RNAi-mediated inhibition of phosphodiesterase type 4 for treatment of cAMP-related ocular disorders

1. A method of attenuating expression of a PDE4 mRNA in a subject, the method comprising:

(a) administering to an eye of the subject a composition comprising an effective amount of interfering RNA having a length of 19 to 49 nucleotides and a pharmaceutically acceptable carrier, the interfering RNA comprising:

(i) any one of SEQ ID NO 146, SEQ ID NO:149-158, SEQ ID NO:161, SEQ ID NO:167, SEQ ID NO:169-171, or SEQ ID NO:173-199,

(ii) wherein the expression of the PDE4 mRNA is attenuated thereby.

2. The method of claim 1 wherein the composition further comprises a second interfering RNA having a length of 19 to 49 nucleotides and comprising any one of SEQ ID NO:5, SEQ ID NO:11-146, SEQ ID NO:149-158, SEQ ID NO:161, SEQ ID NO:167, SEQ ID NO:169-171, SEQ ID NO:173-199 or SEQ ID NO:205.

3. The method of claim 1 wherein interfering RNA comprises a sense nucleotide strand and a antisense nucleotide strand connected by a hairpin loop.

4. The method of claim 1 wherein the interfering RNA is an shRNA, siRNA, or miRNA.

5. The method of claim 1 wherein the composition is administered via a topical, intravitreal, transcleral, periocular, conjunctival, subtenon, intracameral, subretinal, subconjunctival, retrobulbar, or intracanalicular route.

6. The method of claim 1 wherein the composition is administered via in vivo expression from an interfering RNA expression vector.

7. A composition comprising an interfering RNA with a sense strand having a length of 19 to 49 nucleotides containing at least one non-naturally occurring nucleotide and comprising the base sequence of any one of SEQ ID NO:5, SEQ ID NO:11-146, SEQ ID NO:149-158, SEQ ID NO: 161, SEQ ID NO:167, SEQ ID NO:169-171, or SEQ ID NO:173-199, or a complement thereof, and a pharmaceutically acceptable carrier.

8. The composition of claim 7 wherein the interfering RNA is an shRNA, siRNA, or miRNA.