ArticleNature methods2023
Improving the sensitivity of in vivo CRISPR off-target detection with DISCOVER-Seq.
Article in Nature methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Preclinical Anticipation of On- and Off-Target Resistance Mechanisms to Anti-Cancer Drugs: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Tracking-seq: a universal off-target detection approach for CRISPR-Cas genome editing.Nature protocols · 2026Review
- Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2.Nature communications · 2026Article
- abCRISPR: deep learning-based design of abasic gRNA sequences for specific CRISPR-Cas9 genome editing.Bioinformatics (Oxford, England) · 2026Article
- Precision modification of heart failure signaling by CRISPR-Cas9 base editing.Journal of molecular and cellular cardiology · 2026Review
- CRISPR-Cas9-based therapies for Huntington's disease and Friedreich's ataxia: mechanisms, advances, and future perspectives.Neurogenetics · 2026Review
- DisTAL-Seq: A TALEN-specific adaptation of DISCOVER-Seq for off-target profiling.Molecular therapy. Nucleic acids · 2026Article
- CRISPRessoSea: streamlined analysis and comparison of pooled amplicon CRISPR screens.BMC bioinformatics · 2026Article
- POCKET-seq enables genome-wide profiling of on- and off-target transcriptional regulation events by dCas9-KRAB during CRISPR interference experiments.bioRxiv : the preprint server for biology · 2026Article
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- AviTag-seq unifies nucleotide-resolution maps of CRISPR off-targets and AAV vector integrations.Communications biology · 2026Article
- CRISPR/Cas9 in perspective: evaluating efficacy, delivery methods, and ethical challenges in genome editing.Molecular biology reports · 2026Review
- Deep learning-driven prediction of on-target activity, off-target risk, and repair outcomes in CRISPR/Cas9: current landscape and multi-scale perspectives.Journal of translational medicine · 2026Review
- CRISPR-Cas9 Therapeutics in Early Clinical Development: Delivery and Molecular Diagnostics.Cells · 2026Review
- Efficient high-precision transgene knock-in by Recombinases (Redα/β)-enhanced DNA integration-CRISPR-Cas9 (RED-CRISPR).Nature communications · 2025Article
- Design principle of successful genome editing applications using CRISPR-based toolkits.Journal of applied genetics · 2025Review
- Gene Editing Applications as Future Cardiovascular Therapies.Annual review of genetics · 2025Review
- Sensitive, direct detection of non-coding off-target base editor unwinding and editing in primary cells.bioRxiv : the preprint server for biology · 2025Article
- Off-target effects in CRISPR-Cas genome editing for human therapeutics: Progress and challenges.Molecular therapy. Nucleic acids · 2025Review
- Targeted gene editing and near-universal cDNA insertion of CYBA and CYBB as a treatment for chronic granulomatous disease.Nature communications · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Discovery of off-target CRISPR-Cas activity in patient-derived cells and animal models is crucial for genome editing applications, but currently exhibits low sensitivity. We demonstrate that inhibition of DNA-dependent protein kinase catalytic subunit accumulates the repair protein MRE11 at CRISPR-Cas-targeted sites, enabling high-sensitivity mapping of off-target sites to positions of MRE11 binding using chromatin immunoprecipitation followed by sequencing. This technique, termed DISCOVER-Seq+, discovered up to fivefold more CRISPR off-target sites in immortalized cell lines, primary human cells and mice compared with previous methods. We demonstrate applicability to ex vivo knock-in of a cancer-directed transgenic T cell receptor in primary human T cells and in vivo adenovirus knock-out of cardiovascular risk gene PCSK9 in mice. Thus, DISCOVER-Seq+ is, to our knowledge, the most sensitive method to-date for discovering off-target genome editing in vivo.
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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.