ACCEPTED ARTICLE PREVIEW
Accepted Article Preview: Published ahead of advance online publication In Vivo Zinc Finger Nuclease-Mediated Targeted Integration of a Glucose-6Phosphatase Transgene Promotes Survival in Mice with Glycogen Storage Disease Type IA
Dustin J. Landau, Elizabeth Drake Brooks, Pablo Perez-Pinera, Hiruni Amarasekara, Adam Mefferd, Songtao Li, Andrew Bird, Charles A. Gersbach, and Dwight D. Koeberl
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Cite this article as: Dustin J. Landau, Elizabeth Drake Brooks, Pablo Perez-Pinera, Hiruni Amarasekara, Adam Mefferd, Songtao Li, Andrew Bird, Charles A. Gersbach, and Dwight D. Koeberl, In Vivo Zinc Finger Nuclease-Mediated Targeted Integration of a Glucose-6-Phosphatase Transgene Promotes Survival in Mice with Glycogen Storage Disease Type IA, Molecular Therapy accepted article preview online 11 February 2016; doi:10.1038/mt.2016.35
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This is a PDF file of an unedited peer-reviewed manuscript that has been accepted for publication. NPG is providing this early version of the manuscript as a service to our customers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
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Received 25 May 2015; accepted 27 January 2016; Accepted article preview online 11 February 2016
© 2016 The American Society of Gene & Cell Therapy. All rights reserved
ACCEPTED ARTICLE PREVIEW In Vivo Zinc Finger Nuclease-Mediated Targeted Integration of a Glucose-6-Phosphatase Transgene Promotes Survival in Mice with Glycogen Storage Disease Type IA
Dustin J. Landau1,2, Elizabeth Drake Brooks1,3, Pablo Perez-Pinera4,5, Hiruni Amarasekara1,6, Adam Mefferd2, Songtao Li1, Andrew Bird1, Charles A. Gersbach4, and Dwight D. Koeberl1,2*. 1
Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center;
2
Department of Molecular Genetics and Microbiology, Duke University; 3Division of Laboratory
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Animal Resources, Duke University Medical Center; 4Department of Biomedical Engineering,
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5
Duke University, Durham, NC, United States, 27710; Current address: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801; 6Current address:
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Michael E. DeBakey Department of Surgery, Division of Cardiothoracic Surgery, CHI St. Luke's Health-Baylor St. Luke's Medical Center, Houston, Texas 77030.
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*To whom correspondence should be addressed at: Box 103856, Duke University Medical Center, Durham, NC 27710. Tel: (919)681-9919; FAX: (919)684-0983; Email:
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[email protected]
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© 2016 The American Society of Gene & Cell Therapy. All rights reserved
ACCEPTED ARTICLE PREVIEW ABSTRACT Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (p
Accepted Article Preview: Published ahead of advance online publication In Vivo Zinc Finger Nuclease-Mediated Targeted Integration of a Glucose-6Phosphatase Transgene Promotes Survival in Mice with Glycogen Storage Disease Type IA
Dustin J. Landau, Elizabeth Drake Brooks, Pablo Perez-Pinera, Hiruni Amarasekara, Adam Mefferd, Songtao Li, Andrew Bird, Charles A. Gersbach, and Dwight D. Koeberl
t p
i r c
Cite this article as: Dustin J. Landau, Elizabeth Drake Brooks, Pablo Perez-Pinera, Hiruni Amarasekara, Adam Mefferd, Songtao Li, Andrew Bird, Charles A. Gersbach, and Dwight D. Koeberl, In Vivo Zinc Finger Nuclease-Mediated Targeted Integration of a Glucose-6-Phosphatase Transgene Promotes Survival in Mice with Glycogen Storage Disease Type IA, Molecular Therapy accepted article preview online 11 February 2016; doi:10.1038/mt.2016.35
a m
s u n
This is a PDF file of an unedited peer-reviewed manuscript that has been accepted for publication. NPG is providing this early version of the manuscript as a service to our customers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.
d e t
p e c c A
Received 25 May 2015; accepted 27 January 2016; Accepted article preview online 11 February 2016
© 2016 The American Society of Gene & Cell Therapy. All rights reserved
ACCEPTED ARTICLE PREVIEW In Vivo Zinc Finger Nuclease-Mediated Targeted Integration of a Glucose-6-Phosphatase Transgene Promotes Survival in Mice with Glycogen Storage Disease Type IA
Dustin J. Landau1,2, Elizabeth Drake Brooks1,3, Pablo Perez-Pinera4,5, Hiruni Amarasekara1,6, Adam Mefferd2, Songtao Li1, Andrew Bird1, Charles A. Gersbach4, and Dwight D. Koeberl1,2*. 1
Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center;
2
Department of Molecular Genetics and Microbiology, Duke University; 3Division of Laboratory
t p ri
Animal Resources, Duke University Medical Center; 4Department of Biomedical Engineering,
c us
5
Duke University, Durham, NC, United States, 27710; Current address: Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801; 6Current address:
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Michael E. DeBakey Department of Surgery, Division of Cardiothoracic Surgery, CHI St. Luke's Health-Baylor St. Luke's Medical Center, Houston, Texas 77030.
d e t
*To whom correspondence should be addressed at: Box 103856, Duke University Medical Center, Durham, NC 27710. Tel: (919)681-9919; FAX: (919)684-0983; Email:
p e c
[email protected]
c A
© 2016 The American Society of Gene & Cell Therapy. All rights reserved
ACCEPTED ARTICLE PREVIEW ABSTRACT Glycogen storage disease type Ia (GSD Ia) is caused by glucose-6-phosphatase (G6Pase) deficiency in association with severe, life-threatening hypoglycemia that necessitates lifelong dietary therapy. Here we show that use of a zinc-finger nuclease (ZFN) targeted to the ROSA26 safe harbor locus and a ROSA26-targeting vector containing a G6PC donor transgene, both delivered with adeno-associated virus (AAV) vectors, markedly improved survival of G6Pase knockout (G6Pase-KO) mice compared with mice receiving the donor vector alone (p
