Institute for Biomedicine and Glycomics, Griffith University, QLD, Australia
Lipid nanoparticle (LNP)-based delivery of nucleic acids in vivo is now a clinically accepted modality for vaccination and treatment of a range of diseases such as amyloidosis and to treat hypercholesteremia. However, these first-generation particles suffer from several deficiencies in that they only deliver 1% of their payload, they have limited biodistribution and biocompatibility, and the use of polyethylene glycol (PEG) to stabilize them can evoke serious immune reactions. EVs are natural LNPs but are difficult to load to high efficiency. Cell-based and in vitro methods have been used but methods need improving. I will outline our efforts in this area using biomimetic EVs from a range of cell types to create synthetic EVs that have very high efficiency of loading and delivery. These particles show distinct organ distributions. Indeed targeted LNPs are a hot area of research with a number of papers show that altering the lipid makeup can markedly change organ deposition. I will present EV lipodomic data that may explain the biodistribution of EVs in the body. Importantly, EV biomimetic particles do not use PEG making them safer. We believe these new particles will allow for improvements in the use of RNA and DNA medicines going forward.