ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Genotoxic potential of lineage-specific lentivirus vectors carrying the beta-globin locus control region.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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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.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.Nature medicine · 2025Trial
- 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
- Assessing the safety of gene therapy vectors expressing an enhanced gamma-globin gene for the cure of sickle cell anemia.Molecular therapy. Methods & clinical development · 2025Article
- Article
- Differential CXCR4 expression on hematopoietic progenitor cells versus stem cells directs homing and engraftment.JCI insight · 2022Article
- Hurdles to the Adoption of Gene Therapy as a Curative Option for Transfusion-Dependent Thalassemia.Stem cells translational medicine · 2022Article
- Review
- Article
- Investigating the Barrier Activity of Novel, Human Enhancer-Blocking Chromatin Insulators for Hematopoietic Stem Cell Gene Therapy.Human gene therapy · 2021Article
- Preclinical Evaluation of a Novel Lentiviral Vector Driving Lineage-Specific BCL11A Knockdown for Sickle Cell Gene Therapy.Molecular therapy. Methods & clinical development · 2020Article
- Enhanced Transduction of Human Hematopoietic Stem Cells by AAV6 Vectors: Implications in Gene Therapy and Genome Editing.Molecular therapy. Nucleic acids · 2020Article
- Foamy Virus Vector Carries a Strong Insulator in Its Long Terminal Repeat Which Reduces Its Genotoxic Potential.Journal of virology · 2018Article
- Development of the First World Health Organization Lentiviral Vector Standard: Toward the Production Control and Standardization of Lentivirus-Based Gene Therapy Products.Human gene therapy methods · 2017Article
- Gene Therapy for β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Evidence for the in vivo safety of insulated foamy viral vectors.Gene therapy · 2017Article
- Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives.Journal of translational medicine · 2016Review
- Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype.The Journal of clinical investigation · 2016Article
- Evaluating the Safety of Retroviral Vectors Based on Insertional Oncogene Activation and Blocked Differentiation in Cultured Thymocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.Biomedicines · 2016Article
- Insulated Foamy Viral Vectors.Human gene therapy · 2016Article
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 at 2 institutions in 2 countries.
Funding
Abstract
Insertional mutagenesis by long terminal repeat (LTR) enhancers in gamma-retrovirus-based vectors (GVs) in clinical trials has prompted deeper investigations into vector genotoxicity. Experimentally, self-inactivating (SIN) lentivirus vectors (LVs) and GV containing internal promoters/enhancers show reduced genotoxicity, although strong ubiquitously-active enhancers dysregulate genes independent of vector type/design. Herein, we explored the genotoxicity of beta-globin (BG) locus control region (LCR), a strong long-range lineage-specific-enhancer, with/without insulator (Ins) elements in LV using primary hematopoietic progenitors to generate in vitro immortalization (IVIM) assay mutants. LCR-containing LV had approximately 200-fold lower transforming potential, compared to the conventional GV. The LCR perturbed expression of few genes in a 300 kilobase (kb) proviral vicinity but no upregulation of genes associated with cancer, including an erythroid-specific transcription factor occurred. A further twofold reduction in transforming activity was observed with insulated LCR-containing LV. Our data indicate that toxicology studies of LCR-containing LV in mice will likely not yield any insertional oncogenesis with the numbers of animals that can be practically studied.
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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.