Translational research to enable personalized treatment of cystic fibrosis

Abstract

Translational research efforts in cystic fibrosis (CF) aim to develop therapies for all subjects with CF. To reach this goal new therapies need to be developed that target multiple aspects of the disease. To enable individuals to benefit maximally from these treatments will require improved methods to tailor these therapies specifically to individuals who suffer from CF. This report highlights current examples of translational CF research efforts to reach this goal. The use of intestinal organoids and genetics to better understand individual assessment of CFTR modulator treatment effects to ultimately enable a better personalized treatment for CF subjects will be discussed. In addition, development of viral vectors and non-viral synthetic nanoparticles for delivery of mRNA, sgRNA and DNA will be highlighted. New approaches to restore function of CFTR with early premature termination codons using nanoparticle delivery of suppressor tRNAs and new insights into mechanisms of airway epithelial repair will be reviewed as well. The state-of-the-art approaches that are discussed in this review demonstrate significant progress towards the development of optimal individual therapies for CF patients, but also reveal that remaining challenges still lie ahead.

Keywords: CFTR modulator; Cystic fibrosis; Gene therapy; Nanoparticles; Personalized medicine; Translational research; tRNA.