Engineering exosomes for cellular delivery

Exosomes and extracellular vesicles are small; exosomes 50-200 nm, extracellular vesicles 100 to 1000nm, particles composed of a phospholipid bilayer encapsulating a subfraction of molecules derived from the contents of the parent cell. These sub cellular vesicles have been implicated in cell-cell communication via transfer of RNA, microRNA, etc. and believed to be produced by all mammalian cells and cell lines. The ability of exosomes and extracellular vesicles to fuse with cells and so deliver their intra vesicular 'cargo' allied with their lack of immunogenicity has generated a lot of interest over the last few years in using these nanoparticles as effectors of cell signalling. The project will focus on generating and characterising engineered exosomes and extracellular vesicles. We will operate the project in a modular fashion. Macromolecular composition of the nanoparticles and targeting will be defined by a combination of parent cell genetic engineering and appropriate loading of harvested vesicles. Small molecule cargo delivery will be achieved by developing and optimising loading process for harvested vesicles. Scale up and harvesting of vesicles will be achieved by a combination of genetic engineering of the parent cell and materials engineering to provide particle capture and quality control of the process. Engineered vesicles generated by these methods will be analysed by state of the art imaging methods that are available within the group and insights generated into vesicle-enabled cell signalling