Guntaka Ramareddy V, Varma Balwantkumar R, Weber Karl T
Department of Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Ave., Memphis, TN 38163, USA.
Int J Biochem Cell Biol. 2003 Jan;35(1):22-31. doi: 10.1016/s1357-2725(02)00165-6.
Triplex-forming oligonucleotides (TFOs) have gained prominence in the recent years because of their potential applications in antigene therapy. In particular they have been used as (i) inducers of site-specific mutations, (ii) reagents that selectively and specifically cleave target DNA, and (iii) as modulators of gene expression. In this mini-review, we have made an attempt to highlight the characteristics of these TFOs and the effects of various modifications in the phosphate backbone as well as in the purine and pyrimidine moieties, which contribute to the stability and efficiency of triplex formation. Studies to explore the mechanism of down-regulation of transcription of various genes suggest that at least some TFOs exert their effect by inhibiting binding of specific transcription factors to their cognate cis-acting elements. Recent reports indicate the presence of these potential triplex-forming DNA structures in the genomes of prokaryotes and eukaryotes that may play a major role in target site selection and chromosome segregation as well as in the cause of heritable diseases. Finally, some potential problems in the development of these TFOs as antigene therapeutic agents have also been discussed.
近年来，三链形成寡核苷酸（TFOs）因其在反基因治疗中的潜在应用而备受关注。特别是，它们已被用作（i）位点特异性突变的诱导剂，（ii）选择性和特异性切割靶DNA的试剂，以及（iii）基因表达的调节剂。在这篇小型综述中，我们试图强调这些TFOs的特性，以及磷酸骨架以及嘌呤和嘧啶部分各种修饰的影响，这些修饰有助于三链形成的稳定性和效率。探索各种基因转录下调机制的研究表明，至少一些TFOs通过抑制特定转录因子与其同源顺式作用元件的结合来发挥作用。最近的报告表明，这些潜在的三链形成DNA结构存在于原核生物和真核生物的基因组中，可能在靶位点选择、染色体分离以及遗传性疾病的病因中起主要作用。最后，还讨论了将这些TFOs开发为反基因治疗剂时的一些潜在问题。
