The Animal Models Core will provide technical support to Projects I, II and III to allow for the evaluation of various in vivo strategies for adeno-associated virus-based gene therapy for ornithine transcarbamylase deficiency (OTCD). The Gene Therapy Program at the University of Pennsylvania has extensive experience with the in vivo characterization of vectors in various murine models of OTCD. In the context of this P01 application, the Animal Models Core will provide full support at all levels of the in vivo gene transfer studies including study design;animal acquisition;breeding of OTC and FRG mice, management of in-life phase of studies including organization of the study, technical support for procedures and harvesting of samples;and necropsy. The Core will maintain four colonies that include the spf[ash], spf, OTC-KO and FRG mice to support the experimental needs of Projects I, II and III.
The Animal Models Core is pivotal to the success of this POI. The Core will expand and maintain the spf, spf[ash], OTC and FRG mouse colonies that are critical for the experiments of all three projects of this program The Core has the technical expertise to perform all animal-related experiments that have been designed to address the barriers to effective gene transfer in humans in an effort to bring AAVS to the clinic.
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|Mays, Lauren E; Wang, Lili; Lin, Jianping et al. (2014) AAV8 induces tolerance in murine muscle as a result of poor APC transduction, T cell exhaustion, and minimal MHCI upregulation on target cells. Mol Ther 22:28-41|
|Bryant, Laura M; Christopher, Devin M; Giles, April R et al. (2013) Lessons learned from the clinical development and market authorization of Glybera. Hum Gene Ther Clin Dev 24:55-64|
|Zhong, Li; Malani, Nirav; Li, Mengxin et al. (2013) Recombinant adeno-associated virus integration sites in murine liver after ornithine transcarbamylase gene correction. Hum Gene Ther 24:520-5|
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|Wang, Lili; Morizono, Hiroki; Lin, Jianping et al. (2012) Preclinical evaluation of a clinical candidate AAV8 vector for ornithine transcarbamylase (OTC) deficiency reveals functional enzyme from each persisting vector genome. Mol Genet Metab 105:203-11|
|Wang, Lili; Bell, Peter; Lin, Jianping et al. (2011) AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta). Mol Ther 19:2012-20|
|Bell, Peter; Wang, Lili; Gao, Guangping et al. (2011) Inverse zonation of hepatocyte transduction with AAV vectors between mice and non-human primates. Mol Genet Metab 104:395-403|
|Wang, Lili; Calcedo, Roberto; Bell, Peter et al. (2011) Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors. Hum Gene Ther 22:1389-401|
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