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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-12-3859. This Article Full Text (PDF) All Versions of this Article: 2002-12-3859v1 102/3/843    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 McCauslin, C. S Articles by Keller, J. R Search for Related Content PubMed PubMed Citation Articles by McCauslin, C. S Articles by Keller, J. R Social Bookmarking                   What's this? Submitted December 20, 2002 Accepted March 27, 2003 In vivo retroviral gene transfer by direct intrafemoral injection results in correction of the SCID phenotype in Jak3 knockout animals Christine S McCauslin, John Wine, Linzhao Cheng, Kim D Klarmann, Fabio Candotti, Peter A Clausen, Sally E Spence, and Jonathan R Keller* Basic Research Program-SAIC,Inc.,LMI and LEI, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD, USA Division of Immunology and Hematopoiesis, Johns Hopkins University School of Medicine, Baltimore, MD, USA Clinical Gene Therapy Branch, National Human Genome Research Institute, Bethesda, MD, USA * Corresponding author; email: kellerj{at}mail.nciifcrf.gov. Efficient retroviral gene transfer to pluripotential hematopoietic stem cells (PHSC) requires ex vivo culture in multiple hematopoietic growth factors (HGF) to promote cell division. While treatment of PHSC with HGF can render stem cells viable targets for retroviral infection, HGF can promote differentiation, loss of self-renewal potential, and affect the homing/engraftment capacity of PHSC. To avoid the negative impacts observed with ex vivo transduction protocols, we developed a murine model for in vivo retroviral infection by direct intrafemoral injection (DII), thus abolishing the need for removal of cells from their native microenvironment and the signals necessary to maintain their unique physiology. Using this approach we have demonstrated in vivo retroviral gene transfer to CFU-c, short term reconstituting cells and PHSC. Moreover, direct intrafemoral injection of Jak3 knockout mice with retroviral particles encoding the Jak3 gene, resulted in reconstitution of normally deficient lymphocyte populations concomitant with improved immune function. In addition, DII can be used to target the delivery of other gene therapy vectors including adenoviral vectors to bone marrow cells in vivo. Taken together, these results demonstrate that in vivo retroviral gene transfer by direct intrafemoral injection may be a viable alternative to current ex vivo gene transfer approaches. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Liu, J. Daviau, C. N. Nichols, and D. S. Strayer In vivo gene transfer into rat bone marrow progenitor cells using rSV40 viral vectors Blood, October 15, 2005; 106(8): 2655 - 2662. [Abstract] [Full Text] [PDF] T. M. Cao, J. A. Shizuru, R. M. Wong, K. Sheehan, G. G. Laport, K. E. Stockerl-Goldstein, L. J. Johnston, M. J. Stuart, F. C. Grumet, R. S. Negrin, et al. Engraftment and survival following reduced-intensity allogeneic peripheral blood hematopoietic cell transplantation is affected by CD8+ T-cell dose Blood, March 15, 2005; 105(6): 2300 - 2306. [Abstract] [Full Text] [PDF] M. J. Walter, J. S. Park, S. K. M. Lau, X. Li, A. A. Lane, R. Nagarajan, W. D. Shannon, and T. J. Ley Expression Profiling of Murine Acute Promyelocytic Leukemia Cells Reveals Multiple Model-Dependent Progression Signatures Mol. Cell. Biol., December 15, 2004; 24(24): 10882 - 10893. [Abstract] [Full Text] [PDF]

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