The Viral Vector Core Facility is an integral component of the UNC Gene Therapy Center. It has been in operation for over 7 years and has maintained an exponential level of production growth over this time. This has been accomplished by rapid incorporation of new technological developments as they become available, and by a commitment to making the proceeds of these technologies as widely accessible to researchers as possible. The pursuit of these goals will continue within the proposed research program. Projects 1 and 2 are particularly illustrative of the reciprocal interactions between the core and affiliated researchers. For Project 1, the Vector Core will be responsible for the large-scale production of mutant (double stranded vectors) and chimeric and serotype specific rAAV vectors, thus facilitating the characterization of these reagents. Vectors that offer new capabilities will then be added to the list of services currently available from the vector core (e.g. type I specific vectors). In Project 2, new methods for the establishment of lentivirus producer cell lines promise greater safety and predictability. We will then develop these techniques into routine services to be offered to investigators who lack the facilities or expertise to create these invaluable resources (e.g. projects 3 and 4). Access to the expertise of the Vector Core will be critical to projects 3 and 4 in supplying the prodigious quantities of viral vectors needed for experimentation in vivo. Thus, we can prevent a conceptually simple but technically demanding aspect of these proposals from becoming a serious obstacle to their success. Apart from the routine output of vector material, the availability of the highly trained personnel of the Vector Core provides additional benefits to this research program. Although not within the scope of this PPG, the Vector Core is also responsible for the maintenance and operations of the Human Applications Laboratory, ensuring that basic vector techniques translate to implementation when clinical vector trials are justified (i.e. new Haparin sulfate (HS) purification of AAV type 2). This will ensure the production and assay of viral.