1. ¹Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, USA
2. ²Division of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA
3. ³Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA

Correspondence: David J Mooney, Division of Engineering and Applied Sciences, Harvard University, 29 Oxford Street, 325 Pierce Hall, Cambridge, Massachusetts 02138, USA. E-mail: mooneyd@deas.harvard.edu

Received 16 December 2005; Accepted 28 August 2006.

Abstract

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.