Antisense compounds targeted to connexins and methods of use thereof
View Patent ↗Methods and compositions for modulating the activities of connexins are provided, including, for example, for use in post-surgical, trauma, or tissue engineering applications. These compounds and methods can be used therapeutically, for example, to reduce the severity of adverse effects associated diseases and disorders where localized disruption in direct cell-cell communication is desirable.
1. A method for treating a subject for a penetrating eye trauma, comprising administering a connexin 43-downregulating amount of a connexin 43 antisense compound to the eye of said subject.
2. A method of claim 1 wherein the eye trauma is chemical trauma.
3. A method of claim 1 wherein the eye trauma is mechanical trauma.
4. A method of claim 1 wherein the eye trauma results in corneal epithelial damage.
5. A method of claim 1 wherein the connexin 43 antisense compound is administered to a subject having an amniotic membrane graft.
6. A method of claim 1 wherein said antisense compound is selected from the group consisting of antisense, oligonucleotides and antisense polynucleotides.
7. The method of claim 6 wherein said antisense compound comprises a nucleobase sequence selected from SEQ ID NO:1-3.
8. The method of claim 6 wherein said antisense compound is targeted to at least about 8 nucleobases of a nucleic acid molecule encoding a connexin having a nucleobase sequence selected from SEQ ID NO:12.
9. The method of any of claim 1 - 4 or 5 wherein said antisense compound is an antisense oligonucleotide between 15 and 35 nucleobases in length.
10. The method of claim 9 wherein said antisense compound is an antisense oligonucleotide comprising naturally occurring nucleobases and an unmodified internucleoside linkage.
11. The method of claim 9 wherein said antisense compound is antisense oligonucleotide comprising at least one modified internucleoside linkage, at least one modified sugar moiety, and/or at least one modified nucleobase.
12. The method of claim 11 wherein said modified internucleoside linkage is a phosphorothioate linkage.
13. A method of claim 1 wherein said antisense compound is administered by topical administration.
14. A method of claim 1 wherein said antisense compound is administered by local administration.
15. A method of claim 1 wherein said antisense compound is administered by intraocular injection.
16. A method of claim 9 wherein the antisense compound is formulated with a pluronic gel.
17. A method of claim 16 wherein the pluronic gel comprises pluronic F127.
18. A method of claim 9 wherein the antisense compound is administered once.
19. A method of claim 9 wherein the antisense compound is administered more than once.
20. A method of claim 1 wherein the subject is a human.