Weber and colleagues use the CRISPR/Cas9 system to multiplex functional genomic analyses. In models of intrahepatic cholangiocarcinoma and hepatocellular carcinoma, the authors perform an in vivo screen targeting a panel of tumor suppressor genes. Plasmid delivery to hepatocytes via hydrodynamic tail vein injection enabled in vivo screening of 10 single guide RNA sequences (sgRNA) in combination with oncogenic Kras G12D and 18 sgRNAs in combination with CCl 4 treatment. High mutant read

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... ies using next-generation sequencing in distinct tumor nodules suggest applications towards dissecting intratumoral heterogeneity and phylogenetic relationships among tumor foci. In addition, a multiplexed in vivo screen has the potential to assess the role for complex genetic interactions and tumor-tumor microenvironment interactions. (Image courtesy of Wikimedia Commons.