ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
On- and off-target effects of paired CRISPR-Cas nickase in primary human cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Molecular plasticity of LAMA3 across the disease spectrum: pathogenic mechanisms and clinical translation.Histochemistry and cell biology · 2026Pooled it
- Non-Viral CRISPR carriers: transient delivery with lasting effects.Drug delivery · 2026Review
- Biomimetic Nanocarriers for Glioblastoma Therapy: Translational Advances and Strategic Challenges.Cancers · 2026Review
- Genotoxicity profiling reveals distinct platform-and cell type-specific effects in therapeutic gene editing for genetic hyperinflammation.Cell stem cell · 2026Article
- Nickase NmCas9 unsilences paternal Ube3a in a mouse model of Angelman syndrome without causing AAV vector integration.Scientific reports · 2026Article
- Simultaneous orthogonal cell engineering by a single CRISPR-Cas9 polyfunctional editor.Nature communications · 2026Article
- Developing CRISPR-Based Therapies for Epidermolysis Bullosa: A Comprehensive Review of Current Strategies.Drugs · 2026Review
- ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks.Nature communications · 2026Article
- Functional correction and genome integrity with duplex base editing of β-thalassemic hematopoietic stem cells.Genome biology · 2026Article
- Review
- The gut‑bone‑cartilage triad: Microbial regulation of the Wnt/β‑catenin signaling pathway in osteoarthritis joint remodeling (Review).Molecular medicine reports · 2026Review
- Gene therapy for genodermatoses at the crossroads of innovation and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Targeted inhibition ofMolecular therapy. Methods & clinical development · 2025Article
- The Genetic Blueprint of Obesity: From Pathogenesis to Novel Therapies.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.Nature biotechnology · 2025Article
- Review
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- Protective antigen-mediated delivery of an anti-CRISPR protein for precision genome editing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeted gene editing and near-universal cDNA insertion of CYBA and CYBB as a treatment for chronic granulomatous disease.Nature communications · 2025Article
- The hidden risks of CRISPR/Cas: structural variations and genome integrity.Nature communications · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Undesired on- and off-target effects of CRISPR-Cas nucleases remain a challenge in genome editing. While the use of Cas9 nickases has been shown to minimize off-target mutagenesis, their use in therapeutic genome editing has been hampered by a lack of efficacy. To overcome this limitation, we and others have developed double-nickase-based strategies to generate staggered DNA double-strand breaks to mediate gene disruption or gene correction with high efficiency. However, the impact of paired single-strand nicks on genome integrity has remained largely unexplored. Here, we developed a novel CAST-seq pipeline, dual CAST, to characterize chromosomal aberrations induced by paired CRISPR-Cas9 nickases at three different loci in primary keratinocytes derived from patients with epidermolysis bullosa. While targeting COL7A1, COL17A1, or LAMA3 with Cas9 nucleases caused previously undescribed chromosomal rearrangements, no chromosomal translocations were detected following paired-nickase editing. While the double-nicking strategy induced large deletions/inversions within a 10 kb region surrounding the target sites at all three loci, similar to the nucleases, the chromosomal on-target aberrations were qualitatively different and included a high proportion of insertions. Taken together, our data indicate that double-nickase approaches combine efficient editing with greatly reduced off-target effects but still leave substantial chromosomal aberrations at on-target sites.
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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.