Chemical Control of CRISPR Gene Editing via Conditional Diacylation Crosslinking of Guide RNAs

Conditional control of RNA structure and function has emerged as an effective toolkit. Here, a strategy based on a one‐step introduction of diacylation linkers and azide groups on the 2′‐OH of RNA is advance. Selected from eight phosphine reagents, it is found that 2‐(diphenylphosphino)ethylamine has excellent performance in reducing azides via a Staudinger reduction to obtain the original RNA. It is demonstrated that the enzymatic activities of Cas13 and Cas9 can be regulated by chemically modified guide RNAs, and further achieved ligand‐induced gene editing in living cells by a controllable CRISPR/Cas9 system.