ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Comparative analysis of CRISPR off-target discovery tools following ex vivo editing of CD34
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Gene therapy for hereditary hematological disorders: From clinical breakthroughs to future horizons.Molecular therapy. Nucleic acids · 2026Review
- In-depth characterization of stem cell potency and genotoxicity for clinical-scaleMolecular therapy. Advances · 2026Article
- UNCOVERseq enables sensitive and controlled gene editing off-target nomination across CRISPR-Cas modalities and systems.Nature communications · 2026Article
- Ultra-sensitive profiling of CRISPR-Cas off-target effects with Tracking-seq2.Nature communications · 2026Article
- DisTAL-Seq: A TALEN-specific adaptation of DISCOVER-Seq for off-target profiling.Molecular therapy. Nucleic acids · 2026Article
- Review
- Article
- Combinatorial base editing couples disease correction with lineage amplification in hematopoietic stem and progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- DNA-PKcs inhibitor AZD7648 reveals sgRNA cross-contaminants and enhanced sensitivity of genome engineering off-target activity in HSPCs.Nucleic acids research · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- CRISPR-Cas systems for plant virus management: detection, surveillance, and host resistance.Frontiers in plant science · 2026Review
- Targeting oncogenic fusion-driven NUT carcinoma with CRISPR-Cas9 genome editing.Molecular therapy. Oncology · 2025Article
- Novel allogeneic CAR T-cell platform involving microhomology-mediated end joining repair and low off-targeting potential.Molecular therapy. Nucleic acids · 2025Article
- Design principle of successful genome editing applications using CRISPR-based toolkits.Journal of applied genetics · 2025Review
- Precision T cell correction platform for inborn errors of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Optimization of hypo-alloimmunogenic multispecific CAR-T and SARS-CoV-2-specific T cells for off-the-shelf adoptive cell therapy.Molecular therapy. Methods & clinical development · 2025Article
- Precise measurement of CRISPR genome editing outcomes through single-cell DNA sequencing.Molecular therapy. Methods & clinical development · 2025Article
- Clinical hematopoietic stem cell-based gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- CRISPR/Cas9-engineering of Kell null erythrocytes to unveil host targeted irresistible antimalarial.Communications biology · 2025Article
- Dual α-globin-truncated erythropoietin receptor knockin restores hemoglobin production in α-thalassemia-derived erythroid cells.Cell reports · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
While a number of methods exist to investigate CRISPR off-target (OT) editing, few have been compared head-to-head in primary cells after clinically relevant editing processes. Therefore, we compared in silico tools (COSMID, CCTop, and Cas-OFFinder) and empirical methods (CHANGE-Seq, CIRCLE-Seq, DISCOVER-Seq, GUIDE-Seq, and SITE-Seq) after ex vivo hematopoietic stem and progenitor cell (HSPC) editing. We performed editing using 11 different gRNAs complexed with Cas9 protein (high-fidelity [HiFi] or wild-type versions), then performed targeted next-generation sequencing of nominated OT sites identified by in silico and empirical methods. We identified an average of less than one OT site per guide RNA (gRNA) and all OT sites generated using HiFi Cas9 and a 20-nt gRNA were identified by all OT detection methods with the exception of SITE-seq. This resulted in high sensitivity for the majority of OT nomination tools and COSMID, DISCOVER-Seq, and GUIDE-Seq attained the highest positive predictive value (PPV). We found that empirical methods did not identify OT sites that were not also identified by bioinformatic methods. This study supports that refined bioinformatic algorithms could be developed that maintain both high sensitivity and PPV, thereby enabling more efficient identification of potential OT sites without compromising a thorough examination for any given gRNA.
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