instmctions): The UNC Molecular/Vector Core Facility is a central component to our efforts to develop gene therapy for hematologic diseases. The Vector Core has supported the UNC Gene Therapy for Pulmonary and Hematologic Disorders projects since 2001 and has achieved a great deal of status in the gene therapy community as a reliable and cost-effective source of recombinant virus vector reagents. The core routinely makes available vectors that are unavailable and/or prohibitively expensive to make commercially. A top to bottom re-organization was initiated in 2005 that included the merging ofthe Research Core with the Clinical Cleanroom Facility (previously the Human Applications Lab), the creation of several other lab sections, and the implementation of standardized GLP/GMP practices across the various labs has brought us to a mature stage of high product quality and operating systems that are consistent with FDA regulatory requirements for drug development. Rapid growth in demand for our reagents in recent years has allowed us to increase staffing, purchase new equipment, begin offering major new resource programs, and justify the construction of a new state of the art manufacturing and testing facility to be located in the Research Triangle Park. These achievements have been paralleled by the creation of several new technological developments that have been incorporated into the Core's manufacturing and testing platforms. These new technologies have allowed the core to manufacture vectors faster and at higher levels of quality than previously possible. The new technologies are also highly scalable and will expand the core's total manufacturing capacity for a single large lot by over 10-fold. This will provide several advantages for investigators including;access to higher- grade vectors for pre-clinical work, better quality and reproducibility between different vector preparations, and improved consistency over time in the vector preparations used for basic-research, pre-clinical testing, Pharm/Tox studies, and clinical trials. These advantages will continue to be extended to the PPG investigators forthe proposed research programs.
(See Instructions): The proposed research is directly relevant to public health because it specifically focuses on developing new drugs for the treatment of hematologic diseases. The research has a broader relevance in that the things that will be discovered during the drug development process can be expanded to other types of disease states. And this knowledge can then aid in the development of new drugs for this broader set of diseases.
|Xiao, Ping-Jie; Mitchell, Angela M; Huang, Lu et al. (2016) Disruption of Microtubules Post-Virus Entry Enhances Adeno-Associated Virus Vector Transduction. Hum Gene Ther 27:309-24|
|Wang, M; Sun, J; Crosby, A et al. (2016) Direct interaction of human serum proteins with AAV virions to enhance AAV transduction: immediate impact on clinical applications. Gene Ther :|
|Li, Chengwen; Wu, Shuqing; Albright, Blake et al. (2016) Development of Patient-specific AAV Vectors After Neutralizing Antibody Selection for Enhanced Muscle Gene Transfer. Mol Ther 24:53-65|
|Berry, Garrett E; Asokan, Aravind (2016) Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction. J Biol Chem 291:939-47|
|Berry, Garrett Edward; Asokan, Aravind (2016) Cellular transduction mechanisms of adeno-associated viral vectors. Curr Opin Virol 21:54-60|
|Nelson, Christopher E; Hakim, Chady H; Ousterout, David G et al. (2016) In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 351:403-7|
|Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A et al. (2016) Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain. JCI Insight 1:e88034|
|Schreiber, Claire A; Sakuma, Toshie; Izumiya, Yoshihiro et al. (2015) An siRNA Screen Identifies the U2 snRNP Spliceosome as a Host Restriction Factor for Recombinant Adeno-associated Viruses. PLoS Pathog 11:e1005082|
|Goodrich, L R; Grieger, J C; Phillips, J N et al. (2015) scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy. Gene Ther 22:536-45|
|Hastie, Eric; Samulski, R Jude (2015) Recombinant adeno-associated virus vectors in the treatment of rare diseases. Expert Opin Orphan Drugs 3:675-689|
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