In Trieste, the RNA Biology Group (Baralle) performs research 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 using transgenic and engineered mouse models of the human syndromes, aiming at the development of therapeutic approaches that could be translated to patients. The applied approaches range from pharmacological therapies to gene therapy and gene editing, using AAV vectors in combination with engineered nucleases. The Human Molecular Genetics Group (Pagani) is interested in translational approaches via a novel RNA based strategy to correct splicing defects associated with haemophilias, cystic fibrosis, familiar dysautonomia and spinal muscular atrophy. The applicative approach is via gene therapy using AAV vectors is offering new therapeutic opportunities.
The Mouse Molecular Genetics Group reported a potential AAV gene replacement vector therapy for the liver ornithine transcarbamylase deficiency (Mol Ther Methods Clin Dev 20:169-180, 2020). The Human Molecular Genetics Group published a major study on the rescue of common exon-skipping mutations of the cystic fibrosis CFTR locus with modified U1 snRNAs (Hum Mut 41:2143-2154, 2020).