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

In vivo profiling of metastatic double knockouts through CRISPR-Cpf1 screens
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DOI:
10.1038/s41592-019-0371-5
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发表时间:
2019-05-01
期刊:
影响因子:
48
通讯作者:
Chen, Sidi
Chen, Sidi
中科院分区:
生物学1区
文献类型:
--
作者:
Chow, Ryan D.;Wang, Guangchuan;Chen, Sidi

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影响转移潜能的遗传相互作用的系统研究一直具有挑战性。在这里,我们开发了大规模平行CRISPR-Cpf 1/Cas 12 a crRNA阵列分析(MCAP),这是一种用于体内双敲除的组合询问方法。我们设计了一个包含11,934个阵列的MCAP文库,靶向325个与转移有关的基因的成对组合。通过评估小鼠中双敲除的转移潜力,我们揭示了驱动转移的遗传相互作用的定量景观。
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.