Gene transfer to human cerebral artery

Gene transfer to cerebral vasculature is a promising strategy for treatment of cerebrovascular diseases. However, gene transfer to human cerebral blood vessels has not been studied. Moreover, different levels of cerebral transgene expression have been reported in different animal species. The present study was therefore undertaken to determine the levels of transgene expression in different animal species and human cerebral arteries. Replication-incompetent adenoviral vector (10⁹-10¹⁰ pfu/mL)-mediated β-galactosidase reporter gene expression was determined morphologically and quantitatively 24 hours after ex vivo gene transfer. Transgene was expressed both in the adventitia and endothelium of large cerebral arteries from dog, rabbit, and pig, as well as in human pial arteries. Recombinant protein levels in these arteries were significantly different among three animal species in the order of canine > rabbit > porcine (P<0.05). In human pial arteries, the levels of transgene expression were similar to those in porcine vessels. Expression of adenoviral receptor mRNA was detected in human vessels by RT-PCR technique. This study demonstrates the feasibility of gene transfer in human cerebral arteries, and indicates the existence of considerable heterogeneity of transgene expression in different animal species.