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Semin Cancer Biol. 2019 Apr;55:106-119. doi: 10.1016/j.semcancer.2018.04.001. Epub 2018 Apr 16.

CRISPR/Cas9 for cancer research and therapy.

Author information

1
German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics, and Heidelberg University, Department Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg, Germany; Heidelberg University, Department of Internal Medicine II, Medical Faculty Mannheim, Mannheim, Germany.
2
German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics, and Heidelberg University, Department Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg, Germany; Heidelberg University, Medical Faculty Heidelberg, Heidelberg, Germany.
3
Heidelberg University, Department of Internal Medicine II, Medical Faculty Mannheim, Mannheim, Germany.
4
German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics, and Heidelberg University, Department Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: m.boutros@dkfz.de.

Abstract

CRISPR/Cas9 has become a powerful method for making changes to the genome of many organisms. First discovered in bacteria as part of an adaptive immune system, CRISPR/Cas9 and modified versions have found a widespread use to engineer genomes and to activate or to repress the expression of genes. As such, CRISPR/Cas9 promises to accelerate cancer research by providing an efficient technology to dissect mechanisms of tumorigenesis, identify targets for drug development, and possibly arm cells for cell-based therapies. Here, we review current applications of the CRISPR/Cas9 technology for cancer research and therapy. We describe novel Cas9 variants and how they are used in functional genomics to discover novel cancer-specific vulnerabilities. Furthermore, we highlight the impact of CRISPR/Cas9 in generating organoid and mouse models of cancer. Finally, we provide an overview of the first clinical trials that apply CRISPR/Cas9 as a therapeutic approach against cancer.

KEYWORDS:

CRISPR; Cancer; Cas9; Genome-engineering; High-throughput screening; Immune therapy; Organoids; Synthetic lethality

PMID:
29673923
DOI:
10.1016/j.semcancer.2018.04.001
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