REVERSIR TM COMPOUNDS
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)