IMPROVED EFFICIENCY OF ARTERIAL GENE-TRANSFER BY USE OF POLOXAMER-407AS A VEHICLE FOR ADENOVIRAL VECTORS

Improvement in the efficiency of adenovirus-mediated arterial gene tra nsfer may augment the utility of cardiovascular gene therapy. In vitro studies suggest that poloxamer 407 enhances transfection efficiency o f adenoviral vectors in vascular smooth muscle cells. The aim of the p resent study was to investigate whether poloxamer 407 facilities adeno virus-mediated arterial transfection in vivo as well. Gene transfer wa s performed in balloon-injured rat carotid arteries using E1- adenovir al vectors diluted in either poloxamer 407 or phosphate buffered salin e (PBS). Transfection efficiency was significantly higher in rats tran sfected using a nuclear p-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 beta-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 c ompromising transfection efficiency. Poloxamer 407 did not evoke speci fic tissue toxicity. Site-specificity of arterial gene transfer, asses sed by PCR, was not altered by administration of poloxamer 407. These findings suggest that poloxamer 407 may be useful to improve the effic iency of adenovirus-mediated arterial gene transfer.