ArticleNature biotechnology2021
Optimization of AsCas12a for combinatorial genetic screens in human cells.
Article in Nature biotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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
135 citing papers in PubMed, 2 syntheses or guidelines pooled it, 236 citations in OpenAlex.
- Pooled it
- Bidirectional genome-wide CRISPR screens reveal host factors regulating SARS-CoV-2, MERS-CoV and seasonal HCoVs.Nature genetics · 2022Pooled it
- Inducible dCas12a system expands CRISPRi/a capabilities for functional genomics in malaria parasiteiScience · 2026Article
- CRISPR-HAWK: haplotype- and variant-aware guide design toolkit for CRISPR-Cas.Bioinformatics (Oxford, England) · 2026Article
- Article
- Towards efficient perturbation for the noncoding genome.Nature communications · 2026Article
- Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026Review
- BASELINE: a CRISPR base editing platform for mammalian-scale single-cell lineage tracing.Nucleic acids research · 2026Article
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- A screen of chromatin-targeting compounds identifies TAF1 as a novel regulator of HIV latency.mBio · 2026Article
- Article
- A tunable Cas12a platform for single-cell perturbation screening and CRISPRi.Nature communications · 2026Article
- Balancing off-target and on-target considerations for optimized CRISPR-Cas9 knockout library design.Cell genomics · 2026Article
- BEstimate: a computational tool for the design and interpretation of CRISPR base editing experiments.Genome biology · 2026Article
- A rapid and highly sensitive CRISPR-Cas12a ortholog-assisted assay for genotyping of myostatin knockout pigs.Cell & bioscience · 2026Article
- Mechanistic basis for improved activity of Engineered AsCas12a.Communications biology · 2026Article
- Variation in guide RNA library representation results in gene effect score bias in genome-wide CRISPR screens.BMC genomics · 2026Article
- Proximity labeling of thebioRxiv : the preprint server for biology · 2026Article
- dHyperCas12a enables multiplexed CRISPRi screens.Nature communications · 2026Article
- Analysis of Combinatorial Knockout CRISPR Screens with GRAPE: Genetic interaction Regression Analysis of Pairwise Effects.bioRxiv : the preprint server for biology · 2026Article
75 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
15 authors at 3 institutions in 1 country.
Funding
Abstract
Cas12a RNA-guided endonucleases are promising tools for multiplexed genetic perturbations because they can process multiple guide RNAs expressed as a single transcript, and subsequently cleave target DNA. However, their widespread adoption has lagged behind Cas9-based strategies due to low activity and the lack of a well-validated pooled screening toolkit. In the present study, we describe the optimization of enhanced Cas12a from Acidaminococcus (enAsCas12a) for pooled, combinatorial genetic screens in human cells. By assaying the activity of thousands of guides, we refine on-target design rules and develop a comprehensive set of off-target rules to predict and exclude promiscuous guides. We also identify 38 direct repeat variants that can substitute for the wild-type sequence. We validate our optimized AsCas12a toolkit by screening for synthetic lethalities in OVCAR8 and A375 cancer cells, discovering an interaction between MARCH5 and WSB2. Finally, we show that enAsCas12a delivers similar performance to Cas9 in genome-wide dropout screens but at greatly reduced library size, which will facilitate screens in challenging models.
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What OpenQuestion holds
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.