Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Biotechnol Adv. 2011 Jan-Feb;29(1):1-10. doi: 10.1016/j.biotechadv.2010.07.005. Epub 2010 Jul 22.
Monogenic diseases are often severe, life-threatening disorders for which lifelong palliative treatment is the only option. Over the last two decades, a number of strategies have been devised with the aim to treat these diseases with a genetic approach. Gene therapy has been under development for many years, yet suffers from the lack of an effective and safe vector for the delivery of genetic material into cells. More recently, gene targeting by homologous recombination has been proposed as a safer treatment, by specifically correcting disease-causing mutations. However, low efficiency is a major drawback. The emergence of two technologies could overcome some of these obstacles. Terminally differentiated somatic cells can be reprogrammed, using defined factors, to become induced pluripotent stem cells (iPSCs), which can undergo efficient gene mutation correction with the aid of fusion proteins known as zinc finger nucleases (ZFNs). The amalgamation of these two technologies has the potential to break through the current bottleneck in gene therapy and gene targeting.
单基因疾病通常是严重的、危及生命的疾病，其唯一的治疗方法是终身姑息治疗。在过去的二十年中，已经设计了许多策略，旨在通过基因方法治疗这些疾病。基因治疗已经开发了多年，但由于缺乏有效的和安全的载体将遗传物质递送到细胞中，因此受到限制。最近，同源重组的基因靶向被提议作为一种更安全的治疗方法，通过特异性地纠正致病突变。然而，效率低是一个主要的缺点。两种技术的出现可能会克服其中的一些障碍。终末分化的体细胞可以使用定义的因子重编程为诱导多能干细胞(iPSCs)，借助称为锌指核酸酶(ZFNs)的融合蛋白，iPSCs 可以有效地进行基因突变纠正。这两种技术的结合有可能突破基因治疗和基因靶向的当前瓶颈。
