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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.
Pharmaceutics
|January 21, 2022
Summary
This study compared four methods for delivering messenger ribonucleic acid (mRNA) to the skin. Microneedle and laser ablation showed promising results for targeted mRNA delivery and expression in skin cells.
Area of Science:
- Biotechnology
- Dermatology
- Pharmacology
Background:
- Messenger ribonucleic acid (mRNA) therapeutics are a rapidly advancing field with broad clinical potential.
- Effective delivery of mRNA to target tissues, particularly the skin, remains a critical challenge for therapeutic development.
Purpose of the Study:
- To systematically compare the efficacy of four distinct technologies for topical cutaneous mRNA delivery: intradermal injection, microneedle injection, jet injection, and fractional laser ablation.
- To evaluate the biodistribution and expression of mRNA within ex vivo skin models following delivery via these different modalities.
Main Methods:
- Utilized a viable ex vivo porcine skin model to assess delivery of Cy5-labeled mRNA and enhanced green fluorescent protein (eGFP)-expressing mRNA.
- Employed confocal laser scanning microscopy and immunohistochemistry on 40 µm-thick skin sections to visualize mRNA localization and eGFP expression.
- Quantified mRNA and protein distribution using a pixel-based method to generate semi-quantitative biodistribution profiles over 48 hours.
Main Results:
- Observed distinct spatial distributions of Cy5-labeled mRNA and eGFP expression patterns dependent on the delivery technology used.
- Demonstrated that localization of eGFP expression correlated with specific cell types, indicating successful cellular uptake and translation.
- Microneedle injection and fractional laser ablation showed potential for deeper and more targeted mRNA delivery compared to other methods.
Conclusions:
- The choice of delivery technology significantly impacts the biodistribution and cellular localization of mRNA within the skin.
- Understanding the delivery site and efficiency of different modalities is crucial for optimizing the development of targeted mRNA-based therapies.
- Further research into these delivery systems can accelerate the clinical translation of topical mRNA therapeutics.
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