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Curr Opin Genet Dev. 2019 May 8;54:88-96. doi: 10.1016/j.gde.2019.04.001. [Epub ahead of print]

Engineering CRISPR mouse models of cancer.

Author information

1
Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, Technische Universität München, Germany; Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, Technische Universität München, Germany.
2
Institute of Molecular Oncology and Functional Genomics, TUM School of Medicine, Technische Universität München, Germany; Center for Translational Cancer Research (TranslaTUM), TUM School of Medicine, Technische Universität München, Germany; Department of Medicine II, TUM School of Medicine, Technische Universität München, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: roland.rad@tum.de.

Abstract

Gene targeting in mammals has revolutionized the study of complex diseases, involving the interaction of multiple genes, cells, and organ systems. In cancer, genetically engineered mouse models deciphered biological principles by integrating molecular mechanisms, cellular processes, and environmental signals. Major advances in manipulative mouse genetics are currently emerging from breakthroughs in gene editing, which open new avenues for rapid model generation. Here, we review recent developments in engineering CRISPR mouse models of cancer. We describe engineering strategies, including germline manipulation of zygotes or embryonic stem cells, direct in vivo somatic gene editing, and ex vivo targeting of cellular transplant models. We also discuss promises and limitations of the expanding spectrum of CRISPR applications, ranging from engineering of simple mutations over complex genomic rearrangements to gene and epigenome regulation. Fast and scalable in vivo CRISPR methodologies pave the way for a new phase of functional cancer genomics.

PMID:
31078083
DOI:
10.1016/j.gde.2019.04.001

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