Abstract：
Following the first proof of concept of using small nucleic acids to modulate gene expression, a long period of maturation led, at the end of the last century, to the first marketing authorization of an oligonucleotide-based therapy. Since then, 12 more compounds have hit the market and many more are in late clinical development. Many companies were founded to exploit their therapeutic potential and Big Pharma was quickly convinced that oligonucleotides could represent credible alternatives to protein-targeting products. Many technologies have been developed to improve oligonucleotide pharmacokinetics and pharmacodynamics. Initially targeting rare diseases and niche markets, oligonucleotides are now able to benefit large patient populations. However, there is still room for oligonucleotide improvement and further breakthroughs are likely to emerge in the coming years. In this review we provide an overview of therapeutic oligonucleotides. We present in particular the different types of oligonucleotides and their modes of action, the tissues they target and the routes by which they are administered to patients, and the therapeutic areas in which they are used. In addition, we present the different ways of patenting oligonucleotides. We finally discuss future challenges and opportunities for this drug-discovery platform.
摘要：
在首次证明使用小核酸调节基因表达的概念之后，长时间的成熟导致，在上个世纪末,基于寡核苷酸的疗法的第一个上市授权。从那以后,12更多的化合物进入市场，更多的是在临床开发后期。许多公司的成立是为了利用他们的治疗潜力，大型制药公司很快就确信寡核苷酸可以代表蛋白质靶向产品的可靠替代品。已经开发了许多技术来改善寡核苷酸药代动力学和药效学。最初针对罕见疾病和利基市场，寡核苷酸现在能够使大量患者群体受益。然而,寡核苷酸仍有改进的空间，未来几年可能会有进一步的突破。在这篇综述中，我们提供了治疗性寡核苷酸的概述。我们特别介绍了不同类型的寡核苷酸及其作用方式，它们的目标组织和给患者施用它们的途径，以及使用它们的治疗领域。此外,我们提出了寡核苷酸的不同方法。我们最后讨论了这个药物发现平台未来的挑战和机遇。
