Treatment of methionine sulfoxide reductase a (MSRA) related diseases by inhibition of natural antisense transcript to MSRA
AssigneeCuRNA, Inc.
InventorsJoseph Collard, Olga Khorkova Sherman
Life of this patent
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Abstract
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Methionine Sulfoxide Reductase A (MSRA), in particular, by targeting natural antisense polynucleotides of Methionine Sulfoxide Reductase A (MSRA). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of MSRA.
Claims18
A method of upregulating a function of and/or the expression of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide having SEQ ID NO:
- 1 in a mammal comprising:
- contacting said mammal with at least one antisense oligonucleotide 12 to 30 nucleotides in length wherein said at least one oligonucleotide has at least 80% sequence identity to a reverse complement of a natural antisense of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
- thereby upregulating a function of and/or the expression of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide.
A method of upregulating a function of and/or the expression of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide having SEQ ID NO:
- 1 in mammalian cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with at least one antisense oligonucleotide 12 to 30 nucleotides in length wherein said oligonucleotide has at least 90% sequence identity to an RNA transcribed from the Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
- thereby upregulating a function of and/or the expression of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide in mammalian cells or tissues in vivo or in vitro.
A method of upregulating a function of and/or the expression of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide having SEQ ID NO:
- 1 in a mammalian system comprising:
- contacting said system with at least one antisense oligonucleotide of 12 to 28 nucleotides in length that specifically targets and hybridizes to a region of a natural antisense polynucleotide of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
- thereby upregulating a function of and/or the expression of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide.
A method of upregulating a function of and/or the expression of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide having SEQ ID NO:
- 1 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 12 to 30 nucleotides in length, said at least one siRNA oligonucleotide being specific for a natural antisense polynucleotide of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide, wherein said at least one siRNA oligonucleotide has at least 90% sequence complementarity to at least about 19 nucleotides of the natural antisense polynucleotide of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
- and, upregulating a function of and/or the expression of Methionine Sulfoxide Reductase A (MSRA) in mammalian cells or tissues in vivo or in vitro.
A method of upregulating a function of and/or the expression of Methionine Sulfoxide Reductase A (MSRA) polynucleotide having SEQ ID NO:
- 1 in mammalian cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with at least one antisense oligonucleotide of about 12 to 30 nucleotides in length specific for noncoding and/or coding sequences of a natural antisense strand of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide wherein said at least one antisense oligonucleotide has at least 90% sequence identity to a 12 to 30 nucleotide region of a nucleic acid sequence set forth as SEQ ID NO:
- 1;
- and, upregulating the function and/or expression of the Methionine Sulfoxide Reductase A (MSRA) in mammalian cells or tissues in vivo or in vitro.
A method of treating a disease associated with at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide having SEQ ID NO:
- 1, comprising:
- administering to a patient a therapeutically effective dose of at least one antisense oligonucleotide of 12 to 30 nucleotides in length that binds and specifically hybridizes to a natural antisense sequence of said at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide and upregulates expression of said at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
- thereby treating the disease associated with the at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide and/or at least one encoded product thereof and wherein the disease or condition associated with the at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide is selected from cellular oxidative stress or a neurological disease or disorder or a retinal disease or disorder.
Dependencies are inferred from the claim text.