Dhuri Karishma, Bechtold Clara, Quijano Elias, Pham Ha, Gupta Anisha, Vikram Ajit, Bahal Raman
Department of Pharmaceutical Science, University of Connecticut, Storrs, CT 06269, USA.
Department of Genetics, Yale University, New Haven, CT 06520, USA.
J Clin Med. 2020 Jun 26;9(6):2004. doi: 10.3390/jcm9062004.
Antisense oligonucleotides (ASOs) bind sequence specifically to the target RNA and modulate protein expression through several different mechanisms. The ASO field is an emerging area of drug development that targets the disease source at the RNA level and offers a promising alternative to therapies targeting downstream processes. To translate ASO-based therapies into a clinical success, it is crucial to overcome the challenges associated with off-target side effects and insufficient biological activity. In this regard, several chemical modifications and diverse delivery strategies have been explored. In this review, we systematically discuss the chemical modifications, mechanism of action, and optimized delivery strategies of several different classes of ASOs. Further, we highlight the recent advances made in development of ASO-based drugs with a focus on drugs that are approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for clinical applications. We also discuss various promising ASO-based drug candidates in the clinical trials, and the outstanding opportunity of emerging microRNA as a viable therapeutic target for future ASO-based therapies.
反义寡核苷酸（ASO）可特异性地与靶RNA序列结合，并通过几种不同机制调节蛋白质表达。ASO领域是一个新兴的药物研发领域，它在RNA水平上靶向疾病源头，为针对下游过程的疗法提供了一种有前景的替代方案。为了使基于ASO的疗法取得临床成功，克服与脱靶副作用和生物活性不足相关的挑战至关重要。在这方面，人们已经探索了几种化学修饰和多样的递送策略。在本综述中，我们系统地讨论了几类不同ASO的化学修饰、作用机制和优化的递送策略。此外，我们重点介绍了基于ASO的药物开发的最新进展，重点关注已获美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准用于临床的药物。我们还讨论了临床试验中各种有前景的基于ASO的候选药物，以及新兴的微小RNA作为未来基于ASO疗法的可行治疗靶点所带来的绝佳机遇。
