Rogers Faye A, Lloyd Janice A, Glazer Peter M
Department of Therapeutic Radiology and Genetics, Yale University School of Medicine, 15 York St., HRT 313, New Haven, CT 06520, USA.
Curr Med Chem Anticancer Agents. 2005 Jul;5(4):319-26. doi: 10.2174/1568011054222300.
Triplex-forming oligonucleotides (TFOs) bind in the major groove of duplex DNA at polypurine/ polypyrimidine stretches in a sequence-specific manner. The binding specificity of TFOs makes them potential candidates for use in directed genome modification. A number of studies have shown that TFOs can introduce permanent changes in a target sequence by stimulating a cell's inherent repair pathways. TFOs have also been demonstrated to inhibit gene expression providing a possible role for these compounds in cancer therapy. This review summarizes the dual roles of TFOs for use in delivering DNA reactive compounds to a specific site in the genome or for introducing permanent changes in the target sequence through the introduction of an altered helical structure. In addition to compiling the ways in which TFOs have been successfully utilized, this review will explore conflicting reports of TFO bioactivity focusing on the variables which affect the efficacy in vitro of TFO mediated genomic modification which in turn may represent the obstacles encountered using TFOs to modulate gene expression in vivo.
三链形成寡核苷酸（TFOs）以序列特异性方式结合于双链DNA在聚嘌呤/聚嘧啶区段的大沟中。TFOs的结合特异性使其成为用于定向基因组修饰的潜在候选物。许多研究表明，TFOs可通过刺激细胞固有的修复途径在靶序列中引入永久性变化。TFOs也已被证明可抑制基因表达，为这些化合物在癌症治疗中提供了可能的作用。本综述总结了TFOs在将DNA反应性化合物递送至基因组中的特定位点或通过引入改变的螺旋结构在靶序列中引入永久性变化方面的双重作用。除了汇编TFOs已被成功利用的方式外，本综述还将探讨关于TFO生物活性的相互矛盾的报道，重点关注影响TFO介导的基因组修饰体外效力的变量，这些变量反过来可能代表在体内使用TFOs调节基因表达时遇到的障碍。
