Biodistribution of lipid nanoparticle, eGFP mRNA and translated protein following subcutaneous administration in mouse.

Bioanalysis

Integrated Bioanalysis, Clinical Pharmacology & Safety Sciences, BioPharmaceutical R&D, AstraZeneca, Pepparredsleden 1, Mölndal, SE 43183, Sweden.

Published: September 2024

Increased knowledge of biodistribution and pharmacokinetics of lipid nanoparticle (LNP)-encapsulated mRNA drug components may aid efficacy and safety evaluation. Mice were subcutaneously administrated LNP encapsulated enhanced green fluorescent protein mRNA and sampled up to 72 h after dosing. LNP, mRNA and translated protein were quantified by LC-MS, branched DNA and ELISA. Highest levels of LNP and mRNA were detected in skin, followed by spleen, but also rapidly distributed to circulation. Translated protein showed high concentration in skin and spleen, but also in liver and kidney across 24 h where the LNP was cleared at 4 h. Subcutaneously dosing LNP encapsulated mRNA in mice resulted in a nonlinear relationship of LNP, mRNA and protein concentration across multiple tissues.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389730PMC
http://dx.doi.org/10.1080/17576180.2024.2360361DOI Listing

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