Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of an Antiviral gene, in particular, by targeting natural antisense polynucleotides of an Antiviral gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Antiviral genes.
1. A synthetic, modified oligonucleotide of 12 to 30 nucleotides in length comprising at least one modification wherein the at least one modification is selected from: at least one modified sugar moiety; at least one modified internucleotide linkage; at least one modified nucleotide, and combinations thereof; wherein said oligonucleotide is an antisense compound which specifically hybridizes to a natural antisense polynucleotide of an Antiviral gene having SEQ ID NO: 3 and upregulates the function and/or expression of said Antiviral gene in vivo or in vitro as compared to a normal control.
2. The oligonucleotide of claim 1 , wherein the at least one modification comprises an internucleotide linkage selected from the group consisting of: phosphorothioate, alkylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphorarnidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, and combinations thereof.
3. The oligonucleotide of claim 1 , wherein said oligonucleotide comprises at least one phosphorothioate internucleotide linkage.
4. The oligonucleotide of claim 1 , wherein said oligonucleotide comprises a backbone of phosphorothioate internucleotide linkages.
5. The oligonucleotide of claim 1 , wherein the oligonucleotide comprises at least one modified nucleotide, said modified nucleotide selected from: a peptide nucleic acid, a locked nucleic acid (LNA), analogue, derivative, and a combination thereof.
6. The oligonucleotide of claim 1 , wherein the oligonucleotide comprises a plurality of modifications, wherein said modifications comprise modified nucleotides selected from: phosphorothioate, alkylphosphonate, phosphotodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, and a combination thereof.
7. The oligonucleotide of claim 1 , wherein the oligonucleotide comprises a plurality of modifications, wherein said modifications comprise modified nucleotides selected from: peptide nucleic acids, locked nucleic acids (LNA), analogues, derivatives, and a combination thereof.
8. The oligonucleotide of claim 1 , wherein the oligonucleotide comprises at least one modified sugar moiety selected from a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety a 2′-O-alkyl modified sugar moiety, a bicyclic sugar moiety, and a combination thereof.
9. The oligonucleotide of claim 1 , wherein the oligonucleotide comprises a plurality of modifications, wherein said modifications comprise modified sugar moieties selected from: a 2′-O-methoxyethyl modified sugar moiety, a 2′-methoxy modified sugar moiety, a 2′-O-alkyl modified sugar moiety, a bicyclic sugar moiety, and a combination thereof.
10. The oligonucleotide of claim 1 , wherein the oligonucleotide is of at least about 12 to 30 nucleotides in length wherein said oligonucleotide has at least about 20% sequence identity to a sequence of at least about 12 consecutive nucleic acids of the sense coding and/or noncoding nucleic acid sequences of the Antiviral gene polynucleotide.
11. The oligonucleotide of claim 1 , wherein the oligonucleotide has at least about 80% sequence identity to a sequence of at least about 12 consecutive nucleic acids of the sense coding and/or noncoding nucleic acid sequence of the Antiviral gene polynucleotide.
12. The oligonucleotide of claim 1 , wherein the oligonucleotide comprises the sequences set forth as SEQ ID NOS: 27 to 30.
13. A composition comprising one or more oligonucieotides according to claim 1 and a pharmaceutically acceptable excipient.
14. The composition of claim 13 , wherein the oligonucleotides have at least about 40% sequence identity as compared to any one of the nucleotide sequences set forth as SEQ ID NOS: 27 to 30.
15. The composition of claim 13 , wherein the oligonucleotides comprise nucleotide sequences set forth as SEQ ID NOS: 27 to 30.
16. The composition of claim 15 , wherein the oligonucleotides set forth as SEQ ID NOS: 10 to 30 comprise one or more modifications or substitutions.
17. The composition of claim 16 , wherein the one or more modifications are selected from: phosphorothioate, methylphosphonate, peptide nucleic acid, locked nucleic acid (LNA) molecules, and combinations thereof.