ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in vivo.
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 120 papers.
What it found
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Who cites it
120 citing papers in PubMed, 181 citations in OpenAlex.
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- Dual AAV vectors for efficient delivery of large transgenes.Nature protocols · 2026Review
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026Review
- Adaptation of lentiviral vectors for viral gene therapy and their impact on host cell biology.Journal of translational medicine · 2026Review
- In vivo engineering of CAR-T cells: delivery strategies and clinical translation.Biomarker research · 2026Review
- Gene Therapy for the Treatment of Osteoarthritis: Advances and Prospective.Current pharmaceutical design · 2026Review
- Mesenchymal stem cell-derived exosomes as cell-free therapeutics: mechanistic insights and engineering strategies for liver disease treatment.Stem cell research & therapy · 2025Review
- Hematopoietic stem cell gene therapy for the treatment of X-linked agammaglobulinemia.Molecular therapy. Methods & clinical development · 2025Article
- Microfluidic Platforms for Ex Vivo and In Vivo Gene Therapy.Biosensors · 2025Review
- Preclinical efficacy of a modified gamma-globin lentivirus gene therapy in Berkeley sickle cell anemia mice and human xenograft models.Molecular therapy. Methods & clinical development · 2025Article
- Current landscape of vector safety and genotoxicity after hematopoietic stem or immune cell gene therapy.Leukemia · 2025Review
- Response to: Safety and efficacy considerations of HSC-based gene therapy for RAG1-deficient SCID.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The deLIVERed promises of gene therapy: Past, present, and future of liver-directed gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.Exploration (Beijing, China) · 2025Review
- Balancing efficacy and safety in lentiviral vector-mediated hematopoietic stem cell gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- RNA Structure: Past, Future, and Gene Therapy Applications.International journal of molecular sciences · 2024Review
- Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
Self-inactivating (SIN) lentiviral vectors (LV) have an excellent therapeutic potential as demonstrated in preclinical studies and clinical trials. However, weaker mechanisms of insertional mutagenesis could still pose a significant risk in clinical applications. Taking advantage of novel in vivo genotoxicity assays, we tested a battery of LV constructs, including some with clinically relevant designs, and found that oncogene activation by promoter insertion is the most powerful mechanism of early vector-induced oncogenesis. SIN LVs disabled in their capacity to activate oncogenes by promoter insertion were less genotoxic and induced tumors by enhancer-mediated activation of oncogenes with efficiency that was proportional to the strength of the promoter used. On the other hand, when enhancer activity was reduced by using moderate promoters, oncogenesis by inactivation of tumor suppressor gene was revealed. This mechanism becomes predominant when the enhancer activity of the internal promoter is shielded by the presence of a synthetic chromatin insulator cassette. Our data provide both mechanistic insights and quantitative readouts of vector-mediated genotoxicity, allowing a relative ranking of different vectors according to these features, and inform current and future choices of vector design with increasing biosafety.
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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.