ArticleProceedings of the National Academy of Sciences of the United States of America2006
Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 186 citations in OpenAlex.
- Haploidentical HSCT: a 15-year experience at San Raffaele.Bone marrow transplantation · 2015Trial
- Integration profile of retroviral vector in gene therapy treated patients is cell-specific according to gene expression and chromatin conformation of target cell.EMBO molecular medicine · 2011Trial
- Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy.The Journal of clinical investigation · 2007Trial
- Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo.The Journal of clinical investigation · 2007Trial
- Profibrotic Molecules Are Reduced in CRISPR-Edited Emery-Dreifuss Muscular Dystrophy Fibroblasts.Cells · 2025Article
- Current landscape of vector safety and genotoxicity after hematopoietic stem or immune cell gene therapy.Leukemia · 2025Review
- Prenatal AAV9-GFP administration in fetal lambs results in transduction of female germ cells and maternal exposure to virus.Molecular therapy. Methods & clinical development · 2024Article
- Time to evolve: predicting engineered T cell-associated toxicity with next-generation models.Journal for immunotherapy of cancer · 2022Review
- Article
- Inclusion of the Inducible Caspase 9 Suicide Gene in CAR Construct Increases Safety of CAR.CD19 T Cell Therapy in B-Cell Malignancies.Frontiers in immunology · 2021Article
- Nanopore sequencing as a scalable, cost-effective platform for analyzing polyclonal vector integration sites following clinical T cell therapy.Journal for immunotherapy of cancer · 2020Article
- TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Generation of High-Titer Self-Inactivated γ-Retroviral Vector Producer Cells.Molecular therapy. Methods & clinical development · 2019Article
- Review
- A Potent Tumor-Reactive p53-Specific Single-Chain TCR without On- or Off-Target Autoimmunity In Vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Multiple Integrated Non-clinical Studies Predict the Safety of Lentivirus-Mediated Gene Therapy for β-Thalassemia.Molecular therapy. Methods & clinical development · 2018Article
- Chimeric antigen receptor modified T-cells for cancer treatment.Chronic diseases and translational medicine · 2018Article
- CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies.Blood · 2017Article
- Current Strategies and Challenges for Purification of Cardiomyocytes Derived from Human Pluripotent Stem Cells.Theranostics · 2017Review
- Driving gene-engineered T cell immunotherapy of cancer.Cell research · 2017Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of retroviral vectors in gene therapy has raised safety concerns for the genotoxic risk associated with their uncontrolled insertion into the human genome. We have analyzed the consequences of retroviral transduction in T cells from leukemic patients treated with allogeneic stem cell transplantation and donor lymphocytes genetically modified with a suicide gene (HSV-TK). Retroviral vectors integrate preferentially within or near transcribed regions of the genome, with a preference for sequences around promoters and for genes active in T cells at the time of transduction. Quantitative transcript analysis shows that one fifth of these integrations affect the expression of nearby genes. However, transduced T cell populations maintain remarkably stable gene expression profiles, phenotype, biological functions, and immune repertoire in vivo, with no evidence of clonal selection up to 9 yr after administration. Analysis of integrated proviruses in transduced cells before and after transplantation indicates that integrations interfering with normal T cell function are more likely to lead to clonal ablation than expansion in vivo. Despite the potentially dangerous interactions with the T cell genome, retroviral integration has therefore little consequence on the safety and efficacy of T cell transplantation.
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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.