Trial reportEMBO molecular medicine2011
Integration profile of retroviral vector in gene therapy treated patients is cell-specific according to gene expression and chromatin conformation of target cell.
Trial report in EMBO molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed.
- Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency.Blood · 2021Trial
- Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.The Journal of clinical investigation · 2017Trial
- Trial
- Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.Science (New York, N.Y.) · 2013Trial
- Modeling integration site data for safety assessment with MELISSA.Nature communications · 2025Article
- Donor insertion into CX3CR1 allows epigenetic modulation of a constitutive promoter on hematopoietic stem cells and its activation upon myeloid differentiation.Nucleic acids research · 2025Article
- Turning "trashed" genomic loci into treasurable sites for integrating chimeric antigen receptors in T and NK cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Longitudinal analysis of lentiviral and retroviral chimeric antigen receptors' integration sites reveals distinct clonal evolutionary patterns.British journal of haematology · 2025Article
- A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.Nature communications · 2024Article
- Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.Oncology research · 2024Review
- Tagmentation-based analysis reveals the clonal behavior of CAR-T cells in association with lentivector integration sites.Molecular therapy oncolytics · 2023Article
- Site-specific transgene integration in chimeric antigen receptor (CAR) T cell therapies.Biomarker research · 2023Review
- Gene therapy for inborn errors of immunity: past, present and future.Nature reviews. Immunology · 2023Review
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- Nonconditioned ADA-SCID gene therapy reveals ADA requirement in the hematopoietic system and clonal dominance of vector-marked clones.Molecular therapy. Methods & clinical development · 2021Article
- Gene therapy using haematopoietic stem and progenitor cells.Nature reviews. Genetics · 2021Review
- Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans.Nature communications · 2021Article
- Gene Therapy for Primary Immunodeficiency.HemaSphere · 2021Review
- TEG001 Insert Integrity from Vector Producer Cells until Medicinal Product.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Pre-clinical Development of a Lentiviral Vector Expressing the Anti-sickling βAS3 Globin for Gene Therapy for Sickle Cell Disease.Molecular therapy. Methods & clinical development · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
The analysis of genomic distribution of retroviral vectors is a powerful tool to monitor 'vector-on-host' effects in gene therapy (GT) trials but also provides crucial information about 'host-on-vector' influences based on the target cell genetic and epigenetic state. We had the unique occasion to compare the insertional profile of the same therapeutic moloney murine leukemia virus (MLV) vector in the context of the adenosine deaminase-severe combined immunodeficiency (ADA-SCID) genetic background in two GT trials based on infusions of transduced mature lymphocytes (peripheral blood lymphocytes, PBL) or a single infusion of haematopoietic stem/progenitor cells (HSC). We found that vector insertions are cell-specific according to the differential expression profile of target cells, favouring, in PBL-GT, genes involved in immune system and T-cell functions/pathways as well as T-cell DNase hypersensitive sites, differently from HSC-GT. Chromatin conformations and histone modifications influenced integration preferences but we discovered that only H3K27me3 was cell-specifically disfavoured, thus representing a key epigenetic determinant of cell-type dependent insertion distribution. Our study shows that MLV vector insertional profile is cell-specific according to the genetic/chromatin state of the target cell both in vitro and in vivo in patients several years after GT.
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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.