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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 20, 2005 Accepted August 29, 2005 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, Michele Malassis-Seris, 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 Universite Paris-Descartes, Faculte de medecine, Inserm Unit 429, site Necker-Enfants Malades, Paris, France Department of Biotherapy AP-HP, Hopital Necker-Enfants Malades, Paris, France Centre National de la Recherche Scientifique, UMR 8115, Genethon, Evry, France Immunite Anti-virale, Biotherapie et Vaccins, Inserm U668, Institut Pasteur, Paris, France Universite Paris-Descartes, Faculte de medecine, Inserm Unit 429, site Necker-Enfants Malades, Paris, France; Assistance Publique, Hopitaux de Paris (AP/HP), Paris, France Universite Paris-Descartes, Faculte de medecine, Inserm Unit 429, site Necker-Enfants Malades, Paris, France; Unite d'Immunologie et d'Hematologie Pediatriques, AP/HP, Hopital Necker-Enfants Malades, Paris, France Universite Paris-Descartes, Faculte de medecine, Inserm Unit 429, site Necker-Enfants Malades, Paris, France; Department of Biotherapy AP-HP, Hopital Necker-Enfants Malades, Paris, France * Corresponding author; email: lagresle{at}necker.fr. Severe combined immunodeficiency (SCID) caused by mutations in RAG-1 or RAG-2 genes is characterized by a complete block in T and B cell development. The only curative treatment is allogenic hematopoietic stem cell transplantation which gives a high survival rate (90%) when an HLA-genoidentical donor exist 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 RAG-1 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 for a selective advantage of transduced progenitors. Noteworthy, 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 in order 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]

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