VECTORS BASED ON SEMLIKI-FOREST-VIRUS FOR RAPID AND EFFICIENT GENE-TRANSFER INTO NON-ENDOTHELIAL CARDIOVASCULAR CELLS - COMPARISON TO ADENOVIRUS

Objective: Replication-deficient, recombinant adenovirus is used as a carrier for gene transfer, but it is unspecific and the onset of trans gene expression is relatively late. Here, we evaluated the efficiency and selectivity of gene transfer mediated by recombinant Semliki Fores t virus (SFV). Methods: We compared the efficiency of a SFV-based vect or with an adenoviral vector, using LacZ as a reporter gene. Firstly, the affinity for vascular smooth muscle cells, endothelial cells and c ardiac myocytes was assessed. Secondly, we compared the time course of LacZ expression and cytotoxicity in vascular smooth muscle cells. Res ults: The SFV-based vector infects vascular smooth muscle cells and ca rdiomyocytes as efficiently as adenovirus. In contrast to adenovirus, SFV hardly transfers LacZ to endothelial cells (2.6% or less). SFV-med iated expression was visible after 1 h, reaching a maximum after 6 h. In contrast, adenovirus-mediated expression became visible after 6 h, and reached a maximum after 48-72 h. Both vectors were cytotoxic. Conc lusions: We demonstrate that SFV efficiently transfers LacZ to vascula r smooth muscle cells and cardiomyocytes, but not to endothelial. cell s. In contrast, adenovirus causes efficient transgene expression in al l cell types tested. Furthermore, SFV-mediated expression is faster th an adenovirus-mediated expression. Therefore, SFV-mediated gene transf er may be a suitable alternative to adenovirus, providing a fast expre ssion in non-endothelial cardiovascular cell types. (C) 1997 Elsevier Science B.V.