MODULATION OF TIMP1 AND TIMP2 EXPRESSION

摘要

Provided herein are compositions, methods and kits for modulating expression of target genes, particularly of tissue inhibitor of metalloproteinase 1 and of tissue inhibitor of metalloproteinase 2 (TIMP1 and TIMP2, respectively). 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 TIMP1 and TIMP2, for example, the gene encoding human TIMP1 and TIMP2. The composition and methods disclosed herein may also be used in treating conditions and disorders associated with TIMP1 and TIMP2 including fibrotic diseases and disorders including liver fibrosis, pulmonary fibrosis, peritoneal fibrosis and kidney fibrosis.

主权项

1. A nucleic acid molecule, wherein:
(a) the nucleic acid molecule comprises a sense strand and an antisense strand; (b) each strand of the nucleic acid molecule is independently 15 to 49 nucleotides in length; (c) a 15 to 49 nucleotide sequence of the antisense strand is complementary to a sequence of an mRNA encoding TIMP1 (SEQ ID NO: 1) or TIMP2 (SEQ ID NO:2); and (d) a 15 to 49 nucleotide sequence of the sense strand is complementary to the antisense strand thereby generating a duplex region and includes a 15 to 49 nucleotide sequence of an mRNA encoding TIMP1 (SEQ ID NO:1) or TIMP2 (SEQ ID NO:2).