{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:50:25Z","timestamp":1781311825762,"version":"3.54.1"},"reference-count":44,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"crossref","award":["CiC013"],"award-info":[{"award-number":["CiC013"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000761","name":"Imperial College London","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000761","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>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\u2005days 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.<\/jats:p>","DOI":"10.1242\/bio.062419","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T12:09:03Z","timestamp":1781266143000},"source":"Crossref","is-referenced-by-count":1,"title":["Investigating the impact of poly(beta amino) ester-mediated\n                    <i>FOXJ1<\/i>\n                    mRNA delivery on differentiation of primary human bronchial epithelial cells"],"prefix":"10.1242","volume":"15","author":[{"given":"Rafaela","family":"Konstantinidi","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Subramanian","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Yates","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-6726","authenticated-orcid":false,"given":"Clare M.","family":"Lloyd","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5192-6418","authenticated-orcid":false,"given":"Sejal","family":"Saglani","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["UK"]},{"name":"Royal Brompton Hospital, Guy's and St Thomas\u2019 NHS Foundation Trust 2 , London SW3 6NP ,","place":["UK"]},{"name":"Centre for Paediatrics and Child Health 3 , Imperial College London, London SW7 2AZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7266-9251","authenticated-orcid":false,"given":"Asha K.","family":"Patel","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London 1 , London W12 0NN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"2026061208085814800_BIO062419C1","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1038\/s41587-021-00822-w","article-title":"Treatment of influenza and SARS-CoV-2 infections via mRNA-encoded Cas13a in rodents","volume":"39","author":"Blanchard","year":"2021","journal-title":"Nat. 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