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首页> 外文期刊>Molecular and Cellular Biology >Recombination induced by triple-helix-targeted DNA damage in mammalian cells.
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Recombination induced by triple-helix-targeted DNA damage in mammalian cells.

机译:在哺乳动物细胞中由三螺旋靶向的DNA损伤诱导的重组。

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Gene therapy has been hindered by the low frequency of homologous recombination in mammalian cells. To stimulate recombination, we investigated the use of triple-helix-forming oligonucleotides (TFOs) to target DNA damage to a selected site within cells. By treating cells with TFOs linked to psoralen, recombination was induced within a simian virus 40 vector carrying two mutant copies of the supF tRNA reporter gene. Gene conversion events, as well as mutations at the target site, were also observed. The variety of products suggests that multiple cellular pathways can act on the targeted damage, and data showing that the triple helix can influence these pathways are presented. The ability to specifically induce recombination or gene conversion within mammalian cells by using TFOs may provide a new research tool and may eventually lead to novel applications in gene therapy.
机译:基因治疗由于哺乳动物细胞中同源重组的频率低而受到阻碍。为了刺激重组,我们研究了使用三螺旋形成寡核苷酸(TFO)将DNA损伤靶向到细胞内选定位点的方法。通过用与补骨脂素连接的TFO处理细胞,在携带两个突变拷贝的supF tRNA报告基因的猿猴病毒40载体中诱导重组。还观察到基因转化事件以及靶位点的突变。产品的多样性表明,多种细胞途径可以作用于靶向损伤,并且提供了表明三重螺旋可以影响这些途径的数据。通过使用TFO特异性诱导哺乳动物细胞内重组或基因转化的能力可能会提供一种新的研究工具,并最终可能在基因治疗中带来新的应用。

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