Modifying the proliferative state of target cells to control DNA expression and identifying cell types transfected in vivo.
Although the majority of current gene transfer techniques have focused on increasing the ability of the DNA to enter the cell, it is possible that changing the proliferative and migratory state of cells will influence the cells ability to take up and express plasmid DNA. This study was designed to test the hypothesis that growth factors (basic fibroblast growth factor (bFGF) and hepatocyte growth factor/scatter factor (HGF/SF)) used to alter the proliferative and migratory state of cells can alter plasmid DNA uptake and expression. In vitro studies indicate that enhancing cell proliferation with growth factor exposure enhances plasmid DNA uptake and expression. Furthermore, dual localized delivery of bFGF and plasmid DNA in vivo increases the expression, 3-6 times over control, as compared to plasmid delivery alone. Dual delivery of a factor promoting cell proliferation and a plasmid led to a further increase in the expression of the plasmid encoding bone morphogenetic protein-2 in a rat cranial defect by specific cell populations. The results of these studies suggest that increasing the proliferative state of target cell populations can enhance non-viral gene transfer.
Riddle
Kathryn W
KW
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA.
Kong
Hyun-Joon
HJ
Leach
J Kent
JK
Fischbach
Claudia
C
Cheung
Charles
C
Anseth
Kristi S
KS
Mooney
David J
DJ
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D012887:Skull Fractures / Q000235:genetics / Q000473:pathology / Q000628:therapy; D014162:Transfection
D019485:Bone Morphogenetic Proteins; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor