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Gene Ther. 2000 Apr;7(8):644-52.

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

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1
Cystic Fibrosis Gene Therapy Research Group, Molecular Genetics, Division of Biomedical Sciences, Imperial College School of Medicine, London, UK.

Abstract

We have investigated the use of polycations to increase adenovirus-mediated expression of transgenic protein to the biliary epithelia with a view to gene therapy for hepatobiliary disease in CF. We have shown that adenovirus carrying the beta-galactosidase transgene transfect both human and mouse biliary epithelia in primary culture and that in both instances adenovirus transfection can be significantly increased by co-complexing with polycation. In vivo administration of 1 x 109 p.f.u. adenovirus co-complexed with the polyamine polyethyenimine (PEI) into the mouse biliary duct leads to >80% positively stained biliary epithelia while adenovirus alone at the same titre infected <5% biliary epithelia. We suggest that the use of low titre polycation enhanced adenoviral delivery to the biliary tree of CF patients could be of therapeutic significance. As a prelude to an extensive in vivo functional investigation in CF null mice we have shown that Ad5/polycation complexes deliver functional CFTR to non-CFTR expressing cells in vitro more efficiently than Ad5 alone.

PMID:
10800087
DOI:
10.1038/sj.gt.3301144
[Indexed for MEDLINE]
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