Oligonucleotides for atn1 modulation
AssigneeUniversity of Massachusetts
InventorsAnastasia Khvorova, Daniel O'Reilly
Life of this patent
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Abstract
This disclosure relates to novel ATN1 targeting sequences. Novel ATN1 targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.
Claims38
A double stranded RNA (dsRNA) molecule comprising a sense strand and an antisense strand,
- wherein the antisense strand comprises a sequence substantially complementary to a ATN1 nucleic acid sequence of any one of SEQ ID NOs:
- 1-7.
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A branched RNA compound comprising:
- two or more RNA molecules comprising 15 to 35 nucleotides in length, and
- a sequence substantially complementary to a ATN1 mRNA,
- wherein the two RNA molecules are connected to one another by one or more moieties independently selected from a linker, a spacer and a branching point.
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A compound of formula (I):
- L-(N)n (I)
- wherein:
- L comprises an ethylene glycol chain, an alkyl chain, a peptide, an RNA, a DNA, a phosphate, a phosphonate, a phosphoramidate, an ester, an amide, a triazole, or combinations thereof, and wherein formula (I) optionally further comprises one or more branch point B, and one or more spacer S, wherein:
- B is independently for each occurrence a polyvalent organic species or derivative thereof;
- S comprises independently for each occurrence an ethylene glycol chain, an alkyl chain, a peptide, an RNA, a DNA, a phosphate, a phosphonate, a phosphoramidate, an ester, an amide, a triazole, or a combination thereof;
- and
- N is a double stranded nucleic acid comprising 15 to 35 bases in length comprising a sense strand and an antisense strand;
- wherein:
- the antisense strand comprises a sequence substantially complementary to a ATN1 nucleic acid sequence of any one of SEQ ID NOs:
- 1-7
- wherein the sense strand and antisense strand each independently comprise one or more chemical modifications;
- and
- wherein n is 2, 3, 4, 5, 6, 7 or 8.
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A method of treating or managing dentatorubral-pallidoluysian atrophy (DRPLA) or a trinucleotide repeat disease or disorder, the method comprising administering to a patient in need of such treatment or management a therapeutically effective amount of an oligonucleotide comprising a sequence substantially complementary to a ATN1 nucleic acid sequence.
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Dependencies are inferred from the claim text.