Sanghvi Yogesh S, Schulte Michael
Rasayan Inc, Encinitas, CA 92024-6615, USA.
Curr Opin Drug Discov Devel. 2004 Nov;7(6):765-76.
Currently, there are over 40 oligonucleotide-based pharmaceutical products in various stages of clinical development for the treatment of an assortment of life-threatening diseases. As a result, the production of synthetic oligonucleotides has become increasingly important, with applications in antisense-, aptamer-, ribozyme-, immunostimulatory CpG molecule- and RNAi-related therapeutics. Due to the enormous commercial interest in these technologies, the manufacturing and purification processes for oligonucleotide production have been furtive and practiced in a confidential environment. As a result, limited information on large-scale processing is available in the scientific literature. The purpose of this article is to review the current state-of-the-art in oligonucleotide purification technologies, which have resulted in drug products meeting stringent therapeutic specifications. An indication of new and emerging purification technologies, including simulated moving bed- and membrane-based separation, is given.
目前，有40多种基于寡核苷酸的药物产品正处于临床开发的不同阶段，用于治疗各种危及生命的疾病。因此，合成寡核苷酸的生产变得越来越重要，其应用于反义、适体、核酶、免疫刺激CpG分子和RNAi相关疗法。由于这些技术具有巨大的商业利益，寡核苷酸生产的制造和纯化过程一直很隐秘，是在保密环境中进行的。因此，科学文献中关于大规模加工的信息有限。本文的目的是回顾寡核苷酸纯化技术的当前发展水平，这些技术已使药品符合严格的治疗规范。文中还介绍了包括模拟移动床和膜分离在内的新兴纯化技术。
