Isis Pharmaceuticals, Inc., Carlsbad, California 92008, USA.
Annu Rev Pharmacol Toxicol. 2010;50:259-93. doi: 10.1146/annurev.pharmtox.010909.105654.
Dramatic advances in understanding of the roles RNA plays in normal health and disease have greatly expanded over the past 10 years and have made it clear that scientists are only beginning to comprehend the biology of RNAs. It is likely that RNA will become an increasingly important target for therapeutic intervention; therefore, it is important to develop strategies for therapeutically modulating RNA function. Antisense oligonucleotides are perhaps the most direct therapeutic strategy to approach RNA. Antisense oligonucleotides are designed to bind to the target RNA by well-characterized Watson-Crick base pairing, and once bound to the target RNA, modulate its function through a variety of postbinding events. This review focuses on the molecular mechanisms by which antisense oligonucleotides can be designed to modulate RNA function in mammalian cells and how synthetic oligonucleotides behave in the body.
在过去的 10 年中，人们对 RNA 在正常健康和疾病中的作用的理解取得了重大进展，这使得人们清楚地认识到，科学家们才刚刚开始理解 RNA 的生物学特性。RNA 很可能成为治疗干预的一个日益重要的靶点；因此，开发治疗性调节 RNA 功能的策略非常重要。反义寡核苷酸可能是最直接的治疗策略来接近 RNA。反义寡核苷酸通过特征明确的 Watson-Crick 碱基配对设计来与靶 RNA 结合，与靶 RNA 结合后，通过多种结合后事件来调节其功能。这篇综述重点介绍了如何设计反义寡核苷酸来调节哺乳动物细胞中 RNA 的功能，以及合成寡核苷酸在体内的行为。
