Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28319113.
- Also identified by DOI 10.1038/nmeth.4225 and PMC identifier 5449203.
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Abstract
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.
Medical subject headings
- Chromosome Mapping
- Clustered Regularly Interspaced Short Palindromic Repeats
- Combinatorial Chemistry Techniques
- Epistasis, Genetic
- Neoplasm Proteins