Organic compositions to treat Beta-ENaC-related diseases

1. A composition comprising a first RNAi agent comprising a first strand and a second strand, wherein:

a. the sequence of first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sequence of SEQ ID NO: 154, or

b. the sequence of the first strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sequence of SEQ ID NO: 208;

wherein the length of the first and second strand are each at least about 15 nucleotides and no more than about 30 nucleotides, and

wherein the first and/or the second strand are modified or unmodified, and

wherein the composition further comprises a second RNAi agent to Beta-ENaC.

2. The composition of claim 1 , wherein the first and/or second RNAi agent comprises at least one modified backbone and/or at least one 2′-modified nucleotide.

3. The composition of claim 1 , wherein the first and/or second RNAi agent is ligated to one or more agents, wherein the one or more agents are selected from: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, 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, polycationic, peptide, polyamine, peptide mimic, and transferrin.

4. A composition comprising a RNAi agent comprising a first strand and a second strand, wherein:

a. the sequence of the first strand comprises the sequence of SEQ ID NO: 154, or

b. the sequence of the first strand comprises the sequence of SEQ ID NO: 208;

wherein the length of the first and second strand are each no more than about 30 nucleotides, and

wherein the first and/or the second strand are modified or unmodified.

5. The composition of claim 4 , wherein the composition further comprises a second RNAi agent to Beta-ENaC.

6. The composition of claim 4 , wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide.

7. The composition of claim 4 , wherein the RNAi agent is ligated to one or more agents, wherein the one or more agents are selected from: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, 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, polycationic, peptide, polyamine, peptide mimic, and transferrin.

8. A method of reducing the expression and/or level of Beta-ENaC in an individual, the method comprising the step of administering to the individual a therapeutically effective amount of a composition comprising a pharmaceutically acceptable carrier and a RNAi agent comprising a first strand and a second strand, wherein:

a. the sequence of the first strand comprises the sequence of SEQ ID NO: 154, or

b. the sequence of the first strand comprises the sequence of SEQ ID NO: 208;

wherein the length of the first and second strand are each no more than about 30 nucleotides, and

wherein the first and/or the second strand are modified or unmodified.

9. The method of claim 8 , wherein the method further comprises the step of administering an additional RNAi agent to Beta-ENaC.

10. A composition comprising a RNAi agent comprising a first strand and a second strand, wherein:

a. the sequence of the first strand is the sequence of SEQ ID NO: 154, and/or the sequence of the second strand is the sequence of SEQ ID NO: 153, or

b. the sequence of the first strand is the sequence of SEQ ID NO: 208, and/or the sequence of the second strand is the sequence of SEQ ID NO: 207; and

wherein the first and/or the second strand are modified or unmodified.

11. The composition of claim 10 , wherein the RNAi agent comprises one or more 2′-modifications 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-DMAEO), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O—NMA).

12. The composition of claim 10 , wherein the RNAi agent is ligated to one or more agents, wherein the one or more agents are selected from: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, 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, polycationic, peptide, polyamine, peptide mimic, and transferrin.

13. The composition of claim 10 , wherein the composition comprises a second RNAi agent to Beta-ENaC.

14. The composition of claim 10 , wherein the RNAi agent comprises a phosphorothioate and/or a 2′-modified nucleotide.

15. A composition comprising a therapeutically effective amount of a composition of claim 4 and a pharmaceutically acceptable carrier.

16. A composition comprising a therapeutically effective amount of a composition of claim 10 and a pharmaceutically acceptable carrier.

17. A composition comprising a RNAi agent comprising a first strand and a second strand, wherein:

a. the sequence of the first strand is the sequence of SEQ ID NO: 154, or

b. the sequence of the first strand is the sequence of SEQ ID NO: 208; and

wherein the first and/or the second strand are modified or unmodified.