ArticleGenome research2022
Target-enriched nanopore sequencing and de novo assembly reveals co-occurrences of complex on-target genomic rearrangements induced by CRISPR-Cas9 in human cells.
Article in Genome research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Cost-effective and flexible preimplantation genetic testing (PGT) by nanopore adaptive sampling.Journal of nanobiotechnology · 2025Article
- Assessment and Mitigation of CRISPR-Cas9-Induced Nontargeted Translocations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transgene Mapping in Animals: What to Choose?International journal of molecular sciences · 2025Review
- Structure-optimized sgRNA selection with PlatinumCRISPr for efficient Cas9 generation of knockouts.Genome research · 2024Article
- Engineering structural variants to interrogate genome function.Nature genetics · 2024Review
- A benchmark of computational methods for correcting biases of established and unknown origin in CRISPR-Cas9 screening data.Genome biology · 2024Article
- High-resolution genome-wide mapping of chromosome-arm-scale truncations induced by CRISPR-Cas9 editing.Nature genetics · 2024Article
- Scrambling the genome in cancer: causes and consequences of complex chromosome rearrangements.Nature reviews. Genetics · 2024Review
- Intrinsic deletion at 10q23.31, including theLife science alliance · 2024Article
- Challenges of CRISPR/Cas-Based Cell Therapy for Type 1 Diabetes: How Not to Engineer a "Trojan Horse".International journal of molecular sciences · 2023Review
- Unintended CRISPR-Cas9 editing outcomes: a review of the detection and prevalence of structural variants generated by gene-editing in human cells.Human genetics · 2023Review
- Delivery challenges for CRISPR-Cas9 genome editing for Duchenne muscular dystrophy.Biophysics reviews · 2023Review
- Assessing and advancing the safety of CRISPR-Cas tools: from DNA to RNA editing.Nature communications · 2023Review
- Article
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Authors and funding
9 authors.
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Abstract
The CRISPR-Cas9 system is widely used to permanently delete genomic regions via dual guide RNAs. Genomic rearrangements induced by CRISPR-Cas9 can occur, but continuous technical developments make it possible to characterize complex on-target effects. We combined an innovative droplet-based target enrichment approach with long-read sequencing and coupled it to a customized de novo sequence assembly. This approach enabled us to dissect the sequence content at kilobase scale within an on-target genomic locus. We here describe extensive genomic disruptions by Cas9, involving the allelic co-occurrence of a genomic duplication and inversion of the target region, as well as integrations of exogenous DNA and clustered interchromosomal DNA fragment rearrangements. Furthermore, we found that these genomic alterations led to functional aberrant DNA fragments and can alter cell proliferation. Our findings broaden the consequential spectrum of the Cas9 deletion system, reinforce the necessity of meticulous genomic validations, and introduce a data-driven workflow enabling detailed dissection of the on-target sequence content with superior resolution.
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