Genome Center and Department of Biochemistry and Molecular Medicine, University of California, Davis, California 95616; email:
Annu Rev Genomics Hum Genet. 2013;14:135-58. doi: 10.1146/annurev-genom-091212-153435. Epub 2013 May 20.
Genome engineering--the ability to precisely alter the DNA information in living cells--is beginning to transform human genetics and genomics. Advances in tools and methods have enabled genetic modifications ranging from the "scarless" correction of a single base pair to the deletion of entire chromosomes. Targetable nucleases are leading the advances in this field, providing the tools to modify any gene in seemingly any organism with high efficiency. Targeted gene alterations have now been reported in more than 30 diverse species, ending the reign of mice as the exclusive model of mammalian genetics, and targetable nucleases have been used to modify more than 150 human genes and loci. A nuclease has also already entered clinical trials, signaling the beginning of genome engineering as therapy. The recent dramatic increase in the number of investigators using these techniques signifies a transition away from methods development toward a new age of exciting applications.
基因组工程——能够精确改变活细胞中的 DNA 信息——开始改变人类遗传学和基因组学。工具和方法的进步使遗传修饰从单个碱基对的“无痕”校正到整个染色体的缺失成为可能。靶向核酸酶引领着该领域的进步，为高效修饰几乎任何生物体中的任何基因提供了工具。目前已经在 30 多种不同的物种中报告了靶向基因改变，结束了老鼠作为哺乳动物遗传学唯一模型的统治地位，并且靶向核酸酶已被用于修饰 150 多个人类基因和基因座。一种核酸酶也已经进入临床试验，标志着基因组工程作为治疗方法的开始。最近使用这些技术的研究人员数量的急剧增加表明，人们已经从方法开发过渡到了激动人心的应用新时代。
