ArticleNature biotechnology2017
Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions.
Article in Nature biotechnology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 292 papers, 1 of them a synthesis that pooled it.
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Who cites it
292 citing papers in PubMed, 1 synthesis or guideline pooled it, 530 citations in OpenAlex.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- CRISPR Screening Identifies SMARCAL1 and MRN as Modulators of WRN Dependency in MSI-H Colorectal Cancer.Cancer research · 2026Article
- Robust prediction of drug combination side effects in realistic settings.PLoS computational biology · 2026Article
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- Erianin induces GSDMD-dependent pyroptosis and synergistically enhances doxorubicin efficacy via the PI3K/AKT signaling pathway in diffuse large B-cell lymphoma.Chinese medical journal · 2026Article
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- A Framework for Benchmarking Pathway Reconstruction Algorithms.bioRxiv : the preprint server for biology · 2026Article
- Advancing risk gene discovery across the allele frequency spectrum.HGG advances · 2026Review
- Comprehensive resistance profiling of chronic myeloid leukaemia associated ABL1 variants against five tyrosine kinase inhibitors using prime editing.Nature biomedical engineering · 2026Article
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- A tunable Cas12a platform for single-cell perturbation screening and CRISPRi.Nature communications · 2026Article
- CRISPR screening reveals NPC1L1 as a key driver of glioblastoma progression via cholesterol metabolic regulation.MedScience · 2026Article
- MVGAE: A Multi-View Graph Auto-Encoder Model for Drug Prediction of Non-Small Cell Lung Cancer Based on Synthetic Lethality.Current issues in molecular biology · 2026Article
- BioMNEDR: mechanism-guided network embedding for drug repurposing.Briefings in bioinformatics · 2026Article
- Vitamin B2 metabolism promotes FSP1 stability to prevent ferroptosis.Nature structural & molecular biology · 2026Article
- CMCL-DDI: Pharmacophore-aware cross-view contrastive learning for drug-drug interaction prediction.PloS one · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Dissecting Epigenetic Drug Response Mechanisms Using CRISPR Knockout Screens.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- A next-generation dual guide CRISPR system for genetic interaction library screening.Nature communications · 2025Article
232 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.