Treatment of methionine sulfoxide reductase a (msra) related diseases by inhibition of natural antisense transcript to msra

A method of modulating a function of and/or the expression of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide in patient cells or tissues in vivo or in vitro comprising:

• contacting said cells or tissues with at least one antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to an antisense oligonucleotide to the Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
• thereby modulating a function of and/or the expression of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide in patient cells or tissues in vivo or in vitro.

A method of modulating a function of and/or the expression of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide in a biological system comprising:

• contacting said system with at least one antisense oligonucleotide that targets a region of a natural antisense oligonucleotide of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
• thereby modulating a function of and/or the expression of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide.

A method of modulating a function of and/or the expression of a Methionine Sulfoxide Reductase A (MSRA) 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 5 to 30 nucleotide's in length, said at, least one siRNA oligonucleotide being specific for an antisense polynucleotide of a Methionine Sulfoxide Reductase A (MSRA) polynucleotide, wherein said at least one siRNA oligonucleotide has at least 50% sequence identity to a complementary sequence of at least about five consecutive nucleic acids of the antisense and/or sense nucleic acid molecule of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
• and, modulating a function and/or the expression of Methionine Sulfoxide Reductase A (MSRA) in mammalian cells or tissues in vivo or in vitro.

A method of modulating a function of and/or the expression of Methionine Sulfoxide Reductase A (MSRA) in mammalian cells or tissues in vivo or in vitro comprising:

• contacting said cells or tissues with at least one antisense oligonucleotide of about 5 to 30 nucleotides in length specific for noncoding and/or coding sequences of a sense and/or natural antisense strand of a Methionine Sulfoxide Reductase A (MSRA, polynucleotide wherein said at least one antisense oligonucleotide has at least 50% sequence identity to at least one nucleic acid sequence set forth as SEQ ID NOS:
• 1 and 2;
• and, modulating the function and/or expression of the Methionine Sulfoxide Reductase A (MSRA) in mammalian cells or tissues in vivo or in vitro.

A synthetic, modified oligonucleotide 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 hybridizes to and modulates the function and/or expression of a Methionine Sulfoxide Reductase A (MSRA) gene in vivo or in vitro as compared to a normal control and wherein said oligonucleotide has at least 50% sequence identity to a sequence of at least about five consecutive nucleic acids that is complementary to the antisense and/or sense nucleic acid molecule of the Methionine Sulfoxide Reductase A (MSRA) polynucleotide and alleles, homologs, isoforms, variants, derivatives, mutants, fragments, or combinations thereof.

A method of preventing or treating a disease associated with at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide and/or at least one encoded product thereof, comprising:

• administering to a patient a therapeutically effective dose of at least one antisense oligonucleotide that binds to a natural antisense sequence of said at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide and modulates expression of said at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide;
• thereby preventing or treating the disease associated with the at least one Methionine Sulfoxide Reductase A (MSRA) polynucleotide and/or at least one encoded product thereof.

A method of identifying and selecting at least one oligonucleotide selective for a natural antisense transcript of a MSRA gene as a selected target polynucleotide for in vivo administration comprising:

• identifying at least one oligonucleotide comprising at least five consecutive nucleotides which are at least partially complementary to a polynucleotide that is antisense to the selected target polynucleotide;
• measuring the thermal melting point of a hybrid of an antisense oligonucleotide and the target polynucleotide or the polynucleotide that is antisense the selected target polynucleotide under stringent hybridization conditions;
• and selecting at least one olignucleotide for in vivo administration, based on the information obtained.