Rna Capable of Suppressing Expression of Klf5 Gene
An RNA capable of suppressing the expression of KLF5 gene, which comprises a sequence consisting of 15 to 30 contiguous nucleotides of KLF5 mRNA and a sequence complementary to the sequence, and which has been designed from the nucleotide sequence of Kruppel-like factor 5 (KLF5) cDNA. Specifically, a double-stranded RNA having a strand of a sequence shown in any one of SEQ ID NOS: 2 to 16 and a strand of a sequence complementary to the sequence, in which 2 uridylic acids are added to the 3′-terminus of each of the strands. By transfecting the RNA or a vector for expression of the RNA into cells, the expression of KLF5 gene in the cells can be suppressed. The RNA or a vector for expression of the RNA can be used as a therapeutic agent for cardiovascular disease or cancer.
1 . An RNA capable of suppressing the expression of KLF5 gene, which comprises a sequence consisting of 15 to 30 contiguous nucleotides of KLF5 mRNA and a sequence complementary to the sequence.
2 . The RNA according to claim 1 , wherein the KLF5 mRNA is human KLF5 mRNA or mouse KLF5 mRNA.
3 . The RNA according to claim 1 , wherein the RNA is a double-stranded RNA consisting of a strand of a sequence consisting of 15 to 30 contiguous nucleotides of KLF5 mRNA and a strand of a sequence complementary to the sequence, in which 1 to 6 nucleotides are added to the 3′-terminus of each of the strands.
4 . The RNA according to claim 1 , wherein the RNA is an RNA forming a hairpin structure, which is obtained by ligating an RNA having a sequence consisting of 15 to 30 contiguous nucleotides of the KLF5 mRNA to an RNA having a sequence complementary to the sequence via a spacer oligonucleotide, and then adding 1 to 6 nucleotides to the 3′-terminus thereof.
5 . An RNA capable of suppressing the expression of KLF5 gene, which is selected from the group consisting of the following (a) to (c):
(a) a double-stranded RNA having a strand of a sequence shown in any one of SEQ ID NOS: 2 to 16 and a strand of a sequence complementary to the sequence, in which 2 to 4 uridylic acids or deoxythymidylic acids are added to the 3′-terminus of each of the strands;
(b) an RNA forming a hairpin structure, which is obtained by ligating an RNA having a sequence shown in any one of SEQ ID NOS: 2 to 16 to an RNA having a sequence complementary to the sequence via spacer oligonucleotide that has 2 uridylic acids or deoxythymidylic acids at the 5′-terminus thereof, and then adding 2 to 4 uridylic acids or deoxythymidylic acids to the 3′-terminus thereof; and
(c) a double-stranded RNA consisting of a strand of a sequence shown in any one of SEQ ID NOS: 2 to 11 and a strand of a sequence complementary to the sequence, in which 2 uridylic acids are added to the 3′-terminus of each of the strands.
6 . A vector, which allows the RNA according to claim 1 to be expressed.
7 . A method of suppressing the expression of KLF5 gene in cells by transfecting the RNA according to claim 1 into the cells.
8 . A method of suppressing the expression of a gene whose transcription is activated by KLF5 in cells by transfecting the RNA according to claim 1 into the cells.
9 . The method according to claim 8 , wherein the gene whose transcription is activated by KLF5 is platelet-derived growth factor A chain gene or a smooth muscle myosin heavy chain SMemb gene.
10 . A pharmaceutical composition, which comprises, as an active ingredient, the RNA according to claim 1 .
11 . A pharmaceutical composition for inhibiting angiogenesis, which comprises, as an active ingredient, the RNA according to claim 1 .
12 . A therapeutic or preventive agent for cardiovascular disease or cancer, which comprises, as an active ingredient, the RNA according to claim 1 .
13 . The therapeutic or preventive agent according to claim 12 , wherein the cardiovascular disease is arteriosclerosis, restenosis occurring after coronary intervention, or cardiac hypertrophy.
14 . A method of suppressing the expression of KLF5 gene in cells by transfecting the vector according to claim 6 into the cells.
15 . A method of suppressing the expression of a gene whose transcription is activated by KLF5 in cells by transfecting the vector according to claim 6 into the cells.
16 . A pharmaceutical composition, which comprises, as an active ingredient, the vector according to claim 6 .
17 . A pharmaceutical composition for inhibiting angiogenesis, which comprises, as an active ingredient, the vector according to claim 6 .
18 . A therapeutic or preventive agent for cardiovascular disease or cancer, which comprises, as an active ingredient, the vector according to claim 6.