ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Dual-regulated lentiviral vector for gene therapy of X-linked chronic granulomatosis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03055247 (A Multicentric, Exploratory, Non-randomised, Non-controlled, Prospective, Open-label Phase II Study Evaluating Safety and Efficacy of IBU, G-CSF and Plerixafor as Stem Cell Mobilization Regimen in Patients Affected by X-CGD), which is not on this map. Cited by 31 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.
A Multicentric, Exploratory, Non-randomised, Non-controlled, Prospective, Open-label Phase II Study Evaluating Safety and Efficacy of IBU, G-CSF and Plerixafor as Stem Cell Mobilization Regimen in Patients Affected by X-CGD
Who cites it
31 citing papers in PubMed, 61 citations in OpenAlex.
- Article
- Review
- CRISPR-Cas9-AAV versus lentivector transduction for genome modification of X-linked severe combined immunodeficiency hematopoietic stem cells.Frontiers in immunology · 2022Article
- Recent advances in lentiviral vectors for gene therapy.Science China. Life sciences · 2021Review
- Review
- Update on Clinical Ex Vivo Hematopoietic Stem Cell Gene Therapy for Inherited Monogenic Diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Antiviral immunity and nucleic acid sensing in haematopoietic stem cell gene engineering.Gene therapy · 2021Review
- Hematopoietic Tumors in a Mouse Model of X-linked Chronic Granulomatous Disease after Lentiviral Vector-Mediated Gene Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Gene Therapy for Primary Immunodeficiency.HemaSphere · 2021Review
- D-mannose suppresses macrophage IL-1β production.Nature communications · 2020Article
- Review
- Article
- Toll-Like Receptors and Relevant Emerging Therapeutics with Reference to Delivery Methods.Pharmaceutics · 2019Review
- Gene therapy targeting haematopoietic stem cells for inherited diseases: progress and challenges.Nature reviews. Drug discovery · 2019Review
- Transcriptional Targeting and MicroRNA Regulation of Lentiviral Vectors.Molecular therapy. Methods & clinical development · 2019Review
- Efficacy of lentivirus-mediated gene therapy in an Omenn syndrome recombination-activating gene 2 mouse model is not hindered by inflammation and immune dysregulation.The Journal of allergy and clinical immunology · 2018Article
- Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A).Journal of clinical immunology · 2018Article
- Foamy Virus Vector Carries a Strong Insulator in Its Long Terminal Repeat Which Reduces Its Genotoxic Potential.Journal of virology · 2018Article
- A Review of Chronic Granulomatous Disease.Advances in therapy · 2017Review
- Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
Regulated transgene expression may improve the safety and efficacy of hematopoietic stem cell (HSC) gene therapy. Clinical trials for X-linked chronic granulomatous disease (X-CGD) employing gammaretroviral vectors were limited by insertional oncogenesis or lack of persistent engraftment. Our novel strategy, based on regulated lentiviral vectors (LV), targets gp91(phox) expression to the differentiated myeloid compartment while sparing HSC, to reduce the risk of genotoxicity and potential perturbation of reactive oxygen species levels. Targeting was obtained by a myeloid-specific promoter (MSP) and posttranscriptional, microRNA-mediated regulation. We optimized both components in human bone marrow (BM) HSC and their differentiated progeny in vitro and in a xenotransplantation model, and generated therapeutic gp91(phox) expressing LVs for CGD gene therapy. All vectors restored gp91(phox) expression and function in human X-CGD myeloid cell lines, primary monocytes, and differentiated myeloid cells. While unregulated LVs ectopically expressed gp91(phox) in CD34(+) cells, transcriptionally and posttranscriptionally regulated LVs substantially reduced this off-target expression. X-CGD mice transplanted with transduced HSC restored gp91(phox) expression, and MSP-driven vectors maintained regulation during BM development. Combining transcriptional (SP146.gp91-driven) and posttranscriptional (miR-126-restricted) targeting, we achieved high levels of myeloid-specific transgene expression, entirely sparing the CD34(+) HSC compartment. This dual-targeted LV construct represents a promising candidate for further clinical development.
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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.