Continuous directed evolution of DNA-binding proteins to improve TALEN specificity
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Updated: Apr 5, 2026

Genome Editing in Astyanax mexicanus Using Transcription Activator-like Effector Nucleases TALENs
Published on: June 20, 2016
Basil P Hubbard1, Ahmed H Badran1, John A Zuris1
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.
Abstract:
Nucleases containing programmable DNA-binding domains can alter the genomes of model organisms and have the potential to become human therapeutics. Here we present DNA-binding phage-assisted continuous evolution (DB-PACE) as a general approach for the laboratory evolution of DNA-binding activity and specificity. We used this system to generate transcription activator-like effectors nucleases (TALENs) with broadly improved DNA cleavage specificity, establishing DB-PACE as a versatile approach for improving the accuracy of genome-editing agents.
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