ENHANCED ANTISENSE OLIGONUCLEOTIDES
First Claim
Patent Images
1. A method of reducing expression of a target RNA in an animal, in need of reducing expression of said target RNA, comprising administering to said animal a gap-widened antisense oligonucleotide 18-24 linked nucleosides in length comprising:
- (a) a gap region having 12 to 18contiguous 2′
-deoxyribonucleosides; and
(b) a first wing region having 1 to 4 contiguous nucleosides; and
(c) a second wing region having 1 to 4 contiguous nucleosides;
wherein the gap region is located between said first wing region and said second wing region and, wherein each nucleoside of said first and second wing region is a 2′
modified nucleoside thereby reducing expression of said target RNA in said animal.
0 Assignments
0 Petitions
Accused Products
Abstract
Described herein are gap-widened antisense oligonucleotides having improved therapeutic index as compared to 5-10-5 MOE gapmer antisense oligonucleotides of the same sequence. Also described are methods of reducing a target RNA in an animal using the gap-widened antisense oligonucleotides of the present invention. Further, are methods for selecting a gap-widened antisense oligonucleotides.
21 Citations
27 Claims
-
1. A method of reducing expression of a target RNA in an animal, in need of reducing expression of said target RNA, comprising administering to said animal a gap-widened antisense oligonucleotide 18-24 linked nucleosides in length comprising:
-
(a) a gap region having 12 to 18contiguous 2′
-deoxyribonucleosides; and(b) a first wing region having 1 to 4 contiguous nucleosides; and (c) a second wing region having 1 to 4 contiguous nucleosides; wherein the gap region is located between said first wing region and said second wing region and, wherein each nucleoside of said first and second wing region is a 2′
modified nucleoside thereby reducing expression of said target RNA in said animal.- View Dependent Claims (4, 5, 6, 7, 8, 9, 10)
-
-
2-3. -3. (canceled)
-
11-25. -25. (canceled)
-
26. A method of modulating gene expression in an animal comprising the step of contacting said animal with the pharmaceutical composition comprising a gap-widened antisense oligoncuelotide 18-24 linked nucleosides in length comprising:
-
(a) a gap region having 12 to 18 contiguous 2′
-deoxyribonucleotides;(b) a first wing region having 1 to 4 contiguous nucleosides; and (c) a second wing region having 1 to 4 contiguous nucleosides; wherein the gap region is located between said first wing region and said second wing region and, wherein each nucleoside of said first and second wing region is a 2′
modified nucleoside thereby modulating gene expression in said animal.
-
-
27-28. -28. (canceled)
Specification