RII Track-2 FEC: Membrane Purification Platform for Continuous Biomanufacturing of Viral Vectors and Virus-like Particles in Arkansas and Beyond

Biologics are large molecule therapeutics and have been used to treat a variety of diseases, including cancer, diabetes, cardiovascular disease, autoimmune disorders, genetic and ophthalmologic diseases to name a few. Biologics include monoclonal antibodies (mAbs) and other therapeutic proteins, vaccines such as mRNA vaccines, cell and gene therapies products such as stem cells, and viral vectors. The impact of biologics on human health has been tremendous with the success of mRNA vaccines for COVID-19 as an example. The market for biologics is increasing exponentially, reaching over $300 billion as of today. The large demand for biologics places great challenge on the manufacturing process. The total cost for downstream process accounts for up to 80% of the total manufacturing cost. The vision of this RII Track-2 FEC project is to create a membrane-based downstream purification platform for the future large scale biomanufacturing of viral vectors and virus-like particles (VLPs) for gene therapy and vaccine applications. This platform will be used to replace the current processes such as centrifugation and resin-based chromatography that are difficult to scale up. The overall goal of this project is to develop innovative and practical unit operations that could be part of a platform for the downstream purification of these virus particle-based therapeutics. The project brings together multidisciplinary researchers with complementary expertise from three EPSCoR jurisdictions from the University of Arkansas (Arkansas), Clemson University (South Carolina) and University of Kentucky (Kentucky). Each of the three institutions offers unique facilities and resources that can rapidly catalyze the technology development. The economic impact of the proposed activities on the entire state of Arkansas as well as on Kentucky and South Carolina will be significant. Regional incubator centers for biotechnology industry of tomorrow will be established in the three EPSCoR states. Successful development of a high-productivity membrane purification platform is expected to improve human health by improving access to revolutionary treatments for genetic and chronic diseases for mid- and low-income families. Workforce development for the future biotechnology industry, a commitment to diversity through collaborations with Minority-serving Institutions, and a focus on early career faculty mentorship are key components of the project. The project will provide internship opportunities for graduate students and research experiences for undergraduates to develop the STEM workforce in this field. In addition, all three universities will outreach to the respective Minority-serving Institutions in the state to foster collaborative research experiences. Development of cost-effective large scale biomanufacturing for the purification of viral vectors and virus-like particles (VLPs) is a major challenge. Membrane based unit operations are attractive; however, membrane capacity, fouling and lack of commercial membranes as well as the robustness of membrane performance under a range of operating conditions have limited applications by industrial practitioners. This project will address key issues and overcome critical barriers for developing a membrane-based bioprocessing platform for viral vectors and VLPs. The project aims to overcome the technical and economic barriers at multiple fronts and involve close collaborations among researchers at three different institutions in three EPSCoR jurisdictions. More specific research objectives include (1) feedstock production of two common viral vectors for gene therapy applications and VLPs for vaccine applications; (2) advanced microfiltration operations for bioreactor harvesting; (3) high capacity affinity membrane design, fabrication and characterization; (4) downstream membrane chromatography for separating full and empty viral capsids; (5) module design, process optimization and process intensification; (6) employing state-of-the-art bioanalytical methods for detection and quantification; and (7) a technology readiness and acceptance study. Through the project's collaborative research efforts across three universities, researchers will build upon existing infrastructure at each institution, expanding it far beyond current capabilities. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.