ArticleNature biotechnology2018
Orthologous CRISPR-Cas9 enzymes for combinatorial genetic screens.
Article in Nature biotechnology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 170 papers, 1 of them a synthesis that pooled it.
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Who cites it
170 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- Towards efficient perturbation for the noncoding genome.Nature communications · 2026Article
- CRISPR/dCas9-mediated tuning of DMPK transcription reveals a quantitative relationship between toxic repeat RNA expression and MBNL1 activity in myotonic dystrophy.Human molecular genetics · 2026Article
- Patient-Derived Organoid-Based CRISPR Screens in Cancer Research: Applications, Advances, and Challenges.Cancer medicine · 2026Review
- Guide RNA reprogramming facilitates minimized tracrRNA-dependent off-target and versatile CRISPR/Cas9 engineering.Nature communications · 2026Article
- Article
- A Rapid Hairy Root-Based Platform for CRISPR/Cas Optimization and Guide RNA Validation in Lettuce.Plants (Basel, Switzerland) · 2026Article
- Double-CRISPR Knockout Simulation (DKOsim): A Monte-Carlo randomization system to model cell growth behavior and infer the optimal library design for growth-based double knockout screens.PLoS computational biology · 2026Article
- Prion propagation is controlled by a hierarchical network involving the nuclear Tfap2c and hnRNP K factors and the cytosolic mTORC1 complex.PLoS pathogens · 2026Article
- Elucidating the kinetics of CRISPR-SaCas9 action to obtain effective HIV DNA excision with two gRNAs.Nucleic acids research · 2026Article
- Analysis of Combinatorial Knockout CRISPR Screens with GRAPE: Genetic interaction Regression Analysis of Pairwise Effects.bioRxiv : the preprint server for biology · 2026Article
- Quantitative analysis of genetic interactions in human cells from genome-wide CRISPR-Cas9 screens.bioRxiv : the preprint server for biology · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Higher order synthetic lethals are keys to minimize cancer treatment effects on non-tumor cells.PloS one · 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
- CROPseq-multi: a universal solution for multiplexed perturbation in high-content pooled CRISPR 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
- CRISPR antiviral inhibits neurotrophic JC polyomavirus in 2D and 3D culture models through dual-gRNA excision by SaCas9.Molecular therapy. Nucleic acids · 2025Article
- Amplified dosage of the NKX2-1 lineage transcription factor controls its oncogenic role in lung adenocarcinoma.Molecular cell · 2025Article
110 more citing papers are in PubMed but not listed here.
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15 authors.
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Abstract
Combinatorial genetic screening using CRISPR-Cas9 is a useful approach to uncover redundant genes and to explore complex gene networks. However, current methods suffer from interference between the single-guide RNAs (sgRNAs) and from limited gene targeting activity. To increase the efficiency of combinatorial screening, we employ orthogonal Cas9 enzymes from Staphylococcus aureus and Streptococcus pyogenes. We used machine learning to establish S. aureus Cas9 sgRNA design rules and paired S. aureus Cas9 with S. pyogenes Cas9 to achieve dual targeting in a high fraction of cells. We also developed a lentiviral vector and cloning strategy to generate high-complexity pooled dual-knockout libraries to identify synthetic lethal and buffering gene pairs across multiple cell types, including MAPK pathway genes and apoptotic genes. Our orthologous approach also enabled a screen combining gene knockouts with transcriptional activation, which revealed genetic interactions with TP53. The "Big Papi" (paired aureus and pyogenes for interactions) approach described here will be widely applicable for the study of combinatorial phenotypes.
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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.