Compositions and methods for inhibition of expression of apolipoprotein C-III (APOC3) genes
View Patent ↗The invention relates to double-stranded ribonucleic acid (dsRNA) targeting an APOC3 gene, and methods of using the dsRNA to inhibit expression of APOC3.
1. A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of an APOC3 gene, wherein the dsRNA comprises a sense strand and an antisense strand, the sense strand consisting of SEQ ID NO:232 (GcuuAAAAGGGAcAGuAuudTsdT) and the antisense strand consisting of SEQ ID NO:313 (AAuACUGUCCCUUUuAAGCdTsdT) wherein each strand includes a 2′-O-methyl ribonucleotide as indicated by a lower case letter “c” or “u,” a 2′-deoxythymidine-3′-phosphate as indicated by a “dT,” and a 2′-deoxy-thymidine-5′phosphate-phosphorothioate as indicated by a “sdT.”.
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. A cell comprising the dsRNA of claim 1 .
6. A vector encoding at least one strand of the dsRNA of claim 1 .
7. A 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 with 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. A method of inhibiting APOC3 expression in a cell, the method comprising:
(a) contacting the cell with the dsRNA of claim 4 ; 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.
15. 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 4 .
16. A method of inhibiting APOC3 expression in a cell, the method comprising:
(a) contacting the cell with the dsRNA of claim 9 ; 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.
17. 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 9 .