Inhibition of influenza virus replication by phosphorothioate and liposomally endocapsulated oligonucleotides.
We have demonstrated that antisense phosphorothioate oligonucleotides (S-ODNs) inhibit influenza virus A replication in MDCK cells. Phosphorothioate and liposomally encapsulated oligonucleotides with two target sites (PB1 and PB2) were synthesized and tested for virus-induced cytopathogenicity effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODNs complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. On the other hand, the inhibitory effect of the liposomally encapsulated S-ODNs targeted to PB1 was considerably decreased in comparison with the PB2 target sites. The liposomally encapsulated oligonucleotides exhibited higher inhibitory activity than the free oligonucleotides. The activities of the modified oligonucleotides are effectively enhanced by using the liposomal carrier.
Abe
T
T
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Hatta
T
T
Takai
K
K
Nakashima
H
H
Yokota
T
T
Takaku
H
H
D000998:Antiviral Agents / Q000138:chemical synthesis*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D004339:Drug Compounding; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000472:pathogenicity*; D010714:Phosphatidylethanolamines / Q000378:metabolism
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D010714:Phosphatidylethanolamines; C020888:1,2-dielaidoylphosphatidylethanolamine; D012321:DNA-Directed RNA Polymerases