Project: SuppRESsion of immunopathology by nanOparticle deLiVEry of mRNA to monocytes

Acronym	RESOLVE (Reference Number: EURONANOMED2017-159)
Duration	05/04/2018
Project Topic	New treatments to fight immunopathologies originating from enhanced immune reactivity against host self-antigens in the course of transplantation (graft vs host disease, GvHD) and autoimmunity (multiple sclerosis) are urgently needed. Therapeutic approaches based on either systemic or local immunosuppression, which eliminate or suppress polyclonal, autoreactive T-cell specificities, do compromise the entire systemic immunity with many side effects, sometime even life threatening. The most promising strategies are represented by either restoration or de novo induction of cells able to induce tolerance. Among these cells, key to this project, are the immune regulatory cells of myeloid origin defined monocytic myeloid-derived suppressor cells (MO-MDSCs). The tolerogenic ability of these cells can be increased by acting on a specific pathway involved in regulating their apoptosis by the administration of genetic material, such as specific mRNA. The members of the present Consortium have identified a main pathway and some of the possible molecular targets that will be further studied and validated within the following years. Thanks to the present project, we will be able to develop, design and produce efficient new nanosystems (lipid nanocapsules- TRL4, lipid nanoparticles-TRL4 and polymeric biodegradable nanoparticles TRL3) able to specifically target MO-MDSC in vivo and effectively deliver mRNA. The nanosystems will be also GMP produced by the development of new microfluidic approaches. We will demonstrate the specific expression of the protein(s) involved in the identified tolerogenic pathways, both at the cellular and tissue level, assess the in vivo nanosystem biodistibution, and their efficacy in the therapy of mouse model of GvHD and multiple sclerosis. We have organized a competitive Consortium involving a multidisciplinary work plan, which will benefit from the academic, industrial and clinical expertise of the participants to guarantee the success of RESOLVE.
Network	EuroNanoMed III
Call	Joint Transnational Call for Proposals (2017) for “European Innovative Research & Technological Development Projects in Nanomedicine”

Project partner

Number	Name	Role	Country
1	University of Angers	Coordinator	France
2	University Claude Bernard - Lyon 1 - ISPB - Faculty of Pharmacy	Partner	France
3	University of Verona	Partner	Italy
4	Norwegian University of Science and Technology, NTNU	Partner	Norway
5	BioNTech RNA Pharmaceuticals	Partner	Germany