CFTR splicing occurs during the transcription process of the genetic code through mRNA molecules, that carry the information for protein synthesis. If the splicing is inefficient, unusually high levels of incorrectly-processed CFTR-mRNAs are produced within the cells. Some CFTR variants are known to modulate its splicing, first of all the so-called TG(9-13)and T(5,7,9) polymorphism, which are associated with monosymptomatic forms of cystic fibrosis. Researchers hypothesize that incorrectly-processed CFTR mRNAs represent an endogenous reservoir of precious precursors of additional CFTR protein, provided that the splicing defect can be partially corrected. They have demonstrated that it is possible to partially correct the splicing defect associated with the TG(9-13) T(5,7,9) polymorphisms by treating patient derived cells with the plant hormone kinetin, and its analogue RECTAS, two small molecules successfully used as splicing correctors in other inherited diseases. With this project, they propose to test the efficacy of kinetin/RECTAS as amplifier drugs to increase the CFTR function in the presence of variants reducing splicing efficiency. First, they will define which is the level of aberrant splicing in different human tissues relevant for CF. Moreover, they will test if kinetin/RECTAS can improve also other splicing defects in the gene. Then they will verify that the increase in wild-type mRNA, that has been already demonstrated to result from kinetin/RECTAS treatment, is accompanied by an increase of CFTR protein and channel function. Finally, they will test if the treatment has a significant impact on the expression of other genes in order to evaluate potential side effects in the view of future therapeutic applications.