In vivo inhibition of duck hepatitis B virus replication and gene expression by phosphorothioate modified antisense oligodeoxynucleotides.
Antisense oligodeoxynucleotide strategies have been employed in a variety of eukaryotic systems both to understand normal gene function and to block gene expression. Pharmacologically, 'code blockers' are ideal agents for antitumour and antimicrobial treatments because of their specific mode of action. Here we report the inhibition of duck hepatitis B virus (DHBV) by antisense oligodeoxynucleotides in primary duck hepatocyte cultures in vitro as well as in DHBV-infected Pekin ducks in vivo. The most effective antisense oligodeoxynucleotide was directed against the 5' region of the pre-S gene and resulted in a complete inhibition of viral replication and gene expression in vitro and in vivo. These results demonstrate the application of antisense oligodeoxynucleotides in vivo and exemplify their potential as human antiviral therapeutics.
Offensperger
W B
WB
Department of Medicine, University of Freiburg, Germany.
Offensperger
S
S
Walter
E
E
Teubner
K
K
Igloi
G
G
Blum
H E
HE
Gerok
W
W
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004372:Ducks; D015870:Gene Expression / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects*; D015611:Hepatitis B Virus, Duck / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy; D008099:Liver / Q000166:cytology / Q000382:microbiology; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects; D014779:Virus Replication
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides