Improved efficiency of arterial gene transfer by use of poloxamer 407 as a vehicle for adenoviral vectors

Abstract

Improvement in the efficiency of adenovirus-mediated arterial gene transfer may augment the utility of cardiovascular gene therapy. In vitro studies suggest that poloxamer 407 enhances transfection efficiency of adenoviral vectors in vascular smooth muscle cells. The aim of the present study was to investigate whether poloxamer 407 facilitates adenovirus-mediated arterial transfection in vivo as well. Gene transfer was performed in balloon-injured rat carotid arteries using E1− adenoviral vectors diluted in either poloxamer 407 or phosphate buffered saline (PBS). Transfection efficiency was significantly higher in rats transfected using a nuclear β-galactosidase expressing adenovector diluted in poloxamer 407 versus PBS (morphometry: 13.2 ± 1.3% versus 4.1 ± 0.4% transfected medial cells, P = 0.0001; chemiluminescence: 1.4 ± 0.2 versus 0.4 ± 0.2 mU β-galactosidase/mg protein, P = 0.004). Moreover, in the presence of poloxamer 407, it was possible to reduce the incubation time of adenoviral vectors from 20 to 10 min without compromising transfection efficiency. Poloxamer 407 did not evoke specific tissue toxicity. Site-specificity of arterial gene transfer, assessed by PCR, was not altered by administration of poloxamer 407. These findings suggest that poloxamer 407 may be useful to improve the efficiency of adenovirus-mediated arterial gene transfer.