Researchers intend to develop SpliceFix, a novel therapeutic approach based on latest technologies of “genome editing”. These techniques rely upon recently discovered system CRISPR/Cas9 able to “cut and paste” the cellular DNA. This project concerns CFTR splicing mutations. These mutations affect gene regulation sites (introns); introns can be manipulated without the risk of interfering with the protein coding parts of the CFTR gene. With the aim to introduce CRISPR/Cas9 into the cell, a novel specific Cas9 variant and a traceless CRISPR/Cas9 delivery system (VLPs, Viral Like Particles) will be designed, possessing safety and deliverability. Special sgRNAs will identify mutated introns, which will be deleted by Cas9. In this way, the correct splicing will be restored and the gene corrected. The targeted mutations will be are 3272 -26 A>G and 3849 +10Kb C>T. Gene repairing will be demonstrated by measuring the functioning of CFTR protein on CF organoids. Splice-Fix for CF project aims to develop innovative therapies for the treatment of genetic defect.