Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression

Pharmaceutics

Thomas Hoffmann¹  Markus Mandler¹  Achim Schneeberger¹  Yogeshvar N. Kalia²  Aditya R. Darade²  Maria Lapteva² 

[1] Accanis Biotech F&E GmbH & Co KG, Vienna Biocenter, Karl-Farkas-Gasse 22/OG 4, 1030 Vienna, Austria;School of Pharmaceutical Sciences, University of Geneva, CMU, 1 Rue Michel-Servet, 1211 Geneva, Switzerland;

关键词: mRNA delivery;    biodistribution;    intradermal injection;    jet injection;    microneedle injection;    fractional laser ablation;   

DOI  :  10.3390/pharmaceutics14010151

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown