Gene Therapy for Cystic Fibrosis

¹ From the Division of Pulmonary and Critical Care Medicine, Department of Medicine, and the Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill

Following the cloning of the cystic fibrosis (CF) gene, in vitro studies rapidly established the feasibility of gene therapy for this disease. Unlike ex vivo approaches that have been utilized for other genetic diseases such as adenosine deaminase deficiency, gene therapy for CF will likely require direct in vivo delivery of gene transfer vectors to the airways of patients with CF. Hence, major research efforts have been directed at the development of efficient gene transfer vectors that are safe for use in human subjects. Several vectors have now emerged from the laboratory for evaluation in clinical safety and efficacy trials in the United States and in the United Kingdom. Adenovirus-mediated gene transfer has been utilized for initial clinical safety and efficacy trials in the United States, while liposome-mediated gene transfer has been chosen for initial clinical safety and efficacy trials in the United Kingdom. The rationale and laboratory studies are reviewed leading to initial clinical safety and efficacy trials. Also reviewed are the currently available vectors for potential use in clinical studies, their advantages and disadvantages, and the promises and pitfalls of current gene therapy efforts for CF in the United States focusing on adenovirus vectors in current clinical trials.

Key Words: adeno-associated virus vectors • adeno virus vectors • airway epithelia • cationic liposomes • cystic fibrosis • gene therapy/transfer • molecular conjugates • retrovirus vectors