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Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats
Development of efficient vectors for transfection is one of the major challenges in genetic engineering. Previous research demonstrated that cationic derivatives of polyisoprenoids (PTAI) may serve as carriers of nucleic acids. In the present study, the effectiveness of two PTAI-based formulations (...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846535/ https://www.ncbi.nlm.nih.gov/pubmed/32767051 http://dx.doi.org/10.1007/s10528-020-09992-9 |
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author | Gawrys, Olga Rak, Monika Baranowska, Iwona Bobis-Wozowicz, Sylwia Szaro, Karolina Madeja, Zbigniew Swiezewska, Ewa Masnyk, Marek Chmielewski, Marek Karnas, Elzbieta Kompanowska-Jezierska, Elzbieta |
author_facet | Gawrys, Olga Rak, Monika Baranowska, Iwona Bobis-Wozowicz, Sylwia Szaro, Karolina Madeja, Zbigniew Swiezewska, Ewa Masnyk, Marek Chmielewski, Marek Karnas, Elzbieta Kompanowska-Jezierska, Elzbieta |
author_sort | Gawrys, Olga |
collection | PubMed |
description | Development of efficient vectors for transfection is one of the major challenges in genetic engineering. Previous research demonstrated that cationic derivatives of polyisoprenoids (PTAI) may serve as carriers of nucleic acids. In the present study, the effectiveness of two PTAI-based formulations (PTAI-6–8 and 10–14) was investigated and compared to the commercial reagents. The purpose of applied gene therapy was to enhance the expression of vascular endothelial growth factor (VEGF-A) in the renal medulla of spontaneously hypertensive rats (SHR) and to test its potential as a novel antihypertensive intervention. In the first part of the study (in vitro), we confirmed that PTAI-based lipoplexes efficiently transfect XC rat sarcoma cells and are stable in 37 °C for 7 days. In the in vivo experiments, we administered selected lipoplexes directly to the kidneys of conscious SHR (via osmotic pumps). There were no blood pressure changes and VEGF-A level in renal medulla was significantly higher only for PTAI-10–14-based formulation. In conclusion, despite the promising results, we were not able to achieve VEGF-A expression level high enough to verify VEGF-A gene therapy usefulness in SHR. However, results of our study give important indications for the future development of PTAI-based DNA carriers and kidney-targeted gene delivery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10528-020-09992-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7846535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-78465352021-02-11 Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats Gawrys, Olga Rak, Monika Baranowska, Iwona Bobis-Wozowicz, Sylwia Szaro, Karolina Madeja, Zbigniew Swiezewska, Ewa Masnyk, Marek Chmielewski, Marek Karnas, Elzbieta Kompanowska-Jezierska, Elzbieta Biochem Genet Original Article Development of efficient vectors for transfection is one of the major challenges in genetic engineering. Previous research demonstrated that cationic derivatives of polyisoprenoids (PTAI) may serve as carriers of nucleic acids. In the present study, the effectiveness of two PTAI-based formulations (PTAI-6–8 and 10–14) was investigated and compared to the commercial reagents. The purpose of applied gene therapy was to enhance the expression of vascular endothelial growth factor (VEGF-A) in the renal medulla of spontaneously hypertensive rats (SHR) and to test its potential as a novel antihypertensive intervention. In the first part of the study (in vitro), we confirmed that PTAI-based lipoplexes efficiently transfect XC rat sarcoma cells and are stable in 37 °C for 7 days. In the in vivo experiments, we administered selected lipoplexes directly to the kidneys of conscious SHR (via osmotic pumps). There were no blood pressure changes and VEGF-A level in renal medulla was significantly higher only for PTAI-10–14-based formulation. In conclusion, despite the promising results, we were not able to achieve VEGF-A expression level high enough to verify VEGF-A gene therapy usefulness in SHR. However, results of our study give important indications for the future development of PTAI-based DNA carriers and kidney-targeted gene delivery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10528-020-09992-9) contains supplementary material, which is available to authorized users. Springer US 2020-08-06 2021 /pmc/articles/PMC7846535/ /pubmed/32767051 http://dx.doi.org/10.1007/s10528-020-09992-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Gawrys, Olga Rak, Monika Baranowska, Iwona Bobis-Wozowicz, Sylwia Szaro, Karolina Madeja, Zbigniew Swiezewska, Ewa Masnyk, Marek Chmielewski, Marek Karnas, Elzbieta Kompanowska-Jezierska, Elzbieta Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats |
title | Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats |
title_full | Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats |
title_fullStr | Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats |
title_full_unstemmed | Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats |
title_short | Polyprenol-Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats |
title_sort | polyprenol-based lipofecting agents for in vivo delivery of therapeutic dna to treat hypertensive rats |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846535/ https://www.ncbi.nlm.nih.gov/pubmed/32767051 http://dx.doi.org/10.1007/s10528-020-09992-9 |
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