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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 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 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 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. Related Collections Hematopoiesis and Stem Cells Immunobiology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 843-848 GENE THERAPY In vivo retroviral gene transfer by direct intrafemoral injection results in correction of the SCID phenotype in Jak3 knock-out animals Christine S. McCauslin, John Wine, Linzhao Cheng, Kim D. Klarmann, Fabio Candotti, Peter A. Clausen, Sally E. Spence, and Jonathan R. Keller From the Basic Research Program, SAIC-Frederick, Laboratory of Experimental Immunology, Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, MD; Division of Immunology and Hematopoiesis, Johns Hopkins University School of Medicine, Baltimore, MD; Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; and Marligen Biosciences, Ijamsville, MD Efficient retroviral gene transfer to pluripotential hematopoietic stem cells (PHSCs) requires ex vivo culture in multiple hematopoietic growth factors (HGFs) to promote cell division. While treatment of PHSCs with HGF can render stem cells viable targets for retroviral infection, HGFs can promote differentiation, loss of self-renewal potential, and affect the homing/engraftment capacity of PHSCs. 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 colony-forming units–c (CFU-c), short-term reconstituting cells, and PHSCs. Moreover, direct intrafemoral injection of Jak3 knock-out 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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