Core Antisense Research, Ionis Pharmaceuticals, Inc, Carlsbad, California, USA.
Core Antisense Research, Ionis Pharmaceuticals, Inc, Carlsbad, California, USA.
J Biol Chem. 2021 Jan-Jun;296:100416. doi: 10.1016/j.jbc.2021.100416. Epub 2021 Feb 16.
Antisense technology is beginning to deliver on the broad promise of the technology. Ten RNA-targeted drugs including eight single-strand antisense drugs (ASOs) and two double-strand ASOs (siRNAs) have now been approved for commercial use, and the ASOs in phase 2/3 trials are innovative, delivered by multiple routes of administration and focused on both rare and common diseases. In fact, two ASOs are used in cardiovascular outcome studies and several others in very large trials. Interest in the technology continues to grow, and the field has been subject to a significant number of reviews. In this review, we focus on the molecular events that result in the effects observed and use recent clinical results involving several different ASOs to exemplify specific molecular mechanisms and specific issues. We conclude with the prospective on the technology.
反义技术开始兑现该技术的广泛承诺。十种 RNA 靶向药物已获得商业批准，包括八种单链反义药物（ASO）和两种双链 ASO（siRNA），而处于 2/3 期临床试验阶段的 ASO 具有创新性，其给药途径多样，针对的疾病既有罕见病也有常见病。事实上，两种 ASO 用于心血管结局研究，还有几种用于非常大型的试验。人们对该技术的兴趣持续增长，该领域已受到大量评论。在这篇综述中，我们重点关注导致观察到的效果的分子事件，并使用最近涉及几种不同 ASO 的临床结果来说明特定的分子机制和具体问题。最后，我们对该技术进行了展望。
