Tripp Valerie T, Young Douglas D
Department of Chemistry, College of William & Mary, Williamsburg, VA, USA.
Methods Mol Biol. 2014;1103:153-63. doi: 10.1007/978-1-62703-730-3_12.
While RNA has traditionally been viewed as a mechanism to transfer genetic information, its importance and functionality has only truly been demonstrated in the past 20 years. One prime example of this significance can be found within microRNAs (miRNAs), which are involved in the regulation of a substantial number of human genes. Consequently, these miRNAs represent a novel target for therapeutic agents towards the treatment of a variety of diseases and disorders. Specifically, misregulation of miR-122 has been demonstrated to be relevant in the cellular propagation of Hepatitis C (HCV), and thus modulators of miR-122 can have a substantial effect on viral loads. This protocol describes the development of an assay for the discovery of small molecule regulators of miR-122, and ultimately HCV therapeutics. Due to the excellent pharmacokinetic properties of small molecule libraries, these regulators represent a substantial advantage over traditional antisense agents.
虽然传统上RNA被视为传递遗传信息的一种机制，但其重要性和功能只是在过去20年才得到真正证明。这种重要性的一个主要例子可以在微小RNA（miRNA）中找到，它们参与了大量人类基因的调控。因此，这些miRNA代表了治疗多种疾病和病症的治疗剂的新靶点。具体而言，已证明miR-122的失调与丙型肝炎病毒（HCV）的细胞增殖有关，因此miR-122的调节剂可对病毒载量产生重大影响。本方案描述了一种用于发现miR-122小分子调节剂以及最终用于HCV治疗的测定方法的开发。由于小分子文库具有优异的药代动力学特性，这些调节剂相对于传统的反义药物具有显著优势。
