Over a thousand diseases are caused by mutations that alter gene expression levels. The potential of nuclease-deficient zinc fingers, TALEs or CRISPR fusion systems to treat these diseases by modulating gene expression has recently emerged. These systems can be applied to modify the activity of gene-regulatory elements — promoters, enhancers, silencers and insulators, subsequently changing their target gene expression levels to achieve therapeutic benefits — an approach termed cis-regulation therapy (CRT). Here, we review emerging CRT technologies and assess their therapeutic potential for treating a wide range of diseases caused by abnormal gene dosage. The challenges facing the translation of CRT into the clinic are discussed.

超过一千种疾病是由改变基因表达水平的突变引起的。最近出现了通过调节基因表达来治疗这些疾病的核酸酶缺陷型锌指、TALE 或 CRISPR 融合系统的潜力。这些系统可用于改变基因调控元件（启动子、增强子、沉默子和绝缘子）的活性，随后改变它们的靶基因表达水平以实现治疗效果——一种称为顺式调节疗法 (CRT) 的方法。在这里，我们回顾了新兴的 CRT 技术，并评估了它们在治疗由异常基因剂量引起的各种疾病方面的治疗潜力。讨论了将 CRT 转化为临床所面临的挑战。