In Vitro and In Vivo Anti-influenza A Virus Activity of Antisense Oligonucleotides |
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| Authors: | Takayuki Abe Tadashi Mizuta Shin-Ichi Suzuki Toshifumi Hatta Kazuyuki Takai Tomoyuki Yokota |
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| Affiliation: | 1. Department of Industrial Chemistry , Chiba Institute of Technology , Tsudanuma, Narashino, Chiba, 275-0016, Japan;2. Rational Drug Design Laboratories (R. D. L) , Misato, Matsukawa, Fukushima, 960-1242, Japan |
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| Abstract: | Abstract 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. |
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