IRNA COMPOSITIONS AND METHODS FOR SILENCING COMPLEMENT COMPONENT 3 (C3)

1 . A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of complement component C3 (C3) in a cell, wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,

(a) wherein the antisense strand comprises a region of complementarity to an mRNA encoding C3, and wherein the region of complementarity comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense nucleotide sequences in any one of Tables 2-5; or

(b) wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than three nucleotides from any one of the nucleotide sequence of nucleotides 809-831, 810-832, 811-831, 812-832, 2632-2654, 2633-2655, 2634-2654, 2634-2656, or 2635-2655 of SEQ ID NO: 901, and the antisense strand comprises at least 15 contiguous nucleotides from the corresponding nucleotide sequence of SEQ ID NO:902.

2 .- 6 . (canceled)

7 . The dsRNA agent of claim 1 , wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a nucleotide modification.

8 . The dsRNA agent of claim 7 , wherein at least one of the nucleotide modifications is selected from the group consisting of a deoxy-nucleotide modification, a 3′-terminal deoxythimidine (dT) nucleotide modification, a 2′-O-methyl nucleotide modification, a 2′-fluoro nucleotide modification, a 2′-deoxy nucleotide modification, a 2′-5′-linked ribonucleotide (3′-RNA) modification, a locked nucleotide modification, an unlocked nucleotide modification, a conformationally restricted nucleotide modification, a constrained ethyl nucleotide modification, an abasic nucleotide modification, a 2′-amino nucleotide modification, a 2′-O-allyl nucleotide modification, 2′-C-alkyl nucleotide modification, 2′-hydroxly nucleotide modification, a 2′-methoxyethyl nucleotide modification, a 2′-O-alkyl nucleotide modification, a morpholino nucleotide modification, a phosphoramidate modification, a non-natural base comprising nucleotide modification, a tetrahydropyran nucleotide modification, a 1,5-anhydrohexitol nucleotide modification, a cyclohexenyl nucleotide modification, a nucleotide comprising a phosphorothioate group modification, a nucleotide comprising a methylphosphonate group modification, a nucleotide comprising a 5′-phosphate modification, a nucleotide comprising a 5′-phosphate mimic modification, a vinyl-phosphonate nucleotide modification, a thermally destabilizing nucleotide modification, a glycol nucleotide (GNA) modification, a nucleotide comprising a 2′ phosphate modification, and a 2-O—(N-methylacetamide) nucleotide modification; and combinations thereof.

9 .- 12 . (canceled)

13 . The dsRNA agent of claim 1 , wherein the double stranded region is 19-30 nucleotide pairs in length.

14 .- 17 . (canceled)

18 . The dsRNA agent of claim 1 , wherein each strand is independently no more than 30 nucleotides in length.

19 .- 24 . (canceled)

25 . The dsRNA agent of claim 1 , further comprising a ligand.

26 . The dsRNA agent of claim 25 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA agent.

27 . The dsRNA agent of claim 25 , wherein the ligand is an N-acetylgalactosamine (GalNAc) derivative.

28 . The dsRNA agent of claim 25 , wherein the ligand is one or more GalNAc derivatives attached through a monovalent, bivalent, or trivalent branched linker.

29 . The dsRNA agent of claim 27 , wherein the ligand is

30 . The dsRNA agent of claim 29 , wherein the dsRNA agent is conjugated to the ligand as shown in the following schematic

and, wherein X is O or S.

31 . The dsRNA agent of claim 30 , wherein X is O.

32 . The dsRNA agent of claim 1 , wherein the dsRNA agent further comprises at least one phosphorothioate or methylphosphonate internucleotide linkage.

33 .- 41 . (canceled)

42 . A cell containing the dsRNA agent of claim 1 .

43 . A pharmaceutical composition for inhibiting expression of a gene encoding complement component C3 (C3) comprising the dsRNA agent of claim 1 and a pharmaceutically acceptable carrier.

44 .- 48 . (canceled)

49 . A method of inhibiting expression of a complement component C3 (C3) gene in a cell, the method comprising contacting the cell with the dsRNA agent of claim 1 , thereby inhibiting expression of the C3 gene in the cell.

50 .- 56 . (canceled)

57 . A method of treating a subject having a disorder that would benefit from reduction in complement component C3 (C3) expression, comprising administering to the subject a therapeutically effective amount of the dsRNA agent of claim 1 , thereby treating the subject having the disorder that would benefit from reduction in C3 expression.

58 . (canceled)

59 . The method of claim 57 , wherein the disorder is a C3-associated disorder.

60 . (canceled)

61 . (canceled)

62 . The method of claim 57 , wherein the subject is a human.

63 .- 75 . (canceled)