COMPOSITIONS AND METHODS FOR SHORT INTERFERING NUCLEIC ACID INHIBITION OF Nav 1.8

Abstract

The invention provides short interfering nucleic acids, either single-stranded or double-stranded, that cause RNAi-induced degradation of mRNA from the Na.sub.v1.8 sodium channel gene; to pharmaceutical compositions comprising such short interfering nucleic acids; recombinant vectors comprising such short interfering nucleic acids; a method for inhibiting translation of an mRNA; a method for inhibiting expression of a polypeptide; a method for blocking the membrane potential in a cell; a method for blocking the sodium current in a cell; and a method for inhibiting chronic pain.

We claim: 
     
         1 . An isolated or recombinant short interfering nucleic acid comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11, or an analogue thereof. 
     
     
         2 . The isolated or recombinant short interfering nucleic acid of  claim 1  comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 5, 9 and 10. 
     
     
         3 . The isolated or recombinant short interfering nucleic acid of  claim 1 , further comprising a 3′ overhang. 
     
     
         4 . A pharmaceutical composition comprising a short interfering nucleic acid of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         5 . The isolated or recombinant short interfering nucleic acid of  claim 1 , further comprising a complementary nucleotide sequence thereto. 
     
     
         6 . The complementary nucleotide sequence of  claim 5 , further comprising a 3′ overhang. 
     
     
         7 . A pharmaceutical composition comprising the short interfering nucleic acid and complementary nucleotide sequence of  claim 5 , and a pharmaceutically acceptable carrier. 
     
     
         8 . The isolated or recombinant short interfering nucleic acid of  claim 5 , wherein said nucleotide sequence and said complementary nucleotide sequence hybridize to form a duplex. 
     
     
         9 . The duplex of  claim 8 , wherein said nucleotide sequence further comprises a 3′ overhang and said complementary nucleotide sequence further comprises a 3′ overhang. 
     
     
         10 . A pharmaceutical composition comprising the duplex of  claim 8 , and a pharmaceutically acceptable carrier. 
     
     
         11 . An isolated or recombinant short interfering nucleic acid comprising a sense strand and an antisense strand, wherein said sense strand and said antisense strand hybridize to form a duplex, wherein said sense strand comprises a nucleotide sequence substantially identical to a target sequence, and wherein said target sequence is selected from the group consisting of SEQ ID NOs: 12-577. 
     
     
         12 . The duplex of  claim 11 , wherein said sense strand further comprises a 3′ overhang and said antisense strand further comprises a 3′ overhang. 
     
     
         13 . A pharmaceutical composition comprising the duplex of  claim 11 , and a pharmaceutically acceptable carrier. 
     
     
         14 . A recombinant vector comprising the nucleotide sequence of  claim 1 . 
     
     
         15 . A method for inhibiting translation of an mRNA to a polypeptide comprising contacting a cell capable of expressing a Na.sub.v1.8 mRNA with the short interfering nucleic acid of  claim 1 . 
     
     
         16 . A method for inhibiting expression of a polypeptide comprising contacting a cell capable of expressing a Na.sub.v1.8 polypeptide with the short interfering nucleic acid of  claim 1 . 
     
     
         17 . A method for blocking the membrane potential in a cell comprising contacting a cell expressing a Na.sub.v1.8 polypeptide with the short interfering nucleic acid of  claim 1 . 
     
     
         18 . A method for blocking the sodium current in a cell comprising contacting a cell expressing a Na.sub.v1.8 polypeptide with the short interfering nucleic acid of  claim 1 . 
     
     
         19 . A method for inhibiting chronic pain comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of  claim 4 . 
     
     
         20 . A method for inhibiting chronic pain comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of  claim 7 .