Comparison between recombinant baculo- and adenoviral-vectors as transfer system in cardiovascular cells.
The development of effective gene-therapeutic applications for cardiovascular disorders is in part limited by the lack of appropriate delivery systems. In an attempt to overcome this deficiency, we investigated the ability of baculoviral vectors to transduce human cardiovascular cells, for which data are missing in literature. Additionally, baculovirus ability to transduce target cells was compared to that of an adenoviral vector, a well characterized and widely used viral vector. Transduction experiments, performed using baculo/adenoviral vectors expressing the enhanced green fluorescence protein, revealed that, under the experimental condition considered, baculoviruses but not adenoviruses efficiently transduce human coronary smooth muscle cells (hCSMC); an opposite behavior was noticed for human coronary endothelial cells (hCEC). Thus, baculoviral vectors are potentially indicated as transfer system in the treatment of coronary restenosis, where growth inhibitory genes should reach hCSMC but not hCEC. When used to transduce human cardiomyocytes and fibroblasts, both vectors behaved similarly. Finally, studies on cellular DNA replication revealed a more prolonged and pronounced negative effect on cells transduced by adenoviral compared to baculoviral vectors. Our data indicate that baculoviruses represent an attractive alternative to adenoviruses as transfer vectors in cardiovascular cells and that baculovirus have the potential to be used as gene transfer system in cardiovascular diseases such as restenosis.
Grassi
G
G
Department of Molecular Pathology, University Hospital of Tübingen, Tübingen, Germany. ggrassi@units.it
Köhn
H
H
Dapas
B
B
Farra
R
R
Platz
J
J
Engel
S
S
Cjsareck
S
S
Kandolf
R
R
Teutsch
C
C
Klima
R
R
Triolo
G
G
Kuhn
A
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D002319:Cardiovascular System / Q000166:cytology*; D002460:Cell Line; D003331:Coronary Vessels / Q000166:cytology; D004274:DNA, Recombinant / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism; D005347:Fibroblasts; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007313:Insecta; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D013552:Swine; D014161:Transduction, Genetic / Q000379:methods*
D004274:DNA, Recombinant