The genome-editing technology derived from the bacterial CRISPR/Cas9 system is revolutionizing biomedical research. Using a CRISPR-based strategy, Feng Zhang, Phillip Sharp and colleagues performed a genome-wide loss-of-function genetic screen in vivo, uncovering new genes involved in tumor growth and metastasis (Cell doi:10.1016/j.cell.2015.02.038; 5 March 2015). They started by transducing a non-metastatic lung cancer cell line with a library of 67,405 single-guide RNAs (sgRNAs). When transplanted into immunocompromised mice, the mutated cell pool readily generated metastases in the lung. These tumors were then analyzed to look for gene-specific sgRNA enrichment. The list of top candidates includes known tumor-suppressor genes but also genes with no previously described role in tumor development. This work advances the understanding of cancer evolution and elegantly underscores the potential of CRISPR/Cas9-based screens to study biological phenomena in vivo. It will be interesting to conduct similar cancer studies in other organs, potentially using gain-of-function approaches to identity novel oncogenes.
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Faial, T. CRISPR screen for metastasis. Nat Genet 47, 311 (2015). https://doi.org/10.1038/ng.3263