RNAi-mediated inhibition of connexin 43 for treatment of IOP-related conditions
RNA interference is provided for inhibition of connexin 43 (Cx43) in intraocular pressure-related conditions, including ocular hypertension and glaucoma such as normal tension glaucoma and open angle glaucoma.
1. An interfering RNA for inhibiting the expression of a connexin 43 (Cx43) gene, wherein the interfering RNA comprises a sense strand and an antisense strand each 19-49 nucleotides in length, wherein the sense strand comprises a nucleotide sequence of SEQ ID NO:13, except that each T can be independently replaced with a U, and the antisense strand comprises a nucleotide sequence that is complementary to the sense strand.
2. The interfering RNA of claim 1 , wherein each strand of the interfering RNA is 19 to 27 nucleotides in length.
3. The interfering RNA of claim 2 , wherein the interfering RNA comprises one or more chemically modified nucleotides, one or more non-nucleotides, one or more deoxyribonucleotides, and/or one or more non-phosphodiester linkages.
4. The interfering RNA of claim 3 , wherein the interfering RNA comprises one or more chemically modified nucleotides having a 2′ amino group, a 2′ O-methyl group, a 2′ methoxyethyl group, or a 2′-O,4′-C methylene bridge.
5. The interfering RNA of claim 3 , wherein the interfering RNA comprises one or more chemically modified nucleotides and one or more non-phosphodiester linkages.
6. The interfering RNA of claim 3 , wherein non-nucleotide material is bound to the 5′ end and/or 3′ end of the sense strand and/or the 3′ end of the antisense strand.
7. The interfering RNA of claim 6 , wherein the non-nucleotide material is bound internally to the sense strand and/or the antisense strand.
8. The interfering RNA of claim 6 , wherein the non-nucleotide material improves cellular uptake, enhances cellular targeting, assists in tracing, improves stability, and/or reduces activation of the interferon pathway.
9. The interfering RNA of claim 3 , wherein the sense strand and/or the antisense strand contains a 3′ overhang.
10. The interfering RNA of claim 3 , wherein the sense strand contains a 5′ overhang.
11. The interfering RNA of claim 3 , wherein the interfering RNA comprises at least one blunt end.
12. A composition for inhibiting the expression of a connexin 43, the composition comprising the interfering RNA of claim 1 and a pharmaceutically acceptable carrier.
13. The composition of claim 12 , wherein the interfering RNA comprises one or more chemically modified nucleotides, one or more non-nucleotides, one or more deoxyribonucleotides, and/or one or more non-phosphodiester linkages.
14. The composition of claim 13 , wherein the interfering RNA comprises one or more chemically modified nucleotides having a 2′ amino group, a 2′ O-methyl group, a 2′ methoxyethyl group, or a 2′-O,4′-C methylene bridge.
15. The composition of claim 13 , wherein the interfering RNA comprises one or more chemically modified nucleotides and one or more non-phosphodiester linkages.
16. The composition of claim 13 , wherein non-nucleotide material is bound to the 5′ end and/or 3′ end of the sense strand and/or the antisense strand.
17. The composition of claim 13 , wherein the non-nucleotide material is bound internally to the sense strand and/or the antisense strand.
18. The composition of claim 16 , wherein the non-nucleotide material improves cellular uptake, enhances cellular targeting, assists in tracing, improves stability, and/or reduces activation of the interferon pathway.
19. The composition of claim 13 , wherein the sense strand and/or the antisense strand contains a 3′ overhang.
20. The composition of claim 13 , wherein the sense strand and/or the antisense strand contains a 5′ overhang.
21. The composition of claim 13 , wherein the interfering RNA molecule comprises at least one blunt end.