Treatment of ‘C terminus of HSP70-interacting protein’ (CHIP)related diseases by inhibition of natural antisense transcript to CHIP
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of ‘C terminus of HSP70-Interacting Protein’ (CHIP), in particular, by targeting natural antisense polynucleotides of ‘C terminus of HSP70-Interacting Protein’ (CHIP). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of CHIP.
1. A method of upregulating a function of and/or the expression of a ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one single stranded antisense oligonucleotide 15 to 30 nucleotides in length or a double stranded oligonucleotide 19-30 nucleotides in length wherein at least one strand of said at least one oligonucleotide leas at least 80% sequence identity to a reverse complement of a polynucleotide comprising 15 to 30 or 19-30 consecutive nucleotides within nucleotides 1 to 2074 of SEQ ID NO: 2 and 1 to 1237 of SEQ ID NO:3; thereby upregulating a function of and/or the expression of the ‘C terminus of HSP70-Interading Protein’ (CHIP) polynucleotide in patient cells or tissues in vivo or in vitro.
2. A method of upregulatin a function of and/or the expression of a ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one antisense oligonucleotide 15 to 30 nucleotides in length or a double stranded oligonucleotide 19-30 nucleotides in length wherein at least one strand of the at least one oligonucleotide has at least 80% sequence identity to a 15-30nucleotide region or a 19-30 nucleotide region of a natural antisense polynucleotide of a ‘C terminus of HSP70-Interacting Protein’ (CHF) polynucleotide; thereby upregulating a function of and/or the expression of the ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide in patient cells or tissues in vivo or in vitro.
3. A method of upregulating a function of and/or the expression of a ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one single stranded antisense oligonucleotide of 15 to 30 nucleotides in length that targets a complementary region of a natural antisense polynucleotide of the ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide having SEQ ID NO; 2 or 3; thereby upregulating a function, of and/or the expression of the ‘C terminus of HSP70-interacting Protein’ (CHIP) polynucleotide in patient cells or tissues in vivo or in vitro.
4. The method of claim 3 , wherein a function of and/or the expression of the ‘C terminus of HSP70-Interacting Protein’ (CHIP) is increased in vivo or in vitro with respect to a control.
5. The method of claim 3 , wherein the at least one antisense oligonucleotide targets a natural antisense polynucleotide of a ‘C terminus of HSP70-interacting Protein’ (CHIP) polynucleotide wherein said natural antisense polynucleotide comprises SEQ ID NO: 2.
6. The method of claim 3 , wherein the at least one antisense oligonucleotide targets a natural antisense polynucleotide antisense to coding and/or non-coding nucleic acid sequences of a ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide.
7. The method of claim 3 , wherein the at least one antisense oligonucleotide targets a natural antisense polynucleotide having overlapping and/or non-overlapping sequences with a ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide.
8. The method of claim 3 , 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.
9. The method of claim 8 , 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.
10. The method of claim 8 , wherein the one or more modifications comprise at least one modified internucleoside linkage selected from: a phosphorothioate, 2- Omethoxyethyl (MOE), 2′-fluoro, allcylphosphonate, phosphorodithioate, alkylphosphonothioate, phosphorarnidate, carbamate, carbonate, phosphate triester, acetamidatc, carboxymethyl ester, and combinations thereof.
11. The method of claim 8 , 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.
12. The method of claim 1 , wherein the at least one oligonucleotide comprises at least one oligonucleotide sequences set forth as SEQ ID NOS: 4 to 11.
13. A method of upregulating a function of and/or the expression of a ‘C terminus of HSP70-Interacting Protein’ (CHIP) gene in mammalian cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one short interfering RNA (siRNA) oligonucleotide 19 to 30 nucleotides in length, said at least one siRNA oligonucleotide being specific for an antisense polynucleotide of a ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide having SEQ ID NOS: 2 or 3; and, upregulating a function of and/or the expression of ‘C terminus of HSP70-Interacting Protein’ (CHIP) in mammalian cells or tissues in vivo or in vitro.
14. The method of claim 13 , wherein said oligonucleotide has at least 90% sequence identity to SEG ID NO: 2 or 3.
15. A method of upregulating a function of and/or the expression, of ‘C terminus Of HSP70-Interacting Protein’ (CHIP) or CHIP gene in mammalian cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one antisense oligonucleotide of about 10 to 30 nucleotides in length specific for noncoding and/or coding sequences of a natural antisense strand of a ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide having SEQ ID NOS: 2 or 3; and, upregulating the function and/or expression of the ‘C terminus of HSP70-Interacting Protein’ (CHIP) in mammalian cells or tissues in vivo or in vitro.
16. A method of preventing or treating a disease associated with at least one ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide and/or at least one encoded product thereof, comprising:
administering to a patient a therapeutically effective dose of at least one antisense oligonucicotide of 15 to 30 nucleotides in length that specifically binds to a natural antisense polynucleotide of said at least one ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide having SEQ ID NOS: 2 or 3 and upregulates_ expression of said at least one ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide; thereby treating the disease associated with the at least one ‘C terminus of HSP70-Interacting Protein’ (CHIP) polynucleotide and/or at least one encoded product thereof wherein the disease is cancer.