Modified oligonucleotides targeting SNPs
AssigneeUniversity of Massachusetts
InventorsAnastasia Khvorova, Julia Alterman, Faith Conroy, Edith Pfister, Neil Aronin, Ken Yamada
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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.
Claims20
A di-branched oligonucleotide compound comprising two RNAs, wherein the RNAs are connected to one another by one or more moieties selected from a linker, a spacer and a branching point, wherein each RNA has a 5′ end, a 3′ end and a seed region, wherein each RNA is complementary to a region of a gene comprising an allelic polymorphism, and wherein each RNA comprises:
- a single nucleotide polymorphism (SNP) position nucleotide at a position within the seed region, the SNP position nucleotide being 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 di-branched oligonucleotide compound comprising two or more nucleic acid sequences, wherein the nucleic acid sequences (N) are connected to one another by one or more moieties selected from a linker (L), a spacer (S) and optionally a branching point (B),
- wherein each nucleic acid sequence is double-stranded and comprises a sense strand and an antisense strand, wherein the sense strand and the antisense strand each have a 5′ end and a 3′ end, wherein the sense strand and the antisense strand each comprises one or more chemically-modified nucleotides,
- wherein each antisense strand has a seed region, wherein each antisense strand is complementary to a region of a gene comprising an allelic polymorphism, and wherein each antisense strand comprises:
- a single nucleotide polymorphism (SNP) position nucleotide at a position within the seed region, the SNP position nucleotide being 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.
Dependencies are inferred from the claim text.