The comparatively easy, non-invasive accessibility of the lungs to aerosols and the monogenic nature of the disease makes Cystic Fibrosis (CF) an attractive candidate for gene therapy and genetic editing. It is suggested that ~10% of endogenous cystic fibrosis transmembrane regulator (CFTR) expression within target cells in vivo is sufficient for prevention of lung disease[1]. This level of gene transfer/correction in patients has not yet been achieved. However, over expression of CFTR and/or the use of CFTR potentiators have been shown to restore some functions of CFTR in vitro more efficiently than endogenous expression alluding to treatments that may allow prevention of CF lung disease with a lower level of gene transfer/correction[2]. We have therefore constructed an enhanced CFTR gene (CFTRenh) with codon optimization, for increased expression, and containing two mutations (K978C and K190C) which have been described to permit a >2 fold increase in CFTR Po[3]. We have shown that this construct was successfully processed into protein that translocated to the membrane when transfected into human cell lines HEK 293T and H441. We showed that CFTRenh produced ~14x more CFTR protein than CFTR WT (n=2) whilst the activity of the CFTRenh was observed to be up to ~9x greater as shown in YFP quenching assay (n=3). We have flanked the CFTRenh gene with guide RNA sites specific for Intron 1 of human CFTR and incorporated an EGFP marker for intended use in Homology-independent targeted integration. We plan to integrate the enhanced CFTR gene into primary CF bronchiole epithelial cells, downstream of the endogenous CFTR promoter. Given that the CFTRenh gene shows increased expression and activity than that of WT CFTR provides support that correcting CF cells with this form of CFTR may restore function with a lower (and achievable) rate of genetic correction.