Coordinator : Pr Jean-Pierre BENOIT

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

 

The aim of RESOLVE is to pursue the development of innovative nanosystems as novel therapeutic approaches based on the engineering of nanomedicine to limit the immune reactivity against host self-antigens in the course of bone marrow transplantation (graft versus host disease, GvHD) and autoimmune diseases (multiple sclerosis, MS).

Currently, therapeutics for these pathologies are based on either systemic or local immunosuppression, which eliminate or suppress polyclonal, autoreactive T-cell specificities while compromising the entire systemic immunity with many side effects, sometimes life threatening. But the most promising strategies to come are represented by either restoration or de novo induction of cells able to induce tolerance, such as  the monocytic myeloid-derived suppressor cells (MO-MDSCs). Their immunosuppressive activity, and consequently their tolerogenic ability, can be enhanced by increasing the cellular level of a protein involved in apoptosis regulation, CFLAR. In the course of the present project, new nanosystems will be designed to specifically target in vivo the MO-MDSCs, and efficiently deliver mRNAs to produce CFLAR. The specific expression of the protein, both at the cellular and tissue levels, the in vivo nanosystem biodistribution and the therapeutic efficacy in mouse models of GvHD and MS, will be assessed.

Consortium

 Jean-Pierre Benoit (Coordinator)

INSERM U1066/CNRS UMR 6021, University of Angers

IBS-CHU

4 Rue Larrey

49933, Angers, France

 

Giovanna Lollo

LAGEP - UMR CNRS 5007 University Claude Bernard Lyon 1

8 avenue Rockefeller

69373, Lyon, France

 

Vincenzo Bronte

Department of Medicine, University of Verona

P.le L. A. Scuro, 10

37134, Verona, Italy

 

Pål Sætrom

Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology – NTNU

Erling Skjalgssons gt. 1

NO-7491, Trondheim, Norway

 

Ugur Sahin

BioNTech RNA Pharmaceuticals

An der Goldgrube 12

55131, Mainz, Rhineland-Palatinate, Germany