CORE--VECTOR PRODUCTION

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Description: (Taken directly from the application) The Vector Production Core is intended to provide batch synthesis of adenoviral and plasmid DNA vectors for preclinical studies of gene transfer. We have identified a substantial need for large scale preparation of these vectors on our campus. We also plan development of improved techniques to minimize replication competent adenovirus (RCA) from batch preparations, and to improve plasmid yield. The principal role of the Vector Production Core Facility will be to assist with the transition between early laboratory proof-of-concept type studies and the scale-up production that becomes crucial in order to support preclinical (predominantly animal) gene therapy trials. The amounts and quality of preclinical grade vector needed for studies of pigs or non-human primates, or even for detailed studies in mice, rats, or rabbits are often well beyond the capabilities of an individual laboratory attempting to validate a particular construct. A Vector Production Core at our center is, therefore, requested on the following basis. First, a number of UAB faculty interested in cystic fibrosis or other gene-transfer experiments have indicated a need for the large-scale production of adenovirus or plasmid batch preparations. Second, a standardized format of preparative and large-scale production will facilitate the reproducibility and consistency of the preparations. Third, issues not normally managed in a single investigator?s laboratory can be best addressed in a centralized facility, such as the presence of replication competent adenovirus (RCA), or optimization of plasmid DNA yields. Finally, although not produced under formal, good manufacturing practice (GMP) conditions, the documentation and record keeping in the facility may help track any variability in the responses observed with different vector preparations and may also help optimize future vector reparations. Moreover, the good laboratory practice (GLP) conditions used in the facility will make vectors produced in Core B useful and relevant with regards to development of human clinical trials of gene therapy.