ArticleThe Journal of clinical investigation2009
The genotoxic potential of retroviral vectors is strongly modulated by vector design and integration site selection in a mouse model of HSC gene therapy.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 306 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
306 citing papers in PubMed, 1 synthesis or guideline pooled it, 571 citations in OpenAlex.
- A systematic review and meta-analysis of gene therapy with hematopoietic stem and progenitor cells for monogenic disorders.Nature communications · 2022Pooled it
- Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy.The New England journal of medicine · 2024Trial
- Trial
- Lentivector cryptic splicing mediates increase in CD34+ clones expressing truncated HMGA2 in human X-linked severe combined immunodeficiency.Nature communications · 2022Trial
- Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.Science (New York, N.Y.) · 2013Trial
- Advances in gene transfer technologies: comparing viral and non-viral vectors for therapeutic applications.3 Biotech · 2026Review
- Oncogenesis as an Adverse Effect of Gene Replacement Therapy in Hematopoietic Stem Cells.International journal of molecular sciences · 2026Review
- Restoration of the immune system with base editing and non-genotoxic conditioning in a Rag2 point-mutant mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- A Comprehensive Evaluation of CAR-T Cell Gene Therapy, Tracing its Revolutionary Clinical Breakthroughs and Advancements Towards Next-Generation Engineering.Expert reviews in molecular medicine · 2026Review
- Enhanced transcriptional insulation of lentiviral vectors using "sequence-upgraded polyA long terminal repeats" or "supA-LTRs".Molecular therapy. Advances · 2026Article
- Spatial perturb-seq: single-cell functional genomics within intact tissue architecture.Nature communications · 2026Article
- Adaptation of lentiviral vectors for viral gene therapy and their impact on host cell biology.Journal of translational medicine · 2026Review
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- Transduction of Quiescent Human Hematopoietic Stem and Progenitor Cells Using Lentiviral Vectors and Virus-Like Particles.Current protocols · 2026Article
- Assessment of Potential Side Effects Related To RAB27A Gene Therapy in Stem Cells.Stem cell reviews and reports · 2026Article
- Gene therapy for genodermatoses at the crossroads of innovation and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
- Gene therapy supports long-term reconstitution of patient hematopoietic stem cells in deficiency of adenosine deaminase 2.Molecular therapy. Methods & clinical development · 2025Article
- Article
- CRISPR-based therapeutic genome editing for inherited blood disorders.Nature reviews. Drug discovery · 2025Review
- Leucine Zipper-based Cell Sorting for Purification of Dual-vector-transduced Cells.Journal of visualized experiments : JoVE · 2025Article
246 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
gamma-Retroviral vectors (gammaRVs), which are commonly used in gene therapy, can trigger oncogenesis by insertional mutagenesis. Here, we have dissected the contribution of vector design and viral integration site selection (ISS) to oncogenesis using an in vivo genotoxicity assay based on transplantation of vector-transduced tumor-prone mouse hematopoietic stem/progenitor cells. By swapping genetic elements between gammaRV and lentiviral vectors (LVs), we have demonstrated that transcriptionally active long terminal repeats (LTRs) are major determinants of genotoxicity even when reconstituted in LVs and that self-inactivating (SIN) LTRs enhance the safety of gammaRVs. By comparing the genotoxicity of vectors with matched active LTRs, we were able to determine that substantially greater LV integration loads are required to approach the same oncogenic risk as gammaRVs. This difference in facilitating oncogenesis is likely to be explained by the observed preferential targeting of cancer genes by gammaRVs. This integration-site bias was intrinsic to gammaRVs, as it was also observed for SIN gammaRVs that lacked genotoxicity in our model. Our findings strongly support the use of SIN viral vector platforms and show that ISS can substantially modulate genotoxicity.
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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.