ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Insertional transformation of hematopoietic cells by self-inactivating lentiviral and gammaretroviral vectors.
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. It is linked to trial NCT03538899 (Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency), which is not on this map. Cited by 217 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.
Phase I/II Safety and Efficacy Study of Gene Transfer for Artemis-Deficient Severe Combined Immunodeficiency (ART-SCID) in Newly Diagnosed Patients Using Self-Inactivating Lentiviral Vector (AProArt) to Transduce Autologous CD34 Hematopoietic Cells
Who cites it
217 citing papers in PubMed, 385 citations in OpenAlex.
- Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study.The Lancet. Haematology · 2019Trial
- Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.Science (New York, N.Y.) · 2013Trial
- Genetically Modified MSCs for Targeted Regeneration: Balancing Efficacy, Biosafety, and GMP Standardization.Cells · 2026Review
- When RNA goes off script: ensuring transcript fidelity in transgene expression.The EMBO journal · 2026Review
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- Therapeutic precision gene editing of cholesterol pathways as a gene therapy strategy for cardiovascular disease.Gene therapy · 2026Review
- Assessment of Potential Side Effects Related To RAB27A Gene Therapy in Stem Cells.Stem cell reviews and reports · 2026Article
- RNA Therapeutics: Delivery Problems and Solutions-A Review.Pharmaceutics · 2025Review
- Preclinical development of lentiviral vector gene therapy for Diamond-Blackfan anemia syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Donor insertion into CX3CR1 allows epigenetic modulation of a constitutive promoter on hematopoietic stem cells and its activation upon myeloid differentiation.Nucleic acids research · 2025Article
- Safe CAR-T: shedding light on CAR-related T-cell malignancies.EMBO molecular medicine · 2025Article
- The design of retroviral vectors used in the CAR-T products, risk management, and future perspective.MedComm · 2025Article
- Long Terminal Repeats of Gammaretroviruses Retain Stable Expression after Integration Retargeting.Viruses · 2024Article
- Mechanisms and Delivery of tRNA Therapeutics.Chemical reviews · 2024Review
- Advancements in Hematopoietic Stem Cell Gene Therapy: A Journey of Progress for Viral Transduction.Cells · 2024Review
- Lentivirus-mediated gene therapy corrects ribosomal biogenesis and shows promise for Diamond Blackfan anemia.JCI insight · 2024Article
- 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
- Advances in HIV Gene Therapy.International journal of molecular sciences · 2024Review
- Chimeric Antigen Receptor T Cell Therapy for Hepatocellular Carcinoma: Where Do We Stand?International journal of molecular sciences · 2024Review
- Article
157 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
12 authors at 3 institutions in 4 countries.
Funding
Abstract
Gene transfer vectors may cause clonal imbalance and even malignant cell transformation by insertional upregulation of proto-oncogenes. Lentiviral vectors (LV) with their preferred integration in transcribed genes are considered less genotoxic than gammaretroviral vectors (GV) with their preference for integration next to transcriptional start sites and regulatory gene regions. Using a sensitive cell culture assay and a series of self-inactivating (SIN) vectors, we found that the lentiviral insertion pattern was approximately threefold less likely than the gammaretroviral to trigger transformation of primary hematopoietic cells. However, lentivirally induced mutants also showed robust replating, in line with the selection for common insertion sites (CIS) in the first intron of the Evi1 proto-oncogene. This potent proto-oncogene thus represents a CIS for both GV and LV, despite major differences in their integration mechanisms. Altering the vectors' enhancer-promoter elements had a greater effect on safety than the retroviral insertion pattern. Clinical grade LV expressing the Wiskott-Aldrich syndrome (WAS) protein under control of its own promoter had no transforming potential. Mechanistic studies support the conclusion that enhancer-mediated gene activation is the major cause for insertional transformation of hematopoietic cells, opening rational strategies for risk prevention.
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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.