Buchini Sabrina, Leumann Christian J
Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland.
Curr Opin Chem Biol. 2003 Dec;7(6):717-26. doi: 10.1016/j.cbpa.2003.10.007.
DNA triple-helix-based approaches to control and modulate cellular functions on the level of genomic DNA (antigene technology) suffered in the past from a stepmother-like treatment in comparison to the flourishing field of oligonucleotide-based control of translation (antisense technology). This was mostly due to lack of affinity of triplex-forming oligonucleotides to their DNA target, to sequence restriction constraints imposed by the triple helical recognition motifs and by open questions to the accessibility of the target DNA. Recent developments in the area have brought about new bases that specifically recognize pyrimidine-purine inversion sites as well as sugar modifications, for example, the 2'-aminoethoxy-oligonucleotides or oligonucleotides based on the locked nucleic acid sugar unit, which greatly enhance triplex stability and alleviate in part the sequence restriction constraints. With this, sequence-specific genomic DNA manipulation is starting to become a useful tool in biotechnology.
与蓬勃发展的基于寡核苷酸的翻译控制领域(反义技术)相比,过去基于DNA三螺旋的方法在基因组DNA水平上控制和调节细胞功能(反基因技术)受到了冷落。这主要是由于三链形成寡核苷酸与其DNA靶标的亲和力不足、三螺旋识别基序施加的序列限制约束以及靶标DNA可及性的悬而未决问题。该领域的最新进展带来了能特异性识别嘧啶-嘌呤反向位点的新碱基以及糖修饰,例如2'-氨基乙氧基寡核苷酸或基于锁核酸糖单元的寡核苷酸,这大大增强了三链体稳定性并部分缓解了序列限制约束。由此,序列特异性基因组DNA操作开始成为生物技术中的一种有用工具。