Treatment of Adiponectin related diseases by inhibition of natural antisense transcript to an Adiponectin
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of an Adiponectin (ADIPOQ), in particular, by targeting natural antisense polynucleotides of an Adiponectin (ADIPOQ). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Adiponectins (ADIPOQ)s.
1. A method of upregulating a function of and/or the expression of an Adiponectin (ADIPOQ) polynucleotide having SEQ ID NO: 1 in patient cells or tissues in vivo or in vitro comprising: contacting said cells or tissues with at least one modified, single stranded antisense oligonucleotide 12 to 30 nucleotides in length that targets and specifically hybridizes to a region of a natural antisense polynucleotide of the Adiponectin (ADIPOQ) polynucleotide; thereby upregulating a function of and/or the expression of the Adiponectin (ADIPOQ) polynucleotide in patient cells or tissues in vivo or in vitro wherein said natural antisense polynucleotide is selected from the group consisting of SEQ ID NOS: 3 or 4.
2. The method of claim 1 , wherein a function of and/or the expression of the Adiponectin (ADIPOQ) is increased in vivo or in vitro as compared to a mock-transfected control.
3. 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 internucleoside linkage, at least one modified nucleotide, and combinations thereof.
4. The method of claim 3 , wherein the one or more modifications comprise at least one modified sugar moiety selected from: a 2′fluoro modified sugar moiety, 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.
5. The method of claim 3 , wherein the one or more modifications comprise at least one modified internucleoside linkage selected from: a phosphorothioate, alkylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, and combinations thereof.
6. The method of claim 3 , wherein the one or more modifications comprise at least one modified nucleotide selected from: a peptide nucleic acid (PNA), a locked nucleic acid (LNA) or an arabino-nucleic acid (FANA).
7. The method of claim 1 , wherein the at least one oligonucleotide is selected from the group consisting of SEQ ID NOS: 7-19, 22 and 23.
8. A method of treating a disease associated with at least one Adiponectin (ADIPOQ) polynucleotide comprising SEQ ID NO: 1, comprising: administering to a patient a therapeutically effective dose of at least one modified, single stranded antisense oligonucleotide of 16-30 nucleotides in length that binds to a natural antisense sequence of said at least one Adiponectin (ADIPOQ) polynucleotide having SEQ ID NOS: 3 or 4 and upregulates expression of said at least one Adiponectin (ADIPOQ) polynucleotide: thereby treating the disease associated with the at least one Adiponectin (ADIPOQ) polynucleotide and/or at least one encoded product thereof wherein the disease associated with the at least one Adiponectin (ADIPOQ) polynucleotide is selected from the group consisting of diabetes, atherosclerosis, diabetic neuropathy, obesity, hyperglycemia, insulin resistance, metabolic syndrome, hypertension, and aberrant blood glucose level.