In vitro and in vivo anti-influenza A virus activity of antisense oligonucleotides.
We have demonstrated that antisense phosphorothioate oligonucleotides (S-ODNs) inhibit influenza virus A replication in MDCK cells. The liposomally encapsulated and the free antisense phosphorothioate oligonucleotides with four target sites (PB1, PB2, PA, and NP) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. Therefore, the antiviral effects of S-ODN-PB2-AUG and PA-AUG were examined in a mouse model of influenza virus A infection. PB2-AUG oligomer treated i.v. significantly prolonged the mean survival time in day (MDS) and increased the survival rates with does dependent manner.
Abe
T
T
Department of Industrial Chemistry, Chiba Institute of Technology, Japan.
Mizuta
T
T
Suzuki
S
S
Hatta
T
T
Takai
K
K
Yokota
T
T
Takaku
H
H
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D004285:Dogs; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides