ArticleCommunications biology2025
A chemically inducible, leakless Cre recombinase by split-protein-based efficient and enhanced degradation (SPEED).
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- A chemically inducible, leakless Cre recombinase by split-protein-based efficient and enhanced degradation (SPEED).Communications biology · 2025Article
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5 authors.
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Abstract
Chemically inducible DNA recombination systems are a very attractive tool for implementing potent genetic applications. However, conventional systems still suffer from leaky properties in the absence of chemicals. Here we describe a chemically inducible, leakless destabilized Cre recombinase (SPEED-Cre) based on a new approach, split-protein-based efficient and enhanced degradation (SPEED), that consists of a self-assembling split-Cre tagged with a destabilizing domain (DD) mutant from the Escherichia coli dihydrofolate reductase that is stabilized by the antibiotic ligand trimethoprim (TMP). We demonstrate that SPEED-Cre has no significant leak activity of background DNA recombination in the absence of TMP; nevertheless, it enables full induction of TMP-dependent Cre-loxP recombination in human cells and living mice. We also demonstrate the general applicability of the SPEED approach, which can be widely applied to other proteins, by showing high TMP-dependent recombination performances of destabilized Flp, VCre and Dre recombinases based on the SPEED approach. This robust platform technology will greatly enhance chemogenetic applications for genome engineering in living systems.
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