Novel cellular model system and therapeutic molecules for the development of a read-through approach for CF caused by stop codon mutations of the CFTR gene-Progetto n°: 02/2010 FFC Finanziato da: Fondazione per la Ricerca sulla Fibrosi Cistica-Bando 2010 Durata: 12 mesi (dal 01/09/2010 al 31/08/2011)

Progetto n°: 02/2010 FFC Finanziato da: Fondazione per la Ricerca sulla Fibrosi Cistica-Bando 2010 Durata: 12 mesi (dal 01/09/2010 al 31/08/2011)- Nonsense mutations promote premature translational termination and are the leading cause of approximately 30% of inherited diseases, including cystic fibrosis. In the last few years, it has been demonstrated that drugs (like aminoglycoside antibiotics) can be designed and produced to suppress premature translation termination, inducing a ribosomal read-through of premature, but not normal termination codons. Moreover the treatments with aminoglycosides may provide a mean of restoring CFTR function in patients with stop mutations and have introduced new hopes for the development of a pharmacologic approach to the cure of CF. The rationale supporting this project is to optimize the read-through molecules leading to restoration of CFTR production in cystic fibrosis caused by non-sense stop codon mutations. The objectives of this project are: development of in vitro cellular model systems and biochemical screening systems; synthesis of novel drugs exhibiting read-through effects on CFTR mRNA carrying stop codon mutations; development of experimental strategies to reduce NMD of the CFTR mRNA and biological assays on treated experimental model systems, testing the activity of the read-through drugs on CFTR function of chloride transport.