Systematic Engineering of Virus-like Particles to Identify Rules for Shifting Particle Size

Nanoparticle tumor delivery is a well-studied method of treating cancer. However, results from these studies over the last decade show limited success in clinical applications. Additional characterization of the key parameters, such as surface charge, chemical composition, shape, and size is required. Nanoparticle size is a known characteristic that affects accumulation in tumors, and I hypothesize that I can comprehensively test changes in this parameter using virus-like particles (VLPs). VLPs are biocompatible, have defined chemical handles that can attach targeting ligands, and can facilitate diagnostic and therapeutic delivery applications. The Tullman-Ercek identified a variant of MS2 virus-like particles that uniformly shifts the particle size, creating a pair of nanoparticle standards where we can confidently attribute changes in observed behavior to size. In this work, We will describe our effort towards understanding which mutations govern the size shift in MS2 VLPs and how we applied similar mutations to MS2 homologs to discern if these mutations are general design rules for VLPs.