Kandimalla Ekambar R, Yu Dong, Agrawal Sudhir
Hybridon Inc., Cambridge, MA 02139, USA.
Curr Opin Mol Ther. 2002 Apr;4(2):122-9.
The goal of using of oligodeoxyribonucleotides containing CpG dinucleotides (CpG DNA) as immunomodulatory agents has been realized in recent years. Therapeutic applications of CpG DNA as monotherapies and as adjuvants in combination with vaccines, antibodies, antigens and allergens for a number of disease indications are rapidly expanding, and the safety and efficacy of several first-generation CpG DNA agents are being evaluated in human clinical trials. The biological effects of CpG DNA have been known for two decades; however, only recently has a specific receptor(s) that recognizes CpG DNA and activates immune cascade been identified. A number of sequence and structural characteristics of CpG DNA and chemical modifications that influence immunostimulatory activity have been identified. In this article we summarize the recent progress in understanding the structural and chemical characteristics of CpG DNA that are significant for molecular recognition. In addition, we describe the design of second-generation CpG DNA agents, and clinical applications of first-generation agents.
近年来，将含CpG二核苷酸的寡脱氧核糖核苷酸（CpG DNA）用作免疫调节剂的目标已得以实现。CpG DNA作为单一疗法以及与疫苗、抗体、抗原和变应原联合用作佐剂在多种疾病适应症中的治疗应用正在迅速扩展，并且几种第一代CpG DNA制剂的安全性和有效性正在人体临床试验中进行评估。CpG DNA的生物学效应已为人所知达二十年之久；然而，直到最近才鉴定出识别CpG DNA并激活免疫级联反应的特异性受体。已确定了CpG DNA的许多序列和结构特征以及影响免疫刺激活性的化学修饰。在本文中，我们总结了在理解对分子识别具有重要意义的CpG DNA的结构和化学特征方面的最新进展。此外，我们描述了第二代CpG DNA制剂的设计以及第一代制剂的临床应用。
