ArticleCommunications biology2023
Whole genome analysis for 163 gRNAs in Cas9-edited mice reveals minimal off-target activity.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- High-throughput Raman-activated cell sorting of microalgal genome-wide edited library revealed a regulatory pathway for carotenoid synthesis.Nature communications · 2026Article
- Article
- The Role of Gene Therapy and RNA-Based Therapeutic Strategies in Diabetes.International journal of molecular sciences · 2025Review
- Identifying genetic determinants of outer retinal function in mice using a large-scale gene-targeted screen.PLoS genetics · 2025Article
- New developments in biotechnology applied to animals: An assessment of the adequacy and sufficiency of current EFSA guidance for animal risk assessment.EFSA journal. European Food Safety Authority · 2025Article
- A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system.Disease models & mechanisms · 2025Article
- Engineering Base Changes and Epitope-Tagged Alleles in Mice Using Cas9 RNA-Guided Nuclease.Current protocols · 2025Article
- Systematic ocular phenotyping of 8,707 knockout mouse lines identifies genes associated with abnormal corneal phenotypes.BMC genomics · 2025Article
- Long read sequencing reveals transgene concatemerization and vector sequences integration following AAV-driven electroporation of CRISPR RNP complexes in mouse zygotes.Frontiers in genome editing · 2025Article
- A graph theoretical approach to experimental prioritization in genome-scale investigations.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Impact of essential genes on the success of genome editing experiments generating 3313 new genetically engineered mouse lines.Scientific reports · 2024Article
- Improving laboratory animal genetic reporting: LAG-R guidelines.Nature communications · 2024Review
- Novel off-Targeting Events Identified after Genome Wide Analysis of CRISPR-Cas Edited Pigs.The CRISPR journal · 2024Article
- An oocyte-specific Cas9-expressing mouse for germline CRISPR/Cas9-mediated genome editing.Genesis (New York, N.Y. : 2000) · 2024Article
- CRISPR/Cas9 as a Mutagenic Factor.International journal of molecular sciences · 2024Review
- Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma.Nucleic acids research · 2023Article
- The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Genome editing with CRISPR-associated (Cas) proteins holds exceptional promise for "correcting" variants causing genetic disease. To realize this promise, off-target genomic changes cannot occur during the editing process. Here, we use whole genome sequencing to compare the genomes of 50 Cas9-edited founder mice to 28 untreated control mice to assess the occurrence of S. pyogenes Cas9-induced off-target mutagenesis. Computational analysis of whole-genome sequencing data detects 26 unique sequence variants at 23 predicted off-target sites for 18/163 guides used. While computationally detected variants are identified in 30% (15/50) of Cas9 gene-edited founder animals, only 38% (10/26) of the variants in 8/15 founders validate by Sanger sequencing. In vitro assays for Cas9 off-target activity identify only two unpredicted off-target sites present in genome sequencing data. In total, only 4.9% (8/163) of guides tested have detectable off-target activity, a rate of 0.2 Cas9 off-target mutations per founder analyzed. In comparison, we observe ~1,100 unique variants in each mouse regardless of genome exposure to Cas9 indicating off-target variants comprise a small fraction of genetic heterogeneity in Cas9-edited mice. These findings will inform future design and use of Cas9-edited animal models as well as provide context for evaluating off-target potential in genetically diverse patient populations.
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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.