Ganglioside-incorporating lipid nanoparticles as a polyethylene glycol-free mRNA delivery platform

Jan 21, 2025Biomaterials science

Lipid nanoparticles with gangliosides as a PEG-free platform for delivering mRNA

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Abstract

Ganglioside-LNPs displayed superior stability during prolonged cold storage compared to stealth-free LNPs.

Anti-PEG neutralizing antibodies have been linked to adverse reactions such as anaphylaxis and accelerated clearance of PEGylated LNPs.
Ganglioside-LNPs prevented particle aggregation, indicating effective stability without the use of PEG.
No significant change in particle size occurred after serum incubation with ganglioside-LNPs, suggesting resistance to unwanted protein adsorption.
Ganglioside-LNPs resulted in significantly higher mRNA transfection following intravenous administration compared to stealth-free LNPs.
Ganglioside shows potential as a natural alternative to PEG in mRNA-LNP delivery systems for gene therapy.

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Incorporation of polyethylene glycol (PEG) is widely used in lipid nanoparticle (LNP) formulation in order to achieve adequate stability due to its stealth properties. However, studies have detected the presence of anti-PEG neutralizing antibodies after PEGylated LNP treatment, which are associated with anaphylaxis, accelerated LNP clearance and premature release of cargo. Here, we report the development of LNPs incorporating ganglioside, a naturally occurring stealth lipid, as a PEG-free alternative. Physicochemical characterization showed that ganglioside-LNPs exhibited superior stability throughout prolonged cold storage compared to stealth-free LNPs, preventing particle aggregation. Additionally, there was no significant change in particle size after serum incubation, indicating the ability of ganglioside to prevent unwanted serum protein adsorption. These results exemplify the effective stealth properties of ganglioside. Furthermore, ganglioside-LNPs exhibited significantly higher mRNA transfectionafter intravenous administration compared to stealth-free LNPs. The ability of ganglioside to confer excellent stealth properties to LNPs while still enablingmRNA expression makes it a promising candidate as a natural substitute for immunogenic PEG in mRNA-LNP delivery platforms, contributing to the future advancement of gene therapy. in vivo in vivo

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Ganglioside-incorporating lipid nanoparticles as a polyethylene glycol-free mRNA delivery platform

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