Journal
NATURE METHODS
Volume 12, Issue 10, Pages 939-942Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH.3515
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Funding
- Defense Advanced Research Projects Agency (DARPA) [HR0011-11-2-0003, DARPA N66001-12-C-4207]
- US National Institutes of Health (NIH)/NIGMS [R01 GM095501, R01 GM065400]
- Howard Hughes Medical Institute
- NIH Director's Pioneer Award [DP1 GM105378]
- NIH [F32 GM105189]
- Harvard Chemical Biology Program
- US National Science Foundation Graduate Research Fellowship
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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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