Antiviral oligonucleotides targeting rsv

Abstract

Random sequence oligonucleotides that have antiviral activity are described, along with their use as antiviral agents. In many cases, the oligonucleotides are greater than 40 nucleotides in length. Also described are methods for the prophylaxis or treatment of a viral infection in a human or animal, and a method for the prophylaxis treatment of cancer caused by oncoviruses in a human or animal. The methods typically involve administering to a human or animal in need of such treatment, a pharmacologically acceptable, therapeutically effective amount of at least oligonucleotide that does not act by a sequence complementary mode of action.

1 . A method for the prophylaxis or treatment of a RSV or parainfluenza virus infection in a subject, comprising administering to a subject in need of such treatment a therapeutically effective amount of a pharmacological acceptable oligonucleotide of at least 20 nucleotides in length, wherein said oligonucleotide comprises at least 19 phosphorothioated linkages, does not comprise a CpG motif, does not have a complement in the genomic sequence of RSV or parainfluenza virus, and wherein the anti-viral activity of said oligonucleotide occurs principally by a non-sequence complementary mode of action. 
     
     
         2 . The method of  claim 1 , wherein said oligonucleotide is a heteropolymer comprised of two different nucleic acids selected from the group consisting of adenosine, guanosine, cytosine and thymine. 
     
     
         3 . The method of  claim 1 , wherein said oligonucleotide is a heteropolymer comprised of alternating adenosine and cytosine residues. 
     
     
         4 . The method of  claim 1 , wherein said oligonucleotide is SEQ ID NO:24. 
     
     
         5 . The method of  claim 1 , wherein said oligonucleotide is a heteropolymer comprised of alternating adenosine and guanosine residues. 
     
     
         6 . The method of  claim 1 , wherein said oligonucleotide is SEQ ID NO:26. 
     
     
         7 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one phosphodiester linkage. 
     
     
         8 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one modification to its chemical structure. 
     
     
         9 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one 2′ modification to the ribose moiety. 
     
     
         10 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one 2′-O methyl modification to the ribose moiety. 
     
     
         11 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one 2′-O (2-methoxyethyl) modification to the ribose moiety. 
     
     
         12 . The method of any of  claims 1  to  6 , wherein said oligonucleotide has all ribose moieties modified with a 2′ modification. 
     
     
         13 . The method of any of  claims 1  to  6 , wherein said oligonucleotide has all ribose moieties modified with a 2′-O methyl modification. 
     
     
         14 . The method of any of  claims 1  to  6 , wherein said oligonucleotide has all ribose moieties modified with a 2′-O (2-methoxyethyl) modification. 
     
     
         15 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one methylphosphonate linkage. 
     
     
         16 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one phosphorodithioated linkage. 
     
     
         17 . The method of any of  claims 1  to  6 , wherein said oligonucleotide comprises at least one locked nucleic acid. 
     
     
         18 . The method of any of  claims 1  to  6 , wherein said oligonucleotide is a concatamer consisting to two or more oligonucleotide sequences joined by a linker.