Nebulisation of IVT mRNA Complexes for Intrapulmonary Administration

PloS One
Sarah M JohlerJ Rosenecker

Abstract

During the last years the potential role of in vitro transcribed (IVT) mRNA as a vehicle to deliver genetic information has come into focus. IVT mRNA could be used for anti-cancer therapies, vaccination purposes, generation of pluripotent stem cells and also for genome engineering or protein replacement. However, the administration of IVT mRNA into the target organ is still challenging. The lung with its large surface area is not only of interest for delivery of genetic information for treatment of e.g. for cystic fibrosis or alpha-1-antitrypsin deficiency, but also for vaccination purposes. Administration of IVT mRNA to the lung can be performed by direct intratracheal instillation or by aerosol inhalation/nebulisation. The latter approach shows a non-invasive tool, although it is not known, if IVT mRNA is resistant during the process of nebulisation. Therefore, we investigated the transfection efficiency of non-nebulised and nebulised IVT mRNA polyplexes and lipoplexes in human bronchial epithelial cells (16HBE). A slight reduction in transfection efficiency was observed for lipoplexes (Lipofectamine 2000) in the nebulised part compared to the non-nebulised which can be overcome by increasing the amount of Lipofectamine. Howe...Continue Reading

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Citations

Jan 5, 2019·Advanced Materials·Asha Kumari PatelDaniel G Anderson
Jan 25, 2020·Nanomaterials·Jorge F Pontes, Ana Grenha
May 14, 2020·Journal of Personalized Medicine·Sean D McCarthyBrendan D Higgins
Jul 28, 2016·Biochemistry. Biokhimii︠a︡·O V SergeevaT S Zatsepin
Jun 9, 2020·Advanced Drug Delivery Reviews·Michael Y T ChowHak-Kim Chan
Jun 25, 2021·Advanced Healthcare Materials·Marcelo Calderón, Sarah Hedtrich
Nov 11, 2021·Accounts of Chemical Research·Ming QinXun Sun

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Methods Mentioned

BETA
transfection
fluorescence
flow
flow cytometry
FCS
transfect
transfecting

Software Mentioned

FCS Express
GraphPad Prism

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