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Recent Advances and Therapeutic Strategies Using CRISPR Genome Editing Technique for the Treatment of Cancer

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Abstract

CRISPR genome editing technique has the potential to target cancer cells in a precise manner. The latest advancements have helped to address one of the prominent concerns about this strategy which is the off-target integrations observed with dsDNA and have resulted in more studies being carried out for potentially safer and more targeted gene therapy, so as to make it available for the clinical trials in order to effectively treat cancer. CRISPR screens offer great potential for the high throughput investigation of the gene functionality in various tumors. It extends its capability to identify the tumor growth essential genes, therapeutic resistant genes, and immunotherapeutic responses. CRISPR screens are mostly performed in in vitro models, but latest advancements focus on developing in vivo models to view cancer progression in animal models. It also allows the detection of factors responsible for tumorigenesis. In CRISPR screens key parameters are optimized in order to meet proficient gene targeting efficiencies. It also detects various molecular effectors required for gene regulation in different cancers, essential pathways which modulate cytotoxicity to immunotherapy in cancer cells, important genes which contribute to cancer cell survival in hypoxic states and modulate cancer long non-coding RNAs. The current review focuses on the recent developments in the therapeutic application of CRISPR technology for cancer therapy. Furthermore, the associated challenges and safety concerns along with the various strategies that can be implemented to overcome these drawbacks has been discussed.

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Abbreviations

NHEJ:

Non-homologous end joining

HDR:

Homology directed repair

ODN:

Oligodeoxynucleotides

ZFNs:

Zinc-finger nucleases

TALENs:

Transcription activator-like effector nucleases

CSCs:

Cancer stem cells

Oct2:

Organic cation transporter 2

Sox2:

SRY-Box Transcription Factor 2

STAT3:

Signal transducer and activator of transcription 3

EMT:

Epithelial-mesenchymal transition

ChIP:

Chromatin immunoprecipitation

Csn2:

Casein Beta

crRNA:

CRISPR RNAs

tracrRNA:

Trans-activating crispr RNA

KHOS:

Angiogenic and non-angiogenic human osteosarcoma cells

U-2OS:

Human Bone Osteosarcoma Epithelial Cells

EWSR1:

Ewing sarcoma breakpoint region 1

FLI1:

Friend leukemia integration 1 transcription factor

MCF-7:

Michigan Cancer Foundation-7

CTCF:

CCCTC-binding factor

LNCaP:

Lymph Node Carcinoma of the prostate

KIF4A:

Kinesin Family Member 4A

WDR62:

WD Repeat Domain 62

AGS:

Adenocarcinoma gastric cell line.

SGC:

Sebaceous gland carcinoma

HEK293:

Human Embryonic Kidney 293 cells)

LGALS2:

Galectin 2

AOM/DSS:

Azoxymethane /Dextran Sodium Sulfate

Pten:

Phosphatase and tensin homolog

Usp-7:

Ubiquitin specific protease 7

PTPM1:

Protein Tyrosine Phosphatase Mitochondrial 1

NF-1:

Neurofibromin 1

DUSP9:

Dual Specificity Phosphatase 9

MAPK:

Mitogen-activated protein kinase

FOXO3:

Forkhead box O3

mTOR:

Mammalian target of rapamycin

TGF-β:

Transforming growth factor-beta

NRAS:

Neuroblastoma RAS viral oncogene homolog

MEK:

Mitogen-activated extracellular signal-regulated kinase

SOCS3:

Suppressor of cytokine signaling 3

USP8:

Ubiquitin Specific Peptidase 8

FANCA:

Fanconi anemia, complementation group A

MGMT:

O6-Methylguanine-DNA-methyltransferase

GDSC:

Genomics of Drug Sensitivity in Cancer

CTRP:

Cancer Therapeutics Response Portal

PI3k:

Phosphoinositide 3-kinase

HER-2:

Human epidermal growth factor receptor 2

LRP8:

Low-density lipoprotein receptor-related protein 8

FGFR2:

Fibroblast growth factor receptor 2

MUC1:

Mucin 1

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  1. Shreyasi Maity and Rishyani Mukherjee have contributed equally to this work.

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  1. School of Bioscience and Technology, Vellore Institute of Technology, Vellore, 632 014, Tamil Nadu, India

    Shreyasi Maity, Rishyani Mukherjee & Satarupa Banerjee

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Maity, S., Mukherjee, R. & Banerjee, S. Recent Advances and Therapeutic Strategies Using CRISPR Genome Editing Technique for the Treatment of Cancer. Mol Biotechnol 65, 206–226 (2023). https://doi.org/10.1007/s12033-022-00550-9

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