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Genome Med. 2015 Jun 9;7(1):53. doi: 10.1186/s13073-015-0178-7. eCollection 2015.

Precision cancer mouse models through genome editing with CRISPR-Cas9.

Author information

1
RNA Therapeutics Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605 USA.
2
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142 USA ; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142 USA ; Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139 USA ; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142 USA.
3
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142 USA.

Abstract

The cancer genome is highly complex, with hundreds of point mutations, translocations, and chromosome gains and losses per tumor. To understand the effects of these alterations, precise models are needed. Traditional approaches to the construction of mouse models are time-consuming and laborious, requiring manipulation of embryonic stem cells and multiple steps. The recent development of the clustered regularly interspersed short palindromic repeats (CRISPR)-Cas9 system, a powerful genome-editing tool for efficient and precise genome engineering in cultured mammalian cells and animals, is transforming mouse-model generation. Here, we review how CRISPR-Cas9 has been used to create germline and somatic mouse models with point mutations, deletions and complex chromosomal rearrangements. We highlight the progress and challenges of such approaches, and how these models can be used to understand the evolution and progression of individual tumors and identify new strategies for cancer treatment. The generation of precision cancer mouse models through genome editing will provide a rapid avenue for functional cancer genomics and pave the way for precision cancer medicine.

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