Prolonged expression of therapeutic levels of human granulocyte colony-stimulating factor in rats following gene transfer to skeletal muscle.
Gene transfer to skeletal muscle was examined as a means of gene therapy for neutropenia. A recombinant retrovirus containing a human granulocyte colony-stimulating factor (G-CSF) gene was introduced into primary human or rat myoblasts, which were then shown to produce biologically active G-CSF. Transplantation of G-CSF-producing rat myoblasts into the muscle of syngeneic rats resulted in a 15-fold increase in absolute neutrophil counts. This increase correlated with detection of circulating human G-CSF protein throughout the 6-month duration of the experiment. These results clearly demonstrate long-term production of therapeutically relevant amounts of a human protein by normal cells in vivo.
Bonham
L
L
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Palmer
T
T
Miller
A D
AD
D000818:Animals; D002478:Cells, Cultured; D002675:Child, Preschool; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D009503:Neutropenia / Q000628:therapy; D009504:Neutrophils / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*; D013997:Time Factors
D011993:Recombinant Fusion Proteins; D016179:Granulocyte Colony-Stimulating Factor