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Journal of Extracellular Vesicles
Article . 2025 . Peer-reviewed
License: CC BY
Data sources: Crossref
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PubMed Central
Article . 2025
License: CC BY
Data sources: PubMed Central
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Hybrid Extracellular Vesicles for Efficient Loading and Functional Delivery of mRNA

Authors: Xiaoqin Wang; Michael J. Munson; Kristina Friis; Anna Marzeda; Andreia M. Silva; Franziska Kohl; Leif Hultin; +2 Authors

Hybrid Extracellular Vesicles for Efficient Loading and Functional Delivery of mRNA

Abstract

ABSTRACT Extracellular vesicles (EVs) are an attractive delivery vehicle with biological activity, intrinsic homing, low immunogenicity, and engineerability; however, challenges remain regarding loading and functional delivery of mRNA. Here, we developed a novel approach to load mRNA through low pH‐induced fusion of EVs with lipid nanoparticles (LNPs) to generate hybrid EVs (HEVs). Conventional characterization showed that HEVs preserved classical features of EVs. Single particle analysis revealed successful loading of mRNA and incorporation of LNP components into HEVs. The combined properties from EV and LNP contributed to the excellent cell tolerability of HEV, overcoming dose‐limit toxicity, and functional delivery of mRNA by HEV. We further elucidated the mechanism of HEV‐mediated intracellular delivery of mRNA. Our results showed that in contrast to source EVs, HEVs were capable of inducing endosomal escape, facilitating intracellular delivery of mRNA. Furthermore, HEVs functionally delivered mRNA in vivo and displayed extrahepatic delivery capacity with predominant functional distribution in spleen. Our results suggest HEVs as a promising EV‐based delivery platform for mRNA delivery.

Related Organizations
Keywords

Extracellular Vesicles, Mice, Liposomes, Gene Transfer Techniques, Animals, Nanoparticles, Humans, RNA, Messenger, Research Article

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    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).
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    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.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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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!
13
Top 10%
Average
Top 10%
Green
gold