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Inhibition of Influenza Virus Replication by Phosphorothioate and Liposomally Endocapsulated Oligonucleotides |
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| Authors: | Takayuki Abe Toshihmi Hatta Kazuyuki Takai Hideki Nakashima Tomoyuki Yokota Hiroshi Takaku |
| Institution: | 1. Department of Industrial Chemistry , Chiba Institute of Technology , Tsudanuma, Narashino, Chiba, 275, Japan;2. Department of Microbiology and Immunology , Kagoshima University Dental School , Sakuragaoka, Kagoshima, 890, Japan;3. Rational Drug Design Laboratories (R.D.L) , Misato, Matsukawa, Fukushima, 960-12, Japan |
| Abstract: | Abstract 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. |
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