Treatment of erythropoietin (epo) related diseases by inhibition of natural antisense transcript to epo
AssigneeOPKO CuRNA, LLC
InventorsJoseph Collard, Olga Khorkova Sherman
Life of this patent
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Abstract
Oligonucleotide compounds modulate expression and/or function of Erythropoietin (EPO) polynucleotides and encoded products thereof. Methods for treating diseases associated with Erythropoietin (EPO) comprise administering one or more oligonucleotide compounds designed to inhibit the EPO natural antisense transcript to patients.
Claims34
A method of modulating a function of and/or the expression of an Erythropoietin (EPO) 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 a reverse complement of a polynucleotide comprising 5 to 30 nucleotides within nucleotides 1 to 156 of SEQ ID NO:
- 2 (FIG. 3);
- thereby modulating a function of and/or the expression of the Erythropoietin (EPO) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of an Erythropoietin (EPO) 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 a reverse complement of an antisense oligonucleotide of the Erythropoietin (EPO) polynucleotide;
- thereby modulating a function of and/or the expression of the Erythropoietin (EPO) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of an Erythropoietin (EPO) 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 Erythropoietin (EPO) polynucleotide;
- thereby modulating a function of and/or the expression of the Erythropoietin (EPO) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of an Erythropoietin (EPO) 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 Erythropoietin (EPO) polynucleotide;
- thereby modulating a function of and/or the expression of the Erythropoietin (EPO) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of an Erythropoietin (EPO) 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 an Erythropoietin (EPO) 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 Erythropoietin (EPO) polynucleotide;
- and, modulating Erythropoietin (EPO) gene expression and/or function in mammalian cells or tissues in vivo or in vitro.
A method of modulating an Erythropoietin (EPO) gene expression and/or function 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 polynucleotide encoding an Erythropoietin (EPO) molecule wherein the 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, 2;
- and, modulating Erythropoietin (EPO) gene expression and/or function 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 expression of and/or a function of an Erythropoietin (EPO) gene in vivo or in vitro as compared to a normal control.
A composition comprising one or more oligonucleotides specific for one or more Erythropoietin (EPO) 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 or disorder associated with at least one Erythropoietin (EPO) 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 antiense sequence of said at least one Erythropoietin (EPO) polynucleotide and modulates expression of said at least one Erythropoietin (EPO) polynucleotide;
- thereby preventing or treating the disease or disorder associated with the at least one Erythropoietin (EPO) 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 oligonucleotides comprising at least five consecutive nucleotides which are complementary to, or in an antisense orientation to the selected target polynucleotide;
- and, measuring the thermal melting point of a hybrid of an antisense oligonucleotide and the 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.