A highly efficient receptor-mediated delivery system for DNA and oligodeoxynucleotides (ODNs) to avian liver cells has been established, using complexes of nonmodified human adenovirus particles and a protein conjugate consisting of N-acetyl-glucosamine-modified bovine serum albumin, streptavidin, and Poly-L-lysine. The newly developed method of protein-conjugate preparation and purification yielded highly stable complexes 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 HBV pregenome causes strong inhibition of HBV replication in vitro. The described, receptor-mediated DNA delivery method should prove useful for investigations of HBV replication, gene expression, and mode of action of antiviral agents in vitro, as well as for model studies of gene therapy for liver diseases from various etiologies, including viral hepatitides.
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