Discovery of peptides for ligand-mediated delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia.

ABSTRACT: For cystic fibrosis patients, a lung-targeted gene therapy would significantly alleviate pulmonary complications associated with morbidity and mortality. However, mucus in the airways and cell entry pose huge delivery barriers for local gene therapy. Here, we used phage display technology to select for and identify mucus- and cell-penetrating peptides against primary human bronchial epithelial cells from cystic fibrosis patients cultured at the air-liquid interface. At the air-liquid interface, primary human bronchial epithelial cells produce mucus and reflect cystic fibrosis disease pathology, making it a clinically relevant model. Using this model, we discovered a lead candidate peptide and incorporated it into lipid nanoparticles to deliver mRNA to primary human bronchial epithelia i

SUBMITTER: Soto MR 

PROVIDER: S-EPMC11617931 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature