Gaddis Sara S, Wu Qi, Thames Howard D, DiGiovanni John, Walborg Earl F, MacLeod Michael C, Vasquez Karen M
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX 78957, USA.
Oligonucleotides. 2006 Summer;16(2):196-201. doi: 10.1089/oli.2006.16.196.
Triplex technology offers a useful approach for site-specific modification of gene structure and function both in vitro and in vivo. Triplex-forming oligonucleotides (TFOs) bind to their target sites in duplex DNA, thereby forming triple-helical DNA structures via Hoogsteen hydrogen bonding. TFO binding has been demonstrated to site-specifically inhibit gene expression, enhance homologous recombination, induce mutation, inhibit protein binding, and direct DNA damage, thus providing a tool for gene-specific manipulation of DNA. We have developed a flexible web-based search engine to find and annotate TFO target sequences within the human and mouse genomes. Descriptive information about each site, including sequence context and gene region (intron, exon, or promoter), is provided. The engine assists the user in finding highly specific TFO target sequences by eliminating or flagging known repeat sequences and flagging overlapping genes. A convenient way to check for the uniqueness of a potential TFO binding site is provided via NCBI BLAST. The search engine may be accessed at spi.mdanderson.org/tfo.
三链体技术为在体外和体内对基因结构和功能进行位点特异性修饰提供了一种有用的方法。三链体形成寡核苷酸（TFO）与双链DNA中的靶位点结合，从而通过Hoogsteen氢键形成三螺旋DNA结构。已证明TFO结合可位点特异性抑制基因表达、增强同源重组、诱导突变、抑制蛋白质结合并直接造成DNA损伤，从而为DNA的基因特异性操作提供了一种工具。我们开发了一个灵活的基于网络的搜索引擎，用于在人类和小鼠基因组中查找和注释TFO靶序列。提供了有关每个位点的描述性信息，包括序列上下文和基因区域（内含子、外显子或启动子）。该引擎通过消除或标记已知的重复序列以及标记重叠基因，帮助用户找到高度特异性的TFO靶序列。通过NCBI BLAST提供了一种检查潜在TFO结合位点唯一性的便捷方法。可通过spi.mdanderson.org/tfo访问该搜索引擎。
