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Continuous directed evolution of DNA-binding proteins to improve TALEN specificity.

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.

SUBMITTER: Hubbard BP

PROVIDER: S-EPMC4589463 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Continuous directed evolution of DNA-binding proteins to improve TALEN specificity.

Hubbard Basil P BP Badran Ahmed H AH Zuris John A JA Guilinger John P JP Davis Kevin M KM Chen Liwei L Tsai Shengdar Q SQ Sander Jeffry D JD Joung J Keith JK Liu David R DR

Nature methods 20150810 10

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 ...[more]

PMID: 26258293

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