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Exceptional Uptake, Limited Protein Expression: Liver Macrophages Lost in Translation of Synthetic mRNA.
Adv Sci (Weinh)
January 2025
Department of Internal Medicine III, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.
Most gene therapies exert their actions via manipulation of hepatocytes (parenchymal cells) and the reasons behind the suboptimal performance of synthetic mRNA in non-parenchymal cells (NPC) such as Kupffer cells (KC), and liver macrophages, remain unclear. Here, the spatio-temporal distribution of mRNA encoding enhanced green fluorescent protein (Egfp), siRNA, or both co-encapsulated into lipid nanoparticles (LNP) in the liver in vivo using real-time intravital imaging is investigated. Although both KC and hepatocytes demonstrate comparable high and rapid uptake of mRNA-LNP and siRNA-LNP in vivo, the translation of Egfp mRNA occurs exclusively in hepatocytes during intravital imaging.
View Article and Find Full Text PDFRelevance of RNA to the therapeutic efficacy of mesenchymal stromal/stem cells extracellular vesicles.
RNA Biol
December 2025
Paracrine Therapeutics Pte. Ltd, Tai Seng Exchange, Singapore, Singapore.
Mesenchymal Stromal/Stem Cells (MSCs) are among the most frequently studied cell types in clinical trials, and their small extracellular vesicles (sEVs) are now being extensively investigated for therapeutic applications. The RNA cargo of MSC-sEVs, particularly miRNAs and mRNAs, is widely believed to be a key therapeutic component of these vesicles. In this review, we critically examine using first principles and peer-reviewed literature, whether MSC- extracellular vesicles (MSC-EVs) can deliver sufficient quantity of functional miRNA or mRNA to target compartments within recipient cells to elicit a pharmacological response.
View Article and Find Full Text PDFControl of iron acquisition by multiple small RNAs unravels a new role for transcriptional terminator loops in gene regulation.
Nucleic Acids Res
December 2024
Expression Génétique Microbienne, UMR8261 CNRS, Université Paris Cité, Institut de Biologie Physico-Chimique, 75005 Paris, France.
Article Synopsis
- Small RNAs (sRNAs) play a crucial role in regulating gene expression in bacteria by base-pairing with mRNAs, influencing genes related to iron homeostasis.
- Five additional sRNAs (RprA, RybB, ArrS, RseX, and SdsR) are identified as repressors of the fepA gene, each using unique mechanisms independent from one another.
- The regulation of fepA involves complex interactions with other molecules, such as the Hfq chaperone and RNase E, indicating that precise control of FepA levels is vital for bacterial adaptation to different environments.
Biomimetic mesenchymal stem cell membrane-coated nanoparticle delivery of MKP5 inhibits hepatic fibrosis through the IRE/XBP1 pathway.
J Nanobiotechnology
November 2024
School of Pharmaceutical Sciences, Jilin University, 1266 Fujin Road, Changchun, 130021, Jilin, China.
Article Synopsis
- Hepatic fibrosis is a serious disease with high rates of illness and death, but its mechanisms are not well understood, making treatment development difficult.
- The study found that lower levels of MKP5 in liver tissues from mice with fibrosis lead to more severe disease and suggested that MKP5 operates by blocking harmful cell activation and apoptosis through a specific cellular pathway.
- Creating nanoparticles that deliver MKP5 effectively reduced liver inflammation and fibrosis in mice, indicating that targeted therapy using MKP5 might be a new way to treat this condition.
Deciphering the biophysical aspects of the interaction of 3,5,4'-trihydroxy-trans-stilbene with ribonuclease A: spectroscopic and computational studies.
Naunyn Schmiedebergs Arch Pharmacol
November 2024
GITAM School of Pharmacy, GITAM Deemed to Be University, Hyderabad, 502329, India.
Drug-receptor interaction is an important aspect in drug action, drug discovery, and pharmacological aspects. The molecule 3,5,4'-trihydroxy-trans-stilbene known as resveratrol is a natural polyphenol and exhibits diverse biological activities. Ribonuclease A catalyses the degradation of RNA by its ribonucleolytic activity.
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