RNA-guided gene activation by CRISPR-Cas9–based transcription factors.

Pablo Perez-Pinera, D Dewran Kocak,Christopher M Vockley, Andrew F AdlerAmi M Kabadi, Lauren R Polstein, Pratiksha I Thakore, Katherine A Glass, David G Ousterout, Kam W Leong, Farshid Guilak, Gregory E Crawford, Timothy E Reddy, Charles A Gersbach

Technologies for engineering synthetic transcription factors have enabled many advances in medical and scientific research. In contrast to existing methods based on engineering of DNA-binding proteins, we created a Cas9-based transactivator that is targeted to DNA sequences by guide RNA molecules. Coexpression of this transactivator and combinations of guide RNAs in human cells induced specific expression of endogenous target genes, demonstrating a simple and versatile approach for RNA-guided gene activation.