Non-viral mRNA cystic fibrosis therapies and their ongoing clinical trials

Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, leading to impaired ion transport by the CFTR protein and accumulation of thick, sticky mucus, resulting in chronic lung disease and other organ complications. Messenger ribonucleic acid (mRNA) therapies hold great potential for CF, as they can be used for both CFTR mRNA replacement and editing of the CFTR gene, which could mitigate the pathophysiological and clinical symptoms of CF.

We provide an overview of non-viral mRNA therapies for CF and their ongoing clinical trials. We begin with a discussion of the pathophysiological functions of CFTR and clinical symptoms of CF. We provide a summary of conventional treatments, modulator therapies, and potential gene therapies for CF. We discuss the pertinence of mRNA therapies for CF as well as the challenges associated with mRNA delivery. We conclude with an overview of non-viral vectors for mRNA delivery and a summary of clinical trials for CFTR mRNA therapies. Literature searches for this review were performed using databases (Google Scholar and PubMed).

With continued innovation and overcoming of delivery challenges, mRNA therapies hold great potential for the treatment of people with CF, regardless of mutation.