Blinded by the light: Activating gene editing in fish with light
Third-year MBSB student Wes Brown and Wenyuan Zhou, a fellow graduate student in the Alex Deiters lab have recently published their work on photocaged gRNA and its application for optical control of CRISPR-Cas9 gene editing in mammalian cells and zebrafish embryos: W. Zhou, W. Brown, A. Bardhan, M. Delaney, A. S. Ilk, R. R. Rauen, S. I. Kahn, M. Tsang, A. Deiters, Angew. Chem. Int. Ed. 2020, 59, 8998.
The Deiters group installed photolabile “cages” in the protospacer region of the gRNA that block target DNA binding until “decaged” with 405 nm light. Controlling CRISPR-Cas9 function by installing caging groups in the gRNA has become a hot field, with several independent groups publishing on the topic recently. Optical control allows for spatial and temporal restriction of gene editing that can be used to reduce off-target editing and to study gene networks in a developing animal. They are also working on applying this technology to other CRISPR-based tools to develop optical control of base editing and RNA editing.