Oligonucleotides for inducing paternal UBE3A expression
AssigneeHoffmann-La Roche Inc.
InventorsVeronica Costa, Maj Hedtjärn, Marius Hoener, Ravi Jagasia, Mads Aaboe Jensen, Christoph Patsch, Lykke Pedersen, Søren Vestergaard Rasmussen
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Abstract
The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.
Claims30
An antisense oligonucleotide comprising a contiguous nucleotide sequence of about 10 to about 30 nucleotides in length with at least 98% complementarity to position 12,179 to 12,256 of SEQ ID NO:
- 1, wherein the antisense oligonucleotide comprises one or more modified nucleosides.
An antisense oligonucleotide gapmer comprising a contiguous nucleotide sequence of about 10 to about 30 nucleotides in length with at least 98% complementarity to position 12,179 to 12,256 of SEQ ID NO:
- 1,
- wherein the gapmer has a formula of 5′-F-G-F′-3′, wherein region F and F′ independently comprise 5 nucleosides and region G comprises 10 nucleosides,
- wherein the antisense oligonucleotide gapmer comprises at least one modified internucleoside linkage and at least one modified nucleoside,
- wherein the modified nucleosides comprise 2′-O-methoxyethyl nucleosides, modified pyrimidines, or a combination thereof, wherein the modified pyrimidines comprise 5-methyl cytosine, and
- wherein at least one modified internucleoside linkage comprises a phosphorothioate internucleoside linkage.
A method for treating a disease in a subject comprising administering a therapeutically effective amount of an antisense oligonucleotide comprising a contiguous nucleotide sequence of about 10 to about 30 nucleotides in length with at least 98% complementarity to position 12,179 to 12,256 of SEQ ID NO:
- 1, wherein the antisense oligonucleotide comprises one or more modified nucleosides.
Dependencies are inferred from the claim text.