硫代磷酸酯和脂质体包封的寡核苷酸对流感病毒复制的抑制作用。

Inhibition of influenza virus replication by phosphorothioate and liposomally endocapsulated oligonucleotides.

作者信息

Abe T, Hatta T, Takai K, Nakashima H, Yokota T, Takaku H

机构信息

Department of Industrial Chemistry, Chiba Institute of Technology, Japan.

出版信息

Nucleosides Nucleotides. 1998 Jan-Mar;17(1-3):471-8. doi: 10.1080/07328319808005191.

DOI:10.1080/07328319808005191

PMID:9708356

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.

摘要

我们已经证明，反义硫代磷酸酯寡核苷酸（S-ODN）可抑制甲型流感病毒在MDCK细胞中的复制。合成了具有两个靶位点（PB1和PB2）的硫代磷酸酯和脂质体包裹的寡核苷酸，并通过使用MDCK细胞的MTT试验检测其对病毒诱导的细胞病变效应。与PB2-AUG起始密码子位点互补的脂质体包裹的S-ODN显示出高度抑制作用。另一方面，与PB2靶位点相比，靶向PB1的脂质体包裹的S-ODN的抑制作用明显降低。脂质体包裹的寡核苷酸比游离寡核苷酸表现出更高的抑制活性。通过使用脂质体载体，修饰寡核苷酸的活性得到有效增强。