The lentivirus vector carrying a hybrid cytosine guanine dinucleotide (CpG)-free CMV enhancer/elongation factor 1 alpha promoter (hCEF) expressed functional CFTR, retained 90–100% transduction efficiency in clinically relevant delivery devices and showed acceptable toxicity and integration site profiles to support the initiation of a clinical trial in CF patients. This evidence concerns the gene CFTR and cystic fibrosis.