PROJECT2018-11-20T14:52:25+01:00

DESCRIPTION

VES4US: Extracellular vesicles from a natural source for tailor-made nanomaterials

Extracellular vesicles (EVs) are cell-derived, membranous particles that mediate intercellular communication by transferring biomolecules such as proteins and RNAs. The discovery of EVs as natural biocarriers and inter-species communication means has raised great interest in the drug delivery field. EVs intrinsically possess many attributes of a drug delivery vehicle, since these particles are well tolerated in the body, have long circulating half-life, are internalised by recipient cells and are able of crossing the blood brain barrier. Native and drug-loaded mammalian cell-derived EVs have recently been developed and are contributing to the expanding research field known as “cell-free therapy”. Despite these promising progresses, translational applications are currently hampered by the lack of suitable processes for the isolation, characterisation and functionalisation of EVs.

The main aim of VES4US is to develop a radically new platform for the efficient production and functionalisation of EVs, which will enable for their exploitation as tailor-made products in the fields of nanomedicine, cosmetics and nutraceutics. A core aspect of the project is to focus vesicles from an identified natural source, which could constitute a more economically viable and sustainable source of EVs. This process will allow the development of natural nanocarriers with unprecedented abilities for drug delivery in specific tissues such as brain, lung, skin, dendritic or tumour cells. VES4US is endorsed by prominent industrial stakeholders with strong interests in market-oriented innovation.

The actively emerging field of EV-based research and industrial/clinical translation will significantly profit from the proposed VES4US innovation of focusing on natural nanovesicles; the new knowledge created will influence the biomedical landscape of the future both within and outside the European Union.

WORK PACKAGES

WORK PACKAGES

The aim of this WP is to select the best EV-producing natural source and the optimisation of EVs obtain conditions. The main results will be a list of tested natural sources characterised and described as EV main producers together with a set of optimal culture conditions to obtain EVs. One or two EVs sources will be selected.

The aim is to evaluate the toxicity and the bioactive potential of the EVs and of their engineered counterparts. Both in vivo and in vitro assays will be applied. Firstly, in vitro assays will be performed using both commercially available primary cells, stablished cell lines and tumorigenic cells. Then invertebrate in vivo assays will be carried out using C. elegans models. Mammalian in vivo assays will complete this set to test short-term/long-term systemic toxicity, biodistribution and in vivo stability. Additionally, anti-microbial and anti fugic activity assays will give light on the active potential of the EVs.

This WP envisions to retrieve of high-quality natural source EVs from the cultivation media of the selected EV sources. Main tasks will be to create a laboratory-scale production of EVs and to implement the optimized novel methods to produce the EVs. Moreover, EVs isolation and handling procedures will be standardized. We will determine experimental parameters along the isolation procedure that critically affect the reproducibility and the chemophysical properties of the isolated nanovesicles, also Standard Operating Procedures (SOPs) related to the EVs isolation and handling including transport conditions will be elaborated and shared.

WP6 will ensure that the project is carried out in accordance with the Grant Agreement (GA), the Consortium Agreement (CA), the Quality management system, and that the objectives that are set out are met in a timely fashion. WP6 has an integrative remit and relies on interconnections between the operational WPs and efficient communication amongst the consortium members. It also integrates a scientific dissemination function for the outcomes of the project, which is further compounded by WP7.

The aim of WP3 is to characterize different EVs populations (micro and nanovesicles) as foundations for future research and industrial applications. This WP is of key importance. We will start by studying the physico-chemical features of isolated EVs. This will allow determining whether or not our harvesting method selectively enriches for phospholipid membranous vesicles (EVs). We will develop microfluidic-based technology for characterising EVs. Approaches will include microfluidic diffusion sizing

in free channels for the determination of size distribution, miniaturisation of SEC in microchannels coupled with light scattering techniques and integration of separation with immunoblotting assays. Additionally, the characterisation of protein and small molecular biocargo of EVs will be approached.

The main objectives of this WP are to define and carry out actions aimed at achieving effective dissemination and communication of the project itself and its results as well as to pave the way for the exploitation of the project results in the medium-long term. Of special interest in this WP will be the elaboration of the business models and exploitation plans for the most promising results with potential to reach the market.

