OLIGONUCLEOTIDE COMPOSITIONS AND METHODS THEREOF
First Claim
1. An oligonucleotide composition, comprising a first plurality of oligonucleotides of a particular oligonucleotide type defined by:
- 1) base sequence;
2) pattern of backbone linkages;
3) pattern of backbone chiral centers; and
4) pattern of backbone phosphorus modifications,which composition is chirally controlled in that it is enriched, relative to a substantially racemic preparation of oligonucleotides having the same base sequence, for oligonucleotides of the particular oligonucleotide type,wherein oligonucleotides of the particular oligonucleotide type each comprise;
1) a 5′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety;
2) a 3′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety; and
3) a middle region between the 5′
-end region and the 3′
-end region, wherein the middle region comprises one or more Rp internucleotidic linkages.
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Accused Products
Abstract
Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.
16 Citations
42 Claims
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1. An oligonucleotide composition, comprising a first plurality of oligonucleotides of a particular oligonucleotide type defined by:
-
1) base sequence; 2) pattern of backbone linkages; 3) pattern of backbone chiral centers; and 4) pattern of backbone phosphorus modifications, which composition is chirally controlled in that it is enriched, relative to a substantially racemic preparation of oligonucleotides having the same base sequence, for oligonucleotides of the particular oligonucleotide type, wherein oligonucleotides of the particular oligonucleotide type each comprise; 1) a 5′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety;2) a 3′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety; and3) a middle region between the 5′
-end region and the 3′
-end region, wherein the middle region comprises one or more Rp internucleotidic linkages.- View Dependent Claims (5, 6, 7, 8, 9, 14, 15, 16, 33, 34, 35)
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2-4. -4. (canceled)
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10-13. -13. (canceled)
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17-32. -32. (canceled)
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36. A method for altering splicing of a target transcript, comprising administering an oligonucleotide composition, wherein the oligonucleotide composition comprises a first plurality of oligonucleotides of a particular oligonucleotide type defined by:
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1) base sequence; 2) pattern of backbone linkages; 3) pattern of backbone chiral centers; and 4) pattern of backbone phosphorus modifications, which composition is chirally controlled in that it is enriched, relative to a substantially racemic preparation of oligonucleotides having the same base sequence, for oligonucleotides of the particular oligonucleotide type, wherein oligonucleotides of the particular oligonucleotide type each comprise; 1) a 5′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety;2) a 3′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety; and3) a middle region between the 5′
-end region and the 3′
-end region, wherein the middle region comprises one or more Rp internucleotidic linkages.- View Dependent Claims (37, 38, 39)
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40. (canceled)
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41. A method for treating Duchenne muscular dystrophy, comprising administering to a subject susceptible thereto or suffering therefrom an oligonucleotide composition, wherein the oligonucleotide composition comprises a first plurality of oligonucleotides of a particular oligonucleotide type defined by:
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1) base sequence; 2) pattern of backbone linkages; 3) pattern of backbone chiral centers; and 4) pattern of backbone phosphorus modifications, which composition is chirally controlled in that it is enriched, relative to a substantially racemic preparation of oligonucleotides having the same base sequence, for oligonucleotides of the particular oligonucleotide type, wherein oligonucleotides of the particular oligonucleotide type each comprise; 1) a 5′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety;2) a 3′
-end region comprising 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more nucleoside units comprising a 2′
-F modified sugar moiety; and3) a middle region between the 5′
-end region and the 3′
-end region, wherein the middle region comprises one or more Rp internucleotidic linkages.- View Dependent Claims (42)
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Specification