Continuous directed evolution of DNA-binding proteins to improve TALEN specificity.
Nat Methods
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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. |
Year of Publication | 2015
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Journal | Nat Methods
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Volume | 12
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Issue | 10
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Pages | 939-42
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Date Published | 2015 Oct
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ISSN | 1548-7105
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DOI | 10.1038/nmeth.3515
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PubMed ID | 26258293
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PubMed Central ID | PMC4589463
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Grant list | DP1 GM105378 / GM / NIGMS NIH HHS / United States
T32 GM007598 / GM / NIGMS NIH HHS / United States
R01 GM065400 / GM / NIGMS NIH HHS / United States
DP1 GM105378 / DP / NCCDPHP CDC HHS / United States
F32 GM105189 / GM / NIGMS NIH HHS / United States
R01 GM095501 / GM / NIGMS NIH HHS / United States
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