RNAi inhibition of alpha-ENaC expression

1. A composition comprising an iRNA agent for inhibiting the expression of an alpha-ENaC gene, wherein the iRNA agent comprises a sense strand and an antisense strand, wherein:

nucleotides 2-19 (5′→3′) of the antisense strand comprise the nucleobase sequence of nucleotides 2-19 of SEQ ID NO: 1298 (5′→3′) (AUUUGUUCUGGUUGCACA);

the nucleotide at position 1 (5′→3′) of the antisense strand forms a base pair with the sense strand;

the sense strand comprises the nucleobase sequence of nucleotides 1-18 of SEQ ID NO: 1297 (5′→3′) (UGUGCAACCAGAACAAAU); and

the antisense strand, the sense strand, or both strands comprise at least one modified nucleotide and/or at least one phosphate linker modification.

2. The composition of claim 1 , wherein the antisense strand of the iRNA agent and the sense strand of the iRNA agent are each 19 to 23 nucleotides in length.

3. The composition of claim 1 , wherein the iRNA agent comprises one or more 2′-modified nucleotides and/or one or more phosphorothioates.

4. The composition of claim 3 , wherein the one or more 2′-modified nucleotides are independently selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylarninopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA).

5. The composition of claim 3 , wherein the sense strand and/or the antisense strand comprises a 3′ overhang.

6. The composition of claim 3 , wherein the sense strand and/or the antisense strand comprises a 5′ overhang.

7. The composition of claim 3 , wherein the iRNA agent comprises at least one blunt end.

8. The composition of claim 3 , further comprising a buffer, diluent, penetration enhancer, carrier compound, and/or pharmaceutically acceptable carrier or excipient.

9. The composition of claim 3 , wherein the composition is presented in unit dosage form.

10. The composition of claim 1 , wherein the iRNA agent is ligated to one or more diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecogenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, Oligo Lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, epithelial receptor ligand, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.

11. The composition of claim 3 , further comprising one or more known agents effective in treatment of ENaC-related disorders.

12. The composition of claim 11 , wherein the known agent is selected from the group consisting of: anti-inflammatory drug, bronchodilatory drug, antihistamine, anti-tussive drug, antibiotic, DNase drug substance, epithelial sodium channel blocker.

13. The composition of claim 3 , wherein the iRNA agent comprises:

an antisense strand comprising a nucleotide sequence of nucleotides 1-19 of SEQ ID NO: 1298 and a sense strand comprising a nucleotide sequence of nucleotides 1-19 of SEQ ID NO: 1297.