Delivering genes to the organ-localized immune system: long-term results of direct intramarrow transduction.
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.
Louboutin
Jean-Pierre
JP
Department of Pathology, Jefferson Medical College, Philadelphia, PA 19107, USA. jplouboutin@hotmail.com
Liu
Bianling
B
Chekmasova
Alena A
AA
Reyes
Beverly A S
BA
van Bockstaele
Elisabeth J
EJ
Strayer
David S
DS
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D019070:Cell Lineage; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D007150:Immunohistochemistry; D007267:Injections; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology; D016676:Macrophages, Alveolar / Q000378:metabolism*; D009842:Oligopeptides; D009928:Organ Specificity; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013539:Simian virus 40 / Q000235:genetics; D013154:Spleen / Q000276:immunology; D014161:Transduction, Genetic; D019076:Transgenes
D009842:Oligopeptides; D010455:Peptides; C085706:FLAG peptide