UC San Diego

Plant virus-like particles (VLPs) are proteinaceous nanoparticles that exhibit high structural symmetry and stability, while offering a large amount of chemically addressable sites for modification. In addition, they are noninfectious because they lack genomic material and can be efficiently produced in heterologous expression systems (e.g., E. coli fermentation). These features make them attractive platforms for applications in drug delivery, material science, and agriculture. The core of my thesis work focuses on utilizing the icosahedral physalis mottle virus-like particle (PhMV VLP), specifically, an engineered cysteine-added mutant variant (A31C S137C), described in previous work, that offers internal and external sites for bioconjugation. My research focused on the chemical modification of the PhMV VLP with the aim of broadening its application in drug delivery. In this context, I probed the chemical reactivity of PhMV VLPs and investigated the site-selectivity of a bifunctional crosslinker. I then utilized a crosslinking strategy to produce VLPs stable under high temperature and mechanical stress, which allowed their application to hot melt-extrusion processes and manufacture of slow-release formulations. In addition, I developed a scalable, nuclease-free method of purifying PhMV VLPs expressed in E. coli, which may further the translation of this VLP platform in biomedical applications. Overall, my work establishes the applicability of this VLP platform to harsh manufacturing processes and a method for high volume production and advances its translation to drug delivery applications.