Lentiviral-mediated gene therapy leads to improvement of B-cell functionality in a murine model of Wiskott-Aldrich syndrome

Bosticardo, Marita; Drăghici, Elena; Schena, Francesca; Sauer, Aisha V.; Fontana, Elena; Castiello, Maria Carmina; Catucci, Marco; Locci, Michela; Naldini, Luigi; Aiuti, Alessandro; Roncarolo, Maria Grazia; Poliani, Pietro Luigi; Traggiai, Elisabetta; Villa, Anna

doi:10.1016/j.jaci.2011.03.030

Cited by 34 publications

(42 citation statements)

References 28 publications

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Section: New Developments In the Treatment Of Primary Immunodeficienciesmentioning

confidence: 98%

“…Of note, Gruyembaum and collaborators 62 reported the development of an adipose tumor with incomplete correction of purine metabolism 3 years in an ADA-SCID patient after gene therapy, underscoring the limitations of hematopietic stem cell-based gene therapy for the treatment of multi-organ disease. Bosticardo et al 63 expanded on the clinical evidence supporting gene therapy for WAS, and showed reconstitution of B cell function, as well as presence of WASP in B cells of splenic marginal zone and improvement of splenic architecture in a WAS murine model. …”

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confidence: 99%

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Advances in basic and clinical immunology in 2014

Chinen

Notarangelo

Shearer

2015

Journal of Allergy and Clinical Immunology

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Section: New Developments In the Treatment Of Primary Immunodeficienciesmentioning

confidence: 98%

mentioning

confidence: 99%

Advances in basic and clinical immunology in 2014

Chinen

Notarangelo

Shearer

2015

Journal of Allergy and Clinical Immunology

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“…Transplantation corrects the immune deficiency, while reducing the production of autoantibodies. [39][40][41][42][43][44] These advances, together with improvements in the transcription vectors and promoters, have permitted the evaluation of gene therapy trials to treat some of these patients. 45,46…”

Section: 33mentioning

confidence: 99%

The contribution of mouse models to the understanding of constitutional thrombocytopenia

et al. 2016

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Article summary• Constitutional thrombocytopenias of hereditary origin have long been poorly studied due to the difficulties of obtaining invasive marrow samples.• Genetic engineering has allowed the generation of numerous mouse models for all these pathologies, providing invaluable information to understanding these diseases and serving as preclinical models to test new therapies.Constitutional thrombocytopenias result from genetic mutations affecting platelet production. These rare diseases are still underdiagnosed, especially in adults, because they remain little-known and have a highly variable expression. Autoimmune thrombocytopenia is still often wrongly diagnosed, thereby leading to the inadequate management of patients, with occasionally inappropriate splenectomy. The diagnosis of congenital thrombocytopenia relies on cytological and functional platelet analyses performed almost exclusively in specialized laboratories. Furthermore, about 50% of thrombocytopenias, associated or not with a thrombopathy, still remain of unknown origin. 1 In cases where platelet studies orient the diagnosis to a known disease, the detection of mutations in the suspected genes can C onstitutional thrombocytopenias result from platelet production abnormalities of hereditary origin. Long misdiagnosed and poorly studied, knowledge about these rare diseases has increased considerably over the last twenty years due to improved technology for the identification of mutations, as well as an improvement in obtaining megakaryocyte culture from patient hematopoietic stem cells. Simultaneously, the manipulation of mouse genes (transgenesis, total or conditional inactivation, introduction of point mutations, random chemical mutagenesis) have helped to generate disease models that have contributed greatly to deciphering patient clinical and laboratory features. Most of the thrombocytopenias for which the mutated genes have been identified now have a murine model counterpart. This review focuses on the contribution that these mouse models have brought to the understanding of hereditary thrombocytopenias with respect to what was known in humans. Animal models have either i) provided novel information on the molecular and cellular pathways that were missing from the patient studies; ii) improved our understanding of the mechanisms of thrombocytopoiesis; iii) been instrumental in structure-function studies of the mutated gene products; and iv) been an invaluable tool as preclinical models to test new drugs or develop gene therapies. At present, the genetic determinants of thrombocytopenia remain unknown in almost half of all cases. Currently available high-speed sequencing techniques will identify new candidate genes, which will in turn allow the generation of murine models to confirm and further study the abnormal phenotype. In a complementary manner, programs of random mutagenesis in mice should also identify new candidate genes involved in thrombocytopenia.The contribution of mouse models to the understanding of constitutional thrombocytope...

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“…Some typical features of these diseases, such as skin lesions, arthritis, renal diseases, and cutaneous vasculitis, are also present in a proportion of WAS patients. Moreover, autoantibodies that are known to convert self-nucleic acid into potent triggers of pDCs are abundant in a murine model of WAS deficiency and are also detected in a proportion of WAS patients (DupuisGirod et al, 2003;Meyer-Bahlburg et al, 2008;Trifari et al, 2010;Becker-Herman et al, 2011;Bosticardo et al, 2011). To investigate a possible contribution of altered pDC homeostasis to the pathophysiology of WAS, we first analyzed spleen sections and peripheral blood of WAS patients.…”

Section: Frequency Of Pdcs and Expression Of Type-i Ifn-inducible Genmentioning

confidence: 99%

Wiskott-Aldrich syndrome protein–mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells

Prete¹,

Catucci²,

Labrada³

et al. 2013

J Cell Biol

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Lentiviral-mediated gene therapy leads to improvement of B-cell functionality in a murine model of Wiskott-Aldrich syndrome

Cited by 34 publications

References 28 publications

Advances in basic and clinical immunology in 2014

Advances in basic and clinical immunology in 2014

The contribution of mouse models to the understanding of constitutional thrombocytopenia

Wiskott-Aldrich syndrome protein–mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells

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