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SWITCHER, a CRISPR-inducible floxed wild-type Cre regulating CRISPR activity.
Björn Schuster1,2, Ivana Dobiášovská3, Jovana Ćurčić3
1Laboratory of Cell Differentiation, Institute of Molecular Genetics of the Czech Academy of Sciences, Vídeňská 1083, 142 20, Prague 4, Czech Republic. bjoern.schuster@img.cas.cz.
Communications Biology
|July 2, 2025
Summary
Researchers developed SWITCHER, a novel genetic system. This CRISPR-Cas12a-controlled Cre-recombinase system acts as an inducible switch for gene editing programs.
Area of Science:
- Molecular Biology
- Synthetic Biology
- Gene Editing Technologies
Background:
- Existing Cre-regulated CRISPR/Cas systems are widely used.
- Developing a CRISPR/Cas-controlled Cre system presents significant challenges.
- Novel genetic tools are needed for precise control of gene editing.
Purpose of the Study:
- To engineer a novel genetic switch, termed SWITCHER.
- To create a CRISPR-inducible and self-limiting Cre-recombinase system.
- To demonstrate the dual functionality of SWITCHER as both a recombinase and a CRISPR switch.
Main Methods:
- Utilized a floxed wild-type Cre-construct for the SWITCHER system.
- Leveraged CRISPR/Cas12a-mediated crRNA-array maturation.
- Demonstrated the system's ability to orchestrate distinct Cas12a/crRNA-encoded programs.
Main Results:
- Successfully developed the SWITCHER genetic system.
- Showcased SWITCHER's capability as a CRISPR-inducible Cre-recombinase.
- Demonstrated the self-limiting and programmable nature of the switch.
- Validated the dual role of SWITCHER in controlling gene editing programs.
Conclusions:
- SWITCHER represents a significant advancement in controllable gene editing.
- The system offers a novel approach for precise and inducible control of Cre-recombinase activity.
- SWITCHER's ability to orchestrate distinct CRISPR-encoded programs opens new avenues in synthetic biology.
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