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Vectors based on Semliki Forest virus for rapid and efficient gene transfer into non-endothelial cardiovascular
1Department of Clinical Pharmacology, University of Groningen, The Netherlands.
Objective:
Replication-deficient, recombinant adenovirus is used as a carrier for gene transfer, but it is unspecific and the onset of transgene expression is relatively late. Here, we evaluated the efficiency and selectivity of gene transfer mediated by recombinant Semliki Forest virus (SFV).
Methods:
We compared the efficiency of a SFV-based vector with an adenoviral vector, using LacZ as a reporter gene. Firstly, the affinity for vascular smooth muscle cells, endothelial cells and cardiac myocytes was assessed. Secondly, we compared the time course of LacZ expression and cytotoxicity in vascular smooth muscle cells.
Results:
The SFV-based vector infects vascular smooth muscle cells and cardiomyocytes as efficiently as adenovirus. In contrast to adenovirus, SFV hardly transfers LacZ to endothelial cells (2.6% or less). SFV-mediated 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.
Conclusions:
We demonstrate that SFV efficiently transfers LacZ to vascular smooth muscle cells and cardiomyocytes, but not to endothelial cells. In contrast, adenovirus causes efficient transgene expression in all cell types tested. Furthermore, SFV-mediated expression is faster than adenovirus-mediated expression. Therefore, SFV-mediated gene transfer may be a suitable alternative to adenovirus, providing a fast expression in non-endothelial cardiovascular cell types.