ArticleNature biomedical engineering2025
Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases.
Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed.
- Accurate characterization of CRISPR-Cas9 genome editing outcomes and mosaicism with near-perfect long reads.Genome medicine · 2026Article
- Identifying critical lysines in mammalian histone H3 with high-throughput CRISPR prime editing.Nature genetics · 2026Article
- Optimized Cas9-Enriched Nanopore Sequencing and Analysis Workflow for Clinical Diagnosis of Repeat Expansion Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Precise genomic integration of large DNA fragments by donor-directed annealing using prime editing.Nature biotechnology · 2026Article
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- Single-cell and in vivo profiling reveal heterogeneous and organ-specific CRISPR-Cas9 off-target and translocation outcomes.Nature communications · 2026Article
- Analysing long-read CRISPR experiments with CRISPRLungo.Nature biomedical engineering · 2026Article
- SACF and GILA for in vitro transformation assessment of CRISPR/Cas9-edited cell therapy candidates: a multi-site study.Gene therapy · 2026Article
- Engineered ADARs enable precision A-to-G base editing of DNA.Nature biotechnology · 2026Article
- In vivo systematic detection of the outcomes of CRISPR-Cas9-mediated DNA repair in skeletal muscle stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Illuminating "the dark side of the HBB": Visualizing the full spectrum of Cas9 outcomes.Molecular therapy. Nucleic acids · 2026Article
- Fourth-generation gene editors: Integration-based genome engineering.Molecular therapy. Advances · 2026Review
- Cytosine base editing of LPA in transgenic mice averts large deletions.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Harnessing Deep Learning Models for Guide RNA Optimization and Off-Target Prediction in CRISPR Systems.Biotechnology journal · 2026Review
- Efficient and Safe Knockout ofVeterinary sciences · 2026Article
- CRISPR/Cas9 Genome Editing in Oncology: Mechanisms, Therapeutic Platforms and Translational Challenges.Molecular biotechnology · 2026Review
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- DNA-PKcs inhibitor AZD7648 reveals sgRNA cross-contaminants and enhanced sensitivity of genome engineering off-target activity in HSPCs.Nucleic acids research · 2026Article
- Engineering Compact Base Editors by AlphaFold-Guided Mutation Scan and Escherichia coli-Based Tri-Selection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Antigen-binding affinity is a key determinant of the durable antitumor activity of CD5 CAR-T cells.Molecular therapy. Oncology · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
When used to edit genomes, Cas9 nucleases produce targeted double-strand breaks in DNA. Subsequent DNA-repair pathways can induce large genomic deletions (larger than 100 bp), which constrains the applicability of genome editing. Here we show that Cas9-mediated double-strand breaks induce large deletions at varying frequencies in cancer cell lines, human embryonic stem cells and human primary T cells, and that most deletions are produced by two repair pathways: end resection and DNA-polymerase theta-mediated end joining. These findings required the optimization of long-range amplicon sequencing, the development of a k-mer alignment algorithm for the simultaneous analysis of large DNA deletions and small DNA alterations, and the use of CRISPR-interference screening. Despite leveraging mutated Cas9 nickases that produce single-strand breaks, base editors and prime editors also generated large deletions, yet at approximately 20-fold lower frequency than Cas9. We provide strategies for the mitigation of such deletions.
Indexed as
Identifiers
What OpenQuestion holds
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.