Antiviral oligonucleotides

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 viral infection in a subject, comprising administering to the subject a therapeutically effective amount of at least one pharmacologically acceptable phosphorothioate oligonucleotide, said oligonucleotide is between 20 and 120 nucleotides in length, and wherein the antiviral activity of said oligonucleotide occurs by a non-sequence dependent mode of action, and wherein said oligonucleotide targets a member of herpesviridae, herpes simplex virus-1 (HSV-1), herpes simplex virus-2 (HSV-2), cytomegalovirus, hepadnaviridae, hepatitis B virus, poxviridae, paramyxoviridae, respiratory syncytial virus, parainfluenza virus, bunyaviridae, hantavirus, filoviridae, Ebola virus, Marburg virus, flaviviridae, yellow fever virus, dengue virus, West Nile virus, hepatitis C virus, orthomyxoviridae, influenza virus, influenza A virus, influenza B virus, togaviridae, coronaviridae, rhabdoviridae or arenaviridae. 
     
     
         2 . The method of  claim 1 , wherein said at least one phosphorothioated oligonucleotide is fully phosphorothioated. 
     
     
         3 . The method of  claim 1 , wherein said oligonucleotide comprises at least one deoxyribonucleic acid and one ribonucleic acid. 
     
     
         4 . The method of  claim 1 , wherein said oligonucleotide is a heteropolymer comprised of dinucleotide repeats, wherein each dinucleotide contains two different nucleotides selected from the group consisting of adenosine, guanosine, cytidine, thymine and uridine. 
     
     
         5 . The method of  claim 1 , wherein said oligonucleotide is a heteropolymer comprised of alternating adenosine and cytidine residues. 
     
     
         6 . The method of  claim 1 , wherein said oligonucleotide consists of SEQ ID NO:24. 
     
     
         7 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one 5-methylcytosine base. 
     
     
         8 . The method of  claim 1 , wherein said oligonucleotide is a heteropolymer comprised of alternating adenosine and guanosine residues. 
     
     
         9 . The method of  claim 1 , wherein said oligonucleotide consists of SEQ ID NO:26. 
     
     
         10 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one phosphodiester linkage. 
     
     
         11 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one 2′-O methyl modification to the ribose moiety. 
     
     
         12 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one 2′-O (2-methoxyethyl) modification to the ribose moiety. 
     
     
         13 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one 2′-modification to the ribose moiety. 
     
     
         14 . The method of  claim 1 , wherein said oligonucleotide has all ribose moieties modified with a 2′-O methyl modification. 
     
     
         15 . The method of  claim 1 , wherein said oligonucleotide has all ribose moieties modified with a 2′-O (2-methoxyethyl) modification. 
     
     
         16 . The method of  claim 1 , wherein said oligonucleotide has all ribose moieties modified with a 2′ ribose modification. 
     
     
         17 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one methylphosphonate linkage. 
     
     
         18 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one phosphorodithioated linkage. 
     
     
         19 . The method of  claim 1 , wherein said oligonucleotide further comprises at least one locked nucleic acid. 
     
     
         20 . The method of  claim 1 , wherein said oligonucleotide is a concatemer consisting of two or more oligonucleotide sequences joined by a linker. 
     
     
         21 . The method of  claim 1 , wherein said oligonucleotide is linked or conjugated at one or more nucleotide residues, to a molecule modifying the characteristics of the oligonucleotide to obtain one or more characteristics selected from the group consisting of higher stability, lower serum interaction, higher cellular uptake, higher viral protein interaction, an improved ability to be formulated for delivery, a detectable signal, higher antiviral activity, better pharmacokinetic properties, specific tissue distribution and lower toxicity. 
     
     
         22 . The method of  claim 1 , wherein said oligonucleotide comprises at least one base which is capable of hybridizing via non-Watson-Crick interactions. 
     
     
         23 . The method of  claim 1 , wherein at least a portion of the sequence of said oligonucleotide comprises two or more repeated sequences. 
     
     
         24 . The method of  claim 1 , wherein said oligonucleotide is between 30 and 120 nucleotides in length. 
     
     
         25 . The method of  claim 1 , adapted for a delivery selected from the group consisting of intraocular injection, oral ingestion, enterally, inhalation, cutaneous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, intrathecal injection, intratracheal injection and intravenous injection. 
     
     
         26 . The method of  claim 1 , further comprising administering a delivery system. 
     
     
         27 . The method of  claim 1 , further comprising administering a liposomal formulation. 
     
     
         28 . The method of  claim 1 , further comprising administering at least one other antiviral drug in combination. 
     
     
         29 . The method of  claim 1 , further comprising administering a non-nucleotide antiviral polymer in combination.