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Optical control of Cas9 activity through visible-light cleavable crRNAs
Vanessa Hanff1, Stepan Jerabek2,3,4, Kim A Langer1
1Institute of Organic Chemistry and Chemical Biology, Goethe-University Frankfurt Max-von-Laue-Str. 9 Frankfurt am Main 60438 Germany heckel@uni-frankfurt.de.
RSC Chemical Biology
|February 18, 2026
Summary
Researchers developed visible-light cleavable guide RNAs (crRNAs) to control Cas9 gene editing activity. This method allows for precise, non-invasive regulation of genome editing, enhancing safety for therapeutic applications.
Area of Science:
- Molecular Biology
- Biotechnology
- Synthetic Biology
Background:
- CRISPR-Cas9 technology offers precise genome editing but lacks controllable activity.
- Current methods for regulating Cas9 activity can be invasive or lack spatiotemporal control.
Purpose of the Study:
- To develop a novel system for light-inducible control of Cas9 activity.
- To enable non-invasive, precise spatiotemporal regulation of genome editing for enhanced safety.
Main Methods:
- Design and synthesis of CRISPR RNA (crRNA) molecules incorporating photocleavable linkers (PL).
- Testing crRNA cleavage and Cas9 inhibition using an in vitro Cas9 assay.
- Demonstration of visible-light mediated control over Cas9 activity.
Main Results:
- Visible-light cleavable crRNAs were successfully synthesized and incorporated photocleavable linkers.
- Cleavage of crRNAs by visible light efficiently inhibited Cas9 nuclease activity.
- An in vitro assay confirmed the light-dependent downregulation of Cas9.
Conclusions:
- Visible-light cleavable crRNAs provide a novel mechanism for regulating Cas9 activity.
- This approach enables precise, non-invasive, and harm-free control over genome editing.
- The developed system holds promise for safer and more targeted CRISPR-Cas9 applications.
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