提高外源基因表达水平的方法综述.pdfVIP

Review TRENDS in Biotechnology Vol.24 No.3 March 2006 Employing epigenetics to augment the expression of therapeutic proteins in mammalian cells Ted H.J. Kwaks1 and Arie P. Otte1,2,3 1ChromaGenics, Kruislaan 406, 1098 SM, Amsterdam, The Netherlands 2Crucell, Archimedesweg 4, 2333 CN, Leiden, The Netherlands 3Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 406, 1098 SM, Amsterdam, The Netherlands Recombinant proteins form an increasingly large part of bacteria and yeast. Improving yield and stability of the portfolio of biopharmaceutical companies. Pro- protein expression are, therefore, of considerable value duction of these often complex transgenic proteins is to the industry. Such improvements have, during the achieved predominantly in mammalian cell lines but the years, mainly originated from optimizing downstream process is hampered by low yields and unstable production processes and media development [2]; how- expression. Some of these problems are caused by ever, recent insights into epigenetic gene regulation have gene silencing at the level of chromatin – so-called resulted in the development of tools to achieve higher and epigenetic gene silencing. Here, we describe more reliable therapeutic protein production, and these approaches, which have emerged during the past few form the focus of this review. years, designed to interfere with epigenetic gene silencing with the aim of enhancing and stabilizing Epigenetic gene regulation transgene expression. These include targeting histones, When a transgene is transfected into a cell and integrated the inclusion of specific DNA elements and targeting