Nucleic acid drug suppressing production of myostatin gene MRNA
View Patent ↗An antisense oligonucleotide of 15-30 bases or a salt or a solvate thereof, wherein the antisense oligonucleotide has a nucleotide sequence complementary to a target site in exon 1 of the myostatin gene and is capable of inhibiting the production of the mRNA of the myostatin gene. A pharmaceutical drug, a food, a feed, an agent for promoting myocyte proliferation and/or hypertrophy, an agent for increasing muscle mass and/or inhibiting muscle weakness, an agent for inhibiting production of the mRNA of the myostatin gene, and an inhibitor of the function of myostatin, each of which comprises the above antisense oligonucleotide or a salt or a solvate thereof.
1 . An antisense oligonucleotide or a salt or a solvate thereof, wherein the antisense oligonucleotide has a nucleotide sequence complementary to a target site in exon 1 of the myostatin gene and is capable of inhibiting the production of mRNA of the myostatin gene by inhibiting splicing of the myostatin gene,
wherein the antisense oligonucleotide has 18 bases, and
wherein the nucleotide sequence of the antisense oligonucleotide is any one of the sequences set forth in SEQ ID NOs: 3, 7, 8, 9, 10, 11, 12, 13, 18 and 24 (wherein “t” may be “u”, and “u” may be “t”).
2 . The antisense oligonucleotide or a salt or a solvate thereof of claim 1 , wherein the nucleotide sequence of exon 1 of the myostatin gene is the nucleotide sequence as shown in SEQ ID NO: 1, and the target site in exon 1 of the myostatin gene is located within the region of nucleotide Nos. 22-420 of the nucleotide sequence as shown in SEQ ID NO: 1.
3 . The antisense oligonucleotide or a salt or a solvate thereof of claim 1 , wherein at least one nucleotide is modified.
4 . The antisense oligonucleotide or a salt or a solvate thereof of claim 3 , wherein the sugar constituting the modified nucleotide is D-ribofuranose and the hydroxy group at 2′-position of D-ribofuranose is modified.
5 . The antisense oligonucleotide or a salt or a solvate thereof of claim 4 , wherein D-ribofuranose is 2′-O-alkylated and/or 2′-O,4′-C-alkylenated.
6 . A pharmaceutical drug comprising the antisense oligonucleotide of claim 1 or a pharmaceutically acceptable salt or solvate thereof.
7 . The pharmaceutical drug of claim 6 for preventing and/or treating a pathological condition and/or a disease in which myostatin is involved.
8 . The pharmaceutical drug of claim 7 , wherein the condition and/or disease in which myostatin is involved is muscular atrophy.
9 . The pharmaceutical drug of claim 8 , wherein muscular atrophy is at least one selected from the group consisting of muscular dystrophy, myopathy, spinal muscular atrophy, sarcopenia and disuse muscle atrophy.
10 . The pharmaceutical drug of claim 7 , wherein the condition and/or disease in which myostatin is involved is a condition and/or a disease in which therapeutic effect is gained through muscle mass recovery.
11 . The pharmaceutical drug of claim 10 , wherein the condition and/or disease in which therapeutic effect is gained through muscle mass recovery is at least one selected from the group consisting of cancer cachexia, diabetes, cardiovascular diseases, renal diseases and bone diseases.
12 . The pharmaceutical drug of claim 11 , wherein the cardiovascular disease is cardiac failure and/or arteriosclerosis; the renal disease is chronic renal failure; and the bone disease is inflammatory arthritis.
13 . A food comprising the antisense oligonucleotide of claim 1 or a salt or a solvate thereof that are acceptable as a food ingredient.
14 . A feed comprising the antisense oligonucleotide of claim 1 or a salt or solvate thereof that are acceptable as a feed ingredient.
15 . An agent for promoting myocyte proliferation and/or hypertrophy, comprising the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
16 . An agent for increasing muscle mass and/or suppressing muscle weakness, comprising the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
17 . An agent for inhibiting the production of the mRNA of the myostatin gene, comprising the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
18 . An inhibitor of the function of myostatin, comprising the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
19 . A method of preventing and/or treating a disease in which myostatin is involved, comprising administering to a subject an effective amount of the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
20 . A method of promoting myocyte proliferation and/or hypertrophy, comprising administering to a subject an effective amount of the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
21 . A method of increasing muscle mass and/or suppressing muscle weakness, comprising administering to a subject an effective amount of the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
22 . A method of inhibiting the production of the mRNA of the myostatin gene, comprising administering to a subject an effective amount of the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .
23 . A method of inhibiting the function of myostatin, comprising administering to a subject an effective amount of the antisense oligonucleotide or a salt or a solvate thereof of claim 1 .