Modulation of HSP47 expression

摘要

Provided herein are compositions, methods and kits for modulating expression of target genes, particularly heat shock protein 47 (hsp47). The compositions, methods and kits may include nucleic acid molecules (for example, short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA) or short hairpin RNA (shRNA)) that modulate a gene encoding hsp47, for example, the gene encoding human hsp47. The composition and methods disclosed herein may also be used in treating conditions and disorders associated with hsp47 such as liver fibrosis, pulmonary fibrosis, peritoneal fibrosis and kidney fibrosis.

主权项

1. A double stranded nucleic acid molecule having a structure (A2) set forth below:
(A2) 5′ N1-(N)x-Z 3′ (antisense strand)
3′ Z′-N2-(N′)y-z″ 5′ (sense strand) wherein each of N2, N and N′ is independently an unmodified or modified ribonucleotide, or an unconventional moiety; wherein each of (N)x and (N′)y is an oligonucleotide in which each consecutive N or N′ is joined to the adjacent N or N′ by a covalent bond; wherein each of x and y is independently an integer between 17 and 39; wherein the sequence of (N′)y has complementarity to the sequence of (N)x and the sequence of (N)x has complementarity to a consecutive sequence in a mRNA encoding hsp47; wherein N1 is covalently bound to (N)x and is mismatched to the mRNA encoding hsp47; or is a complementary DNA moiety to the mRNA encoding hsp47; wherein N1 is a moiety selected from natural or modified uridine, deoxyribouridine, ribothymidine, deoxyribothymidine, adenosine or deoxyadenosine; wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′ terminus of N2—(N′)y; wherein each of Z and Z′ is independently present or absent, but if present is independently 1-5 consecutive nucleotides, consecutive non-nucleotide moieties or a combination thereof covalently attached at the 3′ terminus of the strand in which it is present; and wherein the sense strand and the antisense strand comprise the oligonucleotides described as SERPINH1—45a (SEQ ID NOs: 98 and 165) or SERPINH1—51 (SEQ ID NOs: 101 and 168).