Compositions and methods for the treatment of hypercholesterolemia

Abstract

Provided herein are, inter alia, compositions and methods for the treatment of hypercholesterolemia. The compositions include double-stranded and single-stranded RNAs capable of repressing IncRNA and concomitantly increasing LDLR activation. The compositions are useful for activating LDLR in liver cells.

1 .- 53 . (canceled) 
     
     
         54 . A method of treating hypercholesterolemia, said method comprising administering to a subject in need thereof an effective amount of a ribonucleic acid compound, said ribonucleic acid compound comprising an RNA sequence having at least 95% sequence identity to the complement of at least 15 consecutive nucleotides of SEQ ID NO:1,
 wherein said RNA sequence is capable of hybridizing to nucleotides 133-153, 169-189, 194-217 or 281-301 of SEQ ID NO:1.   
     
     
         55 . The method of  claim 54 , wherein said RNA sequence comprises SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, or SEQ ID NO:9. 
     
     
         56 . A method of treating hypercholesterolemia, said method comprising administering to a subject in need thereof an effective amount of a ribonucleic acid compound, said ribonucleic acid compound comprising an RNA sequence having at least 95% sequence identity to the complement of at least 15 consecutive nucleotides of SEQ ID NO:2,
 wherein said RNA sequence is capable of hybridizing to nucleotides 55-77, 236-256, 287-307 or 515-535 of SEQ ID NO:2.   
     
     
         57 . The method of  claim 56 , wherein said RNA sequence comprises SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:19, or SEQ ID NO:21. 
     
     
         58 . The method of  claim 54  or  56 , wherein said RNA sequence is a single-stranded RNA sequence or a double-stranded RNA sequence. 
     
     
         59 . The method of  claim 54  or  56 , wherein said RNA sequence is a siRNA. 
     
     
         60 . The method of  claim 54 , wherein said RNA sequence is a transcriptional gene silencing (TGS) RNA. 
     
     
         61 . The method of  claim 56 , wherein said RNA sequence is a post-transcriptional gene silencing (PTGS) RNA. 
     
     
         62 . The ribonucleic acid compound of  claim 54  or  56 , comprising a compound moiety covalently attached to said RNA sequence. 
     
     
         63 . The method of  claim 62 , wherein said compound moiety is a trivalent (triantennary)N-acetylgalactosamine moiety or a cholesterol moiety. 
     
     
         64 . A method of treating hypercholesterolemia, said method comprising administering to a subject in need thereof:
 (i) an effective amount of a first ribonucleic acid compound comprising an RNA sequence having at least 95% sequence identity to the complement of at least 15 consecutive nucleotides of SEQ ID NO:1, wherein said RNA sequence is capable of hybridizing to nucleotides 33-53 of SEQ ID NO:1; and   (ii) an effective amount of a second ribonucleic acid compound comprising an RNA sequence having at least 95% sequence identity to the complement of at least 15 consecutive nucleotides of SEQ ID NO:2, wherein said RNA sequence is capable of hybridizing to nucleotides 57-77 of SEQ ID NO:2.   
     
     
         65 . The method of  claim 64 , wherein said first RNA sequence comprises the sequence of SEQ ID NO:11 and second RNA sequence comprises the sequence of SEQ ID NO:21. 
     
     
         66 . The method of  claim 64 , wherein said first RNA sequence is a siRNA or said second RNA sequence is a siRNA. 
     
     
         67 . The method of  claim 64 , wherein a compound moiety is covalently attached to said first RNA sequence or said second RNA sequence.