RNAi Inhibition of Alpha-ENaC Expression
First Claim
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1. A composition comprising an iRNA agent comprising a sense strand and an antisense strand, wherein:
- a. the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sense strand of ND8396 (SEQ ID NO;
223), and the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the antisense strand of ND8396 (SEQ ID NO;
224);
orb. the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sense strand of ND8612 (SEQ ID NO;
527), and the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the antisense strand of ND8612 (SEQ ID NO;
528);
orc. the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sense strand of ND10781 (SEQ ID NO;
1281), and the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the antisense strand of ND10781 (SEQ ID NO;
1282).
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Abstract
The invention relates to compositions and methods for modulating the expression of alpha-ENaC, and more particularly to the downregulation of alpha-ENaC expression by chemically modified oligonucleotides.
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20 Claims
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1. A composition comprising an iRNA agent comprising a sense strand and an antisense strand, wherein:
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a. the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sense strand of ND8396 (SEQ ID NO;
223), and the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the antisense strand of ND8396 (SEQ ID NO;
224);
orb. the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sense strand of ND8612 (SEQ ID NO;
527), and the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the antisense strand of ND8612 (SEQ ID NO;
528);
orc. the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the sense strand of ND10781 (SEQ ID NO;
1281), and the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2 or 3 nucleotides from the antisense strand of ND10781 (SEQ ID NO;
1282). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 18, 19, 20)
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16. A composition comprising an iRNA agent to alpha-ENaC, wherein the iRNA agent comprises
a sense strand and an antisense strand, wherein the sense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the sense strand of an iRNA agent selected from the group consisting of ND8396 (SEQ ID NO: - 223), ND8612 (SEQ ID NO;
527), and ND10781 (SEQ ID NO;
1281), andwherein the antisense strand comprises at least 15 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from the antisense strand of an iRNA agent selected from the group consisting of ND8396 (SEQ ID NO;
224), ND8612 (SEQ ID NO;
528), and ND10781 (SEQ ID NO;
1282),the composition further comprising an epithelial receptor ligand. - View Dependent Claims (17)
- 223), ND8612 (SEQ ID NO;
Specification