Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
System Biology Institute, Integrated Science & Technology Center, Yale University, West Haven, CT, USA.
Nat Methods. 2019 May;16(5):405-408. doi: 10.1038/s41592-019-0371-5. Epub 2019 Apr 8.
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.
系统地研究影响转移潜能的遗传相互作用一直具有挑战性。在这里,我们开发了大规模并行 CRISPR-Cpf1/Cas12a crRNA 阵列分析(MCAP),这是一种在体内组合检测双敲除的方法。我们设计了一个包含 11934 个阵列的 MCAP 文库,这些阵列靶向 325 对涉及转移的基因的双敲除组合。通过评估小鼠中双敲除的转移潜能,我们揭示了驱动转移的遗传相互作用的定量图谱。