Abstract

Nucleic acid sensing and cell intrinsic innate immune mechanism may hamper the efficacy and safety of gene therapies as well as contribute to several autoimmune and inflammatory pathologies. As all current and emerging gene transfer and editing technologies expose cells to exogenous nucleic acids and/or viral vectors, they may activate harmful antiviral and inflammatory cascades impacting efficacy and safety of genetic manipulation. In this context, our research is focused on identifying innate immune barriers that prevent efficient modification of relevant gene therapy targets such as cells of the hematopoietic and central nervous systems. By understanding the underlying mechanisms, we aim to develop strategies to mitigate these effects and enhance therapeutic outcomes. On the other hand, the very same immune sensors that protect against viral infections and influence gene engineering can also drive disease when aberrantly activated. In this context, we investigate the molecular mechanisms behind disorders characterized by excessive type I IFN and inflammatory signaling. In this talk, I will present our latest findings on how pathogen recognition and innate immune activation impact gene therapies, as well as how these pathways contribute to autoimmune and inflammatory neurodegenerative diseases.