471851 Development of a Virus-like Particle for Targeted Delivery of Therapeutic Biomolecules
To address this problem, we are developing a nanoparticle-based delivery system to load a therapeutic cargo and deliver it specifically to the intended site-of-action. This system will increase the therapeutic index while reducing side-effects caused by the typical systemic delivery. In addition, using a nanoparticle to deliver the therapeutic allows us to use cargo, such as nucleic acids and proteins, which would not ordinarily reach the intended tissue.
Here we used advances in cell-free protein synthesis and synthetic biology to engineer a Virus-Like Particle (VLP) - a hollow, non-infectious protein-based nanoparticle - derived from Hepatitis B to efficiently load nucleic acids and proteins and specifically deliver the cargo to the targeted cells. Cell-free protein synthesis is a powerful platform that harnesses the capabilities of natural biological systems without using living cells. This allows us to efficiently express properly folded viral proteins and incorporate non-natural amino acids. These non-natural amino acids provide for easy conjugation points using the Copper(I)-Catalyzed Azide-Alkyne Cycloaddition reaction and allows us to functionalize the surface of the VLP with targeting ligands. The ligands used are antibody fragments or aptamers with high affinity towards receptors overexpressed on the targeted cells, allowing the VLP to enter the cells via receptor-mediated endocytosis. Furthermore, the VLP has been engineered such that it will disassemble once inside the cytosol, allowing the cargo to be delivered. These advantages, combined with extensive engineering of the viral protein itself to allow concurrent cargo loading and capsid assembly, will allow us to develop an ideal delivery vehicle.
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division