RECEPTOR-MEDIATED DELIVERY OF HEPATITIS-B VIRUS-DNA AND ANTISENSE OLIGODEOXYNUCLEOTIDES TO AVIAN LIVER-CELLS

A highly efficient receptor-mediated delivery system for DNA and oligo deoxynucleotides (ODNs) to avian Liver cells has been established, usi ng complexes of nonmodified human adenovirus particles and a protein c onjugate consisting of N-acetyl glucosamine-modified bovine serum albu min, streptavidin, and poly-L-lysine. The newly developed method of pr otein-conjugate preparation and purification yielded highly stable com plexes with high DNA delivery efficiency for constructs expressing the lacZ gene, hepatitis B virus (HBV) DNA, and ODNs, Using this delivery system, an antisense ODN targeted to the encapsidation site of the HB V pregenome causes strong inhibition of HBV replication in vitro, The described, receptor-mediated DNA delivery method should prove useful f or investigations of HBV replication, gene expression, and mode of act ion of antiviral agents in vitro, as well as for model studies of gene therapy for liver diseases from various etiologies, including viral h epatitides.