The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions
Open accessAbstract
Identification of effective combination therapies is critical to address the emergence of drug-resistant cancers, but direct screening of all possible drug combinations is infeasible. Here we introduce a CRISPR-based double knockout (CDKO) system that improves the efficiency of combinatorial genetic screening using an effective strategy for cloning and sequencing paired single guide RNA (sgRNA) libraries and a robust statistical scoring method for calculating genetic interactions (GIs) from CRISPR-deleted gene pairs. We applied CDKO to generate a large-scale human GI map, comprising 490,000 double-sgRNAs directed against 21,321 pairs of drug targets in K562 leukemia cells and identified synthetic lethal drug target pairs for which corresponding drugs exhibit synergistic killing. These included the BCL2L1 and MCL1 combination, which was also effective in imatinib-resistant cells. We further validated this system by identifying known and previously unidentified GIs between modifiers of ricin toxicity. This work provides an effective strategy to screen synergistic drug combinations in high-throughput and a CRISPR-based tool to dissect functional GI networks.
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Pickar-Oliver, A., & Gersbach, C. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0131-5 · Cited by 1,459
Zitnik, M., Nguyen, F., Wang, B., Leskovec, J., Goldenberg, A., & Hoffman, M. M. (2019) · Information Fusion · doi:10.1016/j.inffus.2018.09.012 · Cited by 675
Synthetic lethality and cancer
O'Neil, N. J., Bailey, M. L., & Hieter, P. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.47 · Cited by 658
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Metadata
- Authors
- Han, K., Jeng, E. E., Hess, G. T., Morgens, D. W., Li, A., & Bassik, M. C.
- Venue
- Nature Biotechnology
- Published
- 2017-03-20
- Volume
- 35
- Issue
- 5
- Pages
- 463-474
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2597646117
- Cited by
- 498
- References
- 28
- FWCI
- 19.12
- Type
- journal article
- Language
- en
- Open access
- green
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- Han, K., Jeng, E. E., Hess, G. T., Morgens, D. W., Li, A., & Bassik, M. C. (2017). Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature Biotechnology. https://doi.org/10.1038/nbt.3834
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