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Abstract The placenta is a transient organ that forms during pregnancy and acts as a biological barrier, mediating exchange between maternal and fetal circulation. Placental disorders, such as preeclampsia, fetal growth restriction, placenta accreta spectrum, and gestational trophoblastic disease, originate in dysfunctional placental development during pregnancy and can lead to severe complications for both the mother and fetus. Unfortunately, treatment options for these disorders are severely lacking. Challenges in designing therapeutics for use during pregnancy involve selectively delivering payloads to the placenta while protecting the fetus from potential toxic side effects. Nanomedicine holds great promise in overcoming these barriers; the versatile and modular nature of nanocarriers, including prolonged circulation times, intracellular delivery, and organ‐specific targeting, can control how therapeutics interact with the placenta. In this review, nanomedicine strategies are discussed to treat and diagnose placental disorders with an emphasis on understanding the unique pathophysiology behind each of these diseases. Finally, prior study of the pathophysiologic mechanisms underlying these placental disorders has revealed novel disease targets. These targets are highlighted here to motivate the rational design of precision nanocarriers to improve therapeutic options for placental disorders. 

Abstract With six therapies approved by the Food and Drug Association, chimeric antigen receptor (CAR) T cells have reshaped cancer immunotherapy. However, these therapies rely on ex vivo viral transduction to induce permanent CAR expression in T cells, which contributes to high production costs and long‐term side effects. Thus, this work aims to develop an in vivo CAR T cell engineering platform to streamline production while using mRNA to induce transient, tunable CAR expression. Specifically, an ionizable lipid nanoparticle (LNP) is utilized as these platforms have demonstrated clinical success in nucleic acid delivery. Though LNPs often accumulate in the liver, the LNP platform used here achieves extrahepatic transfection with enhanced delivery to the spleen, and it is further modified via antibody conjugation (Ab‐LNPs) to target pan‐T cell markers. The in vivo evaluation of these Ab‐LNPs confirms that targeting is necessary for potent T cell transfection. When using these Ab‐LNPs for the delivery of CAR mRNA, antibody and dose‐dependent CAR expression and cytokine release are observed along with B cell depletion of up to 90%. In all, this work conjugates antibodies to LNPs with extrahepatic tropism, evaluates pan‐T cell markers, and develops Ab‐LNPs capable of generating functional CAR T cells in vivo. 

Abstract During healthy pregnancy, the placenta develops to allow for exchange of nutrients and oxygen between the mother and the fetus. However, placental dysregulation can lead to several pregnancy disorders, such as preeclampsia and fetal growth restriction. Recently, lipid nanoparticle (LNP)‐mediated delivery of messenger RNA (mRNA) has been explored as a promising approach to treat these disorders. Here, iterative libraries of LNPs with varied excipient molar ratios are screened in vitro for enhanced mRNA delivery to placental cells with minimal cytotoxicity when compared to an LNP formulation with a standard excipient molar ratio. LNP C5, the top formulation identified by these screens, demonstrates a fourfold increase in mRNA delivery in vitro compared to the standard formulation. Intravenous administration of LNP C5 to pregnant mice achieves improved in vivo placental mRNA delivery compared to the standard formulation and mediates mRNA delivery to placental trophoblasts, endothelial cells, and immune cells. These results identify LNP C5 as a promising optimized LNP formulation for placental mRNA delivery and further validates the design of experiments strategy for LNP excipient optimization to enhance mRNA delivery to cell types and organs of interest. 

Wastewater surveillance for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging approach to help identify the risk of a coronavirus disease (COVID-19) outbreak. This tool can contribute to public health surveillance at both community (wastewater treatment system) and institutional (e.g., colleges, prisons, and nursing homes) scales. This paper explores the successes, challenges, and lessons learned from initial wastewater surveillance efforts at colleges and university systems to inform future research, development and implementation. We present the experiences of 25 college and university systems in the United States that monitored campus wastewater for SARS-CoV-2 during the fall 2020 academic period. We describe the broad range of approaches, findings, resources, and impacts from these initial efforts. These institutions range in size, social and political geographies, and include both public and private institutions. Our analysis suggests that wastewater monitoring at colleges requires consideration of local information needs, sewage infrastructure, resources for sampling and analysis, college and community dynamics, approaches to interpretation and communication of results, and follow-up actions. Most colleges reported that a learning process of experimentation, evaluation, and adaptation was key to progress. This process requires ongoing collaboration among diverse stakeholders including decision-makers, researchers, faculty, facilities staff, students, and community members.