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@article{Thyme:2014:nar/gkt1212,
author = {Thyme, SB and Boissel, SJS and Quadri, SA and Nolan, T and Baker, DA and Park, RU and Kusak, L and Ashworth, J and Baker, D},
doi = {nar/gkt1212},
journal = {Nucleic Acids Research},
pages = {2564--2576},
title = {Reprogramming homing endonuclease specificity through computational design and directed evolution},
url = {http://dx.doi.org/10.1093/nar/gkt1212},
volume = {42},
year = {2014}
}

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TY  - JOUR
AB  - Homing endonucleases (HEs) can be used to induce targeted genome modification to reduce the fitness of pathogen vectors such as the malaria-transmitting Anopheles gambiae and to correct deleterious mutations in genetic diseases. We describe the creation of an extensive set of HE variants with novel DNA cleavage specificities using an integrated experimental and computational approach. Using computational modeling and an improved selection strategy, which optimizes specificity in addition to activity, we engineered an endonuclease to cleave in a gene associated with Anopheles sterility and another to cleave near a mutation that causes pyruvate kinase deficiency. In the course of this work we observed unanticipated context-dependence between bases which will need to be mechanistically understood for reprogramming of specificity to succeed more generally.
AU  - Thyme,SB
AU  - Boissel,SJS
AU  - Quadri,SA
AU  - Nolan,T
AU  - Baker,DA
AU  - Park,RU
AU  - Kusak,L
AU  - Ashworth,J
AU  - Baker,D
DO  - nar/gkt1212
EP  - 2576
PY  - 2014///
SN  - 0305-1048
SP  - 2564
TI  - Reprogramming homing endonuclease specificity through computational design and directed evolution
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkt1212
UR  - http://hdl.handle.net/10044/1/69994
VL  - 42
ER  -

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