Antidotes to antisense compounds
View Patent ↗The present invention relates to antisense antidote compounds and uses thereof. Such antidote compounds reduce the magnitude and/or duration of the antisense activity of an antisense compound.
1. A method of reducing the activity of an antisense compound comprising identifying an animal that has received an antisense compound and administering to said animal an antidote compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound.
2. The method of claim 1 , wherein the animal is a human.
3. A method of inhibiting antisense activity in a cell comprising contacting the cell with an antidote compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to an antisense compound and thereby inhibiting the antisense activity in the cell.
4. The method of claim 3 , wherein the cell is in an animal.
5. The method of claim 4 , wherein the animal is a human.
6. A method comprising:
contacting a cell with an antisense compound;
detecting antisense activity; and
contacting the cell with an antidote compound.
7. The method of claim 6 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound.
8. The method of claim 6 , wherein the detecting antisense activity comprises measuring a parameter selected from the group consisting of an amount of target mRNA present, an amount of target protein present, and an activity of a target protein.
9. A method of ameliorating a side-effect of antisense treatment comprising:
contacting a cell with an antisense compound;
detecting a side-effect;
contacting the cell with an antidote compound; and
thereby ameliorating the side effect of the antisense compound.
10. The method of claim 9 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound.
11. A method of treating a patient comprising:
administering to the patient an antisense compound;
monitoring the patient for antisense activity; and
if the antisense activity becomes higher than desired, administrating an antidote compound.
12. The method of claim 11 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense compound.
13. The method of claim 11 , wherein the monitoring antisense activity comprises measuring a parameter selected from the group consisting of an amount of target mRNA present, an amount of target protein present, and an activity of a target protein.
14. The method of claim 11 further comprising detecting antidote activity by measuring antisense activity after administration of the antidote compound.
15. The method of claim 11 , wherein the patient is a human.
16. A method of treating a patient comprising:
administering to the patient an antisense compound;
monitoring the patient for one or more side effect; and
if the one or more side effect reaches an undesirable level, administrating an antidote compound.
17. The method of claim 16 , wherein the antidote compound comprises a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence complementary to said antisense.
18. The method of claim 16 , wherein the patient is a human.