Team:
Mario Milani, Eloise Mastrangelo, Bianca Braggiotti, Silvia Ferrara
Collaborators:
Luca Muzio, Andrea Menegon (Ospedale San Raffaele), Pierfausto Seneci (UNIMI)
Chronic inflammation in Multiple Sclerosis (MS) is sustained by stabilization of pro-inflammatory mRNAs due to dysfunction of RNA-binding proteins (RBPs) such as TTP and MCPIP1 (Regnase-1), which normally drive inflammation resolution.
Based on their structural features, we engineered chimeric proteins (REcTOs) combining TTP RNA-binding specificity with MCPIP1 RNase activity, enabling selective recognition and degradation of pro-inflammatory transcripts. Among these, REcTO4 shows broad activity against key mediators of MS pathology. REcTO4 is being developed as a gene-therapy strategy to modulate neuroinflammation in circulating myeloid cells and microglia, and is validated in the EAE mouse model using targeted viral delivery to assess effects on inflammation, demyelination, and neurodegeneration.
Funding:
FISM (Fondazione italiana Sclerosi Multipla); Ricerca Finalizzata (Ministero della Salute)
