Discovery and characterisation of proteins that bind Lipid Nanoparticles and Dendritic cell targets

The current clinically approved mRNA vaccines are packaged in Lipid Nanoparticles (LNPs), and biodistribution studies show that upon injection there is significant off-target effects where most of the LNPs are taken up by local muscle cells, while a residual portion reaches the blood stream to end up mainly in the liver and spleen, contributing to off-target effects. The targeting of mRNA vaccines to immune cells, specifically DCs, could reduce off-targeting and enhance the efficacy and duration of the immune response. Additional benefits include reducing vaccine doses, need for additional boosters, and reducing adverse side effects. There are currently no rapid and simple ways to target LNPs to specific disease sites.  

The goal of this project is to use protein display libraries to discover proteins that bind to lipid nanoparticles and Dendritic cell targets.  These proteins will be engineered into bispecific antibodies and coupled with LNPs to enhance targeting of mRNA vaccines and therapies.  Additional bioconjugation strategies for coupling proteins to LNPs will also be explored, for example the utilisation of genetic code expansion with unnatural amino acids.  The resulting bioconjugates will be trialled for targeting to specific cell type, DCs in vitro and also evaluated in vivo using mouse models.