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Translational Advances of Hydrofection by Hydrodynamic Injection

Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic...

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Autores principales: Sendra, Luis, Herrero, María José, Aliño, Salvador F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867857/
https://www.ncbi.nlm.nih.gov/pubmed/29494564
http://dx.doi.org/10.3390/genes9030136
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author Sendra, Luis
Herrero, María José
Aliño, Salvador F.
author_facet Sendra, Luis
Herrero, María José
Aliño, Salvador F.
author_sort Sendra, Luis
collection PubMed
description Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic symptoms and signs. The therapeutic potential of hydrofection led different groups to work on the clinical translation of the procedure. In order to prevent the hemodynamic side effects derived from the rapid injection of a large volume, the conditions had to be moderated to make them compatible with its use in mid-size animal models such as rat, hamster and rabbit and large animals as dog, pig and primates. Despite the different approaches performed to adapt the conditions of gene delivery, the results obtained in any of these mid-size and large animals have been poorer than those obtained in murine model. Among these different strategies to reduce the volume employed, the most effective one has been to exclude the vasculature of the target organ and inject the solution directly. This procedure has permitted, by catheterization and surgical procedures in large animals, achieving protein expression levels in tissue close to those achieved in gold standard models. These promising results and the possibility of employing these strategies to transfer gene constructs able to edit genes, such as CRISPR, have renewed the clinical interest of this procedure of gene transfer. In order to translate the hydrodynamic gene delivery to human use, it is demanding the standardization of the procedure conditions and the molecular parameters of evaluation in order to be able to compare the results and establish a homogeneous manner of expressing the data obtained, as ‘classic’ drugs.
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spelling pubmed-58678572018-03-27 Translational Advances of Hydrofection by Hydrodynamic Injection Sendra, Luis Herrero, María José Aliño, Salvador F. Genes (Basel) Review Hydrodynamic gene delivery has proven to be a safe and efficient procedure for gene transfer, able to mediate, in murine model, therapeutic levels of proteins encoded by the transfected gene. In different disease models and targeting distinct organs, it has been demonstrated to revert the pathologic symptoms and signs. The therapeutic potential of hydrofection led different groups to work on the clinical translation of the procedure. In order to prevent the hemodynamic side effects derived from the rapid injection of a large volume, the conditions had to be moderated to make them compatible with its use in mid-size animal models such as rat, hamster and rabbit and large animals as dog, pig and primates. Despite the different approaches performed to adapt the conditions of gene delivery, the results obtained in any of these mid-size and large animals have been poorer than those obtained in murine model. Among these different strategies to reduce the volume employed, the most effective one has been to exclude the vasculature of the target organ and inject the solution directly. This procedure has permitted, by catheterization and surgical procedures in large animals, achieving protein expression levels in tissue close to those achieved in gold standard models. These promising results and the possibility of employing these strategies to transfer gene constructs able to edit genes, such as CRISPR, have renewed the clinical interest of this procedure of gene transfer. In order to translate the hydrodynamic gene delivery to human use, it is demanding the standardization of the procedure conditions and the molecular parameters of evaluation in order to be able to compare the results and establish a homogeneous manner of expressing the data obtained, as ‘classic’ drugs. MDPI 2018-03-01 /pmc/articles/PMC5867857/ /pubmed/29494564 http://dx.doi.org/10.3390/genes9030136 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sendra, Luis
Herrero, María José
Aliño, Salvador F.
Translational Advances of Hydrofection by Hydrodynamic Injection
title Translational Advances of Hydrofection by Hydrodynamic Injection
title_full Translational Advances of Hydrofection by Hydrodynamic Injection
title_fullStr Translational Advances of Hydrofection by Hydrodynamic Injection
title_full_unstemmed Translational Advances of Hydrofection by Hydrodynamic Injection
title_short Translational Advances of Hydrofection by Hydrodynamic Injection
title_sort translational advances of hydrofection by hydrodynamic injection
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867857/
https://www.ncbi.nlm.nih.gov/pubmed/29494564
http://dx.doi.org/10.3390/genes9030136
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