Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells

Abstract Gene electrotransfer is an attractive method of non-viral gene delivery. However, the mechanism of DNA penetration across the plasma membrane is widely discussed. To explore this process for even larger structures, like viruses, we applied various combinations of short/long and high/low-amp...

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Autores principales:	Angela Tesse, Franck M. André, Thierry Ragot
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1779cd4d627b483688d7f8a47ef2409d
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spelling	oai:doaj.org-article:1779cd4d627b483688d7f8a47ef2409d2021-12-02T17:19:17ZAluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells10.1038/s41598-021-96781-y2045-2322https://doaj.org/article/1779cd4d627b483688d7f8a47ef2409d2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96781-yhttps://doaj.org/toc/2045-2322Abstract Gene electrotransfer is an attractive method of non-viral gene delivery. However, the mechanism of DNA penetration across the plasma membrane is widely discussed. To explore this process for even larger structures, like viruses, we applied various combinations of short/long and high/low-amplitude electric pulses to L929 cells, mixed with a human adenovirus vector expressing GFP. We observed a transgene expression increase, both in the number of GFP-converted cells and GFP levels, when we added a low-voltage/millisecond-pulse treatment to the adenovirus/cell mixture. This increase, reflecting enhanced virus penetration, was proportional to the applied electric field amplitude and pulse number, but was not associated with membrane permeabilization, nor to direct cell modifications. We demonstrated that this effect is mainly due to adenovirus particle interactions with aggregated aluminum particles released from energized electrodes. Indeed, after centrifugation of the pulsed viral suspension and later on addition to cells, the activity was found mainly associated with the aluminum aggregates concentrated in the lower fraction and was proportional to generated quantities. Overall, this work focused on the use of electrotransfer to facilitate the adenovirus entry into cell, demonstrating that modifications of the penetrating agent can be more important than modifications of the target cell for transfer efficacy.Angela TesseFranck M. AndréThierry RagotNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Angela Tesse Franck M. André Thierry Ragot Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells
description	Abstract Gene electrotransfer is an attractive method of non-viral gene delivery. However, the mechanism of DNA penetration across the plasma membrane is widely discussed. To explore this process for even larger structures, like viruses, we applied various combinations of short/long and high/low-amplitude electric pulses to L929 cells, mixed with a human adenovirus vector expressing GFP. We observed a transgene expression increase, both in the number of GFP-converted cells and GFP levels, when we added a low-voltage/millisecond-pulse treatment to the adenovirus/cell mixture. This increase, reflecting enhanced virus penetration, was proportional to the applied electric field amplitude and pulse number, but was not associated with membrane permeabilization, nor to direct cell modifications. We demonstrated that this effect is mainly due to adenovirus particle interactions with aggregated aluminum particles released from energized electrodes. Indeed, after centrifugation of the pulsed viral suspension and later on addition to cells, the activity was found mainly associated with the aluminum aggregates concentrated in the lower fraction and was proportional to generated quantities. Overall, this work focused on the use of electrotransfer to facilitate the adenovirus entry into cell, demonstrating that modifications of the penetrating agent can be more important than modifications of the target cell for transfer efficacy.
format	article
author	Angela Tesse Franck M. André Thierry Ragot
author_facet	Angela Tesse Franck M. André Thierry Ragot
author_sort	Angela Tesse
title	Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells
title_short	Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells
title_full	Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells
title_fullStr	Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells
title_full_unstemmed	Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells
title_sort	aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in l929 cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1779cd4d627b483688d7f8a47ef2409d
work_keys_str_mv	AT angelatesse aluminumparticlesgeneratedduringmillisecondelectricpulseapplicationenhanceadenovirusmediatedgenetransferinl929cells AT franckmandre aluminumparticlesgeneratedduringmillisecondelectricpulseapplicationenhanceadenovirusmediatedgenetransferinl929cells AT thierryragot aluminumparticlesgeneratedduringmillisecondelectricpulseapplicationenhanceadenovirusmediatedgenetransferinl929cells
_version_	1718381011798065152

Aluminum particles generated during millisecond electric pulse application enhance adenovirus-mediated gene transfer in L929 cells

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