ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Lymphomagenesis in SCID-X1 mice following lentivirus-mediated phenotype correction independent of insertional mutagenesis and gammac overexpression.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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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.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Selection of human hematopoietic stem cells bearing the intended functional edit by transient AND-gate reporters.Nature biotechnology · 2026Article
- A case of T-cell acute lymphoblastic leukemia in retroviral gene therapy for ADA-SCID.Nature communications · 2024Article
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- Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition.The Journal of experimental medicine · 2023Article
- Gene modification therapies for hereditary diseases in the fetus.Prenatal diagnosis · 2023Review
- Enhanced Biosafety of theBiomolecules · 2023Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- Multiple Integrated Non-clinical Studies Predict the Safety of Lentivirus-Mediated Gene Therapy for β-Thalassemia.Molecular therapy. Methods & clinical development · 2018Article
- Thymocyte self-renewal and oncogenic risk in immunodeficient mouse models: relevance for human gene therapy clinical trials targeting haematopoietic stem cell populations?Mammalian genome : official journal of the International Mammalian Genome Society · 2018Review
- Rapid immune reconstitution of SCID-X1 canines after G-CSF/AMD3100 mobilization and in vivo gene therapy.Blood advances · 2018Article
- Limiting Thymic Precursor Supply Increases the Risk of Lymphoid Malignancy in Murine X-Linked Severe Combined Immunodeficiency.Molecular therapy. Nucleic acids · 2017Article
- A novel intranuclear RNA vector system for long-term stem cell modification.Gene therapy · 2016Article
- Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?Human gene therapy · 2016Review
- Lentiviral Engineered Fibroblasts Expressing Codon-Optimized COL7A1 Restore Anchoring Fibrils in RDEB.The Journal of investigative dermatology · 2016Article
- An international effort to cure a global health problem: A report on the 19th Hemoglobin Switching Conference.Experimental hematology · 2015Review
- Antiangiogenic and Neurogenic Activities of Sleeping Beauty-Mediated PEDF-Transfected RPE Cells In Vitro and In Vivo.BioMed research international · 2015Article
- Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease.Current gene therapy · 2015Article
- Impact of next-generation sequencing error on analysis of barcoded plasmid libraries of known complexity and sequence.Nucleic acids research · 2014Article
- Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Current progress on gene therapy for primary immunodeficiencies.Gene therapy · 2013Review
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
The development of leukemia as a consequence of vector-mediated genotoxicity in gene therapy trials for X-linked severe combined immunodeficiency (SCID-X1) has prompted substantial research effort into the design and safety testing of integrating vectors. An important element of vector design is the selection and evaluation of promoter-enhancer elements with sufficient strength to drive reliable immune reconstitution, but minimal propensity for enhancer-mediated insertional mutagenesis. In this study, we set out to explore the effect of promoter-enhancer selection on the efficacy and safety of human immunodeficiency virus-1-derived lentiviral vectors in gammac-deficient mice. We observed incomplete or absent T- and B-cell development in mice transplanted with progenitors expressing gammac from the phosphoglycerate kinase (PGK) and Wiscott-Aldrich syndrome (WAS) promoters, respectively. In contrast, functional T- and B-cell compartments were restored in mice receiving an equivalent vector containing the elongation factor-1-alpha (EF1alpha) promoter; however, 4 of 14 mice reconstituted with this vector subsequently developed lymphoma. Extensive analyses failed to implicate insertional mutagenesis or gammac overexpression as the underlying mechanism. These findings highlight the need for detailed mechanistic analysis of tumor readouts in preclinical animal models assessing vector safety, and suggest the existence of other ill-defined risk factors for oncogenesis, including replicative stress, in gene therapy protocols targeting the hematopoietic compartment.
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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.