Optimization of cargo-loaded paramyxovirus virus-like particles production in suspension cells would set the stage for future efforts at large-scale production in conjunction with the CSL Behring Fermentation Facility at Penn State.
Nathaniel Meyer, an Immunology and Infectious Disease major, received a scholarship from the Center of Excellence in Industrial Biotechnology to work in the Schmitt Virology Lab over the summer, where researchers have developed a novel technology that facilitates packaging of foreign proteins as cargo into paramyxovirus virus-like particles (VLPs).
“The components of the VLPs are actually paramyxovirus proteins. If you express them in the right ratio, they self-assemble into virus-like particles so that they look a virus, they're shaped like a virus, they function like one, except they're not infectious. Several vaccines are headed in the direction of virus-like particles. We tag a cargo molecule with a segment of viral protein that causes our cargo to be incorporated into the VLP. The virus will dock onto cells and deliver the cargo. Instead of just taking a pill and hoping that molecule Y gets to location Z, we're basically hijacking the viral mechanisms that have been evolving for millions of years to infect cells and are instead using them to deliver therapeutic molecules,” he explained.
By using this technology instead of traditional delivery methods, Meyer can directly deliver the protein to a specific type of cell with minimal modification to the cargo (15-30 amino acid extensions).
One barrier this system faces is the reliance on adherent 293T cell transfection for production of cargo-loaded VLPs. Adherent 293T transfection is both expensive and challenging on an industrial scale. In order to overcome this barrier, he proposed to adapt and optimize VLP production technology for use in suspension cell cultures. Production in suspension cultures would allow for much higher cell density and lower cost production of cargo-loaded VLPs, taking this technology one step closer to commercial use. Optimization of cargo-loaded VLP production in suspension cells would set the stage for future efforts at large-scale production in conjunction with the CSL Behring Fermentation Facility at Penn State.
Two commonly used suspension cell lines for large-scale bioproduction are Expi 293F and CHO-K1S cells; neither of these have been used for production of cargo loaded paramyxovirus-like particles before; Meyer will compare the two cell lines to determine which is better-suited for production of VLPs.
“So far, we have achieved much higher yields of our cargo loaded VLPs using adapted suspension culture transfection. Currently, we are testing the quality and efficacy of the VLPs produced by our new methods,” he said. “Delivery assays are being optimized with results forthcoming.”
Receiving the scholarship meant a lot to Meyer; for one, he was able to stay on campus over the summer and conduct his thesis research. “I got to do an in-depth experiment from beginning to end instead of just tagging along and taking notes,” he said.
Meyer started at Penn State as a biochemistry major but switched to premed after shadowing a doctor who works with the Amish community in Franklin County, mostly with Lyme disease. That’s where his interest in infectious diseases was sparked, and eventually became a passion.
“It seems like every specialty is moving closer to immunology; no matter what specialty you choose, immune treatments and immune technologies are the hot zone for medical science at this point. For example, the 2018 Nobel Prize in Physiology or Medicine went to two researchers who were able to reprogram immune cells to target tumors,” he said.
Meyer has applied to medical school with the intent of studying infectious diseases. “The career I'm looking at ideally would be bridging the gap between pure science and clinical science, where I would still be working with patients, and investigating cases using new technology as treatments, but I’d also like to still study the technology itself,” he said.