Selective reduction of allelic variants
AssigneesIsis Pharmaceuticals, Inc., The University of British Columbia
InventorsC. Frank Bennett, Michael Hayden, Susan M. Freier, Sarah Greenlee, Jeffrey Carroll, Simon Warby, Eric E. Swayze
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Abstract
Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).
Claims20
A method of selectively reducing the expression of a mutant huntingtin allele in a cell, tissue, or animal comprising administering to the cell, tissue, or animal a compound comprising a modified, single-stranded antisense oligonucleotide complementary to the mutant huntingtin allele at a position comprising a single nucleotide polymorphism, wherein the modified oligonucleotide consists of 12 to 30 linked nucleosides and comprises a wing-gap-wing motif with a 5′ wing region positioned at the 5′ end of a deoxynucleoside gap, and a 3′ wing region positioned at the 3′ end of the deoxynucleoside gap, wherein position 8, 9, or 10 of the modified oligonucleotide, as counted from the 5′ terminus of the modified oligonucleotide, aligns with the single nucleotide polymorphism, wherein the expression of the mutant huntingtin allele is selectively reduced, and wherein the single nucleotide polymorphism is rs362306, rs362331, rs2298969, rs7685686, rs4690072, rs2024115, or rs363088.
A method of treating, ameliorating, or slowing the onset or progression of Huntington's Disease, comprising administering to an animal a compound comprising a modified, single-stranded antisense oligonucleotide complementary to a mutant huntingtin allele at a position on the allele comprising a single nucleotide polymorphism site, wherein the modified oligonucleotide consists of 12 to 30 linked nucleosides and comprises a wing-gap-wing motif with a 5′ wing region positioned at the 5′ end of a deoxynucleoside gap, and a 3′ wing region positioned at the 3′ end of the deoxynucleoside gap, wherein position 8, 9, or 10 of the modified oligonucleotide, as counted from the 5′ terminus of the modified oligonucleotide, aligns with the single nucleotide polymorphism, wherein the compound administered to the animal treats, ameliorates or slows the onset or progression Huntington's Disease by selectively reducing the mutant huntingtin allele, and wherein the single nucleotide polymorphism site is rs362306, rs362331, rs2298969, rs7685686, rs4690072, rs2024115, or rs363088.
Dependencies are inferred from the claim text.