ArticleLeukemia2010
Correction of B-cell development in Btk-deficient mice using lentiviral vectors with codon-optimized human BTK.
Article in Leukemia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- ABO: A 3D stroma-supported culture platform enabling full human B-lymphopoiesis for disease modeling and gene therapy development.Cell reports. Medicine · 2026Article
- Hematopoietic stem cell gene editing rescues B-cell development in X-linked agammaglobulinemia.The Journal of allergy and clinical immunology · 2024Article
- A comparison of DNA repair pathways to achieve a site-specific gene modification of the Bruton's tyrosine kinase gene.Molecular therapy. Nucleic acids · 2022Article
- Optimizing Integration and Expression of Transgenic Bruton's Tyrosine Kinase for CRISPR-Cas9-Mediated Gene Editing of X-Linked Agammaglobulinemia.The CRISPR journal · 2021Article
- Effective, safe, and sustained correction of murine XLA using a UCOE-BTK promoter-based lentiviral vector.Molecular therapy. Methods & clinical development · 2021Article
- Gene Therapy for Primary Immunodeficiency.HemaSphere · 2021Review
- Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives.Frontiers in pediatrics · 2019Review
- Hematopoietic Stem Cell Gene Therapy: Progress and Lessons Learned.Cell stem cell · 2017Review
- Evolving Gene Therapy in Primary Immunodeficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Advances of gene therapy for primary immunodeficiencies.F1000Research · 2016Review
- Article
- Bruton's tyrosine kinase: from X-linked agammaglobulinemia toward targeted therapy for B-cell malignancies.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014Article
- Gene transfer into hematopoietic stem cells as treatment for primary immunodeficiency diseases.International journal of hematology · 2014Review
- Biosafety features of lentiviral vectors.Human gene therapy · 2013Review
- Tyrosine kinase Btk is required for NK cell activation.The Journal of biological chemistry · 2012Article
- The β-globin locus control region in combination with the EF1α short promoter allows enhanced lentiviral vector-mediated erythroid gene expression with conserved multilineage activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- New frontiers of primary antibody deficiencies.Cellular and molecular life sciences : CMLS · 2012Review
- Correction of murine Rag1 deficiency by self-inactivating lentiviral vector-mediated gene transfer.Leukemia · 2011Article
- Lentiviral vector design and imaging approaches to visualize the early stages of cellular reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked agammaglobulinemia (XLA) is the most common primary immunodeficiency (PID) in man and caused by mutations in the Bruton's tyrosine kinase (BTK) gene. XLA is characterized by a B-cell differentiation arrest in bone marrow, absence of mature B cells and immunoglobulins (Igs), and recurrent bacterial infections. We used self-inactivating lentiviral vectors expressing codon-optimized human BTK under the control of three different ubiquitous or B cell-specific promoters. Btk-/- mice engrafted with transduced cells showed correction of both precursor B-cell and peripheral B-cell development. Lentiviral vectors containing the wildtype BTK sequence did not correct the phenotype. All treated mice with codon-optimized BTK exhibited the recovery of B1 cells in the peritoneal cavity, and of serum IgM and IgG3 levels. Calcium mobilization responses upon B-cell receptor stimulation as well as in vivo responses to T cell-independent antigens were restored. Viral promoters overexpressing BTK >100-fold above normal resulted in erythro-myeloid proliferations independent of insertional mutagenesis. However, transplantation into secondary Btk-/- recipients using cellular promoters resulted in functional restoration of peripheral B cells and IgM levels, without any adverse effects. In conclusion, transduction of human BTK corrects B-cell development and antigen-specific antibody responses in Btk-/- mice, thus indicating the feasibility of lentiviral gene therapy for XLA, provided that BTK expression does not vastly exceed normal levels.
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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.