ArticleNature communications2021
CRISPR-Cas9 globin editing can induce megabase-scale copy-neutral losses of heterozygosity in hematopoietic cells.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 84 citations in OpenAlex.
- Article
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Precise, predictable genome integrations by deep-learning-assisted design of microhomology-based templates.Nature biotechnology · 2026Article
- Complex HBB gene editing outcomes revealed by a fluorescent reporter cell model.Molecular therapy. Nucleic acids · 2026Article
- Improved in vivo gene knockout with high specificity using multiplexed Cas12a sgRNAs.Nature communications · 2026Article
- Single-cell multiplex approaches deeply map ON-target CRISPR-genotoxicity and reveal its mitigation by palbociclib and long-term engraftment.Nature communications · 2026Article
- Precision Without Selection: A Marker-Free CRISPR/Cas9-Based Protocol for Multiplexed Genome Editing in Trypanosomatids.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease.bioRxiv : the preprint server for biology · 2025Article
- Megabase-scale loss of heterozygosity provoked by CRISPR-Cas9 DNA double-strand breaks.Molecular cell · 2025Article
- Genome editing with the HDR-enhancing DNA-PKcs inhibitor AZD7648 causes large-scale genomic alterations.Nature biotechnology · 2025Article
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- Dissecting the epigenetic regulation of the fetal hemoglobin genes to unravel a novel therapeutic approach for β-hemoglobinopathies.Nucleic acids research · 2025Article
- DurableMolecular therapy. Nucleic acids · 2025Article
- Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases.Nature biotechnology · 2025Article
- Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.Cell stem cell · 2025Article
- Targeting of acute myeloid leukemia by five-gene engineered T cells expressing transgenic T-cell receptor specific to WT1, chimeric antigenic receptor specific to GM-CSF receptor, bispecific T-cell engager specific to CD33, and tEGFR suicide gene system.Immunotherapy advances · 2025Article
- Efficient GBA1 editing via HDR with ssODNs by outcompeting pseudogene-mediated gene conversion upon CRISPR/Cas9 cleavage.Frontiers in genome editing · 2025Article
- Safety and efficacy studies of CRISPR-Cas9 treatment of sickle cell disease highlights disease-specific responses.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.Genome biology · 2024Article
- Gene editing of NCF1 loci is associated with homologous recombination and chromosomal rearrangements.Communications biology · 2024Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR-Cas9 is a promising technology for gene therapy. However, the ON-target genotoxicity of CRISPR-Cas9 nuclease due to DNA double-strand breaks has received little attention and is probably underestimated. Here we report that genome editing targeting globin genes induces megabase-scale losses of heterozygosity (LOH) from the globin CRISPR-Cas9 cut-site to the telomere (5.2 Mb). In established lines, CRISPR-Cas9 nuclease induces frequent terminal chromosome 11p truncations and rare copy-neutral LOH. In primary hematopoietic progenitor/stem cells, we detect 1.1% of clones (7/648) with acquired megabase LOH induced by CRISPR-Cas9. In-depth analysis by SNP-array reveals the presence of copy-neutral LOH. This leads to 11p15.5 partial uniparental disomy, comprising two Chr11p15.5 imprinting centers (H19/IGF2:IG-DMR/IC1 and KCNQ1OT1:TSS-DMR/IC2) and impacting H19 and IGF2 expression. While this genotoxicity is a safety concern for CRISPR clinical trials, it is also an opportunity to model copy-neutral-LOH for genetic diseases and cancers.
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