ArticleThe Journal of clinical investigation2005
In vivo correction of ZAP-70 immunodeficiency by intrathymic gene transfer.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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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.
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Who cites it
20 citing papers in PubMed.
- Combined immunodeficiency caused by pathogenic variants in theFrontiers in immunology · 2023Article
- A Minimally Invasive, Accurate, and Efficient Technique for Intrathymic Injection in Mice.Journal of visualized experiments : JoVE · 2022Article
- Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells.The Journal of allergy and clinical immunology · 2020Article
- Baboon envelope LVs efficiently transduced human adult, fetal, and progenitor T cells and corrected SCID-X1 T-cell deficiency.Blood advances · 2019Article
- Correction of T cell deficiency in ZAP-70 knock-out mice by simple intraperitoneal adoptive transfer of thymocytes.Clinical and experimental immunology · 2018Article
- Retrogradely Transportable Lentivirus Tracers for Mapping Spinal Cord Locomotor Circuits.Frontiers in neural circuits · 2018Article
- Gene therapy for primary immune deficiencies: a Canadian perspective.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2017Review
- Intrathymic Injection.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Advances of gene therapy for primary immunodeficiencies.F1000Research · 2016Review
- Thymocytes inFrontiers in immunology · 2016Article
- Free-hand ultrasound guidance permits safe and efficient minimally invasive intrathymic injections in both young and aged mice.Ultrasound in medicine & biology · 2015Article
- Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases.International journal of hematology · 2014Review
- Review
- Recent advances in lentiviral vector development and applications.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Review
- Efficient intrathymic gene transfer following in situ administration of a rAAV serotype 8 vector in mice and nonhuman primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Article
- Immunodeficiency in childhood.Current allergy and asthma reports · 2006Review
- Immunodeficiencies: injecting some safety into SCID gene therapy?Gene therapy · 2006Article
- Intrathymic administration of hematopoietic progenitor cells enhances T cell reconstitution in ZAP-70 severe combined immunodeficiency.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- A new direction for gene therapy: intrathymic T cell-specific lentiviral gene transfer.The Journal of clinical investigation · 2005Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SCID patients have been successfully treated by administration of ex vivo gene-corrected stem cells. However, despite its proven efficacy, such treatment carries specific risks and difficulties. We hypothesized that some of these drawbacks may be overcome by in situ gene correction of T lymphoid progenitors in the thymus. Indeed, in vivo intrathymic transfer of a gene that provides a selective advantage for transduced prothymocytes should result in the generation of functional T lymphocyte progeny, allowing long-term immune reconstitution. We assessed the feasibility of this approach in a murine model of ZAP-70-deficient SCID. A T cell-specific ZAP-70-expressing lentiviral vector was injected into thymi of adult ZAP-70-/- mice without prior conditioning. This resulted in the long-term differentiation of mature TCR-alphabeta+ thymocytes, indicating that the vector had integrated into progenitor cells. Moreover, peripheral ZAP-70-expressing T cells demonstrated a partially diversified receptor repertoire and were responsive to alloantigens in vitro and in vivo. Improved treatment efficacy was achieved in infant ZAP-70-/- mice, in which the thymus is proportionately larger and a higher percentage of prothymocytes are in cycle. Thus, intrathymic injection of a lentiviral vector could represent a simplified and potentially safer alternative to ex vivo gene-modified hematopoietic stem cell transplantation for gene therapy of T cell immunodeficiencies.
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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.