Hubbard, Basil P.Badran, AhmedZuris, John A.Guilinger, John P.Davis, KevinChen, LiweiTsai, Shengdar Q.Sander, Jeffry D.Joung, J. KeithLiu, David2016-05-022015Hubbard, Basil P., Ahmed H. Badran, John A. Zuris, John P. Guilinger, Kevin M. Davis, Liwei Chen, Shengdar Q. Tsai, Jeffry D. Sander, J. Keith Joung, and David R. Liu. 2015. “Continuous directed evolution of DNA-binding proteins to improve TALEN specificity.” Nature methods 12 (10): 939-942. doi:10.1038/nmeth.3515. http://dx.doi.org/10.1038/nmeth.3515.1548-7091http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860137Nucleases 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 TALE nucleases with broadly improved DNA cleavage specificity, establishing DB-PACE as a versatile approach for improving the accuracy of genome-editing agents.en-USJournal Article2016-05-0210.1038/nmeth.3515