Treatment of nanog related diseases by inhibition of natural antisense transcript to nanog
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 NANOG, in particular, by targeting natural antisense polynucleotides of NANOG. The invention also related to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of NANOG.
Claims44
A method of modulating a function of and/or the expression of an NANOG polynucleotide in a biological system comprising:
- contacting said system 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 an NANOG polynucleotide;
- thereby modulating a function of and/or the expression of the NANOG polynucleotide.
A method of modulating a function of and/or the expression of an NANOG 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 NANOG polynucleotide;
- thereby modulating a function of and/or the expression of the NANOG polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of an NANOG 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 NANOG polynucleotide;
- thereby modulating a function of and/or the expression of the NANOG polynucleotide.
A method of modulating a function of and/or the expression of an NANOG 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 NANOG 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 NANOG polynucleotide;
- and, modulating a function of and/or the expression of NANOG in mammalian cells or tissues in vivo or in vitro.
A method of modulating a function of and/or the expression of NANOG 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 an NANOG 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 NANOG 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 nucleoside, and combinations thereof;
- wherein said oligonucleotide is an antisense compound which hybridizes to and modulates the function and/or expression of an NANOG 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 NANOG 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 NANOG 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 NANOG polynucleotide and modulates expression of said at least one NANOG polynucleotide;
- thereby preventing or treating the disease associated with the at least one NANOG polynucleotide and/or at least one encoded product thereof.
A method of inducing apoptosis in a biological system comprising administration of an oligonucleotide of 5 to 30 nucleotides in length and which is at least 50% identical to 5 to 30 consecutive nucleotides within a reverse complement of a natural antisense transcript to a NANOG polynucleotide to said system.
A method of inducing apoptosis in a biological system comprising administration of an oligonucleotide of about 5 to 30 nucleotides in length to said system wherein said oligonucleotide upregulates a target gene by targeting to a natural antisense transcript of the gene and wherein said oligonucleotide is at least 50% identical to a reverse complement of the natural antisense transcript of the upregulated gene.
A method of identifying and selecting at least one oligonucleotide selective for a natural antisense transcript of an NANOG 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 to the selected target polynucleotide under stringent hybridization conditions;
- and selecting at least one oligonucleotide for in vivo administration based on the information obtained.
A method of repairing impaired DNA in a patient comprising administering to the patient a therapeutically effective dose of at least one antisense oligonucleotide that binds to a natural antisense sequence of said at least one NANOG polynucleotide and modulates expression of said at least one NANOG polynucleotide;
- thereby repairing the impaired DNA of said patient.
Dependencies are inferred from the claim text.