Dimitra Stamkopoulou presented an overview of Panosome's innovative nanoVAST technology, a platform for nucleic acid delivery using extracellular vesicles derived from the parasite Trypanosoma brucei. Panosome, a startup based in Heidelberg, Germany, collaborated closely with the German Cancer Research Centre on this technology.
nanoVAST vesicles were derived from Trypanosoma brucei, which had a dense coat of variant surface glycoprotein (VSG) proteins. This unique feature allowed for versatile surface modifications due to over 1000 VSG variations. The technology aimed to address three main challenges in nucleic acid delivery: targeting specific cells, efficient cargo release, and scalable manufacturing.
The VSG array by sortase tagging (VAST) technology enabled the covalent attachment of targeting molecules, such as peptides or antibodies, to the VSG coat, allowing for cell-specific targeting. Preliminary data showed increased interaction with target cells using this method. Unlike typical non-viral delivery systems that relied on endocytosis, nanoVAST vesicles appeared to fuse directly with the cell membrane, transferring cargo directly into the cytoplasm. This was supported by flow cytometry and electron microscopy data.
A proof of concept using RNA editing demonstrated a nearly one-to-one correlation between cargo presence and functional activity inside cells, suggesting efficient cytoplasmic delivery compared to standard methods like Lipofectamine. The platform showed the ability to deliver various nucleic acid cargos, including fluorescent RNA, GFP mRNA, and plasmids, indicating broad potential for therapeutic delivery.
Manufacturing scalability was addressed by culturing trypanosomes in mass using roller bottles, with nanoVAST vesicles produced by sonication and purification. The ability to incorporate sortagging for targeting suggested feasible scale-up for production.
Future applications included exploring in vivo CAR T cell therapy, where nanoVAST could deliver CAR mRNA directly to T cells, offering a less costly and faster alternative to current ex vivo manipulation methods. Overall, nanoVAST was presented as a unique and versatile technology with significant potential for targeted nucleic acid delivery and therapeutic applications.
