ArticleBiology open2026
Investigating the impact of poly(beta amino) ester-mediated FOXJ1 mRNA delivery on differentiation of primary human bronchial epithelial cells.
Article in Biology open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Primary human basal bronchial epithelial cells (HBECs) are an important population of progenitor cells capable of self-renewal and differentiation to maintain airway homeostasis. In air-liquid interface (ALI) culture, HBECs undergo mucociliary differentiation, providing a robust physiologic model to evaluate novel therapeutics such as in vitro-transcribed messenger RNA (IVT-mRNA). However, the impact of IVT-mRNA delivery on the differentiation potential of basal HBECs remains poorly characterised. Poly(beta amino) ester (PBAE) nanoparticles have demonstrated effective airway delivery of IVT-mRNA in various preclinical studies. Here, we aimed to understand the impact of PBAE-mediated mRNA transfection on basal HBEC differentiation at the ALI. We investigated IVT-mRNA encoding the ciliogenesis transcription factor Forkhead box J1 (FOXJ1) as a model tool for transient overexpression in primary basal HBECs and characterised its subsequent impact on epithelial integrity and differentiation at the ALI. PBAE-mediated delivery of FOXJ1 mRNA to submerged primary HBECs resulted in approximately 50% FOXJ1-positive cells and transient upregulation of key ciliogenesis-related genes, including DNALI1 and RSPH9. Following 28 days of differentiation at the ALI, FOXJ1- or reporter mRNA-transfected cultures displayed normal epithelial morphology, with tight junction and differentiation markers, proportions of secretory and ciliated cells, and ciliary ultrastructure comparable to those of non-transfected controls. These data indicate that PBAE-mediated IVT-mRNA delivery can transiently increase encoded protein expression in basal primary HBECs without impeding mucociliary differentiation.
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