Current status of CF gene therapy

Abstract

RICHARD C. BOUCHER rbouch~med.unc.edu CF~Tta.~o.x~Y tlk-~_~Ta .~xo T~a3~_~,T C~'¢ffa, SCHOOL OF ,~NE, T~ UNr~.srrr OF Normt CAROUNA AT CHmEt HILt, CH~.PEt HiLL NC T/599-7248, USA. Studies of gene therapy for the treat- ment of cystic fibrosis (CF) lung dis- ease have been under way ha the lab- oratory for approximately five years and in clinical trials for the past two years. In this commentary, I shall review the goals for CF gene therapy, predinical data and results of human clinical trims, and directions for the future. Because most oftbe published data relate to adenoviral vectors, the emphasis will be on these vectors, although more limited, but interest- ing, experiments with other vectors will also be cited. Goals of CF gene theral~ In general, CF lung disease can be viewed as a failure of airway defense against bacterial infection. The goal of gene therapy in young children is to prevent the generation of infectious lung disease, whereas the realistic goal in CF patients with established lung disease is to prevent a further loss of lung function. A pressing problem in CF research is that the pathophysiology of CF air- way infection has not been eluci- dated. The simplest .scenario is that the loss of function of the cystic fi- brosis transmembrane conductance regulator (C.~I'R) protein, due to a mutation in the CFTR gene, perturbs the salt and water composition of secretions, slows the mucociliary clearance of airways and promotes infection. This ~co.nario does not explain the predilection for infection in CF with