The Vector Core has been and will continue to serve as a critical component of the """"""""Cytokine Gone Therapy for Cancer Program, providing serotype 5 adenoviral viral vectors as well as additional novel reagents to Projects 1-3. The Vecto Core will function within the framework of the Program as a dynamic resource that can provide state-of-the-at adenoviral vector technology. In addition to the ability to construct and propagate adenoviral vectors, the Vector Cor also is able to generate retroviral, adeno-associated virus and lentivirus vectors for gone delivery and is developin expression vectors for use in liposome and particle-mediated gone transduction. While these are not """"""""line-itemed"""""""" in an of the projects, our ability to provide such diversified vector systems may prospectively facilitate individual project goals The Vector Core has also developed an algorithm for the generation of codon optimized cDNAs, allowing for highe levels of gone expression following gone transfer. Specifically, the role of the Vector Core in this PPG will be t construct and provide the necessary Ad5, and if needed novel serotype-based adenoviral vectors expressing th appropriate (and possibly codon-optimized) genes, as required for the performance of studies outlined in each of the thre proposed projects. In addition, the core will propagate already constructed adenoviral vectors, and provide high-titer quality-tested stocks of vectors for the broad range of experiments described in this application. There will be constan two-way dialogue between Core B and each of the projects at all times, and particularly in all cases where adenovira gone delivery must be further optimized. Furthermore, the Core will provide any technical assistance and training t individuals in the use of adenoviral viral vectors for gone transfer as needed.
The Specific Aims of the Vector Core are: 1. To provide each investigator with adenoviml vectors expressing the required therapeutic and possibly eodon-optimize genes appropriate for their proposed experiments. 2. To develop improved adenoviral vectors for more efficient gene transfer into tumor cells and dendritic cells. 3. To assist in the development of methods for efficient adenoviral gene delivery to mouse and human tumors cells an dendritic cells. 4. To provide technical assistance and protocols to each of the projects in the use of adenoviral gene delivery
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