Compositions and methods for inhibition of expression of apolipoprotein C-III (APOC3) genes

1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of an APOC3 gene, wherein the dsRNA comprises a sense strand consists of UfCfCfCfUfGAAAGACfUfACfUfGGAdTsdT (SEQ ID NO: 215) and an antisense strand consists of UCCfAGUfAGUCUUUCfAGGGAdTsdT (SEQ ID NO:296), wherein “Cf” “Af” “Uf” and Gf” are 2′-fluoro nucleotides and “dTsdT” is a dT-phosphorothioate-dT linkage.

2. The dsRNA of claim 1 , further comprising a ligand.

3. The dsRNA of claim 2 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA.

4. The dsRNA of claim 1 , further comprising at least one N-Acetyl-Galactosamine.

5. An isolated cell comprising the dsRNA of claim 1 .

6. A vector encoding at least one strand of the dsRNA of claim 1 .

7. An isolated cell comprising the vector of claim 6 .

8. A pharmaceutical composition for inhibiting expression of an APOC3 gene comprising the dsRNA of claim 1 .

9. The pharmaceutical composition of claim 8 , comprising a lipid formulation.

10. The pharmaceutical composition of claim 8 , comprising a lipid formulation comprising MC3.

11. A method of inhibiting APOC3 expression in a cell, the method comprising:

(a) contacting the cell the dsRNA of claim 1 ; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of an APOC3 gene, thereby inhibiting expression of the APOC3 gene in the cell.

12. The method of claim 11 , wherein the APOC3 expression is inhibited by at least 30%.

13. A method of treating a disorder mediated by APOC3 expression comprising administering to a human in need of such treatment a therapeutically effective amount of the APOC3 dsRNA of claim 1 .

14. The method of claim 13 , wherein the disorder is elevated triglyceride levels.

15. The method of claim 13 , wherein the disorder is triglyceride levels >150 mg/dL or >500 mg/dL.