ArticleProceedings of the National Academy of Sciences of the United States of America2016
Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- A base-editing and auxotrophic selection platform for linking epigenetic regulators to silent biosynthetic gene clusters inSynthetic and systems biotechnology · 2027Article
- Patient-Derived Organoid-Based CRISPR Screens in Cancer Research: Applications, Advances, and Challenges.Cancer medicine · 2026Review
- Expression-linked promoter selection (ELiPS) engineers short, strong ubiquitous promoters for gene therapy applications.bioRxiv : the preprint server for biology · 2026Article
- Article
- dHyperCas12a enables multiplexed CRISPRi screens.Nature communications · 2026Article
- A cost-effective and scalable barcoded library construction method for deep mutational scanning studies.PLoS biology · 2026Article
- Uncovering genetic interactions in the DNA repair network in response to endogenous damage and ionizing radiation.Cell reports · 2026Article
- RAPID-DASH: fast and efficient assembly of guide RNA arrays for multiplexed CRISPR-Cas9 applications.Synthetic biology (Oxford, England) · 2026Article
- A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025Article
- Combinatorial protein engineering identifies potent CRISPR activators with reduced toxicity.Nature communications · 2025Article
- A multi-layer encoder prediction model for individual sample specific gene combination effect (MLEC-iGeneCombo).PLoS computational biology · 2025Article
- RAPID-DASH: Fast and Efficient Assembly of Guide RNA Arrays for Multiplexed CRISPR-Cas9 Applications.bioRxiv : the preprint server for biology · 2025Article
- Highly replicated experiments studying complex genotypes using nested DNA barcodes.G3 (Bethesda, Md.) · 2025Article
- HyperCas12a enables multiplexed CRISPRi screens.bioRxiv : the preprint server for biology · 2025Article
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- Combinatorial CRISPR screen revealseLife · 2025Article
- Evaluation of Cas13d as a tool for genetic interaction mapping.Nature communications · 2025Article
- A multilineage screen identifies actionable synthetic lethal interactions in human cancers.Nature genetics · 2025Article
- CRISPR/Cas9 technology in tumor research and drug development application progress and future prospects.Frontiers in pharmacology · 2025Review
76 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
The orchestrated action of genes controls complex biological phenotypes, yet the systematic discovery of gene and drug combinations that modulate these phenotypes in human cells is labor intensive and challenging to scale. Here, we created a platform for the massively parallel screening of barcoded combinatorial gene perturbations in human cells and translated these hits into effective drug combinations. This technology leverages the simplicity of the CRISPR-Cas9 system for multiplexed targeting of specific genomic loci and the versatility of combinatorial genetics en masse (CombiGEM) to rapidly assemble barcoded combinatorial genetic libraries that can be tracked with high-throughput sequencing. We applied CombiGEM-CRISPR to create a library of 23,409 barcoded dual guide-RNA (gRNA) combinations and then perform a high-throughput pooled screen to identify gene pairs that inhibited ovarian cancer cell growth when they were targeted. We validated the growth-inhibiting effects of specific gene sets, including epigenetic regulators KDM4C/BRD4 and KDM6B/BRD4, via individual assays with CRISPR-Cas-based knockouts and RNA-interference-based knockdowns. We also tested small-molecule drug pairs directed against our pairwise hits and showed that they exerted synergistic antiproliferative effects against ovarian cancer cells. We envision that the CombiGEM-CRISPR platform will be applicable to a broad range of biological settings and will accelerate the systematic identification of genetic combinations and their translation into novel drug combinations that modulate complex human disease phenotypes.
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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.