Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template

Weifeng Zhang; Hao Chen; Xiaojing Zheng; Dongyang Wang; Haiyan Ji; Haibin Xia; Qinwen Mao

doi:10.1016/j.jbiotec.2014.08.003

Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template

Weifeng Zhang, Hao Chen, Xiaojing Zheng, Dongyang Wang, Haiyan Ji, Haibin Xia^*, Qinwen Mao

^*Corresponding author for this work

Pathology

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Zinc finger nuclease (ZFN) technology, which can be used to induce targeted genome correction in the presence of a DNA donor template, is becoming an attractive strategy for treating monogenic diseases. This strategy requires efficient delivery of ZFN and donor template into cells, ideally, in a single viral vector to achieve efficient genome editing and to avoid unwanted mutagenesis. In this study, we successfully produced a single adenoviral (Ad) vector with high titer that carried a ZFN expression cassette and a donor template simultaneously. We then demonstrated that this single Ad system could mediate efficient site-specific genome correction in vitro and ex vivo. The gene correction efficiency of the single Ad was significantly higher than that of the double Ad system. This novel vector will be a promising ZFN and donor delivery system for treatment of monogenic diseases.

Original language	English (US)
Pages (from-to)	1-6
Number of pages	6
Journal	Journal of Biotechnology
Volume	188
DOIs	https://doi.org/10.1016/j.jbiotec.2014.08.003
State	Published - Oct 20 2014

Funding

This work was supported by the “ Foundation for Excellent Doctor Degree Dissertation ” ( X2010YB03 ) of Shaanxi Normal University and by the Fundamental Research Funds for the Central Universities ( GK201301010 and GK201104004 ) and research grants to H.X. and X.Z. from the National Natural Science Foundation of China (Nos. 81272543 and 81301957 ).

Keywords

Adenoviral vector
Genome editing
Homologous recombination
Site-specific integration
Zinc finger nuclease

ASJC Scopus subject areas

Applied Microbiology and Biotechnology
Bioengineering
Biotechnology

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10.1016/j.jbiotec.2014.08.003

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title = "Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template",

abstract = "Zinc finger nuclease (ZFN) technology, which can be used to induce targeted genome correction in the presence of a DNA donor template, is becoming an attractive strategy for treating monogenic diseases. This strategy requires efficient delivery of ZFN and donor template into cells, ideally, in a single viral vector to achieve efficient genome editing and to avoid unwanted mutagenesis. In this study, we successfully produced a single adenoviral (Ad) vector with high titer that carried a ZFN expression cassette and a donor template simultaneously. We then demonstrated that this single Ad system could mediate efficient site-specific genome correction in vitro and ex vivo. The gene correction efficiency of the single Ad was significantly higher than that of the double Ad system. This novel vector will be a promising ZFN and donor delivery system for treatment of monogenic diseases.",

keywords = "Adenoviral vector, Genome editing, Homologous recombination, Site-specific integration, Zinc finger nuclease",

author = "Weifeng Zhang and Hao Chen and Xiaojing Zheng and Dongyang Wang and Haiyan Ji and Haibin Xia and Qinwen Mao",

note = "Funding Information: This work was supported by the “ Foundation for Excellent Doctor Degree Dissertation ” ( X2010YB03 ) of Shaanxi Normal University and by the Fundamental Research Funds for the Central Universities ( GK201301010 and GK201104004 ) and research grants to H.X. and X.Z. from the National Natural Science Foundation of China (Nos. 81272543 and 81301957 ). Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.jbiotec.2014.08.003",

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AU - Zhang, Weifeng

AU - Chen, Hao

AU - Zheng, Xiaojing

AU - Wang, Dongyang

AU - Ji, Haiyan

AU - Xia, Haibin

AU - Mao, Qinwen

N1 - Funding Information: This work was supported by the “ Foundation for Excellent Doctor Degree Dissertation ” ( X2010YB03 ) of Shaanxi Normal University and by the Fundamental Research Funds for the Central Universities ( GK201301010 and GK201104004 ) and research grants to H.X. and X.Z. from the National Natural Science Foundation of China (Nos. 81272543 and 81301957 ). Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 2014/10/20

Y1 - 2014/10/20

N2 - Zinc finger nuclease (ZFN) technology, which can be used to induce targeted genome correction in the presence of a DNA donor template, is becoming an attractive strategy for treating monogenic diseases. This strategy requires efficient delivery of ZFN and donor template into cells, ideally, in a single viral vector to achieve efficient genome editing and to avoid unwanted mutagenesis. In this study, we successfully produced a single adenoviral (Ad) vector with high titer that carried a ZFN expression cassette and a donor template simultaneously. We then demonstrated that this single Ad system could mediate efficient site-specific genome correction in vitro and ex vivo. The gene correction efficiency of the single Ad was significantly higher than that of the double Ad system. This novel vector will be a promising ZFN and donor delivery system for treatment of monogenic diseases.

AB - Zinc finger nuclease (ZFN) technology, which can be used to induce targeted genome correction in the presence of a DNA donor template, is becoming an attractive strategy for treating monogenic diseases. This strategy requires efficient delivery of ZFN and donor template into cells, ideally, in a single viral vector to achieve efficient genome editing and to avoid unwanted mutagenesis. In this study, we successfully produced a single adenoviral (Ad) vector with high titer that carried a ZFN expression cassette and a donor template simultaneously. We then demonstrated that this single Ad system could mediate efficient site-specific genome correction in vitro and ex vivo. The gene correction efficiency of the single Ad was significantly higher than that of the double Ad system. This novel vector will be a promising ZFN and donor delivery system for treatment of monogenic diseases.

KW - Adenoviral vector

KW - Genome editing

KW - Homologous recombination

KW - Site-specific integration

KW - Zinc finger nuclease

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Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template

Abstract

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Keywords

ASJC Scopus subject areas

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