Extracellular vesicles as non viral drug carriers

5 October 2023

J. Dancourt 1, B. Sheryl 1, E. Piovesana 2, G.Lavieu 1
1. Université Paris Cité, INSERM U1316, UMR 7057/CNRS, Paris, France
2. Current address: Laboratory for Aging Disorders, Laboratory for Translational Research, EOC Bellinzona (Bios+), Switzerland.

Extracellular vesicles (EVs) are biological vehicles that are thought to mediate cell-cell communication via the transfer of biomolecules from donor to acceptor cells. Repurposing those natural vesicles into therapeutics delivery vectors is a high priority challenge for translational science. Here we engineer donor cells to produce copious amount of fusogenic EVs loaded with the catalytic domain of the Diphteria Toxin, known to trigger cell death through protein synthesis inhibition. We show that, when incubated with cancer acceptor cells, these Killer EVs block protein synthesis and lead to cell death. This proof of concept establishes the efficacy of Killer EVs in vitro, and suggests that further development may lead to tumor ablation in vivo, expanding the existing cancer therapeutics arsenal. Importantly, Killer EVs are engineered to contain a non-viral fusogen, which may increase their in vivo tolerance as compared to previously used vectors. Moreover, our preliminary efforts to target these EVs to specific cell types promises tropism control compatible with advanced therapeutics delivery.

Keywords: Extracellular Vesicles; Oncolytic; DTA

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