Engineering a tolerogenic synthetic niche for in situ tolerogenic dendritic cell induction as an auto-immune therapeutic approach

Autoimmune diseases represent a class of conditions resulting from anomalous responses of the immune system, that mistakenly attacks healthy parts of the body.

More than 80 conditions have been classified as autoimmune diseases, including multiple sclerosis and type 1 diabetes, affecting up to 10% of the population. A promising immunotherapy of such diseases is the use of tolerogenic dendritic cells (tolDCs).

Dendritic cells (DC) are key regulators of the adaptive immune system: DC can be polarized towards tolDCs, restraining inappropriate autoreactive responses such as those observed in autoimmune diseases.

Conventionally, tolDCs are generated ex vivo from isolated autologous DC cultured with the disease autoantigen and tolerogenic agents.

In this project, we will develop a new biomaterial able to generate tolDCs in the patient directly in vivo, leading to a drastic reduction in the therapy cost.

We will do this through an injectable hydrogel able to recruit DC at the site of implantation, and then deliver to those DC nanoparticles containing mRNA encoding the disease autoantigen, and siRNAs as tolerogenic agents.

Thanks to the use of mRNA, this platform can be easily scaled and adapted to different diseases in a patient-specific manner.

Central to this approach will be the use of new immunologically silent polymeric nanoparticles, able to efficiently deliver RNA to dendritic cells without the inherent immunogenicity of conventional lipid particles used in RNA therapeutics.