Light-activated crRNAs enable controlled CRISPR editing

Chinese researchers have developed star-shaped, multivalent CRISPR RNAs (crRNAs) with single-site chemical modifications that include light-sensitive linkages. These modifications enable the crRNAs to remain inactive until irradiated with specific wavelengths of light, triggering rapid activation of gene editing without unintended background activity.

The system supports orthogonal control, meaning multiple gene targets can be regulated independently by using crRNAs responsive to different light wavelengths. In vitro assays showed minimal leakage in the inactive state and quick switching upon activation. Notably, the method demonstrated effective gene editing in mammalian cells in vivo, following brief photoactivation.

Because the crRNA design is independent of the target sequence, it avoids the need for extensive optimisation and is broadly compatible across CRISPR-Cas9 and Cas12a platforms. The authors suggest that future refinements using reversible and longer-wavelength responsive chemistries may improve tissue penetration and expand therapeutic potential.

The study was led by Liang Cheng at the Institute of Chemistry, Chinese Academy of Sciences in Beijing. It was published this Monday in Angewandte Chemie.