Journal
CURRENT OPINION IN GENETICS & DEVELOPMENT
Volume 54, Issue -, Pages 88-96Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.gde.2019.04.001
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Funding
- Deutsche Krebshilfe [70112480]
- German Research Foundation [RA 1629/2-1, SFB1243, SFB 1321, SFB1335]
- European Research Council [COG 819642]
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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.
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