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

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 th...

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Autores principales: Darade, Aditya R., Lapteva, Maria, Hoffmann, Thomas, Mandler, Markus, Schneeberger, Achim, Kalia, Yogeshvar N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780332/
https://www.ncbi.nlm.nih.gov/pubmed/35057047
http://dx.doi.org/10.3390/pharmaceutics14010151
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author Darade, Aditya R.
Lapteva, Maria
Hoffmann, Thomas
Mandler, Markus
Schneeberger, Achim
Kalia, Yogeshvar N.
author_facet Darade, Aditya R.
Lapteva, Maria
Hoffmann, Thomas
Mandler, Markus
Schneeberger, Achim
Kalia, Yogeshvar N.
author_sort Darade, Aditya R.
collection PubMed
description 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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spelling pubmed-87803322022-01-22 Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression Darade, Aditya R. Lapteva, Maria Hoffmann, Thomas Mandler, Markus Schneeberger, Achim Kalia, Yogeshvar N. Pharmaceutics Article 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. MDPI 2022-01-08 /pmc/articles/PMC8780332/ /pubmed/35057047 http://dx.doi.org/10.3390/pharmaceutics14010151 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Darade, Aditya R.
Lapteva, Maria
Hoffmann, Thomas
Mandler, Markus
Schneeberger, Achim
Kalia, Yogeshvar N.
Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression
title Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression
title_full Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression
title_fullStr Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression
title_full_unstemmed Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression
title_short Effect of mRNA Delivery Modality and Formulation on Cutaneous mRNA Distribution and Downstream eGFP Expression
title_sort effect of mrna delivery modality and formulation on cutaneous mrna distribution and downstream egfp expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780332/
https://www.ncbi.nlm.nih.gov/pubmed/35057047
http://dx.doi.org/10.3390/pharmaceutics14010151
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