ArticleBlood2006
Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 181 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
181 citing papers in PubMed, 322 citations in OpenAlex.
- Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients.The Journal of clinical investigation · 2008Trial
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Non-viral vectors as beacons of hope for reducing genotoxic risks of gene therapy.Nature biomedical engineering · 2026Article
- Ex vivo long-term expansion of human hematopoietic stem and progenitor cells as a tool for modeling vector integration sites and clonality.Journal of translational medicine · 2026Article
- Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny.Nature communications · 2025Article
- Pharmacological and pre-clinical safety profile of rSIV.F/HN, a hybrid lentiviral vector for cystic fibrosis gene therapy.The European respiratory journal · 2025Article
- Advancements in Hematopoietic Stem Cell Gene Therapy: A Journey of Progress for Viral Transduction.Cells · 2024Review
- An empowered, clinically viable hematopoietic stem cell gene therapy for the treatment of multisystemic mucopolysaccharidosis type II.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Preclinical toxicity analyses of lentiviral vectors expressing the HIV-1 LTR-specific designer-recombinase Brec1.PloS one · 2024Article
- Development of anMolecular therapy. Methods & clinical development · 2023Article
- TGFCells · 2023Article
- Meeting FDA Guidance recommendations for replication-competent virus and insertional oncogenesis testing.Molecular therapy. Methods & clinical development · 2023Review
- Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carryingFrontiers in immunology · 2023Article
- Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Time to evolve: predicting engineered T cell-associated toxicity with next-generation models.Journal for immunotherapy of cancer · 2022Review
- Review: Sustainable Clinical Development of CAR-T Cells - Switching From Viral Transduction Towards CRISPR-Cas Gene Editing.Frontiers in immunology · 2022Review
- Application of Small Molecules in the Central Nervous System Direct Neuronal Reprogramming.Frontiers in bioengineering and biotechnology · 2022Review
- Evaluation of twoMolecular therapy. Methods & clinical development · 2021Article
121 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Retroviral vectors with long terminal repeats (LTRs), which contain strong enhancer/promoter sequences at both ends of their genome, are widely used for stable gene transfer into hematopoietic cells. However, recent clinical data and mouse models point to insertional activation of cellular proto-oncogenes as a dose-limiting side effect of retroviral gene delivery that potentially induces leukemia. Self-inactivating (SIN) retroviral vectors do not contain the terminal repetition of the enhancer/promoter, theoretically attenuating the interaction with neighboring cellular genes. With a new assay based on in vitro expansion of primary murine hematopoietic cells and selection in limiting dilution, we showed that SIN vectors using a strong internal retroviral enhancer/promoter may also transform cells by insertional mutagenesis. Most transformed clones, including those obtained after dose escalation of SIN vectors, showed insertions upstream of the third exon of Evi1 and in reverse orientation to its transcriptional orientation. Normalizing for the vector copy number, we found the transforming capacity of SIN vectors to be significantly reduced when compared with corresponding LTR vectors. Additional modifications of SIN vectors may further increase safety. Improved cell-culture assays will likely play an important role in the evaluation of insertional mutagenesis.
Indexed as
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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.