ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 69 citations in OpenAlex.
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- Gene therapy for inborn errors of immunity: past progress, current status and future directions.Rare disease and orphan drugs journal · 2025Article
- Assessment of non-myelotoxic agents as a preparatory regimen for hematopoietic stem cell gene therapy.Human cell · 2024Article
- Bone marrow mesenchymal stromal cells support regeneration of intestinal damage in a colitis mouse model, independent of their CXCR4 expression.Clinical and translational science · 2024Article
- Genetically corrected RAG2-SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency.Blood advances · 2024Article
- The development of anti-PD-1 antibody-induced spinal cord injury in bone marrow transplant C57BL/6Immunotherapy · 2024Article
- Gene therapy for inborn errors of immunity: past, present and future.Nature reviews. Immunology · 2023Review
- Separating the Wheat From the Chaff in Asthma and Bronchiectasis: The Saga Trajectory of a Patient With Adult-Onset RAG1 Deficiency.The journal of allergy and clinical immunology. In practice · 2023Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carryingFrontiers in immunology · 2023Article
- The recombinase activating genes: architects of immune diversity during lymphocyte development.Frontiers in immunology · 2023Review
- Rare immune diseases paving the road for genome editing-based precision medicine.Frontiers in genome editing · 2023Review
- Gene Editing Rescues In vitro T Cell Development of RAG2-Deficient Induced Pluripotent Stem Cells in an Artificial Thymic Organoid System.Journal of clinical immunology · 2021Article
- Development, characterization, and hematopoietic differentiation of Griscelli syndrome type 2 induced pluripotent stem cells.Stem cell research & therapy · 2021Article
- RAG deficiencies: Recent advances in disease pathogenesis and novel therapeutic approaches.European journal of immunology · 2021Review
- Comparison of Genetically Engineered Immunodeficient Animal Models for Nonclinical Testing of Stem Cell Therapies.Pharmaceutics · 2021Review
- Gene Therapy for Primary Immunodeficiency.HemaSphere · 2021Review
- Induction of ER Stress by an AAV5 BDD FVIII Construct Is Dependent on the Strength of the Hepatic-Specific Promoter.Molecular therapy. Methods & clinical development · 2020Article
- Lentiviral Hematopoietic Stem Cell Gene Therapy Corrects Murine Pompe Disease.Molecular therapy. Methods & clinical development · 2020Article
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Recombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We report the development of lentiviral vectors with the spleen focus forming virus (SF) promoter driving codon-optimized human RAG2 (RAG2co), which improved phenotype amelioration compared to native RAG2 in Rag2(-/-) mice. With the RAG2co therapeutic transgene, T-cell receptor (TCR) and immunoglobulin repertoire, T-cell mitogen responses, plasma immunoglobulin levels and T-cell dependent and independent specific antibody responses were restored. However, the thymus double positive T-cell population remained subnormal, possibly due to the SF virus derived element being sensitive to methylation/silencing in the thymus, which was prevented by replacing the SF promoter by the previously reported silencing resistant element (ubiquitous chromatin opening element (UCOE)), and also improved B-cell reconstitution to eventually near normal levels. Weak cellular promoters were effective in T-cell reconstitution, but deficient in B-cell reconstitution. We conclude that immune functions are corrected in Rag2(-/-) mice by genetic modification of stem cells using the UCOE driven codon-optimized RAG2, providing a valid optional vector for clinical implementation.
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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.