In Trieste, the RNA Biology Group (Baralle) has a long-standing interest in elucidating the molecular mechanisms that control the processing of human genes, and their relevance for human disease. In particular, it focuses on the splicing machinery and is addressing the epigenetic mechanisms that control cellular levels of RNA binding proteins. The Mouse Molecular Genetics Group (Muro) focuses on the study of molecular mechanisms of metabolic genetic diseases, and the development of therapeutic approaches for their cure, ranging from pharmacological therapies to gene therapy and gene editing, using transgenic and engineered mouse models of the human syndromes. The Human Molecular Genetics Group (Pagani) explores a novel RNA based strategy to correct splicing defects associated with haemophilias, cystic fibrosis, familiar dysautonomia and spinal muscular atrophy. For these conditions, gene therapy using AAV vectors is offering new therapeutic opportunities.
The Mouse Molecular Genetics Group reported a major advance in the development of genome editing strategies using Crispr/Cas9 technology for treating monogenic diseases of the liver during the neonatal period, such as the Crigler-Najjar Syndrome (De Caneva et al, 2019, JCI Insight). This study provides a proof of concept for the potential application of the approach to other liver diseases. A major advance in the treatment of spinal muscular atrophy, a rare and devastating disease, was recently reported by the Human Molecular Genetics Group, based on the delivery of U1 snRNA molecules by adeno-associated virus (Donadon et al, 2019, NAR). Studies are ongoing, aiming to transfer this technology to the clinic (Donadon et al., 2018, Hum. Mol. Genet., 27, 2466). This proof-of-principle study opens the way for studies aiming to transfer these technologies to the clinic.