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Delivering genes to the organ‐localized immune system: long‐term results of direct intramarrow transduction
Author(s) -
Louboutin JeanPierre,
Liu Bianling,
Chekmasova Alena A.,
Reyes Beverly A. S.,
van Bockstaele Elisabeth J.,
Strayer David S.
Publication year - 2007
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1084
Subject(s) - bone marrow , flag (linear algebra) , biology , spleen , transgene , immune system , progenitor cell , microbiology and biotechnology , pathology , immunology , stem cell , gene , medicine , genetics , mathematics , pure mathematics , algebra over a field
We studied the distribution of transgene‐expressing cells after direct gene transfer into the bone marrow (BM). Rats received direct injection into the femoral BM of SV(Nef‐FLAG), a Tag ‐deleted recombinant SV40 carrying a marker gene (FLAG epitope). Controls received an unrelated rSV40 or saline. Blood cells (5%) and femoral marrow cells (25%) expressed FLAG throughout. FLAG expression was assessed in different organs at 1, 4 and 16 months. FLAG+ macrophages were seen throughout the body, and were prominent in the spleen. FLAG+ cells were common in pulmonary alveoli. The former included alveolar macrophages and type II pneumocytes. These cells were not detected at 1 month, occasional at 4 months and common at 16 months after intramarrow injection. Rare liver cells were positive for both FLAG and ferritin, indicating that some hepatocytes also expressed this BM‐delivered transgene. Control animals were negative. Thus: (a) fixed tissue phagocytes may be accessible to gene delivery by intramarrow transduction of their progenitors; (b) transduced BM‐resident cells or their derivatives may migrate to other organs (lungs) and may differentiate into epithelial cells; and (c) intramarrow injection of rSV40s does not detectably transduce parenchymal cells of other organs. Copyright © 2007 John Wiley & Sons, Ltd.