Treatment of dystrophin family related diseases by inhibition of natural antisense transcript to DMD family
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Dystrophin family, in particular, by targeting natural antisense polynucleotides of Dystrophin family. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of DMD family.
1. A method of upregulating a function of and/or the expression of a Dystrophin family polynucleotide selected from SEQ ID NO 2 or a polyuncleotide encoding such a sequence in patient cells or tissues in vivo or in vitro comprising: contacting said cells or tissues with at least one antisense oligonucleotide of about 15-30 nucleotides in length that is complementary to and specifically hybridizable with a 15-30nucleotide region of a natural antisense polynucleotide; of the UTRN Dystrophin family polynucleotide; thereby upregulating a function of and/or the expression of the Dystrophin family polynucleotide in patient cells or tissues in vivo or in vitro.
2. The method of claim 1 , wherein a function of and/or the expression of the Dystrophin family polynucleotide is increased in vivo or in vitro with respect to a control.
3. The method of claim 1 , wherein the at least one antisense oligonucleotide targets a natural antisense sequence of a Dystrophin family polynucleotide selected from the group consisting of SEQ NO 7.
4. The method of claim 1 , wherein the at least one antisense oligonucleotide targets a natural antisense oligonucleotide antisense to coding and/or non-coding nucleic acid sequences of a Dystrophin family polynucleotide.
5. The method of claim 1 , wherein the at least one antisense oligonucleotide targets a natural antisense oligonueleotide having overlapping and/or non-overlapping sequences with a Dystrophin family polynucleotide.
6. The method of claim 1 , wherein the at least one antisense oligonucleotide comprises one or more modifications selected from: at least one modified sugar moiety, at least one modified intemucleoside linkage, at least one modified nucleotide, and combinations thereof.
7. The method of claim 6 , wherein the one or more modifications comprise 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 combinations thereof.
8. The method of claim 6 , wherein the one or more modifications comprise at least one modified internucleoside linkage selected from: a phosphorodithioate, alkylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, aectamidate, carboxymethyl ester, and combinations thereof.
9. The method of claim 6 , wherein the one or more modifications comprise at least one modified nucleotide selected from: a peptide nucleic acid (PNA), a locked nucleic acid (LNA), an arabino-nucleic acid (FANA), an analogue, a derivative, and combinations thereof.
10. The method according to claim 1 , wherein the natural antisense oligonucleotide is SEQ ID NO: 7.
11. The method of claim 1 , wherein the at least one oligonucleotide comprises at least one oligonucleotide sequences set forth as SEQ ID NOS: 18 and 19.