Researchers demonstrated that the peptide derived from the PI3Kγ enzyme (patent n°WO/2016/103176) acts both as a potentiator and a corrector of CFTR carrying F508del mutation, appearing more efficient than currently used drugs, including the standard potentiator, VX-770, and the combined-action drug (potentiator/corrector) Orkambi® (Project FFC#23/2015 and FFC #4/2016).This project aims at completing the optimization of the PI3Kγ-derived peptide, synthesizing a molecule with preserved biological activity and better pharmacokinetic profile for CF therapy, and clarify the underlying mechanisms of action. The potency and toxicity of newly synthesized PI3Kγ peptide derivatives will be studied in vitro and in vivo (BALB/c mice), the therapeutic efficacy in human F508del intestinal organoids and bronchial epithelial cells. The ultimate goal is to validate a novel therapeutic strategy for CF basic defect treatment, in view of the potential development of PI3Kγ peptide as human medicinal product (Orphan Drug Designation N°EU/3/17/1859).