Modulation of dystrophia myotonica-protein kinase (dmpk) expression

Abstract

Provided herein are methods, compounds, and compositions for reducing expression of a DMPK mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate type 1 myotonic dystrophy, or a symptom thereof.

What is claimed is: 
     
         1 .- 22 . (canceled) 
     
     
         23 . A compound comprising a modified oligonucleotide consisting of 10 to 30 linked nucleosides and having a nucleobase sequence comprising at least 8 contiguous nucleobases of sequence recited in SEQ ID NOs: 44 or 76. 
     
     
         24 . The compound of  claim 23 , wherein the modified oligonucleotide is a single-stranded oligonucleotide. 
     
     
         25 . The compound of  claim 23 , wherein the nucleobase sequence of the modified oligonucleotide is 100% complementary to SEQ ID NO: 2. 
     
     
         26 . The compound of  claim 23 , wherein at least one internucleoside linkage is a modified internucleoside linkage. 
     
     
         27 . The compound of  claim 26 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         28 . The compound of  claim 23 , wherein at least one nucleoside comprises a modified sugar. 
     
     
         29 . The compound of  claim 28 , wherein at least one modified sugar is a bicyclic sugar. 
     
     
         30 . The compound of  claim 28 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl. 
     
     
         31 . The compound of  claim 23 , wherein at least one nucleoside comprises a modified nucleobase. 
     
     
         32 . The compound of  claim 31 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         33 . The compound of  claim 23 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides;   a 3′ wing segment consisting of linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.   
     
     
         34 . The compound of  claim 23 , wherein the modified oligonucleotide consists of 20 linked nucleosides and comprises:
 a gap segment consisting of ten linked deoxynucleosides;   a 5′ wing segment consisting of five linked nucleosides;   a 3′ wing segment consisting of five linked nucleosides;   wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar; and wherein each internucleoside linkage is a phosphorothioate linkage.   
     
     
         35 . The compound of  claim 23 , wherein the modified oligonucleotide consists of 20 linked nucleosides.