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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2655-2662. Prepublished online as a Blood First Edition Paper on June 30, 2005; DOI 10.1182/blood-2005-01-0028. This Article Full Text (PDF) All Versions of this Article: 2005-01-0028v1 106/8/2655    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liu, B. Articles by Strayer, D. S Search for Related Content PubMed PubMed Citation Articles by Liu, B. Articles by Strayer, D. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 5, 2005 Accepted February 23, 2005 In vivo gene transfer into rat bone marrow progenitor cells using rSV40 viral vectors Bianling Liu, Judy Daviau, Carmen N Nichols, and David S Strayer* Department of Pathology, Jefferson Medical College, Philadelphia, PA, USA Division of Animal Resources, Thomas Jefferson University, Philadelphia, PA, USA * Corresponding author; email: david.strayer{at}jefferson.edu. Hematopoietic stem cell (HSC) gene transfer has been attempted almost entirely ex vivo, and has been limited by cytokine-induced loss of self-renewal capacity and transplantation-related defects in homing and engraftment. Here, we attempted to circumvent such limitations by injecting vectors directly into the bone marrow (BM), to transduce HSC in their native environment. SV40-derived gene delivery vectors were used because they transduce resting CD34+ cells very efficiently. Rats received SV(Nef-FLAG), carrying FLAG marker epitope, or a control rSV40, directly into both femoral marrow cavities. Intracellular transgene expression by PB or BM cells was detected by cytofluorimetry. An average of 5.3% of PB leukocytes expressed FLAG for the entire study, 56 weeks. Transgene expression was sustained in multiple cell lineages, including granulocytes (average, 3.3% of leukocytes, 20.4% of granulocytes), CD3+ T lymphocytes (average, 0.53% of leukocytes, 1% of total T cells) and CD45R+ B lymphocytes, indicating gene transfer to long-lived progenitor cells with multilineage capacity. An average of 15% of femoral marrow cells expressed FLAG up to 16.5 months post-transduction. Thus, direct intramarrow administration of rSV40s yields efficient gene transfer to rat BM progenitor cells, and may be worthy of further investigation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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