Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin

Gene-based approaches for protein replacement therapies have the potential to reduce the number of administrations. Our previous work demonstrated that expression could be enhanced and/or the applied voltage reduced by preheating the tissue prior to pulse administration. In the current study, we uti...

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Autores principales:	Chelsea Edelblute, Cathryn Mangiamele, Richard Heller
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	electrotransfer gene delivery electroporation gene therapy multi-electrode array Factor IX Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/35b2e5e109234f19a494aeaecbd72376
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spelling	oai:doaj.org-article:35b2e5e109234f19a494aeaecbd723762021-11-25T18:41:42ZModerate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin10.3390/pharmaceutics131119081999-4923https://doaj.org/article/35b2e5e109234f19a494aeaecbd723762021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1908https://doaj.org/toc/1999-4923Gene-based approaches for protein replacement therapies have the potential to reduce the number of administrations. Our previous work demonstrated that expression could be enhanced and/or the applied voltage reduced by preheating the tissue prior to pulse administration. In the current study, we utilized our 16-pin multi-electrode array (MEA) and incorporated nine optical fibers, connected to an infrared laser, between each set of four electrodes to heat the tissue to 43 °C. For proof of principle, a guinea pig model was used to test delivery of reporter genes. We observed that when the skin was preheated, it was possible to achieve the same expression levels as gene electrotransfer without preheating, but with a 23% reduction of applied voltage or a 50% reduction of pulse number. With respect to expression distribution, preheating allowed for delivery to the deep dermis and muscle. This suggested that this cutaneous delivery approach has the potential to achieve expression in the systemic circulation, thus this protocol was repeated using a plasmid encoding Human Factor IX. Elevated Factor IX serum protein levels were detected by ELISA up to 100 days post gene delivery. Further work will involve optimizing protein levels and scalability in an effort to reduce application frequency.Chelsea EdelbluteCathryn MangiameleRichard HellerMDPI AGarticleelectrotransfergene deliveryelectroporationgene therapymulti-electrode arrayFactor IXPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1908, p 1908 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	electrotransfer gene delivery electroporation gene therapy multi-electrode array Factor IX Pharmacy and materia medica RS1-441
spellingShingle	electrotransfer gene delivery electroporation gene therapy multi-electrode array Factor IX Pharmacy and materia medica RS1-441 Chelsea Edelblute Cathryn Mangiamele Richard Heller Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin
description	Gene-based approaches for protein replacement therapies have the potential to reduce the number of administrations. Our previous work demonstrated that expression could be enhanced and/or the applied voltage reduced by preheating the tissue prior to pulse administration. In the current study, we utilized our 16-pin multi-electrode array (MEA) and incorporated nine optical fibers, connected to an infrared laser, between each set of four electrodes to heat the tissue to 43 °C. For proof of principle, a guinea pig model was used to test delivery of reporter genes. We observed that when the skin was preheated, it was possible to achieve the same expression levels as gene electrotransfer without preheating, but with a 23% reduction of applied voltage or a 50% reduction of pulse number. With respect to expression distribution, preheating allowed for delivery to the deep dermis and muscle. This suggested that this cutaneous delivery approach has the potential to achieve expression in the systemic circulation, thus this protocol was repeated using a plasmid encoding Human Factor IX. Elevated Factor IX serum protein levels were detected by ELISA up to 100 days post gene delivery. Further work will involve optimizing protein levels and scalability in an effort to reduce application frequency.
format	article
author	Chelsea Edelblute Cathryn Mangiamele Richard Heller
author_facet	Chelsea Edelblute Cathryn Mangiamele Richard Heller
author_sort	Chelsea Edelblute
title	Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin
title_short	Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin
title_full	Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin
title_fullStr	Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin
title_full_unstemmed	Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin
title_sort	moderate heat-assisted gene electrotransfer as a potential delivery approach for protein replacement therapy through the skin
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/35b2e5e109234f19a494aeaecbd72376
work_keys_str_mv	AT chelseaedelblute moderateheatassistedgeneelectrotransferasapotentialdeliveryapproachforproteinreplacementtherapythroughtheskin AT cathrynmangiamele moderateheatassistedgeneelectrotransferasapotentialdeliveryapproachforproteinreplacementtherapythroughtheskin AT richardheller moderateheatassistedgeneelectrotransferasapotentialdeliveryapproachforproteinreplacementtherapythroughtheskin
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Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin

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