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Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
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The selection of a drug's delivery route depends upon its physicochemical properties, including lipid or water solubility and ionization, as well as the therapeutic requirement, such as immediate or sustained effect. These routes can be divided into three primary categories: enteral, parenteral, and topical.
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Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of...
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Related Experiment Video

Updated: Aug 19, 2025

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
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Hybrid core-shell particles for mRNA systemic delivery.

Valentina Andretto1, Mathieu Repellin1, Marine Pujol1

  • 1Univ. Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007, 43 Boulevard du 11 Novembre 1918, F-69622, Villeurbanne, France.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|November 28, 2022
PubMed
Summary
This summary is machine-generated.

Hyaluronic acid coating modifies liposome-mRNA complexes, creating hybrid nanoparticles with altered surface charge and efficient mRNA delivery in vitro and in vivo. This surface modification offers a tool for optimizing nanomedicines for therapeutic applications.

Keywords:
Core-shell nanoparticlesHyaluronic acidHybrid lipid-polymer nanoparticlesIVT mRNAIn vivo biodistributionLipoplexes

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Drug Delivery

Background:

  • Messenger RNA (mRNA) therapeutics require effective delivery systems.
  • Lipid-polymer hybrid nanoparticles offer tailored properties for nucleic acid delivery.
  • Hyaluronic acid (HA) coating is explored to modify liposome-mRNA complexes (LRCs).

Purpose of the Study:

  • To investigate the effects of HA coating on LRCs' surface charge, physicochemical characteristics, and biological activity.
  • To evaluate the potential of HA-coated LRCs (HLRCs) as a nanomedicine delivery platform.
  • To assess the in vitro and in vivo performance of HLRCs.

Main Methods:

  • Fabrication of HA-coated LRCs (HLRCs) via electrostatic attachment.
  • Physicochemical characterization including size, surface charge, and mRNA binding.
  • In vitro transfection efficiency assessment in THP-1 and PBMC-derived monocytes.
  • In vivo biodistribution and protein translation studies using radiolabeled particles and bioluminescence in mice.

Main Results:

  • HLRCs exhibited a negative surface charge compared to positive LRCs, with similar size (~200 nm) and mRNA binding.
  • High in vitro transfection efficiency was observed in target immune cells.
  • In vivo studies indicated particle accumulation in the hepatic reticuloendothelial system (RES).
  • mRNA protein expression was predominantly found in the spleen, particularly in macrophages.

Conclusions:

  • Surface modification of LRCs with HA can fine-tune nanoparticle properties.
  • HLRCs demonstrate potential as stable and optimized nanoparticles for mRNA-based nanomedicines.
  • This approach provides a valuable tool for developing advanced nucleic acid therapeutics.