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A chemically controlled Cas9 switch enables temporal modulation of diverse effectors

Nat Chem Biol. 2023-03; 
Cindy T Wei, Nicholas A Popp, Omri Peleg, Rachel L Powell, Elhanan Borenstein, Dustin J Maly, Douglas M Fowler
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Codon Optimization … The Bcl-xL and BH3 components were codon optimized using the Genscript codon optimization tool. nciCas9(F22) constructs were made by introducing a point mutation into the L22 … Get A Quote

摘要

CRISPR-Cas9 has yielded a plethora of effectors, including targeted transcriptional activators, base editors and prime editors. Current approaches for inducibly modulating Cas9 activity lack temporal precision and require extensive screening and optimization. We describe a versatile, chemically controlled and rapidly activated single-component DNA-binding Cas9 switch, ciCas9, which we use to confer temporal control over seven Cas9 effectors, including two cytidine base editors, two adenine base editors, a dual base editor, a prime editor and a transcriptional activator. Using these temporally controlled effectors, we analyze base editing kinetics, showing that editing occurs within hours and that rapid early ed... More

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