Lebedeva I, Stein C A
College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Annu Rev Pharmacol Toxicol. 2001;41:403-19. doi: 10.1146/annurev.pharmtox.41.1.403.
Antisense oligonucleotides have been used for more than a decade to downregulate gene expression. Phosphodiester oligonucleotides are nuclease sensitive, and the more nuclease-resistant phosphorothioate oligonucleotides are now in common use in the laboratory and have entered clinical trials. However, these molecules are highly bioactive and may inhibit gene expression by more than one mechanism. Although some dramatic successes have been demonstrated, it can still be difficult to properly interpret experimental data derived from the use of this class of oligonucleotide. This review discusses some of these issues with particular reference to a major area of current interest--inhibition of bcl-2 expression in tumor cells.
反义寡核苷酸用于下调基因表达已有十多年历史。磷酸二酯寡核苷酸对核酸酶敏感，而如今更耐核酸酶的硫代磷酸寡核苷酸在实验室中已普遍使用，并已进入临床试验阶段。然而，这些分子具有很高的生物活性，可能通过多种机制抑制基因表达。尽管已经取得了一些显著成功，但要正确解读使用这类寡核苷酸获得的实验数据仍可能存在困难。本综述将特别参考当前一个主要研究领域——肿瘤细胞中bcl-2表达的抑制，来讨论其中的一些问题。
