vector transfectionLonger cell survival was observed when compared to cells that were not rectified.
Normal cell function rectified and downregulated polycomb repressive complex 2 genes.
Longer survival in mice with X
enograft of corrected cell lines as opposed to these X
enografted with uncorrected cell lines.
Correction of driver mutations in leukemia cells increases survival in in vivo mice.
[67]
CDK 114th coding exon of CDK11KHOS and U 205 osteosarcoma cell linesHumanIn vitroU6gRNA-cas9-2A-GFPDecreased viability and proliferation of osteosarcoma cells.
Induced apoptosis in KHOS and U20
cell lines. Reduced invasion and migration of cells.
[68]
MCL 1Human Burkitt’s lymphoma cells.
Burkitt’s lymphoma xenograft models.
MouseIn vivoDual lentiviral vector systemApoptosis of lymphoma cells at high frequency.
Tumor regression or impaired growth.
[69]
SGCBP1MCF-7 and MDA-MB-231 cell lines.HumanIn vitroLenti CRISPR/CAS9 vectorInhibited proliferation of breast cancer cells.[70]
KLHDC4Targeting exon 5 of KLHDC4 geneNasopharyngeal carcinoma cellsMouseIn vivopX330 transfection vectorInhibited growth, migration, cell proliferation, migration of cells, and increased apoptosis.[71]

DiabetesINS geneExon 2 and exon 3Porcine primary fibroblast cellsPigletIn vivopx458 vectorSuccessful models generated for study.[72]
Letine/leptine receptor genesExon 2C57BL/6J embryo (mice)MouseIn vivoMicroinjection of Cas9 mRNA and sgRNAsPhenotypically identical to mice models involving the use of obese and diabetic mice.[73]
Hepatocyte nuclear factor 1BHuman iPSCsHumanIn vitroPlasmid vectorsIt provides extensive insight into the influence that HNF1B knockout mutations can have on the development of diabetes and the molecular mechanisms involved with pancreatic development.[74]

Cardiovascular diseasesLMNA1-cell stage zebrafish embryoZebrafishIn vivoMicroinjectionModels for the study of early-onset CCD.[75]
PCSK9 geneExon 1 and exon 2 of the PCSK9 geneHepatocytesMouseIn vivoAdenoviral delivery50% of mice showed loss of function and reduction of LDL levels.[76]
ANGPTL3MouseIn vivoAdenoviral vectorsReduced risk of CHD, reduced blood triglycerides and LDL.[77]
ApoE and LDLR geneExon 2 of ApoE and LDLR genePigIn vivopGL3-U6-gRNA-PGK-puromycin and Cas9 expressing plasmidSuccessful generation of pig models.[78]