Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16041-5. doi: 10.1073/pnas.1214267109. Epub 2012 Sep 17.
Gene regulation by DNA binding small molecules could have important therapeutic applications. This study reports the investigation of a DNA-binding pyrrole-imidazole polyamide targeted to bind the DNA sequence 5'-WGGWWW-3' with reference to its potency in a subcutaneous xenograft tumor model. The molecule is capable of trafficking to the tumor site following subcutaneous injection and modulates transcription of select genes in vivo. An FITC-labeled analogue of this polyamide can be detected in tumor-derived cells by confocal microscopy. RNA deep sequencing (RNA-seq) of tumor tissue allowed the identification of further affected genes, a representative panel of which was interrogated by quantitative reverse transcription-PCR and correlated with cell culture expression levels.
DNA 结合小分子的基因调控可能具有重要的治疗应用。本研究报告了一种针对结合 DNA 序列 5'-WGGWWW-3'的 DNA 结合吡咯-咪唑聚酰胺的研究，该序列与在皮下异种移植肿瘤模型中的效力有关。该分子能够在皮下注射后转运到肿瘤部位，并在体内调节特定基因的转录。该聚酰胺的 FITC 标记类似物可以通过共聚焦显微镜在肿瘤衍生细胞中检测到。肿瘤组织的 RNA 深度测序 (RNA-seq) 允许鉴定出更多受影响的基因，其中一个代表性面板通过定量逆转录-PCR 进行了检测，并与细胞培养表达水平相关联。
