A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus‐specific proteins in MDCK cells

Kabanov, Alexander V.; Vinogradov, Sergei; Овчаренко, А. В.; Krivonos, Alexander V.; Melik‐Nubarov, N. S.; Киселев, В. И.; Severin, E. S.

doi:10.1016/0014-5793(90)80039-l

Cited by 100 publications

(45 citation statements)

References 15 publications

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“…Inhibition of influenza virus production in tissue culture by means of an ODN attached to a hydrophobic substituent has also recently been reported (32).…”

Section: Discussionmentioning

confidence: 92%

Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides.

Leiter

Agrawal

Palese

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Oligodeoxynucleotides (ODNs) were synthesized and tested for their antiviral activity against influenza viruses. ODNs corresponded to the polymerase PB) gene of either influenza A/WSN/33 virus or influenza C/JJ/50 virus.All compounds were 20 nucleotides long, including control ODNs containing mismatches. The phosphodiester ODNs (0-ODNs) failed to inhibit replication of influenza A and influenza C viruses at concentrations up to 80 ,uM, possibly due to intracellular nuclease digestion of the unmodified oligomers. By contrast, the phosphorothioate derivatives (S-ODNs) were found to inhibit replication of both influenza A and influenza C virus. The antiviral effect of S-ODNs against influenza A virus was found at concentrations as low as 1.25 ,uM and was present with mismatched oligomers. In the case of influenza C virus, the S-ODN complementary to the 3' end of the viral RNA of the PB) gene revealed a sequence-specific antiviral activity at a concentration of 20 ,M. (At the same concentration, S-ODNs with one or three mismatches showed little or no antiviral activity.) Reduction in plaque number reached six logarithms when this sequence-specific S-ODN was used at a concentration of 80 ,uM.

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“…Inhibition of influenza virus production in tissue culture by means of an ODN attached to a hydrophobic substituent has also recently been reported (32).…”

Section: Discussionmentioning

confidence: 92%

Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides.

Leiter

Agrawal

Palese

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…Polyaminolipids Are Simple and Relatively Nontoxic Cationic Lipids-Several methods of enhancing oligonucleotide uptake have been established, including lipophilic modification of oligonucleotides (23,25,(43)(44)(45)(46)(47)(48)(49)(50), incorporation of oligonucleotides into liposomes (51)(52)(53), and the coadministration of oligonucleotides with cationic lipids (34,35). We have focused on cationic lipids as uptake enhancers because of ease of use, feasibility in screening large numbers of oligonucleotides, and potential versatility for delivery of other nucleic acid therapeutics.…”

Section: Resultsmentioning

confidence: 99%

Novel Polyaminolipids Enhance the Cellular Uptake of Oligonucleotides

Guy-Caffey¹,

Bodepudi²,

Bishop³

et al. 1995

Journal of Biological Chemistry

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“…The viral RNA polymerase (PB1, PB2, and PA) and the nucleoprotein (NP) genes of influenza A virus are therefore potential targets for antisense oligonucleotides. A few studies have investigated the inhibition of influenza virus replication in cell cultures by antisense oligonucleotides (Zerial et al, 1987;Leiter et al, 1990;Kbanov et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Specific Inhibition of Influenza Virus RNA Polymerase and Nucleoprotein Gene Expression by Liposomally Encapsulated Antisense Phosphorothioate Oligonucleotides in MDCK Cells

Abe

Suzuki

Hatta

et al. 1998

Antivir Chem Chemother

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We have demonstrated that antisense phosphorothioate oligonucleotides (S-ODNs) inhibit influenza A virus replication in MDCK cells. Liposomally encapsulated and free antisense S-ODNs with four target sites (PB1, PB2, PA and NP genes) were tested for their abilities to inhibit virus-induced cytopathogenic effects in a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the site around the PB2 AUG initiation codon showed highly inhibitory effects. In contrast, the inhibitory effect of the liposomally encapsulated S-ODN targeted to PB1 was considerably decreased in comparison with that directed to the PB2 target site. The liposomally encapsulated antisense S-ODNs exhibited higher inhibitory activities than the free oligonucleotides, and showed sequence-specific inhibition, whereas free antisense S-ODNs were observed to inhibit viral adsorption to MDCK cells.Liposomal preparations of oligonucleotides facilitated their release from endocytic vesicles, and thus cytoplasmic and nuclear localization was observed. The activities of the antisense S-ODNs were effectively enhanced by using the liposomal carrier. Interestingly, the liposomally encapsulated FITC-S-ODN-PB2-as accumulated in the nuclear region of MDCK cells. However, weak fluorescence was observed within the endosomes and the cytoplasm of MDCK cells treated with the free antisense S-ODNs. The cationic lipid particles may thus be a potentially useful delivery vehicle for oligonucleotide-based therapeutics and transgenes, appropriate for use in vitro or in vivo.

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A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus‐specific proteins in MDCK cells

Cited by 100 publications

References 15 publications

Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides.

Inhibition of influenza virus replication by phosphorothioate oligodeoxynucleotides.

Novel Polyaminolipids Enhance the Cellular Uptake of Oligonucleotides

Specific Inhibition of Influenza Virus RNA Polymerase and Nucleoprotein Gene Expression by Liposomally Encapsulated Antisense Phosphorothioate Oligonucleotides in MDCK Cells

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