CATIONIC LIPOSOMES ENHANCE ADENOVIRUS ENTRY VIA A PATHWAY INDEPENDENTOF THE FIBER RECEPTOR AND ALPHA(V)-INTEGRINS

The ability of adenoviral vectors to mediate efficient gene delivery b oth in vitro and in vivo is limited by the availability of specific ce ll surface receptors and alpha(v)-containing integrins, We tested whet her this limitation could be overcome by enhancing viral entry with ca tionic liposomes. In cultured vascular smooth muscle cells, delivery o f adenoviral vectors in the presence of cationic liposomes increased v ector-encoded transgene expression up to 20-fold, The increase in tran sgene expression was associated with the formation of adenovirus-lipid aggregates and an increase in the amount of vector DNA in the cells, suggesting that enhanced viral entry was responsible for the increase in gene expression, Treatment of the cells with an ROD-containing pept ide or adenovirus type 5 fiber protein did not diminish liposome enhan cement of transgene expression, indicating that liposomes increase vir al entry via a pathway independent of the fiber receptor and of alpha( v) integrin-assisted endocytosis. Liposomes also significantly enhance d transgene expression from adenoviral vectors delivered to cells defi cient in alpha(v)-containing integrins, The magnitude of liposome enha ncement of transgene expression in cultured smooth muscle cells was gr eatest during brief periods of virus-cell contact and at low concentra tions of virus, Despite these promising in vitro results, addition of liposomes did not improve in vivo adenoviral gene delivery into injure d rat carotid arteries, Liposomes can improve adenoviral gene delivery in vitro; however, application of this observation to accomplish impr oved in vivo gene delivery remains a challenge.