ArticleScience advances2021
Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Digenome-Detect: Accurate, statistics-based analysis software for identifying off-target cleavage sites in genome editing.Molecular therapy. Advances · 2026Article
- Upper bound on the mutational burden imposed by a CRISPR-Cas9 gene-drive element.G3 (Bethesda, Md.) · 2026Article
- POCKET-seq enables genome-wide profiling of on- and off-target transcriptional regulation events by dCas9-KRAB during CRISPR interference experiments.bioRxiv : the preprint server for biology · 2026Article
- Deep learning-driven prediction of on-target activity, off-target risk, and repair outcomes in CRISPR/Cas9: current landscape and multi-scale perspectives.Journal of translational medicine · 2026Review
- Off-target detection of CRISPR-Cas9 nucleaseSynthetic biology (Oxford, England) · 2026Article
- Off-target interactions in the CRISPR-Cas9 Machinery: mechanisms and outcomes.Biochemistry and biophysics reports · 2025Review
- Emerging trends in transgene-free crop development: insights into genome editing and its regulatory overview.Plant molecular biology · 2025Review
- Experimental Test of Evolutionary Safety of a CRISPR-Cas9 Gene-Drive Element.bioRxiv : the preprint server for biology · 2025Article
- Controlling DNA-RNA strand displacement kinetics with base distribution.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dynamic sampling of a surveillance state enables DNA proofreading by Cas9.Cell chemical biology · 2025Article
- Article
- Gene editing of angiotensin for blood pressure management.International journal of cardiology. Cardiovascular risk and prevention · 2024Article
- Engineered transcription-associated Cas9 targeting in eukaryotic cells.Nature communications · 2024Article
- Crispr-SGRU: Prediction of CRISPR/Cas9 Off-Target Activities with Mismatches and Indels Using Stacked BiGRU.International journal of molecular sciences · 2024Article
- Engineered transcription-associated Cas9 targeting in eukaryotic cells.bioRxiv : the preprint server for biology · 2024Article
- CRISPR technology in human diseases.MedComm · 2024Review
- Generating, modeling and evaluating a large-scale set of CRISPR/Cas9 off-target sites with bulges.Nucleic acids research · 2024Article
- Sensing the DNA-mismatch tolerance of catalytically inactive Cas9 via barcoded DNA nanostructures in solid-state nanopores.Nature biomedical engineering · 2024Article
- Advances and applications of CRISPR/Cas-mediated interference inEngineering microbiology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
The RNA-guided nuclease Cas9 has unlocked powerful methods for perturbing both the genome through targeted DNA cleavage and the regulome through targeted DNA binding, but limited biochemical data have hampered efforts to quantitatively model sequence perturbation of target binding and cleavage across diverse guide sequences. We present scalable, sequencing-based platforms for high-throughput filter binding and cleavage and then perform 62,444 quantitative binding and cleavage assays on 35,047 on- and off-target DNA sequences across 90 Cas9 ribonucleoproteins (RNPs) loaded with distinct guide RNAs. We observe that binding and cleavage efficacy, as well as specificity, vary substantially across RNPs; canonically studied guides often have atypically high specificity; sequence context surrounding the target modulates Cas9 on-rate; and Cas9 RNPs may sequester targets in nonproductive states that contribute to "proofreading" capability. Lastly, we distill our findings into an interpretable biophysical model that predicts changes in binding and cleavage for diverse target sequence perturbations.
Identifiers
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.