JPWO2005071082A1 - 抗癌作用を有するアンチセンスオリゴヌクレオチド - Google Patents
抗癌作用を有するアンチセンスオリゴヌクレオチド Download PDFInfo
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- JPWO2005071082A1 JPWO2005071082A1 JP2005517190A JP2005517190A JPWO2005071082A1 JP WO2005071082 A1 JPWO2005071082 A1 JP WO2005071082A1 JP 2005517190 A JP2005517190 A JP 2005517190A JP 2005517190 A JP2005517190 A JP 2005517190A JP WO2005071082 A1 JPWO2005071082 A1 JP WO2005071082A1
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- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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Abstract
Description
Mol.Cell Biol.9,4345−4356(1989) Mol.Carcinog.20,175−188(1997) J.Biol.Chem.274(22),15786−15796(1999)
〔1〕 シグナル認識粒子(SRP)の7SL RNAの47〜51位の塩基配列に対するアンチセンスオリゴヌクレオチド、
〔2〕 配列番号:1記載の塩基配列からなる前記〔1〕記載のアンチセンスオリゴヌクレオチド、
〔3〕 前記〔1〕又は〔2〕に記載のアンチセンスオリゴヌクレオチドを含有してなる癌細胞増殖抑制剤、
〔4〕 前記〔1〕又は〔2〕に記載のアンチセンスオリゴヌクレオチドを含有してなる癌の治療剤又は予防剤、
〔5〕 アンチセンスオリゴヌクレオチドがリポソーム中に存在してなる前記〔4〕記載の治療剤又は予防剤、
〔6〕 アンチセンスオリゴヌクレオチドがベクターと連結されたものである前記〔4〕又は〔5〕記載の治療剤又は予防剤、並びに
〔7〕 前記〔3〕に記載の癌細胞増殖抑制剤、又は前記〔4〕〜〔6〕いずれかに記載の治療剤若しくは予防剤の製造のための前記〔1〕又は〔2〕に記載のアンチセンスオリゴヌクレオチドの使用方法、
を提供するものである。
前記トランスフォーミングRNAは細胞の癌化と分泌タンパク質の合成抑制に関与していることから、細胞の癌化には分泌タンパク質の合成抑制がかかわっているものと推定される。一方、アンチセンスODN(配列番号:6)は分泌タンパク質の合成抑制を減ずる方向に作用することから、当該アンチセンスODNは癌化に抗して働くことが期待される。
前記oligo3の毒性について検討した。すなわち、oligo3を1mg/mLとなるように生理的食塩水に溶解させたものを用いて、雌のマウス(5週齢)に対し、体重1g当たり20μgを静脈内投与した。投与当日(0日)及び投与から2、5、10、12及び14日後のマウスの体重を測定した。
配列番号:3は、トランスフォーミングRNAの部分塩基配列である。
配列番号:4は、トランスフォーミングRNAの部分塩基配列に基づいて作製されたオリゴデオキシヌクレオチドの塩基配列である。
配列番号:5は、オリゴデオキシヌクレオチドの部分塩基配列である。
配列番号:6は、オリゴデオキシヌクレオチドの塩基配列に対するアンチセンスオリゴデオキシヌクレオチドの塩基配列である。
配列番号:7は、アンチセンスオリゴデオキシヌクレオチドの部分塩基配列である。
Claims (7)
- シグナル認識粒子(SRP)の7SL RNAの47〜51位の塩基配列に対するアンチセンスオリゴヌクレオチド。
- 配列番号:1記載の塩基配列からなる請求項1記載のアンチセンスオリゴヌクレオチド。
- 請求項1又は2に記載のアンチセンスオリゴヌクレオチドを含有してなる癌細胞増殖抑制剤。
- 請求項1又は2に記載のアンチセンスオリゴヌクレオチドを含有してなる癌の治療剤又は予防剤。
- アンチセンスオリゴヌクレオチドがリポソーム中に存在してなる請求項4記載の治療剤又は予防剤。
- アンチセンスオリゴヌクレオチドがベクターと連結されたものである請求項4又は5記載の治療剤又は予防剤。
- 請求項3に記載の癌細胞増殖抑制剤、又は請求項4〜6いずれかに記載の治療剤若しくは予防剤の製造のための請求項1又は2に記載のアンチセンスオリゴヌクレオチドの使用方法。
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