Design of Gene Therapy Clinical Trials in CF Patients

On April 17, 1993, Crystal and co-workers initiated the first human gene therapy trial for cystic fibrosis (CF). In that study, a replication-deficient recombinant adenovirus encoding cystic fibrosis transmembrane conductance regulator (CFTR) cDNA was administered to the nasal and bronchial epithelia of four cystic fibrosis patients (1 ). Since then, numerous trials have been conducted to evaluate gene therapy in CF, including both viral and nonviral vectors for the delivery of CFTR cDNA. These have primarily been Phase I and II experiments intended to demonstrate safety and feasibility of gene transfer to the nasal and/or bronchial epithelia of patients by either direct application or nebulization (2 ).