Chapter 11. Cystic Fibrosis: Gene Therapy Approaches

Summary

Cystic fibrosis is a single gene disorder viewed as a good candidate for gene therapy because the affected gene is known, the target tissue, the lung, is accessible and less than 50% gene transfer may confer clinical benefit. The CFTR gene encodes a transmembrane protein that regulates chloride transport, but the pathology, often complicated by bacterial colonisation, remains unclear. Retroviral vectors have been used to transfer the CFTR gene into cultured cells and might work in vivo where the lung has been damaged leading to proliferation of progenitor cells. Adenovirus naturally infects the respiratory epithelia and has been used in clinical studies of CFTR gene transfer. The protein is expressed in some subjects and some have shown improved chloride secretion. Clinical trials have also shown expression of CFTR after transduction via an adeno-associated viral vector or using cationic lipid-mediated gene transfer. Other approaches, including artificial chromosomes, are being explored.