INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN, ACID LABILE SUBUNIT (IGFALS) AND INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) iRNA COMPOSITIONS AND METHODS OF USE THEREOF

1 . A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of an insulin-like growth factor binding protein, acid labile subunit (IGFALS) gene,

a) wherein the dsRNA agent comprises a sense strand and an antisense strand,

wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of any one of SEQ ID NO:1, 3, or 5, wherein said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of any one of SEQ ID NO:2, 4, or 6; and

wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a nucleotide modification;

b) wherein said dsRNA agent comprises a sense strand and an antisense strand,

wherein the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense sequences listed in any one of Table 3, 5, 6, 8, 12, or 14, and

wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a nucleotide modification.

2 .- 6 . (canceled)

7 . A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of an insulin-like growth factor 1 (IGF-1) gene,

a) wherein said dsRNA agent comprises a sense strand and an antisense strand, wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of any one of SEQ ID NO:11 or 13, wherein said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of any one of SEQ ID NO: 12 or 14; and

wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a nucleotide modification;

b) wherein said dsRNA agent comprises a sense strand and an antisense strand, wherein the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the antisense sequences listed in any one of Tables 9, 11, 15, 17, 18, or 20, and

wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a nucleotide modification.

8 .- 21 . (canceled)

22 . The dsRNA agent of claim 1 , wherein at least one of the nucleotide modifications is selected from the group consisting of a deoxy-nucleotide modification, a 3′-terminal deoxy-thymine (dT) nucleotide modification, a 2′-O-methyl nucleotide modification, a 2′-fluoro nucleotide modification, a 2′-deoxy-nucleotide, 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′-hydroxyl-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, a 1,5-anhydrohexitol nucleotide, 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, and a nucleotide comprising a 5′-phosphate mimic modification.

23 .- 26 . (canceled)

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

28 . (canceled)

29 . (canceled)

30 . The dsRNA agent of claim 1 further comprising a ligand.

31 . The dsRNA agent of claim 30 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA agent.

32 . The dsRNA agent of claim 30 , wherein the ligand is an N-acetylgalactosamine (GalNAc) derivative.

33 . The dsRNA agent of claim 32 , wherein the ligand is

34 . The dsRNA agent of claim 33 , wherein the dsRNA agent is conjugated to the ligand as shown in the following schematic

and, wherein X is O or S.

35 . The dsRNA agent of claim 34 , wherein the X is O.

36 .- 50 . (canceled)

51 . The dsRNA agent of claim 1 , wherein the double stranded region is 15-30 nucleotide pairs in length.

52 .- 64 . (canceled)

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

66 .- 100 . (canceled)

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

102 . A pharmaceutical composition for inhibiting expression of an IGFALS gene comprising the dsRNA agent of claim 1 .

103 . A pharmaceutical composition for inhibiting expression of an IGF-1 gene comprising the dsRNA agent of claim 1 .

104 .- 106 . (canceled)

107 . A method of inhibiting IGFALS expression in a cell, the method comprising:

contacting the cell with the dsRNA agent of claim 1 ;

thereby inhibiting expression of the IGFALS gene in the cell.

108 . A method of inhibiting IGF-1 expression in a cell, the method comprising:

contacting the cell with the dsRNA agent of claim 7 ; thereby inhibiting expression of the IGF-1 gene in the cell.

109 .- 111 . (canceled)

112 . A method of treating a subject having a disease or disorder that would benefit from reduction in IGLAS expression or IGF-1 expression, the method comprising administering to the subject a therapeutically effective amount of the dsRNA agent of claim 1 or 7 , thereby treating said subject.

113 .- 127 . (canceled)