In this WP we will identify the best strategy to functionalise EVs membranes and to load bioactive molecule. Of key importance will be to create a strategy to purify functionalised/enriched EVs from unreacted materials. This WP will start with drug encapsulation and in vitro release and will continue with the Functionalisation of the EVs. Finally, microfluidic technology for the purification of engineered EVs will be used in order to obtain the loaded and or functionalized EVs ready to test.

WORK PACKAGES

The aim of this WP is to select the best EV-producing natural source and the optimisation of EVs obtain conditions. The main results will be a list of tested natural sources characterised and described as EV main producers together with a set of optimal culture conditions to obtain EVs. One or two EVs sources will be selected.

The aim is to evaluate the toxicity and the bioactive potential of the EVs and of their engineered counterparts. Both in vivo and in vitro assays will be applied. Firstly, in vitro assays will be performed using both commercially available primary cells, stablished cell lines and tumorigenic cells. Then invertebrate in vivo assays will be carried out using C. elegans models. Mammalian in vivo assays will complete this set to test short-term/long-term systemic toxicity, biodistribution and in vivo stability. Additionally, anti-microbial and anti fugic activity assays will give light on the active potential of the EVs.

This WP envisions to retrieve of high-quality natural source EVs from the cultivation media of the selected EV sources. Main tasks will be to create a laboratory-scale production of EVs and to implement the optimized novel methods to produce the EVs. Moreover, EVs isolation and handling procedures will be standardized. We will determine experimental parameters along the isolation procedure that critically affect the reproducibility and the chemophysical properties of the isolated nanovesicles, also Standard Operating Procedures (SOPs) related to the EVs isolation and handling including transport conditions will be elaborated and shared.

WP6 will ensure that the project is carried out in accordance with the Grant Agreement (GA), the Consortium Agreement (CA), the Quality management system, and that the objectives that are set out are met in a timely fashion. WP6 has an integrative remit and relies on interconnections between the operational WPs and efficient communication amongst the consortium members. It also integrates a scientific dissemination function for the outcomes of the project, which is further compounded by WP7.

The aim of WP3 is to characterize different EVs populations (micro and nanovesicles) as foundations for future research and industrial applications. This WP is of key importance. We will start by studying the physico-chemical features of isolated EVs. This will allow determining whether or not our harvesting method selectively enriches for phospholipid membranous vesicles (EVs). We will develop microfluidic-based technology for characterising EVs. Approaches will include microfluidic diffusion sizing

in free channels for the determination of size distribution, miniaturisation of SEC in microchannels coupled with light scattering techniques and integration of separation with immunoblotting assays. Additionally, the characterisation of protein and small molecular biocargo of EVs will be approached.

The main objectives of this WP are to define and carry out actions aimed at achieving effective dissemination and communication of the project itself and its results as well as to pave the way for the exploitation of the project results in the medium-long term. Of special interest in this WP will be the elaboration of the business models and exploitation plans for the most promising results with potential to reach the market.

In this WP we will identify the best strategy to functionalise EVs membranes and to load bioactive molecule. Of key importance will be to create a strategy to purify functionalised/enriched EVs from unreacted materials. This WP will start with drug encapsulation and in vitro release and will continue with the Functionalisation of the EVs. Finally, microfluidic technology for the purification of engineered EVs will be used in order to obtain the loaded and or functionalized EVs ready to test.

CONSORTIUM

THE NATIONAL RESEARCH COUNCIL OF ITALY (CNR)

Is the largest public research institution in Italy, performing multidisciplinary activities.

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CNR-IBIM

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IBBR

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IBF

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IEOS

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IGB

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INSTITUTE OF TECHNOLOGY SLIGO (ITSLIGO)

Is a 3rd-level institution located on the northwest coast of Ireland that offers regional leadership in education, economic and social development.

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THE SWISS FEDERAL INSTITUTE OF TECHNOLOGY (ETH ZURICH)

Is a well-known institute renowned for its excellent education, ground-breaking fundamental research and for putting its new findings directly into practice.

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UNIVERSITY OF LJUBLJANA (UL)

Implements and promotes basic, applied and developmental research and is pursuing excellence and the highest quality in all scientific fields and art.

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MAX PLANCK INSTITUTE FOR POLYMER RESEARCH (MPG)

Ranks among the top research centers in the field of polymer science worldwide.

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ZABALA INNOVATION CONSULTING, S.A. (ZABALA)

Is a Spanish SME with wide experience in supporting entities in the management of their RTD and innovation activities.

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