ArticleHuman gene therapy2010
Cytotoxicity associated with artemis overexpression after lentiviral vector-mediated gene transfer.
Article in Human gene therapy, 2010. 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 26 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.
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
26 citing papers in PubMed, 32 citations in OpenAlex.
- Lentiviral Gene Therapy for Artemis-Deficient SCID.The New England journal of medicine · 2022Trial
- Base editing of Artemis mutations ex vivo sheds light on gene therapy for Artemis-deficient SCID.Advanced biotechnology · 2026Article
- Parathyroid hormone 1 receptor signaling mediates breast cancer metastasis to bone in mice.JCI insight · 2023Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- AFB1 and OTA Promote Immune Toxicity in Human LymphoBlastic T Cells at Transcriptomic Level.Foods (Basel, Switzerland) · 2023Article
- In Vivo Analysis of Heterogeneous Extracellular Vesicles Using a Red-Shifted Bioluminescence Resonance Energy Transfer Reporter Protein.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Gene Therapy for Primary Immunodeficiency.HemaSphere · 2021Review
- Biosafety Studies of a Clinically Applicable Lentiviral Vector for the Gene Therapy of Artemis-SCID.Molecular therapy. Methods & clinical development · 2019Article
- Microvesicle-Mediated Delivery of Minicircle DNA Results in Effective Gene-Directed Enzyme Prodrug Cancer Therapy.Molecular cancer therapeutics · 2019Article
- Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges.Nature reviews. Drug discovery · 2019Review
- Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs).Biomacromolecules · 2018Article
- Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells.Breast cancer research : BCR · 2017Article
- Article
- Lentivirus Mediated Correction of Artemis-Deficient Severe Combined Immunodeficiency.Human gene therapy · 2017Article
- Lymphopoiesis in transgenic mice over-expressing Artemis.Gene therapy · 2016Article
- Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.Neoplasia (New York, N.Y.) · 2015Article
- Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency.The Journal of allergy and clinical immunology · 2015Article
- Role of transgene regulation in ex vivo lentiviral correction of artemis deficiency.Human gene therapy · 2015Article
- Methods for culturing human femur tissue explants to study breast cancer cell colonization of the metastatic niche.Journal of visualized experiments : JoVE · 2015Article
- Lentiviral vectors for the treatment of primary immunodeficiencies.Journal of inherited metabolic disease · 2014Review
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 3 institutions in 2 countries.
Funding
Abstract
Artemis is a hairpin-opening endonuclease involved in nonhomologous end-joining and V(D)J recombination. Deficiency of Artemis results in radiation-sensitive severe combined immunodeficiency (SCID) characterized by complete absence of T and B cells due to an arrest at the receptor recombination stage. We have generated several lentiviral vectors for transduction of the Artemis sequence, intending to complement the deficient phenotype. We found that transduction by a lentiviral vector in which Artemis is regulated by a strong EF-1alpha promoter resulted in a dose-dependent loss of cell viability due to perturbed cell cycle distribution, increased DNA damage, and increased apoptotic cell frequency. This toxic response was not observed in cultures exposed to identical amounts of control vector. Loss of cell viability was also observed in cells transfected with an Artemis expression construct, indicating that toxicity is independent of lentiviral transduction. Reduced toxicity was observed when cells were transduced with a moderate-strength phosphoglycerate kinase promoter to regulate Artemis expression. These results present a novel challenge in the establishment of conditions that support Artemis expression at levels that are nontoxic yet sufficient to correct the T(-)B(-) phenotype, crucial for preclinical studies and clinical application of Artemis gene transfer in the treatment of human SCID-A.
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.