Reversir tm compounds

Abstract

The present invention relates, in general to agents that modulate the pharmacological activity of conjugated siRNAs.

1 . A method of inhibiting the activity of a siRNA comprising identifying a subject that has received an siRNA and administering to said subject a REVERSIR compound comprising a modified oligonucleotide consisting of 6 to 25 linked nucleotides and having a nucleobase sequence substantially complementary to antisense strand of the siRNA. 
     
     
         2 .- 3 . (canceled) 
     
     
         4 . A method of inhibiting the activity of a siRNA in a cell comprising contacting the cell with a REVERSIR compound comprising a modified oligonucleotide consisting of 6 to 25 linked nucleotides and having a nucleobase sequence substantially complementary to antisense strand of the siRNA. 
     
     
         5 . The method of  claim 4 , wherein said cell is in vivo. 
     
     
         6 .- 8 . (canceled) 
     
     
         9 . A method comprising:
 contacting a cell with a siRNA;   detecting siRNA activity; and   contacting the cell with a REVERSIR compound.   
     
     
         10 . The method of  claim 9 , wherein the REVERSIR compound comprises a modified oligonucleotide consisting of 6 to 25 linked nucleotides and having a nucleobase sequence substantially complementary to antisense strand of the siRNA. 
     
     
         11 . (canceled) 
     
     
         12 . A method of inhibiting a side-effect of siRNA treatment comprising:
 contacting a cell with a siRNA;   detecting a side-effect;   contacting the cell with a REVERSIR compound; and   thereby inhibiting the side-effect of the siRNA.   
     
     
         13 . The method of  claim 12 , wherein the REVERSIR compound comprises a modified oligonucleotide consisting of 6 to 25 linked nucleotides and having a nucleobase sequence substantially complementary to antisense strand of the siRNA. 
     
     
         14 . A method of treating a subject comprising:
 administering to the subject a siRNA;   monitoring the subject for siRNA activity;   if the siRNA activity becomes higher than desired, administering a REVERSIR compound to the subject.   
     
     
         15 . The method of  claim 14 , wherein the REVERSIR compound comprises a modified oligonucleotide consisting of 6 to 25 linked nucleotides and having a nucleobase sequence substantially complementary to antisense strand of the siRNA. 
     
     
         16 . (canceled) 
     
     
         17 . The method of  claim 14  further comprising detecting REVERSIR activity after administration of the REVERSIR compound. 
     
     
         18 .- 19 . (canceled) 
     
     
         20 . A method of treating a subject comprising:
 administering to the subject a siRNA;   monitoring the subject for one or more side-effect;   if one or more side-effect reaches an undesirable level, administering a REVERSIR compound to the subject.   
     
     
         21 . The method of  claim 20 , wherein the REVERSIR compound comprises a modified oligonucleotide consisting of 6 to 25 linked nucleotides and having a nucleobase sequence substantially complementary to antisense strand of the siRNA. 
     
     
         22 .- 23 . (canceled) 
     
     
         24 . The method of  claim 1 , wherein the REVERSIR compound is encapsulated in a lipid formulation. 
     
     
         25 . The method of  claim 1 , wherein the REVERSIR compound is administered via administered via intravenous administration (IV) or via subcutaneous administration (SC). 
     
     
         26 . The method of  claim 1 , wherein the REVERSIR compound is conjugated with a ligand. 
     
     
         27 . The method of  claim 1 , wherein the siRNA is a conjugated with a ligand. 
     
     
         28 . A REVERSIR compound comprising a modified oligonucleotide consisting of 6 to 20 linked nucleotides and having a nucleobase sequence substantially complementary to antisense strand of a siRNA. 
     
     
         29 . (canceled) 
     
     
         30 . The REVERSIR compound of  claim 28 , wherein the modified oligonucleotide is a single-stranded oligonucleotide having at least 90% complementary to the antisense strand. 
     
     
         31 .- 32 . (canceled) 
     
     
         33 . The REVERSIR compound of  claim 28 , wherein the modified oligonucleotide comprises at least one modified internucleotide linkage. 
     
     
         34 . The REVERSIR compound of  claim 28 , wherein the modified oligonucleotide comprises at least one modified internucleotide linkage and at least one unmodified internucleotide linkage. 
     
     
         35 .- 48 . (canceled)