Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy

Chehelgerdi, Mohammad; Chehelgerdi, Matin; Khorramian-Ghahfarokhi, Milad; Shafieizadeh, Marjan; Mahmoudi, Esmaeil; Eskandari, Fatemeh; Rashidi, Mohsen; Arshi, Asghar; Mokhtari-Farsani, Abbas

doi:10.1186/s12943-023-01925-5

Molecular Cancer

Table 2 Preclinical studies of CRISPR-based cancer therapy

From: Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy

Cell/Tissue Type	CRISPR Approach	Results	Limitations/Challenges	Ref
Mouse and Human T cells	Knockout of PD-1	Enhanced T cell activity against cancer cells, prolonged survival in mice	Safety concerns with long-term PD-1 knockout	[59]
Ovarian Cancer Cells	Knockout of oncogene	Reduced cell proliferation and colony formation	Limited assessment of off-target effects	[60]
Lung Cancer Cells	Knockout of mutant EGFR	Reduced cell viability and tumor growth in mice	Off-target effects in some cells	[61]
Triple-Negative Breast Cancer Cells	Knockout of AXL	Reduced tumor growth and increased sensitivity to chemotherapy	Limited assessment of off-target effects	[62]
Various Cancer Cell Lines	Knockout of HIF-1α	Reduced tumor growth and increased sensitivity to radiation therapy	Limited assessment of off-target effects	[63]
Melanoma Cells	Knockout of BRAF V600E	Reduced tumor growth and increased sensitivity to targeted therapy	Off-target effects in some cells	[64]
Leukemia Cells	Knockout of MCL-1	Induced apoptosis and reduced tumor growth	Limited assessment of off-target effects	[65]
Human T cells	Knockout and overexpression of NKG2D	Enhanced tumor cell recognition and killing by CAR-T cells	Safety concerns with long-term NKG2D overexpression	[66, 67]
Pediatric Solid Tumors	Knockout of fusion oncogenes	Reduced tumor growth and increased sensitivity to chemotherapy	Limited assessment of off-target effects	[68]
Prostate Cancer Cells	Knockout of androgen receptor	Reduced cell proliferation and tumor growth in mice	Off-target effects in some cells	[69]
Pancreatic Cancer Cells	Knockout of TGF-β pathway genes	Reduced tumor growth and increased sensitivity to chemotherapy	Limited assessment of off-target effects	[70]
Breast Cancer Cells	Knockout of PAK1 C-terminus	Reduced cell proliferation and tumor growth in mice	Off-target effects in some cells	[71]
Diffuse Large B-cell Lymphoma Cells	Knockout of BCL6	Induced apoptosis and reduced tumor growth	Limited assessment of off-target effects	[72]
Glioblastoma Cells	Knockout of TERT promoter mutations	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[73]
Acute Myeloid Leukemia Cells	Knockout of GATA2	Induced differentiation and reduced tumor growth	Limited assessment of off-target effects	[74]
Human Hematopoietic Stem Cells	Knockout of BCL11A enhancer	Induced fetal hemoglobin expression and reduced sickle cell symptoms	Limited assessment of off-target effects	[75]
B Cell Acute Lymphoblastic Leukemia Cells	Knockout of CD19	Induced apoptosis and reduced tumor growth in mice	Off-target effects in some cells	[76]
Diffuse Large B-cell Lymphoma Cells	Knockout of EZH2	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[77]
Glioma Cells	Knockout of IDH1	Reduced cell viability and tumor growth in mice	Off-target effects in some cells	[78]
Neuroblastoma Cells	Knockout of MYCN	Induced apoptosis and reduced tumor growth	Limited assessment of off-target effects	[79]
Ovarian Cancer Cells	Knockout of MUC16	Reduced cell proliferation and invasion	Limited assessment of off-target effects	[80]
Alveolar Rhabdomyosarcoma Cells	Knockout of PAX7-FOXO1	Reduced cell proliferation and tumor growth in mice	Off-target effects in some cells	[81]
Esophageal Cancer Cells	Knockout of SOX2	Reduced cell proliferation and colony formation	Limited assessment of off-target effects	[82]
Hepatocellular Carcinoma Cells	Knockout of TERT	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[83]
Colorectal Cancer Cells	Knockout of Wnt/β-catenin pathway genes	Reduced cell proliferation and tumor growth in mice	Off-target effects in some cells	[84]
Breast Cancer Cells	Knockout of P53	Increased cell proliferation and colony formation	Off-target effects in some cells	[85]
Pancreatic Cancer Cells	Knockout of KRAS	Reduced cell viability and tumor growth in mice	Limited assessment of off-target effects	[86]
Cervical Cancer Cells	Knockout of BIRC5	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[87]
Prostate Cancer Cells	Knockout of EZH2	Reduced cell proliferation and colony formation	Off-target effects in some cells	[79]
Osteosarcoma Cells	Knockout of HIF-1α	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[88]
Acute Lymphoblastic Leukemia Cells	Knockout of MYB	Induced apoptosis and reduced tumor growth	Limited assessment of off-target effects	[89]
Renal Cell Carcinoma Cells	Knockout of HIF-2α	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[90]
Hepatocellular Carcinoma Cells	Knockout of SALL4	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[91]
Melanoma Cells	Knockout of CDK6	Reduced cell proliferation and tumor growth in mice	Limited assessment of off-target effects	[92]
Acute Myeloid Leukemia Cells	Knockout of ASXL1	Induced differentiation and reduced tumor growth	Limited assessment of off-target effects	[93]

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