ArticleNucleic acids research2022
CRISPR/Cas9-induced structural variations expand in T lymphocytes in vivo.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- Decoding DNA metabolism and its clinical relevance through the lens of high-throughput sequencing assays.Medical review (2021) · 2026Review
- High genotoxicity of CRISPR/Cas9 versus limited efficacy of CRISPRi in chicken primordial germ cells.Poultry science · 2026Article
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Construction and application of a genetically engineered mouse model of gastric adenocarcinoma.Journal of the Chinese Medical Association : JCMA · 2026Article
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- Highly efficient gene knockout in tumor-infiltrating lymphocytes by adenine base editing.Molecular therapy. Oncology · 2025Article
- Identification of a Novel Rice Chromosomal Translocation Line that Could Cause the Heterozygote Semi-Sterility and be Overcome by Genomic Duplication.Rice (New York, N.Y.) · 2025Article
- Robust prediction of synthetic gRNA activity and cryptic DNA repair by disentangling cellular CRISPR cleavage outcomes.Nature communications · 2025Article
- Systematic high-throughput evaluation reveals FrCas9's superior specificity and efficiency for therapeutic genome editing.Science advances · 2025Article
- Characterization of the role of spatial proximity of DNA double-strand breaks in the formation of CRISPR-Cas9-induced large structural variations.Genome research · 2025Article
- Precision Reprogramming in CAR-T Cell Therapy: Innovations, Challenges, and Future Directions of Advanced Gene Editing.International journal of biological sciences · 2025Review
- Large DNA deletions occur during DNA repair at 20-fold lower frequency for base editors and prime editors than for Cas9 nucleases.Nature biomedical engineering · 2025Article
- A bioinformatic analysis of gene editing off-target loci altered by common polymorphisms, using 'PopOff'.Journal of the Royal Society of New Zealand · 2025Article
- Advancements inMolecules (Basel, Switzerland) · 2024Review
- Transfer of mitochondrial DNA into the nuclear genome during induced DNA breaks.Nature communications · 2024Article
- CRISPR-Cas9 applications in T cells and adoptive T cell therapies.Cellular & molecular biology letters · 2024Review
- Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.Clinical and translational medicine · 2024Review
- CRISPR/Cas9-Mediated Customizing Strategies for Adoptive T-Cell Therapy.Pharmaceutics · 2024Review
- CRISPR/Cas9 system: recent applications in immuno-oncology and cancer immunotherapy.Experimental hematology & oncology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CRISPR/Cas9 has been adapted to disrupt endogenous genes in adoptive T-lymphocyte therapy to prevent graft-versus-host disease. However, genome editing also generates prevalent deleterious structural variations (SVs), including chromosomal translocations and large deletions, raising safety concerns about reinfused T cells. Here, we dynamically monitored the progression of SVs in a mouse model of T-cell receptor (TCR)-transgenic T-cell adoptive transfer, mimicking TCR T therapeutics. Remarkably, CRISPR/Cas9-induced SVs persist and undergo clonal expansion in vivo after three weeks or even two months, evidenced by high enrichment and low junctional diversity of identified SVs post infusion. Specifically, we detected 128 expanded translocations, with 20 615 as the highest number of amplicons. The identified SVs are stochastically selected among different individuals and show an inconspicuous locus preference. Similar to SVs, viral DNA integrations are routinely detected in edited T cells and also undergo clonal expansion. The persistent SVs and viral DNA integrations in the infused T cells may constantly threaten genome integrity, drawing immediate attention to the safety of CRISPR/Cas9-engineered T cells mediated immunotherapy.
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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.