ArticleNature biotechnology2026
Sensitive and unbiased genome-wide profiling of base-editor-induced off-target activity using CHANGE-seq-BE.
Article in Nature biotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed.
- Editing around the target: epitope engineering to protect stem cell grafts.Blood advances · 2026Review
- Pharmacological readthrough and base editing forMolecular therapy. Nucleic acids · 2026Article
- Article
- From Design to Single-Cell Cloning: A Complete RNP-Based CRISPR-Cas9 Protocol for Precision Gene Correction in Human iPSCs.Stem cell reviews and reports · 2026Article
- UNCOVERseq enables sensitive and controlled gene editing off-target nomination across CRISPR-Cas modalities and systems.Nature communications · 2026Article
- Precision modification of heart failure signaling by CRISPR-Cas9 base editing.Journal of molecular and cellular cardiology · 2026Review
- From Gene to Hope: Rett Syndrome and the Rise of Molecular Therapies.Molecular diagnosis & therapy · 2026Review
- Fourth-generation gene editors: Integration-based genome engineering.Molecular therapy. Advances · 2026Review
- Connexin 26 in Hearing Health and Disease: StructuralFoundations, Mutation Mechanisms, and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- DNA-PKcs inhibitor AZD7648 reveals sgRNA cross-contaminants and enhanced sensitivity of genome engineering off-target activity in HSPCs.Nucleic acids research · 2026Article
- Clinical Trial Landscape of Gene-Edited Autologous Hematopoietic Stem Cells for Hemoglobinopathies and Immunodeficiencies.International journal of molecular sciences · 2026Review
- Beyond CRISPR: next-gen precision engineering of CAR-NK cells for enhanced persistence, trafficking, and tumor eradication.Cancer cell international · 2026Review
- Bridging science and hope: the evolving story of gene therapy for neuromuscular diseases.Frontiers in cell and developmental biology · 2026Review
- CRISPR-dependent base editing as a therapeutic strategy for rare monogenic disorders.Frontiers in genome editing · 2025Review
Corrections and comments
- Update of
Authors and funding
12 authors.
Funding
Abstract
Detection of the off-target effects of base editors is important for identifying their safety risks but current methods for understanding their global activities have limitations in terms of sensitivity or bias by computationally selecting a subset of sites for experimental analysis. We present CHANGE-seq-BE, a method to assess the guide RNA-dependent off-target profile of both adenine and cytosine base editors that is simultaneously sensitive and unbiased. CHANGE-seq-BE relies on selective sequencing of base-editor-modified genomic DNA in vitro and provides comprehensive identification of genome-wide off-target mutations. We found that 98.8% of validated off-target sites were unique to ABE8e adenine base editors compared to Cas9 nuclease, suggesting substantially higher off-target activity of the former. We further applied CHANGE-seq-BE to support genotoxicity studies in an emergency investigational new drug application for customized adenine base editor treatment for a person with CD40L-deficient X-linked hyper IgM syndrome. Our results emphasize the importance of using a base-editor-specific method for identifying off-target activity.
Identifiers
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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.