Selective in vivo transfection of murine biliary epithelia using polycation-enhanced adenovirus

We have investigated the use of polycations to increase adenovirus-mediated expression of transgenic protein to the biliary epithelia with a view to g ene therapy for hepatobiliary disease in CF. We have shown that adenovirus carrying the P-galactosidase transgene transfect both human and mouse bilia ry epithelia in primary culture and that in both instances adenovirus trans fection can be significantly increased by co-complexing with polycation. in vivo administration of 1 x 10(9) p.f.u. adenovirus co-complexed with the p olyamine polyethyenimine (PEI) into the mouse biliary duct leads to >80% po sitively stained biliary epithelia while adenovirus alone at the same titre infected <5% biliary epithelia. We suggest that the use of low titre polyc ation enhanced adenoviral delivery to the biliary tree of CF patients could be of therapeutic significance. As a prelude to an extensive in vivo funct ional investigation in CF null mice we have shown that Ad5/polycation compl exes deliver functional CFTR to non-CPTR expressing cells in vitro more eff iciently than Ad5 alone.