ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Article
- In vivo adenine base editing rescues adrenoleukodystrophy in a humanized mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Fetal gene therapy.Journal of inherited metabolic disease · 2024Review
- Article
- In Utero Transfer of Adeno-Associated Viral Vectors Produces Long-Term Factor IX Levels in a Cynomolgus Macaque Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects.Journal of inherited metabolic disease · 2017Review
- In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application.Molecular therapy. Methods & clinical development · 2016Review
- Liver-directed lentiviral gene therapy in a dog model of hemophilia B.Science translational medicine · 2015Article
- Specific genomic and transcriptomic aberrations in tumors induced by partial hepatectomy of a chronically inflamed murine liver.Oncotarget · 2014Article
- Transgenic expression of human glial cell line-derived neurotrophic factor from integration-deficient lentiviral vectors is neuroprotective in a rodent model of Parkinson's disease.Human gene therapy · 2014Article
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lentiviral vectors are widely used in basic research and clinical applications for gene transfer and long-term expression; however, safety issues have not yet been completely resolved. In this study, we characterized hepatocarcinomas that developed in mice 1 year after in utero administration of a feline-derived lentiviral vector. Mapped viral integration sites differed among tumors and did not coincide with the regions of chromosomal aberrations. Furthermore, gene expression profiling revealed that no known cancer-associated genes were deregulated in the vicinity of viral integrations. Nevertheless, five of the six tumors exhibited highly significant upregulation of E2F target genes, of which a majority are associated with oncogenesis, DNA damage response, and chromosomal instability. We further show in vivo and in vitro that E2F activation occurs early on following transduction of both fetal mice and cultured human hepatocytes. On the basis of the similarities in E2F target gene expression patterns among tumors and the lack of evidence implicating insertional mutagenesis, we propose that transduction of fetal mice with a feline lentiviral vector induces E2F-mediated major cellular processes that drive hepatocytes toward uncontrolled proliferation culminating in tumorigenesis.
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