ArticleCell2023
Mitigation of chromosome loss in clinical CRISPR-Cas9-engineered T cells.
Registry-linked trialOpen access · hybridAbstract read
In one paragraph
Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03399448 (Phase 1 Trial of Autologous T Cells Engineered to Express NY-ESO-1 TCR and CRISPR Gene Edited to Eliminate Endogenous TCR and PD-1), which is not on this map. Cited by 153 papers.
0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed
26.8field-weighted citation impact, top 1% of its field
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.
Phase 1 Trial of Autologous T Cells Engineered to Express NY-ESO-1 TCR and CRISPR Gene Edited to Eliminate Endogenous TCR and PD-1 (NYCE T Cells)
Who cites it
153 citing papers in PubMed, 174 citations in OpenAlex.
- Human T cell engineering via serial delivery of mRNA encapsulated within lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- CRISPR/Cas9-based nanodelivery systems for precision gene editing in neuroinflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.Signal transduction and targeted therapy · 2026Review
- CRISPR-Cas9 in Cancer Therapy: Overcoming Delivery Barriers and Off-Target Effects for Clinical Translation.Health science reports · 2026Article
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- Depletion of IL-10 in CAR-NK cells augments reprogramming of the tumor microenvironment and ameliorates therapeutic efficacy.Molecular therapy. Oncology · 2026Article
- Article
- Co-delivery of lentiviral vectors and Cas9-containing virus-like particles enables rapid, scalable manufacture of gene-edited CAR T cells.Molecular therapy. Advances · 2026Article
- Integrated epigenetic and genetic programming of primary human T cells.Nature biotechnology · 2026Article
- Article
- CRISPR-Engineered CAR-T Cell Therapy for Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: A Review of Emerging Therapeutic Prospects.Reviews in medical virology · 2026Review
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- Genetic Engineering of Tumor-Infiltrating Lymphocytes (TIL) via a T-Editor Platform to Enhance Anti-Tumor Activity.Cancer science · 2026Article
- Applications of synthetic biology in biomedicine.Molecular biomedicine · 2026Review
- Putative glioblastoma origin-like cells in the subventricular zone: isolation and characterization.Experimental & molecular medicine · 2026Article
- CRISPR integration of an FLT3 CAR into the TRAC locus generates CAR T cells for AML.Genome medicine · 2026Article
- A single chromosome 3p break initiates clear cell renal cell carcinoma evolution.bioRxiv : the preprint server for biology · 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
- Decoding Immune Regulation: From Genetic Variation to Mechanism Through Single-Cell Genomics.Immune network · 2026Review
- Rewriting the epigenome: CRISPR tools for biological discovery and therapeutics.Current opinion in biomedical engineering · 2026Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
- Update of
Authors and funding
23 authors at 9 institutions in 2 countries.
Connor A TsuchidaUniversity of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Nadav BrandesDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Raymund BuenoDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Marena TrinidadInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
Thomas MazumderDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Bingfei YuCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA.
Byungjin HwangDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Christopher ChangBiomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA; Medical Scientist Training Program, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Jamin LiuUniversity of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Yang SunDivision of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Caitlin R HopkinsAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kevin R ParkerCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Yanyan QiDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Laura HofmanInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Graduate School of Life Sciences, Utrecht University, Utrecht, the Netherlands.
Ansuman T SatpathyParker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Edward A StadtmauerAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jamie H D CateDepartment of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Justin EyquemDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Joseph A FraiettaAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Carl H JuneAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, Stanford University School of Medicine, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
Chun Jimmie YeUniversity of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA; Institute for Computational Health Sciences, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: jimmie.ye@ucsf.edu.
Jennifer A DoudnaUniversity of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Department of Chemistry, University of California Berkeley, Berkeley, CA, USA; Howard Hughes Medical Institute, University of California Berkeley, Berkeley, CA, USA. Electronic address: doudna@berkeley.edu.
University of California, San Francisco · USGladstone Institutes · USParker Institute for Cancer Immunotherapy · USQB3 · USStanford University · USHoward Hughes Medical Institute · USInnovative Genomics Institute · USUniversity of Pennsylvania · USUtrecht University · NL
Funding
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7MCenter for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8MThe Role of the Ribosome in the Accuracy of TranslationR01GM065050 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CATE, JAMIE H · 2001 to 2022
$7.4MBMI Bioinformatics Training GrantsT32GM067547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HERNANDEZ, RYAN D. · 2003 to 2022
$6.6MLncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4MMapping gene-by-environment interactions using multiplexed single cell RNA-sequencingR01HG011239 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2020 to 2023
$4.1MGenetic regulation and immunological function of ERAP2 haplotypesR01AI136972 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2018 to 2022
$3.5MExpanding CRISPR-Cas editing technology through exploration of novel Cas proteins and DNA repair systemsU01AI142817 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI BANFIELD, JILLIAN, DOUDNA, JENNIFER A · 2018 to 2022
$2.0MFine mapping rheumatic disease variants using functional genomic sequencingR01AR071522 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2017 to 2020
$1.5MCharacterization and engineering of a compact genome editor for adeno-associated virus delivery to correct mutations causing cystic fibrosisF31HL156468 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI TSUCHIDA, CONNOR ANDREW · 2021 to 2022
$77kHoward Hughes Medical InstituteNCI NIH HHS R35 CA209919NHGRI NIH HHS R01 HG011239NHGRI NIH HHS RM1 HG007735NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS F31 HL156468NIAID NIH HHS R01 AI136972NIAID NIH HHS U01 AI142817NIAMS NIH HHS R01 AR071522NIGMS NIH HHS R01 GM065050NIGMS NIH HHS T32 GM067547
Abstract
CRISPR-Cas9 genome editing has enabled advanced T cell therapies, but occasional loss of the targeted chromosome remains a safety concern. To investigate whether Cas9-induced chromosome loss is a universal phenomenon and evaluate its clinical significance, we conducted a systematic analysis in primary human T cells. Arrayed and pooled CRISPR screens revealed that chromosome loss was generalizable across the genome and resulted in partial and entire loss of the targeted chromosome, including in preclinical chimeric antigen receptor T cells. T cells with chromosome loss persisted for weeks in culture, implying the potential to interfere with clinical use. A modified cell manufacturing process, employed in our first-in-human clinical trial of Cas9-engineered T cells (NCT03399448), reduced chromosome loss while largely preserving genome editing efficacy. Expression of p53 correlated with protection from chromosome loss observed in this protocol, suggesting both a mechanism and strategy for T cell engineering that mitigates this genotoxicity in the clinic.
Indexed as
Chromosome AberrationsCRISPR-Cas SystemsGene EditingT-LymphocytesChromosomesClinical Trials as TopicDNA DamageHumansaneuploidyCAR T cellschromosome lossclinical trialCRISPR-Cas9CRISPR screenDNA repairgenome editingimmunoengineeringT cells
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Read underepoch 390
Registered trials
NCT03399448ClinicalTrials.gov
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.