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Science Advances
Article . 2025 . Peer-reviewed
Data sources: Crossref
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Science Advances
Article . 2025
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PubMed Central
Other literature type . 2025
License: CC BY NC
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Enhancing mRNA therapy through iterative delivery

Authors: Joshua Seaberg; Suresh Kumar Gulla; Jocelyn Labombarde; Ram Roy; Shailendra Kumar Dhar Dwivedi; Chao Xu; Susan Kovats; +2 Authors

Enhancing mRNA therapy through iterative delivery

Abstract

Clinical translation of therapeutic messenger RNA (mRNA) technologies, particularly in solid tumors, has been limited due to unavailability of effective delivery systems. Here, we describe an mRNA delivery system that overcomes current challenges by co-encapsulating gold nanoparticles (AuNPs) and mRNA within non-ionic surfactant vehicles (NSVs) to create “Aurniosoves” (AuNSVs). Through in vitro and in vivo studies, we demonstrate that AuNSVs improve vector accumulation and uptake within the tumor, resulting in enhanced protein expression and therapeutic efficacy. Mechanistically, these effects are the result of an iterative delivery process in which AuNSVs enter cells initially through clathrin-mediated endocytosis (CME) and release AuNPs into the cytoplasm. AuNPs subsequently adsorb and inactivate cellular trafficking regulators PP2A and Rab7, producing two effects: (i) rapid entry of additional AuNSVs through activation of caveolin-mediated endocytosis (CvME) and (ii) endosomal escape through inhibited endolysosomal fusion. We propose that AuNSVs be exploited as next-generation mRNA delivery systems.

Keywords

Gene Transfer Techniques, Metal Nanoparticles, rab7 GTP-Binding Proteins, Endosomes, Endocytosis, Mice, Drug Delivery Systems, rab GTP-Binding Proteins, Cell Line, Tumor, Humans, Animals, Biomedicine and Life Sciences, RNA, Messenger, Gold

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
Green
gold