Enhanced delivery of peptide-morpholino oligonucleotides with a small molecule to correct splicing defects in the lung.

ABSTRACT: Pulmonary diseases offer many targets for oligonucleotide therapeutics. However, effective delivery of oligonucleotides to the lung is challenging. For example, splicing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) affect a significant cohort of Cystic Fibrosis (CF) patients. These individuals could potentially benefit from treatment with splice switching oligonucleotides (SSOs) that can modulate splicing of CFTR and restore its activity. However, previous studies in cell culture used oligonucleotide transfection methods that cannot be safely translated in vivo. In this report, we demonstrate effective correction of a splicing mutation in the lung of a mouse model using SSOs. Moreover, we also demonstrate effective correction of a CFTR splicing mutation in a

SUBMITTER: Dang Y 

PROVIDER: S-EPMC8216463 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature