Orthogonal Genetic Regulation in Human Cells Using Chemically Induced CRISPR/Cas9 Activators

Zehua Bao, Surbhi Jain, Valerie Jaroenpuntaruk, Huimin Zhao

Research output: Contribution to journalArticlepeer-review


The concerted action of multiple genes in a time-dependent manner controls complex cellular phenotypes, yet the temporal regulation of gene expressions is restricted on a single-gene level, which limits our ability to control higher-order gene networks and understand the consequences of multiplex genetic perturbations. Here we developed a system for temporal regulation of multiple genes. This system combines the simplicity of CRISPR/Cas9 activators for orthogonal targeting of multiple genes and the orthogonality of chemically induced dimerizing (CID) proteins for temporal control of CRISPR/Cas9 activator function. In human cells, these transcription activators exerted simultaneous activation of multiple genes and orthogonal regulation of different genes in a ligand-dependent manner with minimal background. We envision that our system will enable the perturbation of higher-order gene networks with high temporal resolution and accelerate our understanding of gene-gene interactions in a complex biological setting.

Original languageEnglish (US)
Pages (from-to)686-693
Number of pages8
JournalACS synthetic biology
Issue number4
StatePublished - Apr 21 2017


  • CRISPR/Cas9
  • chemically induced dimerization
  • genetic regulation
  • orthogonality
  • synthetic transcription factor

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)


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