HIGH DENSITY LIPOPROTEIN BINDING PROTEIN (HDLBP/VIGILIN) iRNA COMPOSITIONS AND METHODS OF USE THEREOF

Abstract

The invention relates to double stranded ribonucleic acid (dsRNA) agents and compositions targeting a High Density Lipoprotein Binding Protein (Hdlbp/Vigilin) gene, as well as methods of inhibiting expression of Hdlbp/Vigilin and methods of treating subjects having a disorder of lipid metabolism, such as mixed hyperlipidemia, hypertriglyceridemia or hypercholesterolemia, using such dsRNA agents and compositions.

1 . A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of a High Density Lipoprotein Binding Protein (Hdlbp/Vigilin) gene, wherein said dsRNA agent comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:11. 
     
     
         2 . (canceled) 
     
     
         3 . The dsRNA agent of  claim 1 , wherein said dsRNA agent comprises at least one nucleotide comprising a nucleotide modification. 
     
     
         4 . The dsRNA agent of a  claim 1 , wherein substantially all of the nucleotides of said sense strand and substantially all of the nucleotides of said antisense strand comprise a nucleotide modification; or all of the nucleotides of said sense strand and all of the nucleotides of said antisense strand comprise a nucleotide modification. 
     
     
         5 . (canceled) 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The dsRNA agent of  claim 1 , wherein the region of complementarity is at least 17 nucleotides in length. 
     
     
         9 . The dsRNA agent of  claim 1 , wherein each strand is no more than 30 nucleotides in length. 
     
     
         10 . The dsRNA agent of  claim 1 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide; or at least one strand comprises a 3′ overhang of at least 2 nucleotides. 
     
     
         11 . The dsRNA agent of  claim 1 , further comprising a ligand. 
     
     
         12 . The dsRNA agent of  claim 1 , wherein said agent further comprises at least one phosphorothioate or methylphosphonate internucleotide linkage. 
     
     
         13 . An isolated cell containing the double stranded RNAi agent of  claim 1 . 
     
     
         14 . A pharmaceutical composition for inhibiting expression of an Hdlbp/Vigilin gene comprising the double stranded RNAi agent of  claim 1 . 
     
     
         15 . A method of inhibiting expression of a High Density Lipoprotein Binding Protein (Hdlbp/Vigilin) gene in a cell, the method comprising:
 (a) contacting the cell with the double stranded RNAi agent of  claim 1 ; and   (b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of an Hdlbp/Vigilin gene, thereby inhibiting epression of the Hdlbp/Vigilin gene in the cell.   
     
     
         16 . The method of  claim 15 , wherein said cell is within a subject. 
     
     
         17 . A method of treating a subject having a disorder that would benefit from a reduction in expression of a High Density Lipoprotein Binding Protein (Hdlbp/Vigilin) gene, comprising administering to the subject a therapeutically effective amount of the double stranded RNAi agent of  claim 1 , thereby treating said subject. 
     
     
         18 . The method of  claim 17 , wherein the subject is human. 
     
     
         19 . The method of  claim 17 , wherein the disorder is a disorder of lipid metabolism. 
     
     
         20 . The method of  claim 19 , wherein the disorder of lipid metabolism is a hyperlipidemia. 
     
     
         21 . The method of  claim 17 , further comprising administering an additional therapeutic agent to the subject. 
     
     
         22 . The method of  claim 17 , wherein the double stranded RNAi agent is administered to the subject at a dose of about 0.01 mg/kg to about 50 mg/kg. 
     
     
         23 . The method of  claim 17 , wherein the double stranded RNAi agent is administered to the subject subcutaneously.