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发明授权
US06339066B1 Antisense oligonucleotides which have phosphorothioate linkages of high chiral purity and which modulate &bgr;I, &bgr;II, &ggr;, &dgr;, &Egr;, &zgr; and &eegr; isoforms of human protein kinase C 失效
具有高手性纯度的硫代磷酸酯键并且调节βI，βII，γ，δ和Egr;和zgr的反义寡核苷酸。 和人类蛋白激酶C的同种异构体

  • 专利标题： Antisense oligonucleotides which have phosphorothioate linkages of high chiral purity and which modulate &bgr;I, &bgr;II, &ggr;, &dgr;, &Egr;, &zgr; and &eegr; isoforms of human protein kinase C
  • 专利标题（中）： 具有高手性纯度的硫代磷酸酯键并且调节βI，βII，γ，δ和Egr;和zgr的反义寡核苷酸。 和人类蛋白激酶C的同种异构体
  • 申请号： US08829637
    申请日： 1997-03-31
  • 公开(公告)号： US06339066B1
    公开(公告)日： 2002-01-15
  • 发明人: C. Frank Bennett , Nicholas M. Dean , Phillip Dan Cook , Glenn Hoke
  • 申请人： C. Frank Bennett , Nicholas M. Dean , Phillip Dan Cook , Glenn Hoke
  • 主分类号： C07H2104
  • IPC分类号： C07H2104
Antisense oligonucleotides which have phosphorothioate linkages of high chiral purity and which modulate &bgr;I, &bgr;II, &ggr;, &dgr;, &Egr;, &zgr; and &eegr; isoforms of human protein kinase C
摘要：
Compositions and methods are provided for the treatment and diagnosis of diseases associated with the expression of one or more of the &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoforms (isozymes) of protein kinase C (PKC). Oligonucleotides are provided which are targeted to nucleic acids encoding PKC-&bgr;I, PKC-&bgr;II, PKC-&ggr;, PKC-&dgr;, PKC-&egr;, PKC-&zgr; or PKC-&eegr;. Provided herein are oligonucleotides specifically hybridizable with a translation initiation site, 5′-untranslated region, 3′-untranslated region or other targeted region of a &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoform of PKC, wherein at least about 75% of the nucleoside units of a given oligonucleotide are joined together by a stereospecific (i.e., Sp or Rp) phosphorothioate 3′ to 5′ linkages. In preferred embodiments, the oligonucleotides of the disclosure additionally contain one or more chemical modifications. Also disclosed are methods of using the oligonucleotides of the invention for modulating the expression of at least one of the &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoforms of PKC and for treating animals suffering from disease amenable to therapeutic intervention by modulating the expression of one or more of the &bgr;I, &bgr;II, &ggr;, &dgr;, &egr;, &zgr; or &eegr; isoforms of PKC.
摘要（中）：

提供组合物和方法用于治疗和诊断与βI，βII，γ，δ，epsi和zgr中的一种或多种的表达相关的疾病。 或蛋白激酶C（PKC）的eta同工型（同工酶）。 提供寡核苷酸，其靶向编码PKC-βI，PKC-βII，PKC-γ，PKC-δ，PKC-epsi，PKC- 或PKC-eta。 本文提供了与翻译起始位点，5'-非翻译区，3'非翻译区或βI，βII，γ，δ，ε1和zgr的其它目标区域特异性杂交的寡核苷酸。 或等位基因型，其中给定寡核苷酸的至少约75％的核苷单位通过立体特异性（即Sp或Rp）硫代磷酸酯3'至5'键连接在一起。 在优选的实施方案中，本公开的寡核苷酸另外含有一种或多种化学修饰。 还公开了使用本发明的寡核苷酸调节βI，βII，γ，δ，epsi和zgr中至少一种的表达的方法。 或eta同种型，并通过调节βI，βII，γ，δ，εi，和zgr中的一种或多种的表达来治疗患有适于治疗性干预的疾病的动物。 或PKC的eta同种型。

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