Platform development of bioengineered extracellular vesicles for targeted RNA delivery

Using mRNA as a gene therapy modality has opened a new avenue for treatment of a range of diseases, however, they need to be encapsulated in nanocarriers to ensure stability and cellular uptake.

Synthetic carriers, including lipid nanoparticles have recently emerged for potent hepatic delivery of RNA but they fail to robustly deliver to other organs in a safe manner.A promising nanocarrier for drug delivery is extracellular vesicles (EVs) that can efficiently convey macromolecules into cells.

As native nanoparticles, EVs benefit from immune tolerance and the ability to cross biological barriers.

We have developed advanced strategies to bioengineer cells to generate EVs loaded with therapeutic mRNAs/proteins and have successfully used them for delivery in different pre-clinical disease models.

However, high EV doses are needed in vivo due to insufficient drug loading.Hence, I propose a platform development to address mRNA loading into EVs and harness these engineered EVs to functionally deliver mRNA to unreachable organs, focusing on brain.

In order to increase CNS targeting, we will screen EVs from different cell sources and decorate EVs, optimised to display Fc receptors, with targeting antibodies to further increase delivery to brain.

Using this combinatorial approach of RNA loading and antibody decoration via functionalisation of EVs will be compatible with loading of other biotherapeutics and can be applied for treatment of virtually any disease.