Primary human basal bronchial epithelial cells (HBECs) are vital for airway homeostasis. Currently, researchers are investigating **FOXJ1 mRNA delivery** through poly(beta amino) ester (PBAE) nanoparticles. Because these progenitor cells undergo mucociliary differentiation, they serve as an ideal model for testing novel therapeutics. Consequently, evaluating how synthetic mRNA affects these cells is essential for clinical progress. Moreover, this specific study aimed to characterize the impact of transfection on long-term epithelial integrity.

Success in FOXJ1 mRNA Delivery and Cellular Integrity

The experimental results showed that PBAE-mediated delivery was highly effective. Specifically, it resulted in approximately 50% FOXJ1-positive cells within the population. Furthermore, the researchers observed a transient upregulation of key ciliogenesis genes. In addition, the expression of DNALI1 and RSPH9 increased significantly following the transfection. Therefore, the treatment successfully induced the desired transcription factor without causing permanent genetic modifications. However, the most important finding was the lack of negative effects on maturation. Consequently, after 28 days of differentiation, the cells displayed normal epithelial morphology. Similarly, the tight junction and differentiation markers remained comparable to non-transfected controls. Thus, the method appears safe for potential therapeutic use in respiratory medicine. For this reason, scientists believe that PBAE-mediated delivery holds great promise for treating chronic airway conditions. Consequently, it enables encoded protein expression without impeding natural cell maturation processes. Additionally, this approach avoids the risks associated with viral delivery systems.

What is the function of the FOXJ1 transcription factor?

FOXJ1 is a critical protein that regulates the development of motile cilia in the human airway. It ensures that the bronchial epithelium can effectively clear mucus and foreign particles through a process known as ciliogenesis.

Can PBAE nanoparticles deliver mRNA safely?

Yes, recent research indicates that PBAE-mediated delivery can transiently increase protein expression without disrupting the normal differentiation or structural integrity of primary human bronchial epithelial cells.

Disclaimer: This content is for informational and educational purposes only. It does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

Konstantinidi R et al. Investigating the impact of poly(beta amino) ester-mediated FOXJ1 mRNA delivery on differentiation of primary human bronchial epithelial cells. Biol Open. 2026 Jun 15. doi: undefined. PMID: 42283488.

Kaczmarek JC et al. Polymer-based nanoparticles for delivery of mRNA to the lung. Genome Med. 2017;9(1):60. doi: 10.1186/s13073-017-0449-3.

Wang H et al. PBAE-PEG based lipid nanoparticles for lung cell-specific gene delivery. ResearchGate. 2026 May. DOI: 10.13140/RG.2.2.14567.89101.