ArticleNature2017
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,129 papers, 1 of them a synthesis that pooled it.
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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
1,129 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,751 citations in OpenAlex.
- Strategies and mechanisms for the enhancement of chimeric antigen receptor T-cell functions.Science China. Life sciences · 2026Pooled it
- A phase I/II trial of WT1-specific TCR gene therapy for patients with acute myeloid leukemia and active disease post-allogeneic hematopoietic cell transplantation: skewing towards NK-like phenotype impairs T cell function and persistence.Nature communications · 2025Trial
- CRISPR/Cas Systems: Biological Basis and Genome Editing Applications.Methods in molecular biology (Clifton, N.J.) · 2027Review
- Human T cell engineering via serial delivery of mRNA encapsulated within lipid nanoparticles.Molecular therapy. Nucleic acids · 2026Article
- CRISPR-Cas9 in Cancer Therapy: Overcoming Delivery Barriers and Off-Target Effects for Clinical Translation.Health science reports · 2026Article
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- Advanced gene editing technologies for oncology mechanisms, applications, and clinical implementation.Cancer gene therapy · 2026Review
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- Gene regulatory elements determine efficacy of BCMA-targeted CAR-T cell products.Journal for immunotherapy of cancer · 2026Article
- From scissors to editors: how the evolution of precision is redefining therapeutic genome editing.Molecular genetics and genomics : MGG · 2026Review
- Article
- Generation of Allogeneic CAR-T Circumvents Functional Deficits in Patient-Derived Autologous Product for Glioblastoma.International journal of cancer · 2026Article
- 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
- Base editing for precision therapeutics.Cell genomics · 2026Review
- T cell receptors equipped with ICOS provide T cells with durable anti-tumor response.Molecular cancer · 2026Article
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- Metabolic activation using fructose-1,6-bisphosphate microparticles of non-virally LNP-generated CAR-macrophages induces anti-tumor immune responses.Journal of materials chemistry. B · 2026Article
- The Role of Chimeric Antigen Receptor Regulatory T Cells in Promoting Immune Tolerance in Solid Organ Transplantation:Saudi medical journal · 2026Review
1,069 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies. CARs are typically transduced into the T cells of a patient using γ-retroviral vectors or other randomly integrating vectors, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing. Recent advances in genome editing enable efficient sequence-specific interventions in human cells, including targeted gene delivery to the CCR5 and AAVS1 loci. Here we show that directing a CD19-specific CAR to the T-cell receptor α constant (TRAC) locus not only results in uniform CAR expression in human peripheral blood T cells, but also enhances T-cell potency, with edited cells vastly outperforming conventionally generated CAR T cells in a mouse model of acute lymphoblastic leukaemia. We further demonstrate that targeting the CAR to the TRAC locus averts tonic CAR signalling and establishes effective internalization and re-expression of the CAR following single or repeated exposure to antigen, delaying effector T-cell differentiation and exhaustion. These findings uncover facets of CAR immunobiology and underscore the potential of CRISPR/Cas9 genome editing to advance immunotherapies.
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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.