Cationic polymer and lipids augment adenovirus-mediated gene transfer to cerebral arteries in vivo

Adenovirus-mediated gene transfer to blood vessels is relatively inefficien t because binding of adenovirus to vessels is limited, The authors have rep orted that incorporation of cationic polymer and lipids with adenovirus aug ments gene transfer to blood vessels ex vivo. In this study, the authors de termined whether complexes of adenovirus and cations improve efficiency of gene transfer in vivo, Poly-L-lysine, lipofectamine. or lipofectin was comp lexed with adenovirus encoding beta -galactosidase. Optimum ratios of the c ations per adenovirus were determined by gene transfer to fibroblasts, Afte r injection of the adenovirus into the cisterna magna of anesthetized rabbi ts, transgene activity was greater in the adventitia of intracranial arteri es and meninges after injection of the complexes than adenovirus alone. Thi rty minutes after application of adenovirus with the cations, binding of ad enovirus to fibroblast cells in vitro or the basilar artery in vivo (by Sou thern blot analysis) was augmented, which suggests that enhanced binding of virus contributes to augmentation of transgene expression. Thus, cationic polymer and lipids improve transgene expression in intracranial arteries, p rimarily in the adventitia, after adenovirus-mediated gene transfer in vivo . This strategy may be applicable to studies of gene transfer and eventuall y for gene therapy.