Trial reportThe Journal of clinical investigation2007
Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy.
Trial report in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02453477 (A Phase I/II Study Evaluating Safety and Efficacy of Autologous Hematopoietic Stem Cells Genetically Modified With GLOBE Lentiviral Vector Encoding for the Human Beta-globin Gene for the Treatment of Patients Affected by Transfusion Dependent Beta-thalassemia), which is not on this map. Cited by 118 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.
A Phase I/II Study Evaluating Safety and Efficacy of Autologous Hematopoietic Stem Cells Genetically Modified With GLOBE Lentiviral Vector Encoding for the Human Beta-globin Gene for the Treatment of Patients Affected by Transfusion Dependent Beta-thalassemia
Who cites it
118 citing papers in PubMed, 253 citations in OpenAlex.
- Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency.Blood · 2021Trial
- Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients.Blood · 2017Trial
- Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.The Journal of clinical investigation · 2017Trial
- Trial
- 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
- Trial
- Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1.The Journal of clinical investigation · 2008Trial
- Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients.Blood · 2008Trial
- Charting single-cell lineages with synthetic and natural barcodes.Nature reviews. Genetics · 2026Review
- Article
- Article
- A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.Nature communications · 2024Article
- Gene therapy for inborn errors of immunity: past, present and future.Nature reviews. Immunology · 2023Review
- Therapeutics in paediatric genetic diseases: Current and future landscape.Singapore medical journal · 2023Review
- Review
- BET-Independent Murine Leukemia Virus Integration Is RetargetedMicrobiology spectrum · 2022Article
- Gene therapy using haematopoietic stem and progenitor cells.Nature reviews. Genetics · 2021Review
- Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders.Open life sciences · 2021Review
- Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side.Pharmaceutics · 2020Review
- Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease.Molecular therapy. Methods & clinical development · 2020Article
58 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 2 countries.
Funding
Abstract
Gene transfer into HSCs is an effective treatment for SCID, although potentially limited by the risk of insertional mutagenesis. We performed a genome-wide analysis of retroviral vector integrations in genetically corrected HSCs and their multilineage progeny before and up to 47 months after transplantation into 5 patients with adenosine deaminase-deficient SCID. Gene-dense regions, promoters, and transcriptionally active genes were preferred retroviral integrations sites (RISs) both in preinfusion transduced CD34(+) cells and in vivo after gene therapy. The occurrence of insertion sites proximal to protooncogenes or genes controlling cell growth and self renewal, including LMO2, was not associated with clonal selection or expansion in vivo. Clonal analysis of long-term repopulating cell progeny in vivo revealed highly polyclonal T cell populations and shared RISs among multiple lineages, demonstrating the engraftment of multipotent HSCs. These data have important implications for the biology of retroviral vectors, the dynamics of genetically modified HSCs, and the safety of gene therapy.
Indexed as
Identifiers
What OpenQuestion holds
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.