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Updated: Oct 6, 2025

Using Lipid Nanoparticles for the Delivery of Chemically Modified mRNA into Mammalian Cells
Published on: June 10, 2022
Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression
Aditya R Darade1,2, Maria Lapteva1,2, Thomas Hoffmann3
1School of Pharmaceutical Sciences, University of Geneva, CMU, 1 Rue Michel-Servet, 1211 Geneva, Switzerland.
Abstract:
In vitro transcribed messenger ribonucleic acid (mRNA) constitutes an emerging therapeutic class with several clinical applications. This study presents a systematic comparison of different technologies-intradermal injection, microneedle injection, jet injection, and fractional laser ablation-for the topical cutaneous delivery of mRNA. Delivery of Cy5 labeled mRNA and non-labeled enhanced green fluorescent protein (eGFP) expressing mRNA was investigated in a viable ex vivo porcine skin model and monitored for 48 h. Forty 10 µm-thick horizontal sections were prepared from each skin sample and Cy5 labeled mRNA or eGFP expression visualized as a function of depth by confocal laser scanning microscopy and immunohistochemistry. A pixel-based method was used to create a semi-quantitative biodistribution profile. Different spatial distributions of Cy5 labeled mRNA and eGFP expression were observed, depending on the delivery modality; localization of eGFP expression pointed to the cells responsible. Delivery efficiencies and knowledge of delivery sites can facilitate development of efficient, targeted mRNA-based therapeutics.
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