The genome editing technology based on CRISPR-Cas is capable of correcting some of the mutations that cause cystic fibrosis (CF) efficiently and accurately. These strategies have proved to be very effective in cellular models derived from people with CF, but the main obstacle remains the in vivo delivery of the CRISPR-Cas system within the body. The main target of these strategies are the lungs, as the organs are mainly affected by the disease. In this project, the researchers aim to develop an efficient delivery system for the genome editing system for the airways. Unlike “conventional” gene therapy approaches, genome editing requires a transient expression of CRISPR nucleases, which must be active only for the time necessary to make the correction into the target DNA. For this reason, the research team will use virus-derived nanoparticles (VEsiCas) that have proven effective as a delivery system and able to modulate the activation of CRISPR. The main objective of the project is to specifically convey the CRISPR-Cas system to the lung epithelium, also acting on its effectiveness by testing new nucleases, such as Cas12a. These new systems based on VEsiCas will be validated in primary lung cells and subsequently tested in vivo in mouse models. The VEsiCas system could also be used for other lung diseases or be adapted to act specifically on other tissues, thus expanding its use for the treatment of other genetic diseases.