VES4US and BOW

Extracellular Vesicles (EVs), such as exosomes, are biological nanoparticles naturally evolved to transport various bioactive molecules (proteins, RNAs, lipids and metabolites) between cells, tissues, organs and even organisms. EVs are considered as one of the most promising bio-nanovehicles for the delivery of indigenous and exogenous bioactive compounds. This has sparked the interest of the pharma industry, given their promise to be used as therapeutic vehicles. However, despite the advances in the field, many challenges with EV-based therapies still stand, such as the non-scalability of the EV production process, the still inefficient EV payload uptake, and the need to optimise tropism and biodistribution while minimizing adverse effects. The H2020-FET VES4US (“Extracellular vesicles from a natural source for tailor-made nanomaterials”, Antonella Bongiovanni coordinator) and BOW (Biogenic Organotropic Wetsuit, Paolo Bergese coordinator) are multidisciplinary projects with the ambition to set-up and validate disruptive platforms for the production, quality control and engineering of EVs and EV-based hybrid nanotechnologies that overcome the current challenges faced by state-of-the-art EV-based therapeutics.

VES4US has validated the key attributes of EVs from microalgae (which we termed NANOALGOSOMES or ALGOSOMES) and the patented process for their lab scale separation that is versatile for a scale-up, fully integrating all the key upstream and downstream elements of a bioprocess. In that, the VES4US team has validated its technology in laboratory conditions, reaching the following milestones: i) 18 microalgae species were screened for their algosome-production ability. ii) Physicochemical features have been in-depth analysed to evaluate algosome yield, shape, stiffness, and molecular cargo. iii) Algosomes are biocompatible as they are efficiently uptaken by human cells without toxic effect. Both uptake and potency were further confirmed using Caenorhabditis elegans in vivo model. Finally, the assessment of biodistribution, pharmacokinetics and safety upon intravenous infusion of labelled algosomes into mice evidenced unprecedented safety, particular organ tropism and long retention. iv) State-of-art EV loading methods were used to accomplish loading of different therapeutic cargo. The VES4US spin off company EVE (https://www.evebiofactory.com/) is further trasforming this novel biotechnology in a product for the pharma and cosmetic industries.

In the context of the ongoing BOW project, algosomes, as well as human-derived EVs, are further exploited to develop a novel hybrid biotechnology capable of lending the biological surface precision, circulation and targeting abilities of EVs to superparamagnetic nanodevices. BOW will proof and set a general and viable paradigm to establish key biomimetic functions including camouflage to the immune system and organ site/tumor targeting to any synthetic nanodevice, while being disruptive as a first example of biogenic nanotechnology. In that, BOW objectives are the production of high-grade extracellular vesicles with biomimetic and organotrophic functions; the synthesis, and functionalization of hybrid particles; engineering a microfluidic device for the fabrication of extracellular vesicle membrane and the control of biological performances and the nanotoxicity in-vitro, ex-vivo and in-vivo. This hybrid technology aims to advance implantable nanodevices and nanomaterials towards sustainable production and clinical translation, proving the possibility of recapitulating biomimetic functions on any toxic synthetic nanodevice.

www.ves4us.eu

www.bowproject.eu