CRISPR RNA-guided activation of endogenous human genes

Nat Methods. 2013 Oct;10(10):977-9. doi: 10.1038/nmeth.2598. Epub 2013 Jul 25.


Short guide RNAs (gRNAs) can direct catalytically inactive CRISPR-associated 9 nuclease (dCas9) to repress endogenous genes in bacteria and human cells. Here we show that single or multiple gRNAs can direct dCas9 fused to a VP64 transcriptional activation domain to increase expression of endogenous human genes. This proof-of-principle work shows that clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems can target heterologous effector domains to endogenous sites in human cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / genetics
  • Clustered Regularly Interspaced Short Palindromic Repeats*
  • HEK293 Cells
  • Humans
  • RNA Editing*
  • RNA, Guide / genetics*
  • Recombinant Fusion Proteins / genetics*
  • Ribonucleases / genetics
  • Streptococcus pyogenes / genetics
  • Transcriptional Activation*
  • Vascular Endothelial Growth Factor A / genetics*


  • Bacterial Proteins
  • RNA, Guide
  • Recombinant Fusion Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Ribonucleases