Lipid-Based Nanoparticles that Controllably Synthesize Proteins

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Delivering proteins and RNA to specific cells and tissues is an important problem because engineering solutions to this problem will have applications for treating diseases and understanding fundamental biological processes. The technologies that have been developed to deliver small molecules, such as cancer-targeting nanoparticles and drug-eluting stents, have been commercially successful. However delivering large biomolecules has proven more challenging, due to their instability in vivo, susceptibility to degradation, and potential to elicit immune responses, and consequently, the full commercial potential has not been reached. The materials and technologies being developed to-date aim to stabilize and shield active biomolecules. My program will explore a fundamentally different approach - to synthesize the active biomolecules only in desired locations at desired times. The main question we will answer in this program is: Can proteins and RNA be controllably expressed inside of lipid nano-vesicles? Our main objective is to develop nanoparticles that are initially inert, but when activated by light will synthesize functional biomolecules for a range of applications. I was part of a team that recently showed that E. coli cell extract (a commonly used protein-expression system) and DNA templates can be encapsulated inside of lipid vesicles, creating nanoparticles that could synthesize model proteins. The specific objectives of my program are to engineer this system to i) increase both the yield and the range of proteins that can be synthesized, ii) synthesize functional small RNA for RNAi, and iii) develop a high-throughput microfluidic system for screening protein libraries. The impact of this program will be the development of a new biochemical technique and drug-delivery technique. It can benefit Canada by helping achieve the full commercial potential of protein and RNA delivery. The program will also benefit Canada by training highly qualified entrepreneurial personnel. Trainees will be exposed to fundamental science and engineering in a collaborative environment while learning a range of state-of-the-art techniques applied to timely problems.