Chemical synthesis of stimuli-responsive guide RNA for conditional control of CRISPR-Cas9 gene editing.

ABSTRACT: CRISPR-Cas9 promotes changes in identity or abundance of nucleic acids in live cells and is a programmable modality of broad biotechnological and therapeutic interest. To reduce off-target effects, tools for conditional control of CRISPR-Cas9 functions are under active research, such as stimuli-responsive guide RNA (gRNA). However, the types of physiologically relevant stimuli that can trigger gRNA are largely limited due to the lack of a versatile synthetic approach in chemistry to introduce diverse labile modifications into gRNA. In this work, we developed such a general method to prepare stimuli-responsive gRNA based on site-specific derivatization of 2'-O-methylribonucleotide phosphorothioate (PS-2'-OMe). We demonstrated CRISPR-Cas9-mediated gene editing in human cells triggered

SUBMITTER: Gu C 

PROVIDER: S-EPMC8317661 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature