RNAi-mediated inhibition of connexin 43 for treatment of IOP-related conditions
View Patent ↗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. A method of treating glaucoma in a patient that has elevated intraocular pressure (IOP), consisting of administering to the eye of the patient an interfering RNA molecule comprising SEQ ID NO: 79 or SEQ ID NO: 80, wherein the interfering RNA molecule comprises an acceptable carrier, and wherein attenuating expression of Cx43 lowers intraocular pressure in the patient.
2. The method of claim 1 , wherein the interfering RNA molecule is double stranded and each strand is independently about 19 to about 27 nucleotides in length.
3. The method of claim 2 , wherein each strand is independently about 19 nucleotides to about 25 nucleotides in length.
4. The method of claim 2 , wherein each strand is independently about 19 nucleotides to about 21 nucleotides in length.
5. The method of claim 2 , wherein the sense and antisense strands are connected by a linker to form an shRNA that can attenuate expression of Cx43 mRNA in a patient.
6. The method of claim 2 , wherein the interfering RNA molecule has blunt ends.
7. The method of claim 2 , wherein at least one strand of the interfering RNA molecule comprises a 3′ overhang.
8. The method of claim 7 , wherein the 3′ overhang comprises about 1 to about 6 nucleotides.
9. The method of claim 8 , wherein the 3′ overhang comprises 2 nucleotides.
10. The method of claim 1 , wherein the interfering RNA molecule is administered via in vivo expression from an expression vector capable of expressing the interfering RNA molecule.
11. The method of claim 1 , wherein the IOP-related condition is glaucoma.
12. The method of claim 1 , wherein the interfering RNA molecule is administered via a topical, intravitreal, transcleral, periocular, conjunctival, subtenon, intracameral, subretinal, subconjunctival, retrobulbar, or intracanalicular route.
13. The method of claim 1 , wherein the interfering RNA molecule comprises at least one modification.
14. The method of claim 1 , wherein the interfering RNA molecule is a shRNA, a siRNA, or a miRNA.