Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences and Medicine, Department of Molecular Genetics, Guy's Hospital, London Bridge, London SE1 9RT, United Kingdom.
MilliporeSigma, Process Solutions, 80 Ashby Road, Bedford, MA 01730, USA.
Biotechnol Adv. 2017 Sep;35(5):557-564. doi: 10.1016/j.biotechadv.2017.05.004. Epub 2017 May 17.
Ubiquitous Chromatin-opening Elements (UCOEs) are defined by their ability to consistently confer stable, site of integration-independent transgene expression that is proportional to copy number, including from within regions of heterochromatin such as centromeres. UCOEs structurally consist of methylation-free CpG islands encompassing single or dual divergently-transcribed housekeeping gene promoters. Since their discovery in 1999, UCOEs and their sub-fragments have found applications in areas of biotechnology requiring stable, reproducible, and high levels of gene expression. This review recounts the discovery of UCOEs and examines their current and future applications in protein therapeutic biomanufacturing and gene therapy.
普遍存在的染色质开放元件 (UCOE) 的定义是其能够一致地赋予稳定的、整合位点独立的转基因表达,其表达与拷贝数成正比,包括来自着丝粒等异染色质区域。UCOE 结构上由包含单个或双个反向转录管家基因启动子的无甲基化 CpG 岛组成。自 1999 年发现以来,UCOE 及其亚片段已在需要稳定、可重复和高水平基因表达的生物技术领域得到应用。本综述回顾了 UCOE 的发现,并探讨了它们在蛋白质治疗性生物制造和基因治疗中的当前和未来应用。