Collaborative Research: Maximizing Therapeutic DNA Process Productivity

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0967932AtaaiDNA vaccines are becoming increasingly important as a way to confer immunity. Ultimately, DNA vaccines should be safer and more effective than traditional vaccines, however, currently, there are limitations in our ability to produce the necessary DNA. To meet the demand for DNA vaccines and other DNA products, it would be beneficial to increase the productivity of production processes. While reducing cost, faster processing would also enable DNA vaccine producers to more quickly respond to pathogen mutations and disease outbreaks. The proposed work addresses this problem. The main idea is when host and plasmid DNA are concurrently engineered, DNA production increases dramatically, while the host grows quickly on simple and inexpensive medium. The investigators will use a combination of metabolic engineering, proteomics, NMR, bioprocessing, and mathematical modeling to achieve their goals. The work will extend metabolic engineering practice from the current foci of small molecules and proteins to DNA products, which is important in advancing the field of metabolic engineering. From a more fundamental standpoint, the integration of plasmid DNA synthesis with host cell metabolism, which is not now well understood, will be improved. The effect of combining mutations in the control of plasmid replication is also not yet well explored. The work will reveal the extent to which the effects are synergistic, which would be of interest to structural molecular biologists. The impact of redox cofactor balancing will also be elucidated, which is of current interest to a number of ongoing metabolic engineering efforts. A successful outcome will accelerate the production of therapeutic DNA products and facilitate clinical trials. This collaborative project would provide broad education and training for the graduate and undergraduate students (including minority students) involved in metabolic engineering, computation, NMR, proteomics, and the bioprocessing of DNA products.