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Blood, 15 April 2006, Vol. 107, No. 8, pp. 3091-3097. Prepublished online as a Blood First Edition Paper on December 29, 2005; DOI 10.1182/blood-2005-10-4057. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-10-4057v1 107/8/3091    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 Ravin, S. S. T.-D. Articles by Felsburg, P. J. Search for Related Content PubMed PubMed Citation Articles by Ravin, S. S. T.-D. Articles by Felsburg, P. J. Related Collections Immunobiology Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Correction of canine X-linked severe combined immunodeficiency by in vivo retroviral gene therapy Suk See Ting–De Ravin, Douglas R. Kennedy, Nora Naumann, Jeffrey S. Kennedy, Uimook Choi, Brian J. Hartnett, Gilda F. Linton, Narda L. Whiting-Theobald, Peter F. Moore, William Vernau, Harry L. Malech, and Peter J. Felsburg From the Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia; and Veterinary Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis. X-linked severe combined immunodeficiency (XSCID) is characterized by profound immunodeficiency and early mortality, the only potential cure being hematopoietic stem cell (HSC) transplantation or gene therapy. Current clinical gene therapy protocols targeting HSCs are based upon ex vivo gene transfer, potentially limited by the adequacy of HSC harvest, transduction efficiencies of repopulating HSCs, and the potential loss of their engraftment potential during ex vivo culture. We demonstrate an important proof of principle by showing achievement of durable immune reconstitution in XSCID dogs following intravenous injection of concentrated RD114-pseudotyped retrovirus vector encoding the corrective gene, the interleukin-2 receptor chain (c). In 3 of 4 dogs treated, normalization of numbers and function of T cells were observed. Two long-term–surviving animals (16 and 18 months) showed significant marking of B lymphocytes and myeloid cells, normalization of IgG levels, and protective humoral immune response to immunization. There were no adverse effects from in vivo gene therapy, and in one dog that reached sexual maturity, sparing of gonadal tissue from gene transfer was demonstrated. This is the first demonstration that in vivo gene therapy targeting HSCs can restore both cellular and humoral immunity in a large-animal model of a fatal immunodeficiency. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Gene therapy goes to the dogs Katherine P. Ponder Blood 2006 107: 3018-3019. [Full Text] [PDF] This article has been cited by other articles: J. U. Pontius, J. C. Mullikin, D. R. Smith, Agencourt Sequencing Team, K. Lindblad-Toh, S. Gnerre, M. Clamp, J. Chang, R. Stephens, B. Neelam, et al. Initial sequence and comparative analysis of the cat genome Genome Res., November 1, 2007; 17(11): 1675 - 1689. [Abstract] [Full Text] [PDF]

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