ArticleBlood2008
An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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
56 citing papers in PubMed, 76 citations in OpenAlex.
- Trial
- Ex Vivo Gene and Cell Therapy in Hematopoietic Stem Cells.International journal of molecular sciences · 2025Review
- Review
- Extracellular Vesicles and Their Use as Vehicles of Immunogens.Methods in molecular biology (Clifton, N.J.) · 2022Article
- High level of fetal-globin reactivation by designed transcriptional activator-like effector.Blood advances · 2020Article
- Determination of the Membrane Transport Properties of Jurkat Cells with a Microfluidic Device.Micromachines · 2019Article
- Barcoding of Macaque Hematopoietic Stem and Progenitor Cells: A Robust Platform to Assess Vector Genotoxicity.Molecular therapy. Methods & clinical development · 2018Article
- Foamy Virus Vector Carries a Strong Insulator in Its Long Terminal Repeat Which Reduces Its Genotoxic Potential.Journal of virology · 2018Article
- Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector.Molecular therapy. Methods & clinical development · 2017Article
- Efficient Transduction of Human and Rhesus Macaque Primary T Cells by a Modified Human Immunodeficiency Virus Type 1-Based Lentiviral Vector.Human gene therapy · 2017Article
- Cellular therapy for sickle cell disease.Cytotherapy · 2016Review
- Generation of transgenic marmosets expressing genetically encoded calcium indicators.Scientific reports · 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
- Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.Blood · 2016Review
- Current and future alternative therapies for beta-thalassemia major.Biomedical journal · 2016Review
- Gene Therapy for X-Linked Severe Combined Immunodeficiency: Where Do We Stand?Human gene therapy · 2016Review
- Genomic discovery of potent chromatin insulators for human gene therapy.Nature biotechnology · 2015Article
- Generation of a lentiviral vector producer cell clone for human Wiskott-Aldrich syndrome gene therapy.Molecular therapy. Methods & clinical development · 2015Article
- Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease.Current gene therapy · 2015Article
- Charting a clear path: the ASGCT Standardized Pathways Conference.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pathogenic activation of the LMO2 proto-oncogene by an oncoretroviral vector insertion in a clinical trial for X-linked severe combined immunodeficiency (X-SCID) has prompted safety concerns. We used an adeno-associated virus vector to achieve targeted insertion of a gamma-retroviral long terminal repeat (LTR) driving a GFP expression cassette with flanking loxP sites in a human T-cell line at the precise location of vector integration in one of the patients with X-SCID. The LTR-GFP cassette was inserted into the first intron of the LMO2 gene, resulting in strong activation of LMO2. Cre-mediated cassette exchange was used to replace the original LTR-GFP cassette with one flanked by insulator elements leading to a several fold reduction in LMO2 expression. The LTR-GFP cassette was also replaced with a globin gene regulatory cassette that failed to activate the LMO2 gene in lymphoid cells. A gamma-retroviral vector with 2 intact LTRs resulted in activation of the LMO2 gene when inserted into the first intron, but a self-inactivating lentiviral vector with an internal cellular promoter and flanking insulator elements did not activate the LMO2 gene. Thus, this system is useful for comparing the safety profiles of vector cassettes with various regulatory elements for their potential for proto-oncogene activation.
Indexed as
Identifiers
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.