Department of Neurological Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH, United States.
Department of Surgery, Duke University Medical Center, Durham, NC, United States.
Curr Med Chem. 2020;27(25):4181-4193. doi: 10.2174/0929867326666191001125101.
The discovery that short oligonucleotides, termed aptamers, can fold into three-dimensional structures that allow them to selectively bind and inhibit the activity of pathogenic proteins is now over 25 years old. The invention of the SELEX methodology heralded in an era in which such nucleic acid-based ligands could be generated against a wide variety of therapeutic targets.
A large number of aptamers have now been identified by combinatorial chemistry methods in the laboratory and moreover, an increasing number have been discovered in nature. The affinities and activities of such aptamers have often been compared to that of antibodies, yet only a few of these agents have made it into clinical studies compared to a large and increasing number of therapeutic antibodies. One therapeutic aptamer targeting VEGF has made it to market, while 3 others have advanced as far as phase III clinical trials.
In this manuscript, we hope the reader appreciates that the success of aptamers becoming a class of drugs is less about nucleic acid biochemistry and more about target validation and overall drug chemistry.
发现短寡核苷酸，称为适体，可以折叠成三维结构，使它们能够选择性地结合并抑制致病蛋白的活性，这一发现已经超过 25 年了。SELEX 方法的发明开创了一个时代，在这个时代，各种治疗靶点都可以产生基于核酸的配体。
现在已经通过组合化学方法在实验室中鉴定了大量的适体，而且，越来越多的适体在自然界中被发现。这些适体的亲和力和活性经常与抗体相媲美，但与大量且不断增加的治疗性抗体相比，只有少数这些药物进入了临床研究。一种针对 VEGF 的治疗性适体已上市，而另外 3 种已进入 III 期临床试验。
在本文中，我们希望读者意识到，适体成为一类药物的成功与其说是核酸生物化学，不如说是靶标验证和整体药物化学。
