Antisense oligonucleotides modified at 5'-end by fatty radicals effectively inhibit reproduction of influenza virus

Abstract

To enhance penetration of oligonucleotides ("oligos") into cells it was suggested that they should be chemically modified by fatty radicals at 5'-end. Two modified by undecanol at 5'-end phosphate group oligos, namely, oligo complementary to the protein binding sites, located at the influenza virus polymerases encoding RNA, and oligo complementary to the polyadenylation signal of the polymerase 3 encoding RNA were synthesized using DNA-synthetisator. These modified oligos effectively suppressed the influenza A/PR8/34 virus reproduction and inhibited the synthesis of virus-specific proteins in MDCK cells. The non-modified antisense oligos and modified nonsense oligos did not affect the virus development under the same conditions.