ArticleGenome biology2024
Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.
Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Article
- DNA-editing 'pencils' probe early human development.Nature · 2026Article
- CRISPR-Cas9 and precision editing technologies linking functional genomics to clinical translation in genetic diseases.Clinical and translational medicine · 2026Review
- Article
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- Adenine base editor for knockout of proteins: A practical guide from design to analysis with updated MultiEditRbatch.Molecular therapy. Nucleic acids · 2026Article
- Simultaneous orthogonal cell engineering by a single CRISPR-Cas9 polyfunctional editor.Nature communications · 2026Article
- Base editing rescues seizures and sudden death in a SCN8A mutation-associated developmental epileptic encephalopathy model.The Journal of clinical investigation · 2026Article
- Hepatic targeting in ASCVD: integrating lipid lowering and inflammation modulation from statins to gene editing.Journal of translational medicine · 2026Review
- Sensitive and unbiased genome-wide profiling of base-editor-induced off-target activity using CHANGE-seq-BE.Nature biotechnology · 2026Article
- Harnessing the potential of gene editing technology for CAR-T cell therapy of solid tumors.Inflammation and regeneration · 2025Review
- The editable landscape of the yeast genome reveals hotspots of structural variant formation.Science advances · 2025Article
- Recent advances in universal chimeric antigen receptor T cell therapy.Journal of hematology & oncology · 2025Review
- Quadruple adenine base-edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease-engineered T cells.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adenine base editors induce off-target structure variations in mouse embryos and primary human T cells.Genome biology · 2024Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe safety of CRISPR-based gene editing methods is of the utmost priority in clinical applications. Previous studies have reported that Cas9 cleavage induced frequent aneuploidy in primary human T cells, but whether cleavage-mediated editing of base editors would generate off-target structure variations remains unknown. Here, we investigate the potential off-target structural variations associated with CRISPR/Cas9, ABE, and CBE editing in mouse embryos and primary human T cells by whole-genome sequencing and single-cell RNA-seq analyses.
resultsThe results show that both Cas9 and ABE generate off-target structural variations (SVs) in mouse embryos, while CBE induces rare SVs. In addition, off-target large deletions are detected in 32.74% of primary human T cells transfected with Cas9 and 9.17% of cells transfected with ABE. Moreover, Cas9-induced aneuploid cells activate the P53 and apoptosis pathways, whereas ABE-associated aneuploid cells significantly upregulate cell cycle-related genes and are arrested in the G0 phase. A percentage of 16.59% and 4.29% aneuploid cells are still observable at 3 weeks post transfection of Cas9 or ABE. These off-target phenomena in ABE are universal as observed in other cell types such as B cells and Huh7. Furthermore, the off-target SVs are significantly reduced in cells treated with high-fidelity ABE (ABE-V106W).
conclusionsThis study shows both CRISPR/Cas9 and ABE induce off-target SVs in mouse embryos and primary human T cells, raising an urgent need for the development of high-fidelity gene editing tools.
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