(81c) Bio-Click Chemistry for Modular Modification of Hepatitis B Viral-like-Particles As a Biosensor Platform for Cancer Detection

In an effort to diagnose and treat disease, we desire to create smart nanodevices which recognize molecular signals, transduce, and amplify desired therapeutic and imaging outputs. The Hepatitis B Virus-Like-Particle (HBV VLP) has been extensively studied and engineered into such a device for a variety of applications including vaccine delivery, drug delivery, biosensing, and imaging. In order to customize HBV VLPs for these applications, it is necessary to covalently attach multiple components. This has previously been done using chemical conjugation, unnatural amino acids, and genetic modification; however, chemical based strategies suffer from harming the integrity of more delicate protein attachments, while unnatural amino acid and genetic fusion strategies can create challenges in protein expression. We have developed an alternative strategy for the decoration of HBV VLPs using â??bio-clickâ? chemistry, allowing a wide range of peptides and proteins to snap directly onto the modified HBV capsids in a controlled, biocompatible manner. Our technology allows us to modularly modify the surface of HBV VLPs with multiple components. We have demonstrated this by creating a biosensing platform that incorporates an array of sensing and reporting domains which can be used to detect cancer biomarkers.