Methods of Inducing Exon Skipping
First Claim
Patent Images
1. A composition comprising:
- means for inducing skipping of exon 51 of a human dystrophin pre-mRNA; and
a backbone covalently associated with said means for inducing, wherein the backbone comprises a chemical modification selected from the group consisting of morpholino phosphorodiamidate and 2′
-O-methyl phosphorothioate.
0 Assignments
0 Petitions
Accused Products
Abstract
Oligonucleotides for inducing exon skipping, including exon 51 of the dystrophin gene. Compositions are disclosed for treating Duchenne Muscular Dystrophy. Disclosed structures include: (1) h51AON1 (SEQ ID NO: 27; UCAA GGAA GAUG GCAU UUCU), which is 20 bases long, (2) h51AON2 (SEQ ID NO: 28; CCUC UGUG AUUU UAUA ACUU GAU), which is 23 bases long, and (3) the combination of h51AON2 and h45AON5 linked by 10 uracils (i.e., SEQ ID NO: 28 (CCUC UGUG AUUU UAUA ACUU GAU) linked to SEQ ID NO: 16 (GCCC AAUG CCAU CCUG G) by UUUU UUUU UU), which combination is 50 bases long.
-
Citations
22 Claims
-
1. A composition comprising:
-
means for inducing skipping of exon 51 of a human dystrophin pre-mRNA; and a backbone covalently associated with said means for inducing, wherein the backbone comprises a chemical modification selected from the group consisting of morpholino phosphorodiamidate and 2′
-O-methyl phosphorothioate. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
-
-
9. An oligonucleotide comprising:
-
means for inducing skipping of exon 51 of a human dystrophin pre-mRNA; and means for providing the oligonucleotide with resistance to RNaseH. - View Dependent Claims (10, 11, 12, 13, 14, 15, 16, 17)
-
-
18. An oligonucleotide of between 20 to 50 nucleotides comprising a sequence containing h51AON1 (UCAAG GAAGA UGGCA UUUCU) (SEQ ID NO:
- 27) or the DNA thereof,
wherein said oligonucleotide binds without mismatches to the complementary sequence of exon 51 of the human dystrophin pre-mRNA, and wherein said oligonucleotide further comprises a chemical modification selected from the group consisting of morpholino phosphorodiamidate and 2′
-O-methyl phosphorothioate. - View Dependent Claims (19, 20)
- 27) or the DNA thereof,
- 21. A morpholino phosphorodiamidate antisense oligonucleotide of 20 to 50 nucleotides in length, wherein said oligonucleotide binds without mismatches to an exon-internal sequence of exon 51 of the human dystrophin pre-mRNA, wherein the exon-internal sequence comprises the sequence of AGUUC CUUCU ACCGU AAAGA.
Specification