Retroviral-mediated gene correction for X-linked severe combined immunodeficiency

Détails

ID Serval
serval:BIB_494D88C6B6A2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Retroviral-mediated gene correction for X-linked severe combined immunodeficiency
Périodique
Blood
Auteur(s)
Candotti F., Johnston J. A., Puck J. M., Sugamura K., O'Shea J. J., Blaese R. M.
ISSN
0006-4971 (Print)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
1996
Volume
87
Numéro
8
Pages
3097-102
Langue
anglais
Notes
Candotti, F
Johnston, J A
Puck, J M
Sugamura, K
O'Shea, J J
Blaese, R M
eng
Blood. 1996 Apr 15;87(8):3097-102.
Résumé
X-linked severe combined immunodeficiency (XSCID) is a lethal disease caused by a defect in the gene encoding the common gamma chain (gamma-c) of the receptor for interleukin-2 (IL-2), IL-4, IL-7, IL-9, and IL-15. Allogeneic bone marrow transplantation, the current therapy of choice for this defect, is often complicated by graft-versus-host disease and/or incomplete reconstitution of B-lymphocyte functions. Correction of the gene defect at the level of the autologous lymphohematopoietic progenitors could therefore represent an improvement in the medical management of these patients. To study the feasibility of a gene therapy approach for XSCID, a retroviral vector expressing gamma-c was used to transduce Epstein-Barr virus-transformed B-cell lines derived from patients with XSCID. After transduction, XSCID cells newly expressed gamma-c on the cell surface at levels comparable to those observed on B-cell lines obtained from normal donors. Moreover, the reconstituted gamma-c restored function to the IL-2 and IL-4 receptors as shown by signal transduction mediated by phosphorylation of the JAK1 and JAK3 members of the Janus family of tyrosine kinases and by restoration of cellular proliferation in response to IL-2.
Mots-clé
B-Lymphocytes/drug effects/*metabolism/pathology, Cell Line, Transformed, Feasibility Studies, Genetic Complementation Test, *Genetic Therapy, Genetic Vectors/*genetics, Herpesvirus 4, Human, Humans, Interleukin-2/pharmacology, Interleukin-4/pharmacology, Janus Kinase 1, Janus Kinase 3, Lymphocyte Activation/drug effects, Male, Phosphorylation, Protein Processing, Post-Translational, Protein-Tyrosine Kinases/metabolism, Receptors, Interleukin-2/biosynthesis/*genetics, Recombinant Fusion Proteins/metabolism, Retroviridae/*genetics, Severe Combined Immunodeficiency/genetics/pathology/*therapy, Transfection, X Chromosome/genetics
Pubmed
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
20/08/2019 14:56
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