Maria Levitin, Group Leader at Evox Therapeutics, presented her company’s work on a novel platform for loading and delivering exosome-based therapies with various cargoes, including RNA and CRISPR-Cas. Exosomes are nanovesicles that are produced within the body and are used in communication between different cells as a delivery and communication modality.
One of their main advantages is that they are innate and therefore avoid immunogenicity. Levitin added that they have a strong safety indication and offer a safe and potent modality for the precise delivery of medicine payloads.
At Evox Therapeutics, the team is focused on delivering multiple therapies of interest through their DeliverEX platform. The platform modulates the exosomes, engineers them, packs them with different drugs of interest, and targets them to distinct tissues of interest.
Two main exogenous loading methods—co-incubation and electroporation—were discussed. Co-incubation uses a lipid that is conjugated to the cargo, which loads molecules onto the surface of the exosome, and this method allows for many molecules to be packaged into the exosomes.
Electroporation creates small pores within the exosome, allowing for cargo to enter the lumen. Although this limits the volume of molecules scientists can fit inside, there is an additional protection of the cargo with your vesicle, and then this is purified further. Levitin noted that by optimising these protocols, she achieved high cargo loading and flexibility for different RNA molecules and indications.
Furthermore, Exosome-mediated delivery of siRNA showed higher efficiency and potency compared to standard methods. Both in vitro and in vivo experiments bore successful achievements, including enhanced delivery to hard-to-reach tissues like the brain.
Beyond CNS delivery, the platform is being expanded to deliver gene editing tools such as CRISPR/Cas9. We all know that CRISPR/CAS is a powerful therapeutic tool that has applications across a range of diseases; however, delivery can be challenging due to reliance on viral vectors. Evox’s DeliverEX platform is seeking to overcome this with its engineered exosomes, which show high editing efficiency in vitro using a GFP-based reporter system.
Compared to LNPs, Exosomes offer broader tissue distribution, particularly in the CNS, which is an area with high unmet need. Exosomes also display superior safety compared to lipid nanoparticles (LNPs), making them excellent contenders for precision medicine. In a nutshell, exosomes offer a safe, scalable, and flexible platform for delivering complex therapeutics like RNA and gene editors.
