Paul Ehrlich proposed the “Magic Bullet” concept 120 years ago. We are still waiting - but there is hope. This talk will describe progress toward a multi-functional, protein based nanoparticle with the potential to realize Ehrlich’s dream.<br/>Perhaps more than any other field of endeavor, biochemical technology empowers an iterative progression in which process innovation is motivated by and then enables visionary product innovation. This is especially important for developing a magic bullet nanoparticle. A 2016 review reported the results of over 200 studies seeking to target therapeutics to tumors. The average delivery efficiency was 0.7%! Paradoxically, such studies tell us that our biggest enemy in this pursuit is the human immune system. It is very good at recognizing and destroying perceived garbage. Still, many viruses are all too effective at delivering their nucleic acid cargoes, and they can provide important design concepts and components.<br/>We have used the inner capsid from the hepatitis B virus as our starting point. Eight different types of mutations have been introduced while maintaining the ability of the 18kDa HepB core protein to fold and to assemble into a capsid composed of 240 monomers. Cell-free protein synthesis (CFPS) has been instrumental in producing the capsid protein as well as a targeting domain and an immune system avoidance signal. Non-natural amino acids are site specifically introduced to enable precise surface display of the latter two entities. Cargo loading with several hundred drug molecules or with proteins or nucleic acids is accomplished during capsid assembly. Conditional stabilization then retains the cargo and stabilizes the capsid until reducing conditions inside the targeted cells trigger cargo release. Throughout this development project, the flexibility offered by CFPS has been highly beneficial. Multiple new functionalities have been introduced into the virus-like particles (VLPs), and this has motivated several advances in CFPS technology. This iterative progression allowed these modular VLPs to become “smart” nanoparticles.<br/>The talk will describe advances in protein synthesis technology and in methods for producing precisely engineered protein-based nanoparticles. Such approaches can now be used for a variety of applications beyond therapeutic delivery. Finally, data from studies with cultured cells and mice will be used to illustrate VLP functionality and delivery performance.

Marvin Johnson award: Targeted therapeutic delivery; can the dream come true?

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.