The Vector Development Core (Core B) is a shared facility that will provide vector reagents to facilitate the hypothesis-driven studies proposed in Project 1 (Fisher) relating to prostate cancer, Project 2 (Dent) investigating malignant glioma and Project 3: (Curiel) studying ovarian cancer. In this regard, all of these projects employ recombinant adenovirus vector systems for in vitro and in vivo studies. The core will construct vectors for each of these projects. Additional adenoviral vectors will be prepared which utilize progression elevated gene-3 promoter to drive virus replication and concomitantly express mda-7/IL-24 for Project 1;(Fisher) and after validation for use in Project 2 (Dent) and Project 3 (Curiel), will also be produced. Specific requirements for non-replicative adenoviruses, including those expressing bcl-2 and bcl-xL Project 1 (Fisher) and Project 2 (Dent), will be provided by Core B. Project 3 (Curiel) will produce and characterize """"""""complex mosaic"""""""" adenoviruses with enhanced cancer infectivity tropisms for enhanced cancer-specific expression of mda-7/IL-24. Once these viruses are characterized, this Core will provide these vectors for use in prostate cancer (Project 1: Fisher) and in malignant gliomas (Project 2: Dent). Core B will also serve to validate the identity, function, and quality of the various viral vector reagents to provide uniform quality controlled materials for the various projects. The Vector Production Core will provide preparative amounts of validate vectors and additional vectors as required by specific projects. The concentration of these activities in a shared resource context will enable these reagents to be derived in an efficient and cost-effective manner and will capitalize on programmatic expertise in this area.
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