A mutation-independent CRISPR-Cas9–mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency

Lili Wang; Yang Yang; Camilo Breton; Peter Bell; Mingyao Li; Jia Zhang; Yan Che; Alexei Saveliev; Zhenning He; John White; Caitlin Latshaw; Chenyu Xu; Deirdre McMenamin; Hongwei Yu; Hiroki Morizono; Mark L. Batshaw; James M. Wilson

doi:10.1126/sciadv.aax5701

Research ArticleHEALTH AND MEDICINE

A mutation-independent CRISPR-Cas9–mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency

View ORCID ProfileLili Wang¹,*,
View ORCID ProfileYang Yang¹,²,*,
View ORCID ProfileCamilo Breton¹,
Peter Bell¹,
Mingyao Li³,
Jia Zhang¹,†,
Yan Che¹,
Alexei Saveliev¹,
View ORCID ProfileZhenning He¹,
John White¹,
View ORCID ProfileCaitlin Latshaw¹,
Chenyu Xu⁴,
Deirdre McMenamin¹,
Hongwei Yu¹,
View ORCID ProfileHiroki Morizono⁴,
View ORCID ProfileMark L. Batshaw ⁴ and
View ORCID ProfileJames M. Wilson ¹,‡

¹Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
²State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China.
³Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴Center for Genetic Medicine Research, Children’s Research Institute, Children’s National Hospital, Washington, DC 20010, USA.

↵‡Corresponding author. Email: wilsonjm{at}upenn.edu

↵* These authors contributed equally to this work.
↵† Present address: Sarepta Therapeutics, Burlington, MA, USA.

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Science Advances 12 Feb 2020:
Vol. 6, no. 7, eaax5701
DOI: 10.1126/sciadv.aax5701

Lili Wang

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Yang Yang

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China.

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Camilo Breton

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Peter Bell

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Mingyao Li

3Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Jia Zhang

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Yan Che

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Alexei Saveliev

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Zhenning He

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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John White

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Caitlin Latshaw

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Chenyu Xu

4Center for Genetic Medicine Research, Children’s Research Institute, Children’s National Hospital, Washington, DC 20010, USA.

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Deirdre McMenamin

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Hongwei Yu

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Hiroki Morizono

4Center for Genetic Medicine Research, Children’s Research Institute, Children’s National Hospital, Washington, DC 20010, USA.

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Mark L. Batshaw

4Center for Genetic Medicine Research, Children’s Research Institute, Children’s National Hospital, Washington, DC 20010, USA.

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James M. Wilson

1Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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For correspondence: wilsonjm@upenn.edu

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A mutation-independent CRISPR-Cas9–mediated gene targeting approach to treat a murine model of ornithine transcarbamylase deficiency

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