Pirollo Kathleen F, Rait Antonina, Sleer Leanne S, Chang Esther H
Department of Oncology, Georgetown University Medical Center, Washington, DC 20007, USA.
Pharmacol Ther. 2003 Jul;99(1):55-77. doi: 10.1016/s0163-7258(03)00053-6.
The use of antisense (AS) oligonucleotides as therapeutic agents was proposed as far back as the 1960s/1970s when the AS strategy was initially developed. However, it has taken almost a quarter of a century for this potential to be realized. The last few years has seen a rapid increase in the number of AS molecules progressing past Phase I in clinical trials, due in part to our increased knowledge of their structure and chemistry. Here, we describe the most prominent of these modifications with respect to clinical applicability. However, the main focus of this review is clinical application, with a focus on cancer. We will discuss in detail both the status of the current AS clinical trials and the molecules that are likely to be the targets of the next group of AS molecules entering the clinic.
早在20世纪60年代/70年代，当反义（AS）策略最初被开发出来时，就有人提出将反义寡核苷酸用作治疗剂。然而，这种潜力的实现花了近25年的时间。在过去几年中，进入临床试验I期的AS分子数量迅速增加，部分原因是我们对其结构和化学的了解有所增加。在此，我们描述这些修饰中在临床适用性方面最突出的部分。然而，本综述的主要重点是临床应用，尤其是癌症方面。我们将详细讨论当前AS临床试验的状况以及可能成为下一批进入临床的AS分子靶点的分子。
