Cargando…
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...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624362/ https://www.ncbi.nlm.nih.gov/pubmed/34834323 http://dx.doi.org/10.3390/pharmaceutics13111908 |
_version_ | 1784606155843043328 |
---|---|
author | Edelblute, Chelsea Mangiamele, Cathryn Heller, Richard |
author_facet | Edelblute, Chelsea Mangiamele, Cathryn Heller, Richard |
author_sort | Edelblute, Chelsea |
collection | PubMed |
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 | Online Article Text |
id | pubmed-8624362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86243622021-11-27 Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin Edelblute, Chelsea Mangiamele, Cathryn Heller, Richard Pharmaceutics Article 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. MDPI 2021-11-11 /pmc/articles/PMC8624362/ /pubmed/34834323 http://dx.doi.org/10.3390/pharmaceutics13111908 Text en © 2021 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 Edelblute, Chelsea Mangiamele, Cathryn Heller, Richard Moderate Heat-Assisted Gene Electrotransfer as a Potential Delivery Approach for Protein Replacement Therapy through the Skin |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624362/ https://www.ncbi.nlm.nih.gov/pubmed/34834323 http://dx.doi.org/10.3390/pharmaceutics13111908 |
work_keys_str_mv | AT edelblutechelsea moderateheatassistedgeneelectrotransferasapotentialdeliveryapproachforproteinreplacementtherapythroughtheskin AT mangiamelecathryn moderateheatassistedgeneelectrotransferasapotentialdeliveryapproachforproteinreplacementtherapythroughtheskin AT hellerrichard moderateheatassistedgeneelectrotransferasapotentialdeliveryapproachforproteinreplacementtherapythroughtheskin |