Improved adenovirus vectors for infection of cardiovascular tissues

To identify improved adenovirus vectors for cardiovascular gene therapy, a library of adenovirus vectors based on adenovirus serotype 5 (Ad5) but carr ying fiber molecules of other human serotypes, was generated. This library was tested for efficiency of infection of human primary vascular endothelia l cells (ECs) and smooth muscle cells (SMCs). Based on luciferase, LacZ, or green fluorescent protein (GFP) marker gene expression, several fiber chim eric vectors were identified that displayed improved infection of these cel l types. One of the viruses that performed particularly well is an Ad5 carr ying the fiber of Ad16 (Ad5.Fib16), a subgroup B virus. This virus showed, on average, 8- and 64-fold-increased luciferase activities on umbilical vei n ECs and SMCs, respectively, compared to the parent vector. GFP and lacZ m arkers showed that approximately 3-fold (ECs) and 10-fold (SMCs) more cells were transduced. Experiments performed with both cultured SMCs and organ c ultures derived from different vascular origins (saphenous vein, iliac arte ry, left interior mammary artery, and aorta) and from different species dem onstrated that Ad5.Fib16 consistently displays improved infection in primat es (humans and rhesus monkeys). SMCs of the same vessels of rodents and pig s were less infectable with Ad5.Fib16 than with Ad5. This suggests that eit her the receptor for human Ad16 is not conserved between different species or that differences in the expression levels of the putative receptor exist . In conclusion, our results show that an Ad5-based virus carrying the fibe r of Ad16 is a potent vector for the transduction of primate cardiovascular cells and tissues.