|
Disease | Manipulated gene | Target | Cell type | Species | In vitro/in vivo | Delivery | Outcome | Ref |
|
Cancer | HPV16 genome | Exon 7 | HPV positive SiHa and Caski cells, HPV negative C33 A HEK 293 | Human | In vitro | Luciferase reporter pSSA Rep3-1 plasmid | Apoptosis 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 simultaneously | | Liver cells | Mouse | In vivo | Hydrodynamic injection to deliver of Cas9 and sgRNAs | Liver tumors similar to those caused by Cre-loxP mediated deletion of p53. | [66] |
Pten gene only | | Liver cells | Mouse | In vivo | Akt phosphorylation and lipid accumulation phenocopying gene deletion using Cre-loxp deletion. | [66] |
AsLX1 homozygous mutation | Genomic region overlapping AsLX1 mutations observed in KBM5 cells | KBM5 cell line | Mouse | In vivo | pX458 vector transfection | Longer 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 11 | 4th coding exon of CDK11 | KHOS and U 205 osteosarcoma cell lines | Human | In vitro | U6gRNA-cas9-2A-GFP | Decreased viability and proliferation of osteosarcoma cells. Induced apoptosis in KHOS and U20 cell lines. Reduced invasion and migration of cells. | [68] |
MCL 1 | | Human Burkitt’s lymphoma cells. Burkitt’s lymphoma xenograft models. | Mouse | In vivo | Dual lentiviral vector system | Apoptosis of lymphoma cells at high frequency. Tumor regression or impaired growth. | [69] |
SGCBP1 | | MCF-7 and MDA-MB-231 cell lines. | Human | In vitro | Lenti CRISPR/CAS9 vector | Inhibited proliferation of breast cancer cells. | [70] |
KLHDC4 | Targeting exon 5 of KLHDC4 gene | Nasopharyngeal carcinoma cells | Mouse | In vivo | pX330 transfection vector | Inhibited growth, migration, cell proliferation, migration of cells, and increased apoptosis. | [71] |
|
Diabetes | INS gene | Exon 2 and exon 3 | Porcine primary fibroblast cells | Piglet | In vivo | px458 vector | Successful models generated for study. | [72] |
Letine/leptine receptor genes | Exon 2 | C57BL/6J embryo (mice) | Mouse | In vivo | Microinjection of Cas9 mRNA and sgRNAs | Phenotypically identical to mice models involving the use of obese and diabetic mice. | [73] |
Hepatocyte nuclear factor 1B | | Human iPSCs | Human | In vitro | Plasmid vectors | It 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 diseases | LMNA | | 1-cell stage zebrafish embryo | Zebrafish | In vivo | Microinjection | Models for the study of early-onset CCD. | [75] |
PCSK9 gene | Exon 1 and exon 2 of the PCSK9 gene | Hepatocytes | Mouse | In vivo | Adenoviral delivery | 50% of mice showed loss of function and reduction of LDL levels. | [76] |
ANGPTL3 | | | Mouse | In vivo | Adenoviral vectors | Reduced risk of CHD, reduced blood triglycerides and LDL. | [77] |
ApoE and LDLR gene | Exon 2 of ApoE and LDLR gene | | Pig | In vivo | pGL3-U6-gRNA-PGK-puromycin and Cas9 expressing plasmid | Successful generation of pig models. | [78] |
|