Modified oligonucleotides targeting SNPs
AssigneeUniversity of Massachusetts
InventorsAnastasia Khvorova, Julia Alterman, Faith Conroy, Edith Pfister, Neil Aronin, Ken Yamada
Life of this patent
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Abstract
Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.
Claims12
A double-stranded RNA (dsRNA) comprising a first strand having 15-35 nucleotides in length, a 5′ end, a 3′ end, and a seed region, wherein the first strand is complementary to a region of a gene comprising an allelic polymorphism, and wherein the first strand comprises:
- a single nucleotide polymorphism (SNP) position nucleotide at a position within the seed region, wherein the SNP position nucleotide is complementary to the allelic polymorphism;
- and a mismatch (MM) position nucleotide located 2-11 nucleotides from the SNP position nucleotide that is a mismatch with a nucleotide in the gene.
An oligonucleotide having 15-35 nucleotides in length, a 5′ end, a 3′ end and a seed region, wherein the oligonucleotide is complementary to a region of a gene comprising an allelic polymorphism, and wherein the oligonucleotide comprises:
- a single nucleotide polymorphism (SNP) position nucleotide at a position within the seed region, wherein the SNP position nucleotide is complementary to the allelic polymorphism;
- and
- a mismatch (MM) position nucleotide located 2-11 nucleotides from the SNP position nucleotide that is a mismatch with a nucleotide in the gene.
A double-stranded RNA (dsRNA) comprising:
- a first strand of 15-35 nucleotides that is complementary to a region of a gene comprising an allelic polymorphism;
- and
- a second strand of 15-35 nucleotides that is complementary a portion of the first strand,
- wherein the first strand comprises a single nucleotide polymorphism (SNP) position nucleotide at position 4 from the 5′ end that is complementary to the allelic polymorphism, and
- wherein the first strand comprises a mismatch (MM) position nucleotide located at position 7 from the 5′ end is a mismatch with a nucleotide in the gene.
A double-stranded RNA (dsRNA) comprising:
- a first strand of 15-35 nucleotides that is complementary to a region of a gene comprising an allelic polymorphism;
- and
- a second strand of 15-35 nucleotides that is complementary to a portion of the first strand,
- wherein the first strand comprises a single nucleotide polymorphism (SNP) position nucleotide at a position 6 from the 5′ end that is complementary to the allelic polymorphism, and
- wherein the first strand comprises a mismatch (MM) position nucleotide located at position 11 from the 5′ end is a mismatch with a nucleotide in the gene.
A nucleic acid having 15-35 nucleotides in length, a 5′ end, a 3′ end, and a seed region, that is complementary to a region of a gene comprising an allelic polymorphism, wherein the nucleic acid comprises:
- a single nucleotide polymorphism (SNP) position nucleotide at a position within the seed region, wherein the SNP position nucleotide is complementary to the allelic polymorphism;
- a mismatch (MM) position that is a mismatch with a nucleotide in the gene;
- and
- at least one modified nucleotide (X) on either side of the SNP position nucleotide, wherein each X is located within four, three or two nucleotides from the SNP position nucleotide.
A nucleic acid having 15-35 nucleotides in length, a 5′ end, a 3′ end and a seed region, that is complementary to a region of a gene comprising an allelic polymorphism, wherein the nucleic acid comprises:
- a single nucleotide polymorphism (SNP) position nucleotide at a position within the seed region, wherein the SNP position nucleotide is complementary to the allelic polymorphism;
- a mismatch (MM) position that is a mismatch with a nucleotide in the gene;
- and
- at least one modified nucleotide (Y) on either side of the MM position nucleotide, wherein each Y is located within four, three or two nucleotides from the MM position nucleotide.
A nucleic acid having 15-35 nucleotides in length, a 5′ end, a 3′ end, and a seed region, that is complementary to a region of a gene comprising an allelic polymorphism, wherein the nucleic acid comprises:
- a single nucleotide polymorphism (SNP) position nucleotide at a position within the seed region, wherein the SNP position nucleotide is complementary to the allelic polymorphism;
- a mismatch (MM) position that is a mismatch with a nucleotide in the gene;
- and
- at least one modified nucleotide (X) on either side of the SNP position nucleotide, wherein each X is located within four, three or two nucleotides from the SNP position nucleotide;
- and
- at least one modified nucleotide (Y) on either side of the MM position nucleotide, wherein each Y is located within four, three or two nucleotides from the MM position nucleotide.
Dependencies are inferred from the claim text.