Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Despite hope that a cure was imminent when the causative gene was cloned nearly 30 years ago, cystic fibrosis (CF [MIM: 219700]) remains a life-shortening disease affecting more than 70 000 individuals worldwide. However, within the last 6 years the Food and Drug Administration's approval of Ivacaftor, the first drug that corrects the defective cystic fibrosis transmembrane conductance regulator protein [CFTR (MIM: 602421)] in patients with the G551D mutation, marks a watershed in the development of novel therapeutics for this devastating disease. Here we review recent progress in diverse research areas, which all focus on curing CF at the genetic, biochemical or physiological level. In the near future it seems probable that development of mutation-specific therapies will be the focus, since it is unlikely that any one approach will be efficient in correcting the more than 2000 disease-associated variants. We discuss the new drugs and combinations of drugs that either enhance delivery of misfolded CFTR protein to the cell membrane, where it functions as an ion channel, or that activate channel opening. Next we consider approaches to correct the causative genetic lesion at the DNA or RNA level, through repressing stop mutations and nonsense-mediated decay, modulating splice mutations, fixing errors by gene editing or using novel routes to gene replacement. Finally, we explore how modifier genes, loci elsewhere in the genome that modify CF disease severity, may be used to restore a normal phenotype. Progress in all of these areas has been dramatic, generating enthusiasm that CF may soon become a broadly treatable disease.

Original publication




Journal article


Human molecular genetics

Publication Date





R173 - R186