In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice

Nat Neurosci. 2018 Mar;21(3):440-446. doi: 10.1038/s41593-017-0060-6. Epub 2018 Jan 15.


Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / physiology
  • Brain Chemistry / genetics*
  • CRISPR-Cas Systems / genetics*
  • DNA-Binding Proteins
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Nervous System / metabolism
  • Neurons / physiology
  • Nuclear Proteins / metabolism
  • Primary Cell Culture
  • RNA, Long Noncoding / genetics
  • Transcriptional Activation / genetics*


  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • NeuN protein, mouse
  • Nuclear Proteins
  • RNA, Long Noncoding