The function of the CRISPR system can be conditionally controlled through rationally guided RNA engineering such that the target sequences can be precisely selected and manipulated. In particular, gRNA, as an important component of the CRISPR system, provides a unique tool for multifunctional control of the system based on the structure of the RNA itself. Therefore, we introduced here a protective group on the 2'-OH position of RNA to inhibit RNA-guided nucleic acid cleavage. Next, the modified gRNA can restore its original function under the chemical stimulation of hydrogen peroxide to realize the control of the CRISPR system. The experiment result demonstrated that the operating mechanism of this strategy may be based on chemical modifications that reduce the number of complementary base pairs between RNAs and targets, and the RNA-protein interaction. This further enriches the toolbox of conditional control of CRISPR function and has broad potential for gene editing in living cells and disease treatment using endogenous hydrogen peroxide.
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