Compositions and methods for modulating UTRN expression
First Claim
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1. A single stranded oligonucleotide produced by a process comprising:
- synthesizing a single stranded oligonucleotide that;
(a) has a sequence 5′
-X-Y-Z, wherein X is any nucleotide, Y is a nucleotide sequence of 6 nucleotides in length that is not a seed sequence of a human microRNA, and Z is a nucleotide sequence of 5 to 8 nucleotides in length,(b) is complementary with at least 8 consecutive nucleotides of a PRC2-associated region of a UTRN gene, wherein the PRC2-associated region is a region of the UTRN gene that has a sequence that occurs at a higher frequency in a sequencing reaction of products of an RNA-immunoprecipitation assay that employs an antibody that targets Ezh2 to immunoprecipitate RNA-associated PRC2 complexes from cells comprising the UTRN gene compared to a control sequencing reaction of products of a control RNA-immunoprecipitation assay that employs a control antibody; and
(c) is 12 to 15 nucleotides in length, wherein, during the synthesis,at least one nucleotide incorporated into the oligonucleotide is a nucleotide analogue and/or a modified internucleotide linkage is incorporated between at least two nucleotides.
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Abstract
Aspects of the invention provide single stranded oligonucleotides for activating or enhancing expression of UTRN. Further aspects provide compositions and kits comprising single stranded oligonucleotides for activating or enhancing expression of UTRN. Methods for modulating expression of UTRN using the single stranded oligonucleotides are also provided. Further aspects of the invention provide methods for selecting a candidate oligonucleotide for activating or enhancing expression of UTRN.
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Citations
32 Claims
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1. A single stranded oligonucleotide produced by a process comprising:
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synthesizing a single stranded oligonucleotide that; (a) has a sequence 5′
-X-Y-Z, wherein X is any nucleotide, Y is a nucleotide sequence of 6 nucleotides in length that is not a seed sequence of a human microRNA, and Z is a nucleotide sequence of 5 to 8 nucleotides in length,(b) is complementary with at least 8 consecutive nucleotides of a PRC2-associated region of a UTRN gene, wherein the PRC2-associated region is a region of the UTRN gene that has a sequence that occurs at a higher frequency in a sequencing reaction of products of an RNA-immunoprecipitation assay that employs an antibody that targets Ezh2 to immunoprecipitate RNA-associated PRC2 complexes from cells comprising the UTRN gene compared to a control sequencing reaction of products of a control RNA-immunoprecipitation assay that employs a control antibody; and (c) is 12 to 15 nucleotides in length, wherein, during the synthesis, at least one nucleotide incorporated into the oligonucleotide is a nucleotide analogue and/or a modified internucleotide linkage is incorporated between at least two nucleotides. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 26, 27, 28, 29, 30, 31, 32)
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24. A single stranded oligonucleotide produced by a process comprising:
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synthesizing a single stranded oligonucleotide that; (a) comprises a region of complementarity that is complementary with at least 8 consecutive nucleotides of a PRC2-associated region of a UTRN gene, wherein the PRC2 associated-region of a UTRN gene, wherein the PRC2-associated region is a region of the UTRN gene that has a sequence that occurs at a higher frequency in a sequencing reaction of products of an RNA-immunoprecipitation assay that employs an antibody that targets Ezh2 to immunoprecipitate RNA-associated PRC2 complexes from cells comprising the UTRN gene compared to a control sequencing reaction of products of a control RNA-immunoprecipitation assay that employs a control antibody; (b) is between 12 and 15 nucleotides in length and has at least one of; i) a sequence that is 5′
X-Y-Z, wherein X is any nucleotide and wherein X is anchored at the 5′
end of the oligonucleotide, Y is a nucleotide sequence of 6 nucleotides in length that is not a human seed sequence of a microRNA, and Z is a nucleotide sequence of 5 to 8 nucleotides in length;ii) a sequence that does not comprise three or more consecutive guanosine nucleotides; iii) a sequence that is complementary to a PRC2-associated region that encodes an RNA that forms a secondary structure comprising at least two single stranded loops; and
/oriv) a sequence that has greater than 60% G-C content, wherein, during the synthesis, at least one nucleotide incorporated into the oligonucleotide is a nucleotide analogue and/or a modified internucleotide linkage is incorporated between at least two nucleotides. - View Dependent Claims (25)
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Specification