Treatment of tumor necrosis factor receptor 2 (tnfr2) related diseases by inhibition of natural antisense transcript to tnfr2
AssigneeCuRNA, Inc.
InventorsJoseph COLLARD, Olga Khorkova Sherman
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Abstract
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Tumor Necrosis Factor Receptor 2 (TNFR2), in particular, by targeting natural antisense polynucleotides of Tumor Necrosis Factor Receptor 2 (TNFR2). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of TNFR2.
Claims37
A method of modulating a function of and/or the expression of a Tumor Necrosis Factor Receptor 2 (TNFR2) 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 at least one oligonucleotide has at least 50% sequence identity to a reverse complement of a polynucleotide comprising 5 to 30 consecutive nucleotides within nucleotides 1 to 413 of SEQ ID NO:
- 2 and 1 to 413 of SEQ ID NO:
- 3;
- thereby modulating a function of and/or the expression of the Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of a Tumor Necrosis Factor Receptor 2 (TNFR2) 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 at least one oligonucleotide has at least 50% sequence identity to a reverse complement of a natural antisense of a Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide;
- thereby modulating a function of and/or the expression of the Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of a Tumor Necrosis Factor Receptor 2 (TNFR2) 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 in length wherein said oligonucleotide has at least 50% sequence identity to an antisense oligonucleotide to the Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide;
- thereby modulating a function of and/or the expression of the Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of a Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with at least one antisense oligonucleotide that targets a region of a natural antisense oligonucleotide of the Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide;
- thereby modulating a function of and/or the expression of the Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of anchor the expression of a Tumor Necrosis Factor Receptor 2 (TNFR2) 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 nucleotides in length, said at least one siRNA oligonucleotide being specific for an antisense polynucleotide of a Tumor Necrosis Factor Receptor 2 (TNFR2) 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 Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide;
- and, modulating a function of and/or the expression of Tumor Necrosis Factor Receptor 2 (TNFR2) in mammalian cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of Tumor Necrosis Factor Receptor 2 (TNFR2) 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 Tumor Necrosis factor Receptor 2 (TNFR2) 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 to 3;
- and, modulating the function and/or expression of the Tumor Necrosis Factor Receptor 2 (TNFR2) 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 Tumor Necrosis Factor Receptor 2 (TNFR2) gene in vivo or in vitro as compared to a normal control.
A composition comprising one or more oligonucleotides specific for one or more Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotides, said polynucleotides comprising antisense sequences, complementary sequences, alleles, homologs, isoforms, variants, derivatives, mutants, fragments, or combinations thereof.
A method of preventing or treating a disease associated with at least one Tumor Necrosis Factor Receptor 2 (TNFR2) 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 Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide and modulates expression of said at least one Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide;
- thereby preventing or treating the disease associated with the at least one Tumor Necrosis Factor Receptor 2 (TNFR2) polynucleotide and/or at least one encoded product thereof.
A method of identifying and selecting at least one oligonucleotide for in vivo administration comprising:
- selecting a target polynucleotide associated with a disease state;
- identifying at least one oligonucleotide comprising at least five consecutive nucleotides which are complementary to the selected target polynucleotide or 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 to the selected target polynucleotide under stringent hybridization conditions;
- and selecting at least one oligonucleotide for in vivo administration based on the information obtained.
Dependencies are inferred from the claim text.