Project Overview: This project addresses an urgent need for alternative therapies for individuals with FA aimed at preserving stem cell function, reducing genome instability, and delaying cancer onset. By developing novel therapeutic strategies utilizing translational-read-through-inducing drugs (TRIDs), nonsense-mediated decay (NMD) inhibitors, and anticodon-engineered tRNAs (ACE-tRNAs) Drs. Cipolli and Bezzerri will evaluate the restorative ability of these drugs and their potential as future therapies for individuals with FA who have nonsense mutations (20-30% of individuals with FA).

Impact Statement: This groundbreaking work aims to restore functional FANC proteins by combining TRIDs, ACE-tRNAs and NMD inhibitors in immortalized FA patient derived cells. This therapeutic strategy for nonsense mutations will guide treatments for a significant proportion of FA individuals and may be utilized in the future for other bone marrow failure syndromes.