Many have proposed that lentiviral vector (LV)-mediated hematopoietic stem cell (HSC) gene therapy may constitute a new safe and efficient approach for the treatment/prevention of the bone marrow failure (BMF) characteristic of FA patients. To further improve the possibilities of developing a safe and efficient gene therapy protocol in FA patients, this collaborative project aims to explore in FA HSCs the relevance of observations showing that the LV itself activates DNA damage and apoptosis-related signaling pathways in HSCs from healthy donors. Because these pathways are already compromised in FA cells, the impact of LV-mediated signaling could be more severe in FA HSCs. Therefore, this projects aims to carefully investigate the short and long-term functional consequences of the LV-mediated signaling in FA HSCs, with the final goal to design safer and more efficient gene therapy protocols to guarantee the best possible therapeutic outcome for FA patients in the future.
Researchers: Anna Kajaste-Rudnitski