HUB MULTIDISCIPLINARE E INTERREGIONALE DI RICERCA E SPERIMENTAZIONE CLINICA PER IL CONTRASTO ALLE PANDEMIE E ALL'ANTIBIOTICO DI RESISTENZA
Spoke 2 focuses on implementing RNA therapeutics and biomarkers to address cancer trunk addictions, synthetic combinatorial approaches targeting interdependent hallmarks of cancer, and expanding the applicability of ICI.The strategy of Spoke 2 involves targeting the undruggable, exploring the unconventional, and addressing the unseen aspects of cancer. Research projects will span different Technology Readiness Levels (TRL), with an emphasis on translational potential. Initial steps involve identifying novel targets through omics and artificial intelligence (AI) while concentrating on determinants of tumorigenesis or oncosuppressor circuits. Simultaneously, lower TRL research aims to identify new targets and biomarkers, including non-coding RNA fractions of the cancer genome. The focus extends to both malignant cells and the tumor stroma, with an emphasis on fostering anti-cancer innate and adaptive immunity and discovering diagnostic, prognostic, and treatment response biomarkers through high-throughput sequencing and AI.
The profound impact of RNA-based technologies has transformed the landscape of treating and preventing infectious and inflammatory diseases. A prime illustration is the dominance of mRNA-based vaccines during the SARS-CoV-2 pandemic. Demonstrating rapid development and high effectiveness in eliciting antigen-specific immune responses, these mRNA-based vaccines are now pivotal in suppressing, rather than priming such responses for treating immune disorders like autoimmune diseases, a primary focus of Spoke 5 activities.
Furthermore, Spoke 5 focuses on the exploration of non-coding RNAs as sensitive non-invasive biomarkers. These biomarkers hold the potential for diagnosing, predicting, and stratifying patients with inflammatory, autoimmune, and infectious diseases while presenting novel therapeutic targets. Circulating extracellular vesicles have also gained attention as potential vectors for RNA and molecule delivery, Spoke 5 will dedicate several activities to their characterization and use as both potential vectors and biomarkers.
Overall, Spoke 5 stands at the forefront of research, encompassing both coding and non-coding RNA as therapeutic targets, vehicles, or biomarkers for infectious and inflammatory diseases.
Additional emerging strategies, such as viral vector and non-viral RNA/DNA delivery for cell-specific gene silencing, are gaining prominence as precision drug delivery approaches in inflammatory and infectious diseases. These strategies exhibit improved efficacy and safety profiles, representing innovative ways to target selective cellular and molecular pathways in the treatment of inflammatory and infectious diseases. While gene regulation through viral vectors, as seen in COVID-19 vaccines, is already in use, Spoke 5 extends its focus to immunological considerations. The widespread application of vectors based on viruses capable of infecting human cells may face challenges from pre-existing antiviral immune responses. This includes the presence of neutralizing antibodies that can block the vector, thereby reducing transduction efficiency and the expression of the conveyed gene product. Finally, Spoke 5 is dedicated to exploring and analyzing immunological responses to both viral and non-viral RNA vectors comprehensively.
Progetto “Extreme phenotypes to identify the patients with type 2 diabetes who are susceptible or resistant to complications and to reveal the mechanisms (EXTREME T2D)” (CUP master D55E22000720006) - PROF. GUIDO SEBASTIANI
Progetto “Artificial intelligence applied to conventional and advanced MRI sequences for improving disease classification and prediction of clinical worsening in patients with multiple sclerosis” - PROF. NICOLA DE STEFANO