SEARCH:   Advanced

Blood, 1 January 2006, Vol. 107, No. 1, pp. 63-72. Prepublished online as a Blood First Edition Paper on September 20, 2005; DOI 10.1182/blood-2005-05-2032. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-05-2032v1 107/1/63    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lagresle-Peyrou, C. Articles by Cavazzana-Calvo, M. Search for Related Content PubMed PubMed Citation Articles by Lagresle-Peyrou, C. Articles by Cavazzana-Calvo, M. Related Collections Gene Therapy Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity Chantal Lagresle-Peyrou, Frank Yates, Michèle Malassis-Séris, Christophe Hue, Estelle Morillon, Alexandrine Garrigue, Allen Liu, Philippe Hajdari, Daniel Stockholm, Olivier Danos, Brigitte Lemercier, Marie-Lise Gougeon, Frederic Rieux-Laucat, Jean-Pierre de Villartay, Alain Fischer, and Marina Cavazzana-Calvo From the Université Paris-Descartes, Faculté demédecine, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité (U) 429, site Necker-Enfants Malades, France; Department of Biotherapy,Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker-Enfants Malades, Paris, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche (UMR) 8115, Généthon, Evry, France; Immunité anti-virale, biothérapie et vaccins, Inserm U668, Institut Pasteur, Paris, France; AP-HP, France; and Unité d'Immunologie et d'Hématologie Pédiatriques, AP-HP, Hôpital Necker-Enfants Malades, Paris, France. Severe combined immunodeficiency (SCID) caused by mutations in RAG1 or RAG2 genes is characterized by a complete block in T- and B-cell development. The only curative treatment is allogeneic hematopoietic stem cell transplantation, which gives a high survival rate (90%) when an HLA-genoidentical donor exists but unsatisfactory results when only partially compatible donors are available. We have thus been interested in the development of a potential alternative treatment by using retroviral gene transfer of a normal copy of RAG1 cDNA. We show here that this approach applied to RAG-1-deficient mice restores normal B- and T-cell function even in the presence of a reduced number of mature B cells. The reconstitution is stable over time, attesting to a selective advantage of transduced progenitors. Notably, a high transgene copy number was detected in all lymphoid organs, and this was associated with a risk of lymphoproliferation as observed in one mouse. Altogether, these results demonstrate that correction of RAG-1 deficiency can be achieved by gene therapy in immunodeficient mice but that human application would require the use of self-inactivated vector to decrease the risk of lymphoproliferative diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. P. Wang, A. Garrigue, A. Ciuffi, K. Ronen, J. Leipzig, C. Berry, C. Lagresle-Peyrou, F. Benjelloun, S. Hacein-Bey-Abina, A. Fischer, et al. DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer Nucleic Acids Res., May 1, 2008; 36(9): e49 - e49. [Abstract] [Full Text] [PDF] G. Mostoslavsky, A. J. Fabian, S. Rooney, F. W. Alt, and R. C. Mulligan Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer PNAS, October 31, 2006; 103(44): 16406 - 16411. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020