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.
|Shen, Shen; Berry, Garrett E; Castellanos Rivera, Ruth M et al. (2015) Functional analysis of the putative integrin recognition motif on adeno-associated virus 9. J Biol Chem 290:1496-504|
|Suwanmanee, Thipparat; Hu, Genlin; Gui, Tong et al. (2014) Integration-deficient lentiviral vectors expressing codon-optimized R338L human FIX restore normal hemostasis in Hemophilia B mice. Mol Ther 22:567-74|
|Lau, A G; Sun, J; Hannah, W B et al. (2014) Joint bleeding in factor VIII deficient mice causes an acute loss of trabecular bone and calcification of joint soft tissues which is prevented with aggressive factor replacement. Haemophilia 20:716-22|
|Nicolson, Sarah C; Samulski, R Jude (2014) Recombinant adeno-associated virus utilizes host cell nuclear import machinery to enter the nucleus. J Virol 88:4132-44|
|Hemphill, Daniel D; McIlwraith, C Wayne; Samulski, R Jude et al. (2014) Adeno-associated viral vectors show serotype specific transduction of equine joint tissue explants and cultured monolayers. Sci Rep 4:5861|
|Mitchell, Angela M; Hirsch, Matthew L; Li, Chengwen et al. (2014) Promyelocytic leukemia protein is a cell-intrinsic factor inhibiting parvovirus DNA replication. J Virol 88:925-36|
|Shen, Shen; Horowitz, Eric D; Troupes, Andrew N et al. (2013) Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency. J Biol Chem 288:28814-23|
|Gurda, Brittney L; DiMattia, Michael A; Miller, Edward B et al. (2013) Capsid antibodies to different adeno-associated virus serotypes bind common regions. J Virol 87:9111-24|
|Asokan, Aravind; Samulski, R Jude (2013) An emerging adeno-associated viral vector pipeline for cardiac gene therapy. Hum Gene Ther 24:906-13|
|Monahan, Paul E; Gui, Tong (2013) Gene therapy for hemophilia: advancing beyond the first clinical success. Curr Opin Hematol 20:410-6|