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Nat Methods. 2019 May;16(5):405-408. doi: 10.1038/s41592-019-0371-5. Epub 2019 Apr 8.

In vivo profiling of metastatic double knockouts through CRISPR-Cpf1 screens.

Chow RD1,2,3,4, Wang G1,2,3, Ye L1,2,3, Codina A1,2,3,5, Kim HR1,2,3, Shen L1,2,3, Dong MB1,2,3,4,6, Errami Y1,2,3, Chen S7,8,9,10,11,12,13,14.

Author information

1
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
2
System Biology Institute, Integrated Science & Technology Center, Yale University, West Haven, CT, USA.
3
Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT, USA.
4
Yale MD-PhD Program, Yale University, New Haven, CT, USA.
5
Yale Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT, USA.
6
Yale Immunobiology Program, The Anlyan Center for Medical Research & Education, New Haven, CT, USA.
7
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. sidi.chen@yale.edu.
8
System Biology Institute, Integrated Science & Technology Center, Yale University, West Haven, CT, USA. sidi.chen@yale.edu.
9
Center for Cancer Systems Biology, Integrated Science & Technology Center, West Haven, CT, USA. sidi.chen@yale.edu.
10
Yale MD-PhD Program, Yale University, New Haven, CT, USA. sidi.chen@yale.edu.
11
Yale Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, CT, USA. sidi.chen@yale.edu.
12
Yale Immunobiology Program, The Anlyan Center for Medical Research & Education, New Haven, CT, USA. sidi.chen@yale.edu.
13
Yale Comprehensive Cancer Center, New Haven, CT, USA. sidi.chen@yale.edu.
14
Yale Stem Cell Center, New Haven, CT, USA. sidi.chen@yale.edu.

Abstract

Systematic investigation of the genetic interactions that influence metastatic potential has been challenging. Here we developed massively parallel CRISPR-Cpf1/Cas12a crRNA array profiling (MCAP), an approach for combinatorial interrogation of double knockouts in vivo. We designed an MCAP library of 11,934 arrays targeting 325 pairwise combinations of genes implicated in metastasis. By assessing the metastatic potential of the double knockouts in mice, we unveiled a quantitative landscape of genetic interactions that drive metastasis.

PMID:
30962622
DOI:
10.1038/s41592-019-0371-5

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