Thermoreversibly Assembled Polymersomes for Highly Efficient Loading, Processing and Delivery of Proteins and RNA Biologics

To expand the capabilities and broaden access to biologics in medicine, formulations for RNA and protein delivery must become streamlined for scalable manufacturing and commercial distribution. In this thesis, I demonstrate an efficient formulation for 100 nm polymer vesicles assembled without organic solvents, complex instrumentation, purification or stringent storage conditions required for current clinical technologies. Polymers are designed and synthesized to be completely soluble in refrigerated (4°C) saline, but rapidly assemble into nanoparticles when warmed to room temperature. This method forms concentrated batches of nanoparticles with predictable size, morphology and high loading efficiency (>75%) for both protein and RNA. With high loading and consistent morphology, these nanomedicines can be directly reconstituted from a dry powder and administered without any purification or processing after self-assembly. This simple but potent formulation outperforms clinically used technologies for protein subunit vaccination and RNA interference therapy in-vivo. Furthermore, we demonstrate the possibilities for this technology in promoting immune tolerance and potential as an mRNA delivery vehicle.