Modulating gene regulation to treat genetic disorders

Nat Rev Drug Discov. 2020 Nov;19(11):757-775. doi: 10.1038/s41573-020-0083-7. Epub 2020 Oct 5.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • CRISPR-Cas Systems / drug effects
  • CRISPR-Cas Systems / genetics
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Genetic Diseases, Inborn / drug therapy*
  • Genetic Diseases, Inborn / genetics
  • Humans
  • Mutation / drug effects
  • Mutation / genetics
  • Pharmaceutical Preparations / administration & dosage*


  • Pharmaceutical Preparations