Compositions and methods for modulation nucleic acids through nonsense mediated decay

1. A method of reducing the amount or activity of a target mRNA that encodes a protein selected from STAT3, SOD1, and HNRNPH1 in a cell through nonsense mediated decay, comprising contacting a cell with an oligomeric compound comprising a modified oligonucleotide, wherein:

the modified oligonucleotide consists of 10 to 30 linked nucleosides,

wherein each nucleoside of the modified oligonucleotide comprises a 2′-MOE modified nucleoside; or the modified oligonucleotide has an A-B 2 -A-B 2 -A-B 2 -A-B 2 -A-B 2 -A motif or an A 2 -B 2 -A-B 2 -A-B 2 -A-B 2 -A-B 2 -A 2 motif, wherein each A comprises a bicyclic sugar moiety, and wherein each B comprises a sugar moiety selected from a 2′-substituted sugar moiety and an unmodified 2′-deoxy sugar moiety,

wherein each internucleoside linkage in the modified oligonucleotide is a phosphorothioate internucleoside linkage, and

wherein the modified oligonucleotide is at least 90% complementary to a pre-mRNA corresponding to the target mRNA;

wherein the oligomeric compound increases exclusion of an exon from the target mRNA and thereby introduces a premature termination codon in the target mRNA; and wherein the target mRNA with the premature termination codon is recognized by the nonsense mediated decay mechanism, thereby reducing the amount or activity of the target mRNA in the cell through nonsense mediated decay.

2. The method of claim 1 , wherein each modified nucleoside comprises a 2′-MOE sugar moiety.

3. The method of claim 1 , wherein the modified oligonucleotide has an A-B 2 -A-B 2 -A-B 2 -A-B 2 -A-B 2 -A motif, wherein each A comprises a bicyclic sugar moiety, and wherein each B comprises a sugar moiety selected from a 2′-substituted sugar moiety and an unmodified 2′-deoxy sugar moiety.

4. The method of claim 1 , wherein each A comprises a cEt sugar moiety or an LNA sugar moiety.

5. The method of claim 3 , wherein each A comprises a cEt sugar moiety or an LNA sugar moiety.

6. The method of claim 1 , wherein each B comprises an unmodified 2′-deoxy sugar moiety or a 2′-MOE sugar moiety.

7. The method of claim 3 , wherein each B comprises an unmodified 2′-deoxy sugar moiety or a 2′-MOE sugar moiety.

8. The method of claim 1 , wherein the cell is in an animal.

9. The method of claim 4 , wherein each B comprises an unmodified 2′-deoxy sugar moiety.

10. The method of claim 5 , wherein each B comprises an unmodified 2′-deoxy sugar moiety.

11. The method of claim 1 , wherein the modified oligonucleotide has an A 2 -B 2 -A-B 2 -A-B 2 -A-B 2 -A-B 2 -A 2 motif, wherein each A comprises a bicyclic sugar moiety, and wherein each B comprises a sugar moiety selected from a 2′-substituted sugar moiety and an unmodified 2′-deoxy sugar moiety.

12. The method of claim 1 , wherein each cytosine in the modified oligonucleotide is a 5-methyl cytosine.