The Viral Vector Core is a critical resource for investigators both within and outside the University of Pennsylvania (UPenn) interested in the use of viral vectors for gene therapy for preclinical research with the potential to translate into the clinic. The Vector Core provides adenoviral vectors, lentiviral vectors and adeno-associated viral vectors (AAV) and offers a full range of services including cloning, DNA amplification and characterization, vector design and consultation. The Core has over a decade of experience in the production of vectors for basic research and is closely associated with one of the premier gene therapy laboratories in the country. Located in a state-of-the art facility on the UPenn campus, the Core is fully equipped with the resources, equipment and dedicated staff of professionals to carry out the objectives and aims described in this application. The Core specializes in the production and distribution of novel AAV serotype vectors developed in the Wilson laboratory at Penn, including AAVS, the Clinical Candidate serotype forthis POI. An integral part of the Core is its quality control program which is carried out by a separate Quality Control Group. Although the vectors produced by the Core are research grade, quality control assays have been developed that are relevant to clinical grade material and graded release criteria are in place which must be met before the release of any vector produced in the facility. The overally objective of the Core is to provide the participants of this POI with advanced vector technologies for preclinical studies focusing on the development of gene therapy for ornithine transcarbamylase deficiency (OTCD).
The Specific Aims are as follows: (1) to produce high quality preclinical vector designed according to the needs of each project;(2) to conduct robust quality control on each vector and adhere to the release criteria established for each vector platform and (3) to conduct process and assay development relevant to the needs ofthe program project.

Public Health Relevance

The Viral Vector Core provides advanced vector technologies to investigators interested in gene delivery using viral-based vectors to study disease mechanisms and develop gene therapies for genetic and metabolic diseases including urea cycle disorders.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD057247-07
Application #
8652992
Study Section
Pediatrics Subcommittee (CHHD)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
7
Fiscal Year
2014
Total Cost
$95,121
Indirect Cost
$35,671
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Yang, Yang; Wang, Lili; Bell, Peter et al. (2016) A dual AAV system enables the Cas9-mediated correction of a metabolic liver disease in newborn mice. Nat Biotechnol 34:334-8
Bissig-Choisat, Beatrice; Wang, Lili; Legras, Xavier et al. (2015) Development and rescue of human familial hypercholesterolaemia in a xenograft mouse model. Nat Commun 6:7339
Wang, Lili; Bell, Peter; Somanathan, Suryanarayan et al. (2015) Comparative Study of Liver Gene Transfer With AAV Vectors Based on Natural and Engineered AAV Capsids. Mol Ther 23:1877-87
Mikals, Kyle; Nam, Hyun-Joo; Van Vliet, Kim et al. (2014) The structure of AAVrh32.33, a novel gene delivery vector. J Struct Biol 186:308-17
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
Wilson, James M; Shchelochkov, Oleg A; Gallagher, Renata C et al. (2012) Hepatocellular carcinoma in a research subject with ornithine transcarbamylase deficiency. Mol Genet Metab 105:263-5
Wang, Lili; Wang, Huan; Bell, Peter et al. (2012) Hepatic gene transfer in neonatal mice by adeno-associated virus serotype 8 vector. Hum Gene Ther 23:533-9
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

Showing the most recent 10 out of 23 publications