Kamila Moskowitzova, Ashlyn E. Whitlock, Yash V. Shroff, David Zurakowski, Dario O. Fauza
{"title":"Transamniotic Fetal Delivery of Cystic Fibrosis (CF) Transmembrane Conductance Regulator (CFTR) mRNA","authors":"Kamila Moskowitzova, Ashlyn E. Whitlock, Yash V. Shroff, David Zurakowski, Dario O. Fauza","doi":"10.1096/fba.2025-00288","DOIUrl":"10.1096/fba.2025-00288","url":null,"abstract":"<p>We sought to determine whether a cystic fibrosis transmembrane conductance regulator (CFTR) mRNA could be administered to the fetus via the transamniotic route as a potential strategy for the perinatal management of cystic fibrosis-associated meconium ileus. Nine pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (<i>n</i> = 109) of either a suspension of a human CFTR mRNA encapsulated by a semi-synthetic composite, lipopolyplex (mRNA group; <i>n</i> = 98), or of a suspension of the same composite free of mRNA (control group; <i>n</i> = 11), on gestational day 17 (E17; term = E21). At daily time points until term, fetal small bowel and lungs, along with maternal serum, were quantitatively screened for the human CFTR protein by ELISA. Statistical analysis was by the nonparametric Wilcoxon rank sum test with Bonferroni adjustment. Overall fetal survival was 85.3% (93/109), with no significant differences between the groups or time points. When controlled by mRNA-free injections, human CFTR was detected in the small bowel from the mRNA group at all time points (<i>p</i> < 0.001 for all), increasing initially over time. Human CFTR was detected comparably in the lungs from both groups, suggesting interspecies homology at that anatomical site. No human CFTR was detected in maternal serum. Encapsulated exogenous mRNA encoding for the cystic fibrosis transmembrane conductance regulator protein can be incorporated and translated by fetal small bowel cells after simple intra-amniotic injection in a healthy rodent model. Transamniotic mRNA delivery could become a novel strategy for the perinatal management of meconium ileus associated with cystic fibrosis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aritra Bhadra, April Scruggs, April Haven, Morgan Malone, Natalie Bauer
{"title":"Pulmonary Endothelial Extracellular Vesicles Preferentially Interact and Are Processed in Pulmonary Endothelial Cells","authors":"Aritra Bhadra, April Scruggs, April Haven, Morgan Malone, Natalie Bauer","doi":"10.1096/fba.2025-00327","DOIUrl":"10.1096/fba.2025-00327","url":null,"abstract":"<p>Extracellular vesicles (EVs) regulate vascular injury and homeostasis; however, the intracellular mechanisms for the EV effects are unknown. While EV components and functions are well studied, their cellular uptake and intracellular processing remain unclear. Following our previous work on EVs, we investigated EV uptake mechanisms and organelle localization. Pulmonary endothelial–derived EVs showed preferential interaction with pulmonary vessels, particularly injured vessels. Co-culture experiments confirmed endothelial cells as exclusive EV targets via energy-dependent, clathrin-mediated endocytosis. Intracellularly, EVs colocalized with lysosomes and trans-Golgi, suggesting degradation and protein recycling pathways. These findings provide insights into temporal EV uptake dynamics and organelle interactions, establishing a foundation for understanding EV processing and content distribution mechanisms.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13052107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simulated Microgravity Causes Faster Replication During Acute Infection of ME49-Toxoplasma Gondii and Alterations in Host Cells","authors":"Musfika Tasnim Shirin, Takafumi Yamada, Iqra Zafar, Daisuke Kondoh, Hiroki Bochimoto, Hironori Bando, Oluyomi Stephen Adeyemi, Yasuhiro Fukuda, Kentaro Kato","doi":"10.1096/fba.2025-00287","DOIUrl":"https://doi.org/10.1096/fba.2025-00287","url":null,"abstract":"<p>Spaceflight is important to explore the universe. However, astronauts face many health challenges in space including the increased risk of infection. During spaceflight, the microgravity weakens immunity, which causes opportunistic infections with pathogens such as herpesvirus. However, we have no information about the effects of microgravity on infections caused by other pathogens with a latent stage in their life cycle. In addition, there are no reports on host cell responses or the mechanisms that modulate changes under microgravity conditions. Due to the high cost and effort required for space study in actual microgravity, simulated microgravity plays an important role in mimicking conditions that allow researchers to study risks during spaceflights. <i>Toxoplasma gondii</i> is one of the top five important economic pathogens; it causes toxoplasmosis, may reactivate from the latent phase in immunocompromised individuals, and there is no active drug or vaccine. In this study, we observed the effect of simulated microgravity on <i>T. gondii</i> and on host cells. Simulated microgravity using a 3D clinostat induced host cell proliferation and caused aggregated cells to form three dimensional multicellular spheroids in Vero cells and HFF. Rapid egress and growth of tachyzoites during the acute phase of type II ME49 infection were observed under simulated microgravity.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 4","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00287","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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