Nat Methods:利用CRISPR-Cas9组合筛选发现癌症弱点

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions

导致癌症的基因突变也会削弱癌细胞，从而使得人们有机会开发选择性地杀死它们同时不影响正常细胞的药物。这一概念被称作”合成致死性（synthetic lethality）”，这是因为这些药物仅对发生突变的（或者说合成的）细胞是致命性的。在一项新的研究中。来自美国加州大学圣地亚哥分校、加州大学旧金山分校、斯坦福大学和癌细胞图谱项目（Cancer Cell Map Initiative）的研究人员开发出一种新的方法来寻找合成致死性的基因组合。

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies.