中外製薬株式会社;TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE;CHUGAI PHARMACEUT CO LTD;公益財団法人東京都医学総合研究所
发明人:
OBARA MICHINORI,小原 道法,SUDO MASAYUKI,須藤 正幸
申请号：
JP2014259763
公开号：
JP2015109842A
申请日:
2014.12.24
申请国别(地区):
JP
年份:
2015
代理人:
摘要：
PROBLEM TO BE SOLVED: To provide a method for designing an oligoribonucleotide which exhibits further effective RNAi activity against hepatitis C virus (HCV) RNA, and an siRNA sequence which exhibits further effective RNAi activity against hepatitis C virus (HCV) RNA.SOLUTION: An analysis is pursued mainly on siE sequences, which have been believed to have an RNAi activity against HCVRNA, by selecting mainly D5-50 and D5-197 regions occurring in an IRES region, and siRNA sequences each having a further effective RNAi activity against HCVRNA are successfully identified. It is also found that the siRNA sequences concerned also have a significant inhibitory effect on in vivo HCV proliferation. The invention relates to a method for inhibiting replication ability of HCV by binding oligoribonucleotide or peptide nucleic acid, which has a specific nucleotide sequence, to RNA of HCV.【課題】Ｃ型肝炎ウイルス（ＨＣＶ）ＲＮＡに対し、より有効なＲＮＡｉ活性を示すオリゴリボヌクレオチド及び、より有効なＲＮＡｉ活性を示すｓｉＲＮＡ配列の設計方法の提供。【解決手段】ＨＣＶＲＮＡに対しＲＮＡｉ活性を示すものとされてきたｓｉＥ配列を中心にして、主にＩＲＥＳ領域内に存在するＤ５－５０、Ｄ５－１９７領域を選定し解析を進めた結果、ＨＣＶＲＮＡに対し、より有効なＲＮＡｉ活性を示すｓｉＲＮＡ配列の同定に成功した。また、当該ｓｉＲＮＡはｉｎ ｖｉｖｏ系においても有意なＨＣＶ増殖抑制効果を示すことが明らかとなった。特定なヌクレオチド配列を有するオリゴリボヌクレオチド又はペプチド核酸をＨＣＶのＲＮＡに結合させて：ＨＣＶの複製能を阻害する方法。【選択図】図３
