Jubair Luqman, McMillan Nigel A J
School of Medical Sciences, Griffith University, Gold Coast, QLD 4222, Australia.
School of Medical Sciences, Griffith University, Gold Coast, QLD 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD 4222, Australia; Diamantina Institute, University of Queensland, Brisbane St. Lucia, QLD 4072, Australia.
Mol Ther Nucleic Acids. 2017 Sep 15;8:56-63. doi: 10.1016/j.omtn.2017.06.006. Epub 2017 Jun 12.
The field of gene editing is undergoing unprecedented growth. The first ex vivo human clinical trial in China started in 2016, more than 1000 US patents have been filed, and there is exponential growth in publications. The ability to edit genes with high fidelity is promising for the development of new treatments for a range of diseases, particularly inherited conditions, infectious diseases, and cancers. For cancer, a major issue is the identification of driver mutations and oncogenes to target for therapeutic effect, and this requires the development of robust models with which to prove their efficacy. The challenge is that there is rarely a single critical gene. However, virally driven cancers, in which cells are addicted to the expression of a single viral oncogene in some cases, may serve as model systems for CRISPR/Cas therapies, as they did for RNAi. These models and systems offer an excellent opportunity to test both preclinical models and clinical conditions to examine the effectiveness of gene editing, and here we review the options and offer a way forward.
基因编辑领域正在经历前所未有的发展。中国首个体外人体临床试验于2016年启动,已提交1000多项美国专利,相关出版物呈指数级增长。高保真编辑基因的能力有望推动一系列疾病新疗法的开发,尤其是遗传性疾病、传染病和癌症。对于癌症而言,一个主要问题是识别驱动突变和致癌基因以实现治疗效果,这需要开发强大的模型来证明其疗效。挑战在于很少存在单一关键基因。然而,在某些情况下细胞对单一病毒致癌基因的表达成瘾的病毒驱动型癌症,可能会像对RNA干扰那样,作为CRISPR/Cas疗法的模型系统。这些模型和系统为测试临床前模型和临床状况以检验基因编辑的有效性提供了绝佳机会,在此我们回顾各种选择并提出前进方向。