Abstract

The microRNAs (miRNAs) are a group of regulatory non-coding RNAs, playing key roles in diverse biological processes, including pulmonary disfunctions. Dysregulation of miRNA levels in disease leads to aberrant downstream effects and offers an emerging area for therapeutic intervention. In particular, we are interested in blocking function of upregulated miRNA by short oligonucleotides – antagomirs. miR34a has gained attention within respiratory field, as it has been reported to play a role in pulmonary fibrosis, lung injury and oxidative stress responses. We have investigated a set of antagomirs targeted at miR34a. Compounds differ in internal chemistry design, length and conjugation. We report free uptake and target engagement of antagomirs on lung epithelial cell line, primary human bronchial epithelial cells and also cells cultured in air-liquid interface (ALI). Results demonstrate how chemical modification can affect properties of synthetic miRNA modulators. This work lays ground for the synthesis of tool antagomirs for in vitro target validation in advanced cell model systems relevant to respiratory disease.